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1.  Assessing and Responding to Palliative Care Needs in Rural Sub-Saharan Africa: Results from a Model Intervention and Situation Analysis in Malawi 
PLoS ONE  2014;9(10):e110457.
Introduction
Palliative care is rarely accessible in rural sub-Saharan Africa. Partners In Health and the Malawi government established the Neno Palliative Care Program (NPCP) to provide palliative care in rural Neno district. We conducted a situation analysis to evaluate early NPCP outcomes and better understand palliative care needs, knowledge, and preferences.
Methods
Employing rapid evaluation methodology, we collected data from 3 sources: 1) chart review of all adult patients from the NPCP’s first 9 months; 2) structured interviews with patients and caregivers; 3) semi-structured interviews with key stakeholders.
Results
The NPCP enrolled 63 patients in its first 9 months. Frequent diagnoses were cancer (n = 50, 79%) and HIV/AIDS (n = 37 of 61, 61%). Nearly all (n = 31, 84%) patients with HIV/AIDS were on antiretroviral therapy. Providers registered 112 patient encounters, including 22 (20%) home visits. Most (n = 43, 68%) patients had documented pain at baseline, of whom 23 (53%) were treated with morphine. A majority (n = 35, 56%) had ≥1 follow-up encounter. Mean African Palliative Outcome Scale pain score decreased non-significantly between baseline and follow-up (3.0 vs. 2.7, p = 0.5) for patients with baseline pain and complete pain assessment documentation. Providers referred 48 (76%) patients for psychosocial services, including community health worker support, socioeconomic assistance, or both. We interviewed 36 patients referred to the NPCP after the chart review period. Most had cancer (n = 19, 53%) or HIV/AIDS (n = 10, 28%). Patients frequently reported needing income (n = 24, 67%) or food (n = 22, 61%). Stakeholders cited a need to make integrated palliative care widely available.
Conclusions
We identified a high prevalence of pain and psychosocial needs among patients with serious chronic illnesses in rural Malawi. Early NPCP results suggest that comprehensive palliative care can be provided in rural Africa by integrating disease-modifying treatment and palliative care, linking hospital, clinic, and home-based services, and providing psychosocial support that includes socioeconomic assistance.
doi:10.1371/journal.pone.0110457
PMCID: PMC4197005  PMID: 25313997
2.  Novel open-source electronic medical records system for palliative care in low-resource settings 
BMC Palliative Care  2013;12:31.
Background
The need for palliative care in sub-Saharan Africa is staggering: this region shoulders over 67% of the global burden of HIV/AIDS and cancer. However, provisions for these essential services remain limited and poorly integrated with national health systems in most nations. Moreover, the evidence base for palliative care in the region remains scarce. This study chronicles the development and evaluation of DataPall, an open-source electronic medical records system that can be used to track patients, manage data, and generate reports for palliative care providers in these settings.
DataPall was developed using design criteria encompassing both functional and technical objectives articulated by hospital leaders and palliative care staff at a leading palliative care center in Malawi. The database can be used with computers that run Windows XP SP 2 or newer, and does not require an internet connection for use. Subsequent to its development and implementation in two hospitals, DataPall was tested among both trained and untrained hospital staff populations on the basis of its usability with comparison to existing paper records systems as well as on the speed at which users could perform basic database functions. Additionally, all participants evaluated this program on a standard system usability scale.
Results
In a study of health professionals in a Malawian hospital, DataPall enabled palliative care providers to find patients’ appointments, on average, in less than half the time required to locate the same record in current paper records. Moreover, participants generated customizable reports documenting patient records and comprehensive reports on providers’ activities with little training necessary. Participants affirmed this ease of use on the system usability scale.
Conclusions
DataPall is a simple, effective electronic medical records system that can assist in developing an evidence base of clinical data for palliative care in low resource settings. The system is available at no cost, is specifically designed to chronicle care in the region, and is catered to meet the technical needs and user specifications of such facilities.
doi:10.1186/1472-684X-12-31
PMCID: PMC3751569  PMID: 23941694
Palliative care; Electronic medical records system; Evidence-based medicine; Africa; Database
3.  Palliative care for HIV in the era of antiretroviral therapy availability: perspectives of nurses in Lesotho 
BMC Palliative Care  2009;8:11.
Background
Southern Africa is disproportionately affected by the HIV/AIDS epidemic. In Lesotho 23% of adults are HIV-positive, and only 26% of those in need are accessing antiretroviral treatment (ART). Consequently, about 18,000 people die from AIDS each year. In this situation, palliative care is needed towards the end of life, but is also recommended throughout the HIV disease trajectory. The World Health Organisation (WHO) has produced the Integrated Management of Adolescent and Adult Illness (IMAI) guidelines, which includes a palliative care guidebook (as well as acute and chronic ART guidebooks). IMAI aims to facilitate the implementation of integrated HIV/AIDS care in resource-poor areas. The opinions of health workers towards this integrated approach to care and the use of IMAI has not been considered in previous research studies. This paper therefore aims to address some of these issues.
Methods
Semi-structured interviews were conducted with six key informants and ten nurses in Lesotho. The interviews were transcribed verbatim and analysed using content thematic analysis.
Results
Many nurses described palliative care as synonymous with chronic care and felt that palliative care is necessary for HIV-positive patients despite the introduction of ART. It was thought that the approach taken should be holistic and integrated throughout the disease trajectory. Pain management was noted to be a particular area of need for palliative care, and it was suggested that this could be improved in Lesotho. The IMAI guidelines were thought to be useful, but knowledge of the palliative care booklet was limited.
Conclusion
Palliative care remains necessary for HIV despite the increasing availability of ART. However, it is currently significantly lacking in Lesotho and many other sub-Saharan African countries. Greater understanding of palliative care amongst health workers is required, as well as strong political will from the Ministry of Health. The IMAI guidelines are a useful tool for holistic HIV care, including palliative care, but they need to be used more effectively. As ART is becoming increasingly available worldwide, the complex chronic care issues for patients with HIV/AIDS should not be neglected.
doi:10.1186/1472-684X-8-11
PMCID: PMC2734542  PMID: 19682391
4.  Barriers to Provider-Initiated Testing and Counselling for Children in a High HIV Prevalence Setting: A Mixed Methods Study 
PLoS Medicine  2014;11(5):e1001649.
Rashida Ferrand and colleagues combine quantitative and qualitative methods to investigate HIV prevalence among older children receiving primary care in Harare, Zimbabwe, and reasons why providers did not pursue testing.
Please see later in the article for the Editors' Summary
Background
There is a substantial burden of HIV infection among older children in sub-Saharan Africa, the majority of whom are diagnosed after presentation with advanced disease. We investigated the provision and uptake of provider-initiated HIV testing and counselling (PITC) among children in primary health care facilities, and explored health care worker (HCW) perspectives on providing HIV testing to children.
Methods and Findings
Children aged 6 to 15 y attending six primary care clinics in Harare, Zimbabwe, were offered PITC, with guardian consent and child assent. The reasons why testing did not occur in eligible children were recorded, and factors associated with HCWs offering and children/guardians refusing HIV testing were investigated using multivariable logistic regression. Semi-structured interviews were conducted with clinic nurses and counsellors to explore these factors. Among 2,831 eligible children, 2,151 (76%) were offered PITC, of whom 1,534 (54.2%) consented to HIV testing. The main reasons HCWs gave for not offering PITC were the perceived unsuitability of the accompanying guardian to provide consent for HIV testing on behalf of the child and lack of availability of staff or HIV testing kits. Children who were asymptomatic, older, or attending with a male or a younger guardian had significantly lower odds of being offered HIV testing. Male guardians were less likely to consent to their child being tested. 82 (5.3%) children tested HIV-positive, with 95% linking to care. Of the 940 guardians who tested with the child, 186 (19.8%) were HIV-positive.
Conclusions
The HIV prevalence among children tested was high, highlighting the need for PITC. For PITC to be successfully implemented, clear legislation about consent and guardianship needs to be developed, and structural issues addressed. HCWs require training on counselling children and guardians, particularly male guardians, who are less likely to engage with health care services. Increased awareness of the risk of HIV infection in asymptomatic older children is needed.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Over 3 million children globally are estimated to be living with HIV (the virus that causes AIDS). While HIV infection is most commonly spread through unprotected sex with an infected person, most HIV infections among children are the result of mother-to-child HIV transmission during pregnancy, delivery, or breastfeeding. Mother-to-child transmission can be prevented by administering antiretroviral therapy to mothers with HIV during pregnancy, delivery, and breast feeding, and to their newborn babies. According to a report by the Joint United Nations Programme on HIV/AIDS published in 2012, 92% of pregnant women with HIV were living in sub-Saharan Africa and just under 60% were receiving antiretroviral therapy. Consequently, sub-Saharan Africa is the region where most children infected with HIV live.
Why Was This Study Done?
If an opportunity to prevent mother-to-child transmission around the time of birth is missed, diagnosis of HIV infection in a child or adolescent is likely to depend on HIV testing in health care facilities. Health care provider–initiated HIV testing and counselling (PITC) for children is important in areas where HIV infection is common because earlier diagnosis allows children to benefit from care that can prevent the development of advanced HIV disease. Even if a child or adolescent appears to be in good health, access to care and antiretroviral therapy provides a health benefit to the individual over the long term. The administration of HIV testing (and counselling) to children relies not only on health care workers (HCWs) offering HIV testing but also on parents or guardians consenting for a child to be tested. However, more than 30% of children in countries with severe HIV epidemics are AIDS orphans, and economic conditions in these countries cause many adults to migrate for work, leaving children under the care of extended families. This study aimed to investigate the reasons for acceptance and rejection of PITC in primary health care settings in Harare, Zimbabwe. By exploring HCW perspectives on providing HIV testing to children and adolescents, the study also sought to gain insight into factors that could be hindering implementation of testing procedures.
What Did the Researchers Do and Find?
The researchers identified all children aged 6 to 15 years old at six primary care clinics in Harare, who were offered HIV testing as part of routine care between 22 January and 31 May 2013. Study fieldworkers collected data on numbers of child attendances, numbers offered testing, numbers who underwent HIV testing, and reasons why HIV testing did not occur. During the study 2,831 children attending the health clinics were eligible for PITC, and just over half (1,534, 54.2%) underwent HIV testing. Eighty-two children tested HIV-positive, and nearly all of them received counselling, medication, and follow-up care. HCWs offered the test to around 75% of those eligible. The most frequent explanation given by HCWs for a diagnostic test not being offered was that the child was accompanied by a guardian not appropriate for providing consent (401 occasions, 59%); Other reasons given were a lack of available counsellors or test kits and counsellors refusing to conduct the test. The likelihood of being offered the test was lower for children not exhibiting symptoms (such as persistent skin problems), older children, or those attending with a male or a younger guardian. In addition, over 100 guardians or parents provided consent but left before the child could be tested.
The researchers also conducted semi-structured interviews with 12 clinic nurses and counsellors (two from each clinic) to explore challenges to implementation of PITC. The researchers recorded the factors associated with testing not taking place, either when offered to eligible children or when HCWs declined to offer the test. The interviewees identified the frequent absence or unavailability of parents or legal guardians as an obstacle, and showed uncertainty or misconceptions around whether testing of the guardian was mandatory (versus recommended) and whether specifically a parent (if one was living) must provide consent. The interviews also revealed HCW concerns about the availability of adequate counselling and child services, and fears that a child might experience maltreatment if he or she tested positive. HCWs also noted long waiting times and test kits being out of stock as practical hindrances to testing.
What Do These Findings Mean?
Prevalence of HIV was high among the children tested, validating the need for PITC in sub-Saharan health care settings. Although 76% of eligible attendees were offered testing, the authors note that this is likely higher than in routine settings because the researchers were actively recording reasons for not offering testing and counselling, which may have encouraged heath care staff to offer PITC more often than usual. The researchers outline strategies that may improve PITC rates and testing acceptance for Zimbabwe and other sub-Saharan settings. These strategies include developing clear laws and guidance concerning guardianship and proxy consent when testing older children for HIV, training HCWs around these policies, strengthening legislation to address discrimination, and increasing public awareness about HIV infection in older children.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001649.
This study is further discussed in a PLOS Medicine Perspective by Davies and Kalk
The Joint United Nations Programme on HIV/AIDS publishes an annual report on the global AIDS epidemic, which provides information on progress towards eliminating new HIV infections
The World Health Organization has more information on mother-to-child transmission of HIV
The World Health Organization's website also has information about treatment for children living with HIV
Personal stories about living with HIV/AIDS, including stories from young people infected with HIV, are available through Avert, through NAM/aidsmap, and through the charity website Healthtalkonline
doi:10.1371/journal.pmed.1001649
PMCID: PMC4035250  PMID: 24866209
5.  Retention in HIV Care between Testing and Treatment in Sub-Saharan Africa: A Systematic Review 
PLoS Medicine  2011;8(7):e1001056.
In this systematic review, Sydney Rosen and Matthew Fox find that less than one-third of patients who tested positive for HIV, but were not eligible for antiretroviral therapy (ART) when diagnosed, were retained in pre-ART care continuously.
Background
Improving the outcomes of HIV/AIDS treatment programs in resource-limited settings requires successful linkage of patients testing positive for HIV to pre–antiretroviral therapy (ART) care and retention in pre-ART care until ART initiation. We conducted a systematic review of pre-ART retention in care in Africa.
Methods and Findings
We searched PubMed, ISI Web of Knowledge, conference abstracts, and reference lists for reports on the proportion of adult patients retained between any two points between testing positive for HIV and initiating ART in sub-Saharan African HIV/AIDS care programs. Results were categorized as Stage 1 (from HIV testing to receipt of CD4 count results or clinical staging), Stage 2 (from staging to ART eligibility), or Stage 3 (from ART eligibility to ART initiation). Medians (ranges) were reported for the proportions of patients retained in each stage. We identified 28 eligible studies. The median proportion retained in Stage 1 was 59% (35%–88%); Stage 2, 46% (31%–95%); and Stage 3, 68% (14%–84%). Most studies reported on only one stage; none followed a cohort of patients through all three stages. Enrollment criteria, terminology, end points, follow-up, and outcomes varied widely and were often poorly defined, making aggregation of results difficult. Synthesis of findings from multiple studies suggests that fewer than one-third of patients testing positive for HIV and not yet eligible for ART when diagnosed are retained continuously in care, though this estimate should be regarded with caution because of review limitations.
Conclusions
Studies of retention in pre-ART care report substantial loss of patients at every step, starting with patients who do not return for their initial CD4 count results and ending with those who do not initiate ART despite eligibility. Better health information systems that allow patients to be tracked between service delivery points are needed to properly evaluate pre-ART loss to care, and researchers should attempt to standardize the terminology, definitions, and time periods reported.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Since 1981, AIDS has killed more than 25 million people, and about 33 million people (mostly living in low- and middle-income countries) are now infected with HIV, the virus that causes AIDS. HIV gradually destroys immune system cells (including CD4 cells, a type of lymphocyte), leaving infected individuals susceptible to other infections. Early in the AIDS epidemic, most HIV-infected people died within ten years of infection. Then, in 1996, highly active antiretroviral therapy (ART) became available, and, for people living in developed countries, HIV infection became a chronic condition. Unfortunately, ART was extremely expensive, and HIV/AIDS remained a fatal illness for people living in developing countries. In 2003, governments, international agencies, and funding bodies began to implement plans to increase ART coverage in resource-limited countries. By the end of 2009, about a third of the people in these countries who needed ART (HIV-positive people whose CD4 count had dropped so low that they could not fight other infections) were receiving treatment.
Why Was This Study Done?
Unfortunately, many HIV-positive people in resource-limited countries who receive ART still do not have a normal life expectancy, often because they start ART when they have a very low CD4 count. ART is more successful if it is started before the CD4 count falls far below 350 cells/mm3 of blood, the threshold recommended by the World Health Organization for ART initiation. Thus, if the outcomes of HIV/AIDS programs in resource-limited settings are to be improved, all individuals testing positive for HIV must receive continuous pre-ART care that includes regular CD4 counts to ensure that ART is initiated as soon as they become eligible for treatment. Before interventions can be developed to achieve this aim, it is necessary to understand where and when patients are lost to pre-ART care. In this systematic review (a study that uses predefined criteria to identify all the research on a given topic), the researchers investigate the retention of HIV-positive adults in pre-ART care in sub-Saharan Africa.
What Did the Researchers Do and Find?
The researchers identified 28 studies that included data on the proportion of adult patients retained between any two time points between testing positive for HIV and starting ART in HIV/AIDS care programs in sub-Saharan Africa. They defined three stages of pre-ART care: Stage 1, the interval between testing positive for HIV and receiving CD4 count results or being clinically assessed; Stage 2, the interval between enrollment in pre-ART care and the determination of eligibility for ART; and Stage 3, the interval between being deemed eligible for ART and treatment initiation. A median of 59% of patients were retained in Stage 1 of pre-ART care, 46% were retained in Stage 2, and 68% were retained in Stage 3. Retention rates in each stage differed greatly between studies—between 14% and 84% for Stage 3 pre-ART care, for example. Because the enrollment criteria and other characteristics of the identified studies varied widely and were often poorly defined, it was hard to combine study results. Nevertheless, the researchers estimate that, taking all the studies together, less than one-third of patients testing positive for HIV but not eligible for ART when diagnosed were retained in pre-ART care continuously.
What Do These Findings Mean?
These findings suggest that there is a substantial loss of HIV-positive patients at every stage of pre-ART care in sub-Saharan Africa. Thus, some patients receiving a positive HIV test never return for the results of their initial CD4 count, some disappear between having an initial CD4 count and becoming eligible for ART, and others fail to initiate ART after having been found eligible for treatment. Because only a few studies were identified (half of which were undertaken in South Africa) and because the quality and design of some of these studies were suboptimal, the findings of this systematic review must be treated with caution. In particular, the estimate of the overall loss of patients during pre-ART care is likely to be imprecise. The researchers call, therefore, for the implementation of better health information systems that would allow patients to be tracked between service delivery points as a way to improve the evaluation and understanding of the loss of HIV-positive patients to pre-ART care in resource-limited countries.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001056.
Information is available from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS
HIV InSite has comprehensive information on all aspects of HIV/AIDS
Information is available from Avert, an international AIDS charity on many aspects of HIV/AIDS, including information on HIV/AIDS treatment and care, on HIV and AIDS in Africa and on universal access to AIDS treatment (in English and Spanish)
The World Health Organization provides information about universal access to AIDS treatment, including the 2010 progress report (in English, French and Spanish); its 2010 ART guidelines can be downloaded (in several languages)
The International AIDS Economics Network posts information about economic, social, and behavioral aspects of HIV care and treatment
Up-to-date research findings about HIV care and treatment are summarized by NAM/aidsmap
doi:10.1371/journal.pmed.1001056
PMCID: PMC3139665  PMID: 21811403
6.  Impact of Antiretroviral Therapy on Incidence of Pregnancy among HIV-Infected Women in Sub-Saharan Africa: A Cohort Study 
PLoS Medicine  2010;7(2):e1000229.
A multicountry cohort study in sub-Saharan Africa by Landon Myer and colleagues reveals higher pregnancy rates in HIV-infected women on antiretroviral therapy (ART).
Background
With the rapid expansion of antiretroviral therapy (ART) services in sub-Saharan Africa there is growing recognition of the importance of fertility and childbearing among HIV-infected women. However there are few data on whether ART initiation influences pregnancy rates.
Methods and Findings
We analyzed data from the Mother-to-Child Transmission-Plus (MTCT-Plus) Initiative, a multicountry HIV care and treatment program for women, children, and families. From 11 programs in seven African countries, women were enrolled into care regardless of HIV disease stage and followed at regular intervals; ART was initiated according to national guidelines on the basis of immunological and/or clinical criteria. Standardized forms were used to collect sociodemographic and clinical data, including incident pregnancies. Overall 589 incident pregnancies were observed among the 4,531 women included in this analysis (pregnancy incidence, 7.8/100 person-years [PY]). The rate of new pregnancies was significantly higher among women receiving ART (9.0/100 PY) compared to women not on ART (6.5/100 PY) (adjusted hazard ratio, 1.74; 95% confidence interval, 1.19–2.54). Other factors independently associated with increased risk of incident pregnancy included younger age, lower educational attainment, being married or cohabiting, having a male partner enrolled into the program, failure to use nonbarrier contraception, and higher CD4 cell counts.
Conclusions
ART use is associated with significantly higher pregnancy rates among HIV-infected women in sub-Saharan Africa. While the possible behavioral or biomedical mechanisms that may underlie this association require further investigation, these data highlight the importance of pregnancy planning and management as a critical but neglected component of HIV care and treatment services.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Human immunodeficiency virus (HIV) causes Acquired Immunodeficiency Syndrome (AIDS), which is a major global cause of disease and death. More than 33 million people around the world are infected with HIV, with nearly 5,500 dying daily from HIV and AIDS-related complications. HIV/AIDS is especially problematic in sub-Saharan Africa, where it is the leading cause of death. There is no cure for HIV/AIDS, but medicines known as “antiretroviral therapy” (ART) can prolong life and reduce complications in patients infected with HIV. 97% of patients with HIV/AIDS live in low- and middle-income countries. According to the World Health Organization, nearly 10 million of these patients need ART. As patients' access to treatment is often hindered by the high cost and low availability of ART, global health efforts have focused on promoting ART use in resource-limited nations. Such efforts also increase awareness of how HIV is spread (contact with blood or semen, in sexual intercourse, sharing needles, or from mother to child during childbirth). ART reduces, but does not remove, the chance of a mother's passing HIV to her child during birth.
Why Was This Study Done?
By the end of 2007, 3 million HIV-infected patients in poor countries were receiving ART. Many of those treated with ART are young women of child-bearing age. Childbirth is an important means of spreading HIV in sub-Saharan Africa, where 60% of all HIV patients are women. This study questions whether the improved health and life expectancy that results from treatment with ART affects pregnancy rates of HIV-infected patients. The study explores this question in seven African countries, by examining the rates of pregnancy in HIV-infected women before and after they started ART.
What Did the Researchers Do and Find?
The authors looked at the records of 4,531 HIV-infected women enrolled in the Mother-to-Child-Transmission-Plus (MTCT-Plus) Initiative in seven African countries. MTCT -Plus, begun in 2002, is a family-centered treatment program that offers regular checkups, blood tests, counseling, and ART treatment (if appropriate) to women and their families. At each checkup, women's CD4+ cell counts and World Health Organization guidelines were used to determine their eligibility for starting ART. Over a 4-year period, nearly a third of the women starting ART experienced a pregnancy: 244 pregnancies occurred in the “pre-ART” group (women not receiving ART) compared to 345 pregnancies in the “on-ART” group (women receiving ART). The chance of pregnancy increased over time in the on-ART group to almost 80% greater than the pre-ART group, while remaining relatively low and constant in the pre-ART group. The authors noted that, as expected, other factors also increased the chances of pregnancy, including younger age, lower educational status, and use of nonbarrier contraception such as injectable hormones.
What Do These Findings Mean?
This study suggests that starting ART is associated with higher pregnancy rates in sub-Saharan Africa, nearly doubling the chances of a woman becoming pregnant. The reasons for this link are unclear. One possible explanation is behavioral: women receiving ART may feel more motivated to have children as their health and quality of life improve. However, the study did not examine how pregnancy desires and sexual activity of women changed while on ART, and cannot discern why ART is linked to increased pregnancy. By using pregnancy data gathered from patient questionnaires rather than laboratory tests, the study is limited by the possibility of inaccurate patient reporting. Understanding how pregnancy rates vary in HIV-infected women receiving ART helps support the formation of responsive, effective HIV programs. Female HIV patients of child-bearing age, who form the majority of patients receiving ART in sub-Saharan Africa, would benefit from programs that combine starting HIV treatment with ART with education and contraception counseling and pregnancy-related care.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000229.
Information is available from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS
HIV InSite has comprehensive information on all aspects of HIV/AIDS, including a list of articles and other sources of information about the primary care of adolescents with HIV
A UNAIDS 2008 report is available on the global AIDS epidemic
The International Planned Parenthood Foundation provides information on sexual and reproductive health and HIV
The International Center for AIDS Care and Treatment Programs at the Columbia University Mailman School of Public health provides information to assist HIV care and treatment programs in resource-limited settings
doi:10.1371/journal.pmed.1000229
PMCID: PMC2817715  PMID: 20161723
7.  The Uptake and Accuracy of Oral Kits for HIV Self-Testing in High HIV Prevalence Setting: A Cross-Sectional Feasibility Study in Blantyre, Malawi 
PLoS Medicine  2011;8(10):e1001102.
Augustine Choko and colleagues assess the uptake and acceptability of home-based supervised oral HIV self-testing in Malawi, demonstrating the feasibility of this approach in a high-prevalence, low-income environment.
Background
Although HIV testing and counseling (HTC) uptake has increased dramatically in Africa, facility-based services are unlikely to ever meet ongoing need to the full. A major constraint in scaling up community and home-based HTC services is the unacceptability of receiving HTC from a provider known personally to prospective clients. We investigated the potential of supervised oral HIV self-testing from this perspective.
Methods and Findings
Adult members of 60 households and 72 members of community peer groups in urban Blantyre, Malawi, were selected using population-weighted random cluster sampling. Participants were offered self-testing plus confirmatory HTC (parallel testing with two rapid finger-prick blood tests), standard HTC alone, or no testing. 283 (95.6%) of 298 selected adults participated, including 136 (48.0%) men. 175 (61.8%) had previously tested (19 known HIV positive), although only 64 (21.5%) within the last year. HIV prevalence was 18.5%. Among 260 (91.9%) who opted to self-test after brief demonstration and illustrated instructions, accuracy was 99.2% (two false negatives). Although 98.5% rated the test “not hard at all to do,” 10.0% made minor procedural errors, and 10.0% required extra help. Most participants indicated willingness to accept self-test kits, but not HTC, from a neighbor (acceptability 94.5% versus 46.8%, p = 0.001).
Conclusions
Oral supervised self-testing was highly acceptable and accurate, although minor errors and need for supervisory support were common. This novel option has potential for high uptake at local community level if it can be supervised and safely linked to counseling and care.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
According to the World Health Organization, despite the dramatic increase in the acceptability of HIV testing, more than 60% of people living with HIV do not know their status—a factor that is seriously hampering the global response to the HIV epidemic. The inconvenience and cost involved in visiting services in addition to a general aversion to visiting health facilities appear to be major barriers. Home-based HIV-testing services bypass these obstacles and are being adopted as national policy in a number of countries. However, given the tension between confidentiality and convenience, many people do not want to be counseled and tested by someone they know well, thus creating logistical difficulties and added costs to the provision of home-based testing services.
Why Was This Study Done?
Self-testing in private has considerable potential to contribute to first-time and repeat HIV testing but raises a number of issues, such as accuracy, the potential for adverse psychological reactions in the absence of face-to-face counseling, and the difficulty in organizing subsequent links to HIV/AIDS care. Self-testing has been used for over a decade in the US, but given the need to further scale up HIV testing and counseling in Africa, and to encourage regular repeat testing, the researchers conducted a mixed quantitative and qualitative study of self-testing for HIV using oral test kits to test whether supervised oral self-testing could yield accurate results. The researchers also wanted to explore reasons for accepting self-testing and respondents' preferences for HIV testing.
What Did the Researchers Do and Find?
The researchers conducted their study in four community health worker catchment areas in three high-density residential suburbs of Blantyre, Malawi. Between March and July 2010, the researchers randomly selected two groups of participants from within these catchment areas and all adults were then invited to participate in interview and optional HIV testing and counseling carried out in their home. Participants were offered the choice between self-test for HIV followed by standard voluntary counseling and testing, standard voluntary counseling and testing only, and no HIV testing or counseling. Pre-and post-test counseling was provided to all participants and after self-testing, a counselor reread the self-test kit, completed a checklist of potential errors and confirmed the result using two rapid HIV test kits run in parallel from a finger-prick blood specimen. All participants testing positive were referred to the nearest primary health center.
All 260 participants who consented to voluntary counseling and testing also opted to self-test, with the remaining 23 (8.1%) choosing not to test. HIV prevalence was 18.5% (48 of 260) and HIV prevalence among participants who had previously tested HIV-negative or not tested at all was 12.0% (29 of 241 participants) meaning that less than half of HIV-infected participants were previously diagnosed, and just over half of undiagnosed HIV infections were in individuals who had previously tested HIV negative. The researchers found self-testing to be highly accurate, with clear and concordant results for 256 (99.2%) of 258 participants with both self-test and blood results. Overall sensitivity for self-test self-read was 97.9% with specificity of 100%. At exit interview, 256 (98.5%) of participants rated self-testing as “very easy” to do but additional help was requested by 26 (10%) of self test participants and procedural errors were identified for 26 participants (10%). Importantly, self-testing was the preferred option for future HIV tests for 56.4% of participants and the most common choice for both men and women.
What Do These Findings Mean?
The findings of this study show that self-testing for HIV (after a brief demonstration and illustrated instructions) is highly accurate and is widely accepted by the community, indicating that there is strong community readiness to adopt self-testing alongside other HIV counseling and testing strategies in high HIV prevalence settings in urban Africa. Self-testing may prove especially valuable for encouraging regular repeat testing, couple testing, and first-time testing in otherwise hard-to-reach groups such as men and older individuals. Finally, given the accuracy achieved and strong preferences around future testing, further exploration of self-testing options could help to make progress towards meeting universal access goals.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001102.
This study is further discussed in a PLoS Medicine Perspective by Walensky and Bassett
Recently published WHO Guidelines explain the principles and processes of adapting HIV guidelines into national programs
The U.S. Centers for Disease Control's initiative Act against AIDS has some user-friendly information on the different types of HIV tests available
A WHO document discusses existing practices and surrounding issues related with HIV self-testing among health workers in sub-Saharan Africa
doi:10.1371/journal.pmed.1001102
PMCID: PMC3186813  PMID: 21990966
8.  Mortality of HIV-Infected Patients Starting Antiretroviral Therapy in Sub-Saharan Africa: Comparison with HIV-Unrelated Mortality 
PLoS Medicine  2009;6(4):e1000066.
Comparing mortality rates between patients starting HIV treatment and the general population in four African countries, Matthias Egger and colleagues find the gap decreases over time, especially with early treatment.
Background
Mortality in HIV-infected patients who have access to highly active antiretroviral therapy (ART) has declined in sub-Saharan Africa, but it is unclear how mortality compares to the non-HIV–infected population. We compared mortality rates observed in HIV-1–infected patients starting ART with non-HIV–related background mortality in four countries in sub-Saharan Africa.
Methods and Findings
Patients enrolled in antiretroviral treatment programmes in Côte d'Ivoire, Malawi, South Africa, and Zimbabwe were included. We calculated excess mortality rates and standardised mortality ratios (SMRs) with 95% confidence intervals (CIs). Expected numbers of deaths were obtained using estimates of age-, sex-, and country-specific, HIV-unrelated, mortality rates from the Global Burden of Disease project. Among 13,249 eligible patients 1,177 deaths were recorded during 14,695 person-years of follow-up. The median age was 34 y, 8,831 (67%) patients were female, and 10,811 of 12,720 patients (85%) with information on clinical stage had advanced disease when starting ART. The excess mortality rate was 17.5 (95% CI 14.5–21.1) per 100 person-years SMR in patients who started ART with a CD4 cell count of less than 25 cells/µl and World Health Organization (WHO) stage III/IV, compared to 1.00 (0.55–1.81) per 100 person-years in patients who started with 200 cells/µl or above with WHO stage I/II. The corresponding SMRs were 47.1 (39.1–56.6) and 3.44 (1.91–6.17). Among patients who started ART with 200 cells/µl or above in WHO stage I/II and survived the first year of ART, the excess mortality rate was 0.27 (0.08–0.94) per 100 person-years and the SMR was 1.14 (0.47–2.77).
Conclusions
Mortality of HIV-infected patients treated with combination ART in sub-Saharan Africa continues to be higher than in the general population, but for some patients excess mortality is moderate and reaches that of the general population in the second year of ART. Much of the excess mortality might be prevented by timely initiation of ART.
Please see later in the article for Editors' Summary
Editors' Summary
Background
Acquired immunodeficiency syndrome (AIDS) has killed more than 25 million people since 1981 and more than 30 million people (22 million in sub-Saharan Africa alone) are now infected with the human immunodeficiency virus (HIV), which causes AIDS. HIV destroys immune system cells (including CD4 cells, a type of lymphocyte), leaving infected individuals susceptible to other infections. Early in the AIDS epidemic, most HIV-positive people died within ten years of infection. Then, in 1996, highly active antiretroviral therapy (ART)—combinations of powerful antiretroviral drugs—was developed and the life expectancy of HIV-infected people living in affluent countries improved dramatically. Now, in industrialized countries, all-cause mortality (death from any cause) among HIV-infected patients treated successfully with ART is similar to that of the general population and the mortality rate (the number of deaths in a population per year) among patients with HIV/AIDS is comparable to that among patients with diabetes and other chronic conditions.
Why Was This Study Done?
Unfortunately, combination ART is costly, so although HIV/AIDS quickly became a chronic disease in industrialized countries, AIDS deaths continued unabated among the millions of HIV-infected people living in low- and middle-income countries. Then, in 2003, governments, international agencies and funding bodies began to implement plans to increase ART coverage in developing countries. By the end of 2007, nearly three million people living with HIV/AIDS in these countries were receiving ART—nearly a third of the people who urgently need ART. In sub-Saharan Africa more than 2 million people now receive ART and mortality in HIV-infected patients who have access to ART is declining. However, no-one knows how mortality among HIV-infected people starting ART compares with non-HIV related mortality in sub-Saharan Africa. This information is needed to ensure that appropriate health services (including access to ART) are provided in this region. In this study, the researchers compare mortality rates among HIV-infected patients starting ART with non-HIV related mortality in the general population of four sub-Saharan countries.
What Did the Researchers Do and Find?
The researchers obtained estimates of the number of HIV-unrelated deaths and information about patients during their first two years on ART at five antiretroviral treatment programs in the Côte d'Ivoire, Malawi, South Africa, and Zimbabwe from the World Health Organization Global Burden of Disease (GBD) project and the International epidemiological Databases to Evaluate AIDS (IeDEA) initiative, respectively. They then calculated the excess mortality rates among the HIV-infected patients (the death rates in HIV-infected patients minus the national HIV-unrelated death rates) and the standardized mortality rate (SMR; the number of deaths among HIV-infected patients divided by the number of HIV-unrelated deaths in the general population). The excess mortality rate among HIV-infected people who started ART when they had a low CD4 cell count and clinically advanced disease was 17.5 per 100 person-years of follow-up. For HIV-infected people who started ART with a high CD4 cell count and early disease, the excess mortality rate was 1.0 per 100 person-years. The SMRs over two years of ART for these two groups of HIV-infected patients were 47.1 and 3.4, respectively. Finally, patients who started ART with a high CD4 cell count and early disease who survived the first year of ART had an excess mortality of only 0.27 per 100 person-years and an SMR over two years follow-up of only 1.14.
What Do These Findings Mean?
These findings indicate that mortality among HIV-infected people during the first two years of ART is higher than in the general population in these four sub-Saharan countries. However, for patients who start ART when they have a high CD4 count and clinically early disease, the excess mortality is moderate and similar to that associated with diabetes. Because the researchers compared the death rates among HIV-infected patients with estimates of national death rates rather than with estimates of death rates for the areas where the ART programs were located, these findings may not be completely accurate. Nevertheless, these findings support further expansion of strategies that increase access to ART in sub-Saharan Africa and suggest the excess mortality among HIV-infected patients in this region might be largely prevented by starting ART before an individual's HIV infection has progressed to advanced stages.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000066.
Information is available from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS
HIV InSite has comprehensive information on all aspects of HIV/AIDS
Information is available from Avert, an international AIDS charity on many aspects of HIV/AIDS including HIV and AIDS in Africa, providing AIDS drug treatment for millions, and on the stages of HIV infection
The World Health Organization provides information about universal access to HIV treatment and about the Global Burden of Disease project (in several languages)
More information about the International epidemiological Databases to evaluate AIDS initiative is available on the IeDEA Web site
doi:10.1371/journal.pmed.1000066
PMCID: PMC2667633  PMID: 19399157
9.  An educational intervention to reduce pain and improve pain management for Malawian people living with HIV/AIDS and their family carers: study protocol for a randomised controlled trial 
Trials  2013;14:216.
Background
Many HIV/AIDS patients experience pain often due to advanced HIV/AIDS infection and side effects of treatment. In sub-Saharan Africa, pain management for people with HIV/AIDS is suboptimal. With survival extended as a direct consequence of improved access to antiretroviral therapy, the prevalence of HIV/AIDS related pain is increasing. As most care is provided at home, the management of pain requires patient and family involvement. Pain education is an important aspect in the management of pain in HIV/AIDS patients. Studies of the effectiveness of pain education interventions for people with HIV/AIDS have been conducted almost exclusively in western countries.
Methods/design
A randomised controlled trial is being conducted at the HIV and palliative care clinics of two public hospitals in Malawi. To be eligible, patient participants must have a diagnosis of HIV/AIDS (stage III or IV). Carer participants must be the individual most involved in the patient’s unpaid care. Eligible participants are randomised to either: (1) a 30-minute face-to-face educational intervention covering pain assessment and management, augmented by a leaflet and follow-up telephone call at two weeks; or (2) usual care. Those allocated to the usual care group receive the educational intervention after follow-up assessments have been conducted (wait-list control group). The primary outcome is pain severity measured by the Brief Pain Inventory. Secondary outcomes are pain interference, patient knowledge of pain management, patient quality of life, carer knowledge of pain management, caregiver motivation and carer quality of life. Follow-up assessments are conducted eight weeks after randomisation by palliative care nurses blind to allocation.
Discussion
This randomised controlled trial conducted in sub-Saharan Africa among people living with HIV/AIDS and their carers will assess whether a pain education intervention is effective in reducing pain and improving pain management, quality of life and carer motivation.
Trial registration
Current Controlled Trials ISRCTN72861423.
doi:10.1186/1745-6215-14-216
PMCID: PMC3717041  PMID: 23849502
HIV/AIDS; Trial; Pain; Carers; Educational intervention; Palliative care
10.  An Autopsy Study of Maternal Mortality in Mozambique: The Contribution of Infectious Diseases 
PLoS Medicine  2008;5(2):e44.
Background
Maternal mortality is a major health problem concentrated in resource-poor regions. Accurate data on its causes using rigorous methods is lacking, but is essential to guide policy-makers and health professionals to reduce this intolerable burden. The aim of this study was to accurately describe the causes of maternal death in order to contribute to its reduction, in one of the regions of the world with the highest maternal mortality ratios.
Methods and Findings
We conducted a prospective study between October 2002 and December 2004 on the causes of maternal death in a tertiary-level referral hospital in Maputo, Mozambique, using complete autopsies with histological examination. HIV detection was done by virologic and serologic tests, and malaria was diagnosed by histological and parasitological examination. During 26 mo there were 179 maternal deaths, of which 139 (77.6%) had a complete autopsy and formed the basis of this analysis. Of those with test results, 65 women (52.8%) were HIV-positive. Obstetric complications accounted for 38.2% of deaths; haemorrhage was the most frequent cause (16.6%). Nonobstetric conditions accounted for 56.1% of deaths; HIV/AIDS, pyogenic bronchopneumonia, severe malaria, and pyogenic meningitis were the most common causes (12.9%, 12.2%, 10.1% and 7.2% respectively). Mycobacterial infection was found in 12 (8.6%) maternal deaths.
Conclusions
In this tertiary hospital in Mozambique, infectious diseases accounted for at least half of all maternal deaths, even though effective treatment is available for the four leading causes, HIV/AIDS, pyogenic bronchopneumonia, severe malaria, and pyogenic meningitis. These observations highlight the need to implement effective and available prevention tools, such as intermittent preventive treatment and insecticide-treated bed-nets for malaria, antiretroviral drugs for HIV/AIDS, or vaccines and effective antibiotics for pneumococcal and meningococcal diseases. Deaths due to obstetric causes represent a failure of health-care systems and require urgent improvement.
Clara Menendez and colleagues analyze 139 complete autopsies following maternal deaths in Maputo, Mozambique and find a predominance of infectious and preventable causes.
Editors' Summary
Background.
Every year, half a million women—many of them living in developing countries—die during pregnancy or childbirth or within a few weeks of delivery. (The term “maternal deaths” is used to designate such deaths.) For women living in sub-Saharan Africa, the situation is particularly grim. Half of all maternal deaths occur in this region. The maternal mortality ratio (MMR)—the number of maternal deaths per 100,000 live births—in sub-Saharan Africa is nearly 1,000; in industrialized countries it is 8. The lifetime risk of maternal death in sub-Saharan Africa is 1 in 22; in industrialized countries it is 1 in 8,000. Faced with the magnitude of the global maternal death toll, in September 2000 the United Nations pledged, as its fifth Millennium Development Goal, that the global MMR would be reduced to a quarter of its 1990 level by 2015. Currently, it seems unlikely that this target will be met. Between 1990 and 2005 global maternal deaths decreased by only 1% per annum. In sub-Saharan Africa the annual reduction was even less—0.1% per annum.
Why Was This Study Done?
One reason for this slow progress is that public-health professionals in developing countries rarely have accurate data about the causes of maternal death, information that they need to guide their efforts to reduce these deaths. A detailed examination of the body after death (a medical autopsy) is the only sure way to ascertain the causes of maternal death, but in most developing countries, clinical records and verbal autopsies (asking relatives about the circumstances of the mother's death) are the main sources of these data and neither source is optimally accurate. The currently available information indicates that birth (obstetric) complications are the most frequent causes of maternal death in developing countries, in particular, hemorrhage (uncontrollable bleeding) after the baby is born. However, little is known about the impact of the HIV/AIDS epidemic (which is worst in Sub-Saharan Africa), malaria, or other infectious diseases on maternal deaths. In this study, the researchers use complete autopsies to determine the causes of maternal death in the Maputo Central Hospital, Mozambique, a tertiary-level hospital to which women with high-risk pregnancies are referred for specialized care.
What Did the Researchers Do and Find?
Between October 2002 and December 2004, there were 179 maternal deaths in the Maputo Central Hospital and 31,135 live births, corresponding to a ratio of 874 maternal deaths per 100,000 live births. (Because the hospital was a referral center, this ratio would not be expected to reflect the actual MMR for the general population of the Maputo area.) Complete autopsies were done on 139 of the women, HIV infection was measured using standard tests, and malaria was diagnosed by looking for parasites and malaria-associated changes in postmortem samples. Of these 139 women, just over one-third died because of obstetric complications; hemorrhage was the most common cause of death (one in six maternal deaths). The commonest nonobstetric causes of maternal death were HIV/AIDS- related conditions, including infections and cancers (about 1 in 8 maternal deaths; about half the women in the study were HIV positive). Other common causes were pyogenic (pus-forming) bacterial infections of the lungs and brain, and malaria. Together, these infectious diseases accounted for nearly half of the maternal deaths.
What Do These Findings Mean?
These findings indicate that infectious diseases account for a large proportion of maternal deaths at Maputo Central Hospital and identify which obstetric complications are responsible for most maternal deaths in this setting. They may not, however, accurately reflect the causes of maternal death elsewhere in Mozambique. For example, maternal deaths from some obstetric complications may be over-represented in this study because women at risk of these complications would have been referred to this hospital. Conversely, the proportion of women dying from hemorrhage may be higher in the community because this complication usually happens shortly after birth, leaving little time for women to reach a hospital for treatment. Nevertheless, these findings suggest that the implementation of effective measures to prevent and treat HIV/AIDS, malaria, and infections with pyogenic bacteria, together with improvements in health services for obstetric complications, should greatly reduce the maternal death toll in Mozambique and perhaps in other countries in sub-Saharan Africa.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050044.
UNICEF (the United Nations Children's Fund) provides information on maternal mortality including the WHO/UNICEF/UNFPA/The World Bank) estimates of maternal mortality for 2005 by country, and an article on maternal mortality in the Cabo Delgado province of Mozambique
More information on the WHO/UNICEF/UNFPA/The World Bank estimates of maternal mortality in 2005
The UK Department for International Development provides information about Millenium Development Goal 5: the improvement of maternal health
The US Centers for Disease Control and Prevention has a page on pregnancy-related deaths (in English and Spanish)
The Partnership for Maternal, Newborn and Child Health provides information on maternal deaths (in English, Spanish, French, Russian, Arabic, and Chinese)
The United Nations Development Fund for Women (UNIFEM) focuses on improving conditions for women worldwide, especially those in poverty
doi:10.1371/journal.pmed.0050044
PMCID: PMC2245982  PMID: 18288887
11.  Treatment Outcomes and Cost-Effectiveness of Shifting Management of Stable ART Patients to Nurses in South Africa: An Observational Cohort 
PLoS Medicine  2011;8(7):e1001055.
Lawrence Long and colleagues report that “down-referring” stable HIV patients from a doctor-managed, hospital-based ART clinic to a nurse-managed primary health facility provides good health outcomes and cost-effective treatment for patients.
Background
To address human resource and infrastructure shortages, resource-constrained countries are being encouraged to shift HIV care to lesser trained care providers and lower level health care facilities. This study evaluated the cost-effectiveness of down-referring stable antiretroviral therapy (ART) patients from a doctor-managed, hospital-based ART clinic to a nurse-managed primary health care facility in Johannesburg, South Africa.
Methods and Findings
Criteria for down-referral were stable ART (≥11 mo), undetectable viral load within the previous 10 mo, CD4>200 cells/mm3, <5% weight loss over the last three visits, and no opportunistic infections. All patients down-referred from the treatment-initiation site to the down-referral site between 1 February 2008 and 1 January 2009 were compared to a matched sample of patients eligible for down-referral but not down-referred. Outcomes were assigned based on vital and health status 12 mo after down-referral eligibility and the average cost per outcome estimated from patient medical record data.
The down-referral site (n = 712) experienced less death and loss to follow up than the treatment-initiation site (n = 2,136) (1.7% versus 6.2%, relative risk = 0.27, 95% CI 0.15–0.49). The average cost per patient-year for those in care and responding at 12 mo was US$492 for down-referred patients and US$551 for patients remaining at the treatment-initiation site (p<0.0001), a savings of 11%. Down-referral was the cost-effective strategy for eligible patients.
Conclusions
Twelve-month outcomes of stable ART patients who are down-referred to a primary health clinic are as good as, or better than, the outcomes of similar patients who are maintained at a hospital-based ART clinic. The cost of treatment with down-referral is lower across all outcomes and would save 11% for patients who remain in care and respond to treatment. These results suggest that this strategy would increase treatment capacity and conserve resources without compromising patient outcomes.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
AIDS has killed more than 25 million people since 1981, and about 33 million people are now infected with HIV, the virus that causes AIDS. Because HIV destroys immune system cells, which leaves infected individuals susceptible to other infections, early in the AIDS epidemic, most HIV-infected people died within ten years of infection. Then, in 1996, antiretroviral therapy (ART), which can keep HIV in check for many years, became available. For people living in developed countries, HIV infection became a chronic condition, but people in developing countries were not so lucky—ART was prohibitively expensive and so a diagnosis of HIV infection remained a death sentence in many regions of the world. In 2003, this situation was declared a global health emergency, and governments, international agencies, and funding bodies began to implement plans to increase ART coverage in developing countries. As a result, nowadays, more than a third of people in low- and middle-income countries who need ART are receiving it.
Why Was This Study Done?
Unfortunately, shortages of human resources in developing countries are impeding progress toward universal ART coverage. In sub-Saharan Africa, for example, where two-thirds of all HIV-positive people live, there are too few doctors to supervise all the ART that is required. Various organizations are therefore encouraging a shift of clinical care responsibilities for people receiving ART from doctors to less highly trained, less expensive, and more numerous members of the clinical workforce. Thus, in South Africa, plans are underway to reduce the role of hospital doctors in ART and to increase the role of primary health clinic nurses. One specific strategy involves “down-referring” patients whose HIV infection is under control (“stable ART patients”) from a doctor-managed, hospital-based ART clinic to a nurse-managed primary health care facility. In this observational study, the researchers investigate the effect of this strategy on treatment outcomes and costs by retrospectively analyzing data collected from a cohort (group) of adult patients initially treated by doctors at the Themba Lethu Clinic in Johannesburg and then down-referred to a nearby primary health clinic where nurses supervised their treatment.
What Did the Researchers Do and Find?
Patients attending the hospital-based ART clinic were invited to transfer to the down-referral site if they had been on ART for at least 11 months and met criteria that indicated that ART was controlling their HIV infection. Each of the 712 stable ART patients who agreed to be down-referred to the primary health clinic was matched to three patients eligible for down-referral but not down-referred (2,136 patients), and clinical outcomes and costs in the patient groups were compared 12 months after down-referral eligibility. At this time point, 1.7% of the down-referred patients had died or had been lost to follow up compared to 6.2% of the patients who continued to receive hospital-based ART. The average cost per patient-year for those in care and responding at 12 months was US$492 for down-referred patients but US$551 for patients remaining at the hospital. Finally, the down-referral site spent US$509 to produce a patient who was in care and responding one year after down-referral on average, whereas the hospital spent US$602 for each responding patient. Thus, the down-referral strategy (nurse-managed care) was more cost-effective than continued hospital treatment (doctor-managed care).
What Do These Findings Mean?
These findings indicate that, at least for this pair of study sites, the 12-month outcomes of stable ART patients who were down-referred to a primary health clinic were as good as or better than the outcomes of similar patients who remained at a hospital-based ART clinic. Moreover, the down-referral strategy saved 11% of costs for patients who remained in care and responded to treatment and appeared to be cost-effective, although additional studies are needed to confirm this last finding. Because this is an observational study (that is, patients eligible for down-referral were not randomly assigned to hospital or primary care facility treatment), it is possible that some unknown factor was responsible for the difference in outcomes between the two patient groups. Nevertheless, these results suggest that the down-referral strategy tested in this study could increase ART capacity and conserve resources without compromising patient outcomes in South Africa and possibly in other resource-limited settings.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/journal.pmed.pmed.1001055.
This study is further discussed in a PLoS Medicine Perspective by Ford and Mills
The US National Institute of Allergy and Infectious Diseases provides information on HIV infection and AIDS
HIV InSite has comprehensive information on HIV/AIDS
Information is available from Avert, an international AIDS charity, on many aspects of HIV/AIDS, including information on HIV and AIDS in Africa and on universal access to AIDS treatment (in English and Spanish)
The World Health Organization provides information about universal access to AIDS treatment, including its 2010 progress report (in English, French and Spanish)
Right to Care, a non-profit organization that aims to deliver and support quality clinical services in Southern Africa for the prevention, treatment, and management of HIV, provides information on down-referral
doi:10.1371/journal.pmed.1001055
PMCID: PMC3139666  PMID: 21811402
12.  Causes of Acute Hospitalization in Adolescence: Burden and Spectrum of HIV-Related Morbidity in a Country with an Early-Onset and Severe HIV Epidemic: A Prospective Survey 
PLoS Medicine  2010;7(2):e1000178.
Rashida Ferrand and colleagues show that HIV infection is the commonest cause of hospitalization among adolescents in a high HIV prevalence setting.
Background
Survival to older childhood with untreated, vertically acquired HIV infection, which was previously considered extremely unusual, is increasingly well described. However, the overall impact on adolescent health in settings with high HIV seroprevalence has not previously been investigated.
Methods and Findings
Adolescents (aged 10–18 y) systematically recruited from acute admissions to the two public hospitals in Harare, Zimbabwe, answered a questionnaire and underwent standard investigations including HIV testing, with consent. Pre-set case-definitions defined cause of admission and underlying chronic conditions. Participation was 94%. 139 (46%) of 301 participants were HIV-positive (median age of diagnosis 12 y: interquartile range [IQR] 11–14 y), median CD4 count = 151; IQR 57–328 cells/µl), but only four (1.3%) were herpes simplex virus-2 (HSV-2) positive. Age (median 13 y: IQR 11–16 y) and sex (57% male) did not differ by HIV status, but HIV-infected participants were significantly more likely to be stunted (z-score<−2: 52% versus 23%, p<0.001), have pubertal delay (15% versus 2%, p<0.001), and be maternal orphans or have an HIV-infected mother (73% versus 17%, p<0.001). 69% of HIV-positive and 19% of HIV-negative admissions were for infections, most commonly tuberculosis and pneumonia. 84 (28%) participants had underlying heart, lung, or other chronic diseases. Case fatality rates were significantly higher for HIV-related admissions (22% versus 7%, p<0.001), and significantly associated with advanced HIV, pubertal immaturity, and chronic conditions.
Conclusion
HIV is the commonest cause of adolescent hospitalisation in Harare, mainly due to adult-spectrum opportunistic infections plus a high burden of chronic complications of paediatric HIV/AIDS. Low HSV-2 prevalence and high maternal orphanhood rates provide further evidence of long-term survival following mother-to-child transmission. Better recognition of this growing phenomenon is needed to promote earlier HIV diagnosis and care.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Acquired immunodeficiency syndrome (AIDS) has killed more than 25 million people since 1981, and more than 30 million people are now infected with the human immunodeficiency virus (HIV) that causes AIDS. HIV destroys the cells in the immune system that normally provide protection against disease-causing organisms. Consequently, people infected with HIV are susceptible to so-called opportunistic infections, including tuberculosis and pneumonia. HIV is most commonly spread through unprotected sex with an infected partner but another major route of transmission is mother-to-child (vertical transmission) during pregnancy or delivery or during breast feeding. Mother-to-child transmission can be prevented by giving antiviral drugs to HIV-positive mothers during their pregnancy and to their newborn children. But, although most mothers in developed countries have access to this intervention, fewer than half of HIV-positive mothers in low- and middle-income countries receive this treatment and, every year, nearly half a million children become infected with HIV.
Why Was This Study Done?
It is generally thought that HIV infections in infants progress rapidly and that half of the children who acquire HIV from their mothers will die before their second birthday if not treated with antiretroviral drugs. However, as the AIDS epidemic matures, more children are surviving to adolescence with untreated, vertically acquired HIV infection in sub-Saharan Africa, the region where most children with HIV/AIDS live. Little is known about the burden of HIV infection and its contribution to illness and death in adolescents in sub-Saharan Africa but this information is needed to help health care providers prepare for this new aspect of the AIDS epidemic. In this study, the researchers examine the causes of acute hospital admissions (admissions for conditions with a sudden onset and usually a short course) among adolescents in Zimbabwe, a country where the HIV epidemic started early and where one in seven adults is HIV-positive and more than 17,000 children are infected with HIV every year, mainly through vertical transmission.
What Did the Researchers Do and Find?
The researchers recruited 301 10–18-year olds who were admitted to each of the two public hospitals in Harare (Zimbabwe) for acute illnesses between September 2007 and April 2008. Each patient completed a questionnaire about themselves and their health and underwent standard investigations, including HIV testing. Nearly half the participants were HIV positive; about a quarter of these HIV-positive individuals only found out about their status during the study. HIV-positive participants were more likely to be stunted, to have pubertal delay, and to be maternal orphans or have an HIV-infected mother than HIV-negative participants. 69% of HIV-positive participants were admitted to hospital because of infections, often tuberculosis or pneumonia whereas only 19% of the HIV-negative participants were admitted for infections. More than a quarter of all the participants had underlying heart, lung, or other chronic conditions. Finally, 22% of the HIV-positive participants died while in hospital compared to only 7% of the HIV-negative participants. Factors that increased the risk of death among all the participants were advanced HIV infection, pubertal immaturity, and chronic conditions.
What Do These Findings Mean?
These findings indicate that HIV infection is the commonest cause of acute adolescent admission to hospital in Harare (and probably elsewhere in Zimbabwe). Most of these admissions are due to opportunistic infections similar to those seen in HIV-positive adults and to long-term complications of having HIV/AIDS as an infant such as delayed puberty. Other findings indicate that most of the HIV-positive adolescents who participated in this study were infected via vertical transmission, which supports the idea that long-term survival after vertical infection is possible. Because the AIDS epidemic started early in Zimbabwe, there is likely to be a lag before adolescent survivors of vertical HIV transmission become common elsewhere. Nevertheless, all African countries and other places where HIV infection in adults is common need to recognize that the burden of HIV in their acutely unwell adolescents is likely to increase over the next few years. To deal with this emerging aspect of the AIDS epidemic, measures must be introduced to ensure early diagnosis of HIV in this previously neglected age group so that treatment can be started before HIV-positive adolescents become critically ill.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000178.
This study is further discussed in a PLoS Medicine Perspective by Glenda Gray
Information is available from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS
HIV InSite has comprehensive information on all aspects of HIV/AIDS, including a list of articles and other sources of information about the primary care of adolescents with HIV
Information is available from Avert, an international AIDS charity on many aspects of HIV/AIDS, including information on the HIV and AIDS in Zimbabwe, and on children, HIV, and AIDS (in English and Spanish)
UNICEF also has information about children and HIV and AIDS (in several languages)
doi:10.1371/journal.pmed.1000178
PMCID: PMC2814826  PMID: 20126383
13.  The Role of HIV-Related Stigma in Utilization of Skilled Childbirth Services in Rural Kenya: A Prospective Mixed-Methods Study 
PLoS Medicine  2012;9(8):e1001295.
Janet Turan and colleagues examined the role of the perception of women in rural Kenya of HIV-related stigma during pregnancy on their subsequent utilization of maternity services.
Background
Childbirth with a skilled attendant is crucial for preventing maternal mortality and is an important opportunity for prevention of mother-to-child transmission of HIV. The Maternity in Migori and AIDS Stigma Study (MAMAS Study) is a prospective mixed-methods investigation conducted in a high HIV prevalence area in rural Kenya, in which we examined the role of women's perceptions of HIV-related stigma during pregnancy in their subsequent utilization of maternity services.
Methods and Findings
From 2007–2009, 1,777 pregnant women with unknown HIV status completed an interviewer-administered questionnaire assessing their perceptions of HIV-related stigma before being offered HIV testing during their first antenatal care visit. After the visit, a sub-sample of women was selected for follow-up (all women who tested HIV-positive or were not tested for HIV, and a random sample of HIV-negative women, n = 598); 411 (69%) were located and completed another questionnaire postpartum. Additional qualitative in-depth interviews with community health workers, childbearing women, and family members (n = 48) aided our interpretation of the quantitative findings and highlighted ways in which HIV-related stigma may influence birth decisions. Qualitative data revealed that health facility birth is commonly viewed as most appropriate for women with pregnancy complications, such as HIV. Thus, women delivering at health facilities face the risk of being labeled as HIV-positive in the community. Our quantitative data revealed that women with higher perceptions of HIV-related stigma (specifically those who held negative attitudes about persons living with HIV) at baseline were subsequently less likely to deliver in a health facility with a skilled attendant, even after adjusting for other known predictors of health facility delivery (adjusted odds ratio = 0.44, 95% CI 0.22–0.88).
Conclusions
Our findings point to the urgent need for interventions to reduce HIV-related stigma, not only for improving quality of life among persons living with HIV, but also for better health outcomes among all childbearing women and their families.
Please see later in the article for the Editors' Summary.
Editors' Summary
Background
Every year, nearly 350,000 women die from pregnancy- or childbirth-related complications. Almost all these “maternal” deaths occur in developing countries. In sub-Saharan Africa, for example, the maternal mortality ratio (the number of maternal deaths per 100,000 live births) is 500 whereas in industrialized countries it is only 12. Most maternal deaths are caused by hemorrhage (severe bleeding after childbirth), post-delivery infections, obstructed (difficult) labor, and blood pressure disorders during pregnancy. All these conditions can be prevented if women have access to adequate reproductive health services and if trained health care workers are present during delivery. Notably, in sub-Saharan Africa, infection with HIV (the virus that causes AIDS) is an increasingly important contributor to maternal mortality. HIV infection causes maternal mortality directly by increasing the occurrence of pregnancy complications and indirectly by increasing the susceptibility of pregnant women to malaria, tuberculosis, and other “opportunistic” infections—HIV-positive individuals are highly susceptible to other infections because HIV destroys the immune system.
Why Was This Study Done?
Although skilled delivery attendants reduce maternal mortality, there are many barriers to their use in developing countries including cost and the need to travel long distances to health facilities. Fears and experiences of HIV-related stigma and discrimination (prejudice, negative attitudes, abuse, and maltreatment directed at people living with HIV) may also be a barrier to the use of skilled childbirth service. Maternity services are prime locations for HIV testing and for the provision of interventions for the prevention of mother-to-child transmission (PMTCT) of HIV, so pregnant women know that they will have to “deal with” the issue of HIV when visiting these services. In this prospective mixed-methods study, the researchers examine the role of pregnant women's perceptions of HIV-related stigma in their subsequent use of maternity services in Nyanza Province, Kenya, a region where 16% women aged 15–49 are HIV-positive and where only 44.2% of mothers give birth in a health facility. A mixed-methods study combines qualitative data—how people feel about an issue—with quantitative data—numerical data about outcomes.
What Did the Researchers Do and Find?
In the Maternity in Migori and AIDS Stigma (MAMAS) study, pregnant women with unknown HIV status living in rural regions of Nyanza Province answered questions about their perceptions of HIV-related stigma before being offered HIV testing during their first antenatal clinic visit. After delivery, the researchers asked the women who tested HIV positive or were not tested for HIV and a sample of HIV-negative women where they had delivered their baby. They also gathered qualitative information about barriers to maternity and HIV service use by interviewing childbearing women, family members, and community health workers. The qualitative data indicate that labor in a health facility is commonly viewed as being most appropriate for women with pregnancy complications such as HIV infection. Thus, women delivering at health facilities risk being labeled as HIV positive, a label that the community associates with promiscuity. The quantitative data indicate that women with more negative attitudes about HIV-positive people (higher perceptions of HIV-related stigma) at baseline were about half as likely to deliver in a health facility with a skilled attendant as women with more positive attitudes about people living with HIV.
What Do These Findings Mean?
These findings suggest that HIV-related stigma is associated with the low rate of delivery by skilled attendants in rural areas of Nyanza Province and possibly in other rural regions of sub-Saharan Africa. Community mobilization efforts aimed at increasing the use of PMTCT services may be partly responsible for the strong perception that delivery in a health facility is most appropriate for women with HIV and other pregnancy complications and may have inadvertently strengthened the perception that women who give birth in such facilities are likely to be HIV positive. The researchers suggest, therefore, that health messages should stress that delivery in a health facility is recommended for all women, not just HIV-positive women or those with pregnancy complications, and that interventions should be introduced to reduce HIV-related stigma. This combined strategy has the potential to increase the use of maternity services by all women and the use of HIV and PMTCT services, thereby reducing some of the most pressing health problems facing women and their children in sub-Saharan Africa.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001295.
The United Nations Children's Fund (UNICEF) provides information on maternal mortality, including the WHO/UNICEF/UNFPA/World Bank 2008 country estimates of maternal mortality; a UNICEF special report tells the stories of seven mothers living with HIV in Lesotho
The World Health Organization provides information on maternal health, including information about Millennium Development Goal 5, which aims to reduce maternal mortality (in several languages); the Millennium Development Goals, which were agreed by world leaders in 2000, are designed to eradicate extreme poverty worldwide by 2015
Immpact is a global research initiative for the evaluation of safe motherhood intervention strategies
Maternal Death: The Avoidable Crisis is a briefing paper published by the independent humanitarian medical aid organization Médecins Sans Frontières (MSF) in March 2012
Information is available from Avert, an international AIDS charity on all aspects of HIV/AIDS, including information on women, HIV and AIDS, on HIV and pregnancy, on HIV and AIDS stigma and discrimination, and on HIV in Kenya (in English and Spanish); Avert also has personal stories from women living with HIV
The Stigma Action Network (SAN) is a collaborative endeavor that aims to comprehensively coordinate efforts to develop and expand program, research, and advocacy strategies for reducing HIV stigma worldwide, including mobilizing stakeholders, delivering program and policy solutions, and maximizing investments in HIV programs and services globally
The People Living with Stigma Index aims to address stigma relating to HIV and advocate on key barriers and issues perpetuating stigma; it has recently published Piecing it together for women and girls, the gender dimensions of HIV-related stigma
The Health Policy Project http://www.healthpolicyproject.com has prepared a review of the academic and programmatic literature on stigma and discrimination as barriers to achievement of global goals for maternal health and the elimination of new child HIV infections (see under Resources)
More information on the MAMAS study is available from the UCSF Center for AIDS Prevention Studies
doi:10.1371/journal.pmed.1001295
PMCID: PMC3424253  PMID: 22927800
14.  Characteristics of a palliative care consultation service with a focus on pain in a German university hospital 
BMC Palliative Care  2014;13:45.
Background
A minority of patients with incurable and advanced disease receive specialised palliative care. Specialised palliative care services that complement the care of difficult and complex cases ought to be integrated with services that deliver general care for most patients. A typical setting in which this integrative concept takes place is the hospital setting, where patients suffering from incurable and advanced disease are treated in many different departments.
The aim of the study is to investigate the profile and spectrum of a palliative care consultation service (PCCS) at a German university hospital with special reference to pain therapy.
Methods
We retrospectively analysed the PCCS documentation of three years.
Results
Most patients were referred from non-surgical departments, 72% were inpatients, and 28% were outpatients. 98% of the patients suffered from cancer. Counselling in pain therapy was one of the key aspects of the consultation: For 76% of all consulted patients, modifications of the analgesic regimen were recommended, which involved opioids in 96%. Recommendations on breakthrough-pain medication were made for 70% of the patients; this was an opioid in most cases (68%). The most commonly used opioid was morphine. For 17% of the patients, additional diagnostic procedures were recommended. Besides pain management palliative care consultation implied a wide range of recommendations and services: In addition to organising home care infrastructure, palliative care services supported patients and their families in understanding the life-limiting diseases. They also coordinated physical therapy and social and legal advice.
Conclusion
This survey clearly shows that for a consultation service to support patients with incurable or advanced disease, a multi-disciplinary approach is necessary to meet the complex requirements of a needs-adapted palliative care in inpatient or outpatient settings. Timely integration of palliative expertise may support symptom control and may give the required advice to patients, their carers, and their families.
doi:10.1186/1472-684X-13-45
PMCID: PMC4177373  PMID: 25276095
15.  The Impact of Monitoring HIV Patients Prior to Treatment in Resource-Poor Settings: Insights from Mathematical Modelling 
PLoS Medicine  2008;5(3):e53.
Background
The roll-out of antiretroviral treatment (ART) in developing countries concentrates on finding patients currently in need, but over time many HIV-infected individuals will be identified who will require treatment in the future. We investigated the potential influence of alternative patient management and ART initiation strategies on the impact of ART programmes in sub-Saharan Africa.
Methods and Findings
We developed a stochastic mathematical model representing disease progression, diagnosis, clinical monitoring, and survival in a cohort of 1,000 hypothetical HIV-infected individuals in Africa. If individuals primarily enter ART programmes when symptomatic, the model predicts that only 25% will start treatment and, on average, 6 life-years will be saved per person treated. If individuals are recruited to programmes while still healthy and are frequently monitored, and CD4+ cell counts are used to help decide when to initiate ART, three times as many are expected to be treated, and average life-years saved among those treated increases to 15. The impact of programmes can be improved further by performing a second CD4+ cell count when the initial value is close to the threshold for starting treatment, maintaining high patient follow-up rates, and prioritising monitoring the oldest (≥ 35 y) and most immune-suppressed patients (CD4+ cell count ≤ 350). Initiating ART at higher CD4+ cell counts than WHO recommends leads to more life-years saved, but disproportionately more years spent on ART.
Conclusions
The overall impact of ART programmes will be limited if rates of diagnosis are low and individuals enter care too late. Frequently monitoring individuals at all stages of HIV infection and using CD4 cell count information to determine when to start treatment can maximise the impact of ART.
Using a stochastic model based on data from Africa, Timothy Hallett and colleagues find that starting HIV treatment based on regular CD4 monitoring, rather than on symptoms, would substantially increase survival.
Editors' Summary
Background.
Acquired immunodeficiency syndrome (AIDS) has killed more than 25 million people since the first case in 1981, and about 33 million people are currently infected with the human immunodeficiency virus (HIV), which causes AIDS. HIV destroys immune system cells (including CD4 cells, a type of lymphocyte), leaving infected individuals susceptible to other infections. Early in the AIDS epidemic, most HIV-positive individuals died within 10 years but in 1996, combination antiretroviral therapy (ART)—a mixture of powerful but expensive antiretroviral drugs—was developed. For HIV-positive people living in affluent, developed countries who could afford ART, AIDS then became a chronic disease, but for those living in low- and middle-income countries it remained a death sentence—ART was too expensive. In 2003, this lack of access to ART was declared a global health emergency and governments, international organizations, and funding bodies began to implement plans to increase ART coverage in developing countries.
Why Was This Study Done?
The roll-out of ART in developing countries has concentrated so far on finding HIV-positive people who currently need treatment. In developing countries, these are often individuals who have AIDS-related symptoms such as recurrent severe bacterial infections. But healthy people are also being diagnosed as HIV positive during voluntary testing and at antenatal clinics. How should these HIV-positive but symptom-free individuals be managed? Should regular health-monitoring appointments be scheduled for them and when should ART be initiated? Management decisions like these will determine how well patients do when they eventually start ART, as well as the demand for ART and other health-care services. The full range of alternative patient management strategies cannot be tested in clinical trials—it would be unethical—but public-health officials need an idea of their relative effectiveness in order to use limited resources wisely. In this study, therefore, the researchers use mathematical modeling to investigate the impact of alternative patient management and ART initiation strategies on the impact of ART programs in resource-poor settings.
What Did the Researchers Do and Find?
The researchers' mathematical model, which includes data on disease progression collected in Africa, simulates disease progression in a group (cohort) of 1,000 HIV-infected adults. It tracks these individuals from infection, through diagnosis and clinical monitoring, and into treatment and predicts how many will receive ART and their length of survival under different management scenarios and ART initiation rules. The model predicts that if HIV-positive individuals receive ART only when they have AIDS-related symptoms, only a quarter of them will ever start ART and the average life-years saved per person treated will be 6 years (that is, they will live 6 years longer than they would have done without treatment). If individuals are recruited to ART programs when they are healthy and are frequently monitored using CD4 cell counts to decide when to start ART, three-quarters of the cohort will be treated and 15 life-years will be saved per person treated. The impact of ART programs will be increased further, the model predicts, by preferentially monitoring people who are more than 35 years old and the most immunosuppressed individuals. Finally, strategies that measure CD4 cells frequently will save more life-years because ART is more likely to be started before the immune system is irreversibly damaged. Importantly for resource-poor settings, these strategies also save more life-years per year on ART.
What Do These Findings Mean?
As with all mathematical models, the accuracy of these predictions depends on the assumptions built into the model and the reliability of the data fed into it. Also, this model does not estimate the costs of the various management options, something that will need to be done to ensure effective allocation of limited resources. Nevertheless, these findings provide several general clues about how ART programs should be implemented in poor countries to maximize their effects. Early diagnosis of infections, regular monitoring of patients, and using CD4 cell counts to decide when to initiate ART should all help to improve the number of life-years saved by ART. In other words, the researchers conclude, effectively managing individuals at all stages of HIV infection is essential to maximize the impact of ART.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/doi:10.1371/journal.pmed.0050053.
Information from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS.
Information from the US Centers for Disease Control and Prevention on global HIV/AIDS topics (in English and Spanish)
HIV InSite, comprehensive and up-to-date information on all aspects of HIV/AIDS from the University of California, San Francisco
Information from Avert, an international AIDS charity, on HIV and AIDS in Africa and on HIV/AIDS treatment and care, including universal access to ART
Progress toward universal access to HIV/AIDS treatment, the latest report from the World Health Organization (available in several languages)
Guidelines for antiretroviral therapy in adults and adolescents are provided by the World Health Organization and by the US Department of Health and Human Services
doi:10.1371/journal.pmed.0050053
PMCID: PMC2265759  PMID: 18336064
16.  Uptake of Home-Based Voluntary HIV Testing in Sub-Saharan Africa: A Systematic Review and Meta-Analysis 
PLoS Medicine  2012;9(12):e1001351.
Kalpana Sabapathy and colleagues conduct a systematic review and meta-analysis to assess the acceptability of home-based voluntary counseling and testing for HIV in sub-Saharan Africa with some encouraging results.
Introduction
Improving access to HIV testing is a key priority in scaling up HIV treatment and prevention services. Home-based voluntary counselling and testing (HBT) as an approach to delivering wide-scale HIV testing is explored here.
Methods and Findings
We conducted a systematic review and random-effects meta-analysis of studies published between 1 January 2000 and 24 September 2012 that reported on uptake of HBT in sub-Saharan Africa, to assess the proportion of individuals accepting HBT and receiving their test result.
Our initial search yielded 1,199 articles; 114 were reviewed as full-text articles, and 19 publications involving 21 studies (n = 524,867 individuals offered HBT) were included for final review and meta-analysis. The studies came from five countries: Uganda, Malawi, Kenya, South Africa, and Zambia.
The proportion of people who accepted HBT (n = 474,377) ranged from 58.1% to 99.8%, with a pooled proportion of 83.3% (95% CI: 80.4%–86.1%). Heterogeneity was high (τ2 = 0.11). Sixteen studies reported on the number of people who received the result of HBT (n = 432,835). The proportion of individuals receiving their results out of all those offered testing ranged from 24.9% to 99.7%, with a pooled proportion of 76.7% (95% CI: 73.4%–80.0%) (τ2 = 0.12). HIV prevalence ranged from 2.9% to 36.5%. New diagnosis of HIV following HBT ranged from 40% to 79% of those testing positive. Forty-eight percent of the individuals offered testing were men, and they were just as likely to accept HBT as women (pooled odds ratio = 0.84; 95% CI: 0.56–1.26) (τ2 = 0.33). The proportion of individuals previously tested for HIV among those offered a test ranged from 5% to 66%. Studies in which <30% of individuals had been previously tested, local HIV prevalence was <10%, incentives were provided, or HBT was offered to household members of HIV-positive individuals showed higher uptake of testing. No evidence was reported of negative consequences of HBT.
Conclusions
HBT could substantially increase awareness of HIV status in previously undiagnosed individuals in sub-Saharan Africa, with over three-quarters of the studies in this review reporting >70% uptake. It could be a valuable tool for treatment and prevention efforts.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Knowledge of HIV status is crucial for both the prevention and treatment of HIV. However, according to the Joint United Nations Programme on HIV/AIDS (the UN agency responsible for HIV/AIDS), in low-and-middle-income countries only ten percent of those who need voluntary counseling and testing, because they may have been exposed to HIV infection, have access to this service. Even in health care settings in which voluntary counseling and HIV testing is routinely offered, such as to pregnant women, the number of people who use these services is low. This situation is partly because of the stigma and discrimination associated with HIV, which makes people reluctant to volunteer to come forward to be tested for HIV. To help overcome this problem, one important strategy in encouraging people to be tested for HIV is to offer them the opportunity to be counseled and tested at home—home-based voluntary counseling and testing (HBT). Using the HBT approach, people are visited in their home by health workers regardless of their perceived risk of HIV. HBT has obvious advantages and upholds the “3 Cs” principles of HIV testing: that testing is confidential, accompanied by counseling, and conducted only with informed consent.
Why Was This Study Done?
The HBT approach has received widespread international support, and the World Health Organization has recently published guidance to service providers and policy makers about the delivery of HBT. However, the acceptability of HBT, that is, whether those offered HBT actually take up the offer and are tested, remains unknown, especially in sub-Saharan Africa, the world region with the highest prevalence of HIV. So, in this study, the researchers systematically compiled all of the available studies on this topic from sub-Saharan Africa to determine the acceptability of HBT and also to and identify any factors associated with the uptake of HBT.
What Did the Researchers Do and Find?
The researchers searched several databases to identify suitable peer-reviewed studies from Africa published between January 2000 and September 2012. The researchers included studies that described any intervention to provide HIV testing at home and also reported the proportions of participants accepting HIV testing out of all individuals offered a home-based HIV test. Because different types of studies were included (such as randomized controlled trials, observational cohort studies, and cross-sectional surveys), the researchers tested the quality of included studies. Then they pooled all of the studies together to calculate the overall proportion of people who accepted HIV testing at home and the proportion who received their result.
Using these methods, the researchers included 21 studies from five African countries: Kenya, Malawi, South Africa, Uganda, and Zambia, comprising a total of 524,867 people. Overall, the proportion of people who accepted HBT ranged from 58.1% to 99.7%, with a pooled proportion of 83.3% accepting HBT (474,377 people). In the eight studies that separated data by gender, men were as likely as women to accept testing (78.5% versus 81.5%). Over three-quarters of everyone who accepted HBT received their result (77% in 16 studies reporting on this), and, importantly, the proportion of people with previously undiagnosed HIV was high (40%–79% of those diagnosed HIV-positive), emphasizing the value of HBT. The researchers also found that providing incentives, local HIV prevalence being less than 10%, and targeting HBT to household members of HIV-positive individuals may be factors associated with increased uptake of HBT, but further research is needed to verify the results of this subgroup analysis.
What Do These Findings Mean?
These findings suggest that voluntary counseling and testing for HIV at home is highly acceptable in five countries in sub-Saharan Africa, with the majority of those tested receiving their test result, highlighting the importance of this approach in the diagnosis of HIV. Therefore, by increasing uptake of testing, HBT may provide an effective tool for governments and health service providers to increase access to HIV treatment and prevention. However, testing is just the first step in the management of HIV, and this study does not address the follow-up of those who tested positive using the home-based approach, such as access to treatment, as well as repeated HBT for ongoing knowledge of HIV status. The option of self-testing was examined in only one of the studies included in this review, but the researchers identify that self-testing at home with the support HBT staff is an important area of future research. Overall, HBT has the potential to substantially increase awareness of HIV status in previously undiagnosed men and women in sub-Saharan Africa.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001351.
The World Health Organization provides extensive information on HIV testing and counseling, and the World Health Organization's guidance on home-based testing mentioned in this summary is also available
The Joint United Nations Programme on HIV/AIDS gives the latest facts and figures about the global status of HIV and about reducing stigma and discrimination around HIV
doi:10.1371/journal.pmed.1001351
PMCID: PMC3514284  PMID: 23226107
17.  An Ethnographic Study of Barriers to Cancer Pain Management and Opioid Availability in India 
The Oncologist  2014;19(5):515-522.
We examined barriers to opioid availability and cancer pain management in India, with an emphasis on the experiences of nurses, who are often the front-line providers of palliative care. Interventions must streamline process details of morphine procurement, work within the existing sociocultural infrastructure to ensure opioids reach patients most in need, target unexpected audiences for symptom management education, and account for role expectations of health care providers.
Background.
The world’s global cancer burden disproportionally affects lower income countries, where 80% of patients present with late-stage disease and have limited access to palliative care and effective pain-relieving medications, such as morphine. Consequently, millions die each year with unrelieved pain.
Objective.
The objective of this study was to examine barriers to opioid availability and cancer pain management in India, with an emphasis on the experiences of nurses, who are often the front-line providers of palliative care.
Methods.
Fifty-nine participants were recruited using a purposive, snowball sampling strategy. Ethnographic data collection included in-depth, semistructured interviews (n = 54), 400+ hours of participant observation, and review of documents over 9 months at a government cancer hospital in South India. Systematic qualitative analysis led to identification of key barriers that are exemplified by representative quotes.
Results.
Morphine is more available at this study site than in most of India, but access is limited to patients seen by the palliative care service, and significant gaps in supply still occur. Systems to measure and improve pain outcomes are largely absent. Key barriers related to pain management include the role of nursing, opioid misperceptions, bureaucratic hurdles, and sociocultural/infrastructure challenges.
Implications.
Interventions must streamline process details of morphine procurement, work within the existing sociocultural infrastructure to ensure opioids reach patients most in need, target unexpected audiences for symptom management education, and account for role expectations of health care providers.
Conclusion.
Macro- and micro-level policy and practice changes are needed to improve opioid availability and cancer pain management in India.
doi:10.1634/theoncologist.2013-0435
PMCID: PMC4012971  PMID: 24755460
Morphine; Palliative care; Cancer; World health; India; Opioids; Nursing; Pain management; Ethnography
18.  Variability in Access to Hospital Palliative Care in the United States 
Journal of Palliative Medicine  2008;11(8):1094-1102.
Abstract
Background
Hospital palliative care programs provide high-quality, comprehensive care for seriously ill patients and their families.
Objective
To examine geographic variation in patient and medical trainee access to hospital palliative care and to examine predictors of these programs.
Methods
Primary and secondary analyses of national survey and census data. Hospital data including hospital palliative care programs were obtained from the American Hospital Association (AHA) Annual Survey Database™ for fiscal year 2006 supplemented by mailed surveys. Medical school-affiliated hospitals were obtained from the American Association of Medical Colleges, Web-site review, and telephone survey. Health care utilization data were obtained from the Dartmouth Atlas of Health Care 2008. Multivariate logistic regression was used to identify characteristics significantly associated with the presence of hospital palliative care.
Results
A total of 52.8% of hospitals with 50 or more total facility beds reported hospital palliative care with considerable variation by state; 40.9% (144/352) of public hospitals, 20.3% (84/413) of for-profit hospitals, and 28.8% (160/554) of Medicare sole community providers reported hospital palliative care. A total of 84.5% of medical schools were associated with at least one hospital palliative care program. Factors significantly associated (p < 0.05) with hospital palliative care included geographic location, owning a hospice program, having an American College of Surgery approved cancer program, percent of persons in the county with a university education, and medical school affiliation. For-profit and public hospitals were significantly less likely to have hospital palliative care when compared with nonprofit institutions. States with higher hospital palliative care penetration rates were observed to have fewer Medicare hospital deaths, fewer intensive care unit/cardiac care unit (ICU/CCU) days and admissions during the last 6 months of life, fewer ICU/CCU admission during terminal hospitalizations, and lower overall Medicare spending/enrollee.
Discussion
This study represents the most recent estimate to date of the prevalence of hospital palliative care in the United States. There is wide geographic variation in access to palliative care services although factors predicting hospital palliative care have not changed since 2005. Overall, medical students have high rates of access to hospital palliative care although complete penetration into academic settings has not occurred. The association between hospital palliative care penetration and lower Medicare costs is intriguing and deserving of further study.
doi:10.1089/jpm.2008.0053
PMCID: PMC2941669  PMID: 18831653
19.  Palliative care making a difference in rural Uganda, Kenya and Malawi: three rapid evaluation field studies 
BMC Palliative Care  2011;10:8.
Background
Many people live and die in pain in Africa. We set out to describe patient, family and local community perspectives on the impact of three community based palliative care interventions in sub-Saharan Africa.
Methods
Three palliative care programmes in Uganda, Kenya and Malawi were studied using rapid evaluation field techniques in each country, triangulating data from three sources: interviews with key informants, observations of clinical encounters and the local health and social care context, and routine data from local reports and statistics.
Results
We interviewed 33 patients with advanced illness, 27 family carers, 36 staff, 25 volunteers, and 29 community leaders and observed clinical care of 12 patients. In each site, oral morphine was being used effectively. Patients valued being treated with dignity and respect. Being supported at home reduced physical, emotional and financial burden of travel to, and care at health facilities. Practical support and instruction in feeding and bathing patients facilitated good deaths at home.
In each country mobile phones enabled rapid access to clinical and social support networks. Staff and volunteers generally reported that caring for the dying in the face of poverty was stressful, but also rewarding, with resilience fostered by having effective analgesia, and community support networks.
Conclusions
Programmes were reported to be successful because they integrated symptom control with practical and emotional care, education, and spiritual care. Holistic palliative care can be delivered effectively in the face of poverty, but a public health approach is needed to ensure equitable provision.
doi:10.1186/1472-684X-10-8
PMCID: PMC3120792  PMID: 21569423
20.  Early and Late Direct Costs in a Southern African Antiretroviral Treatment Programme: A Retrospective Cohort Analysis 
PLoS Medicine  2009;6(12):e1000189.
Gary Maartens and colleagues describe the direct heath care costs and identify the drivers of cost over time in an HIV managed care program in Southern Africa.
Background
There is a paucity of data on the health care costs of antiretroviral therapy (ART) programmes in Africa. Our objectives were to describe the direct heath care costs and establish the cost drivers over time in an HIV managed care programme in Southern Africa.
Methods/Findings
We analysed the direct costs of treating HIV-infected adults enrolled in the managed care programme from 3 years before starting non-nucleoside reverse transcriptase inhibitor-based ART up to 5 years afterwards. The CD4 cell count criterion for starting ART was <350 cells/µl. We explored associations between variables and mean total costs over time using a generalised linear model with a log-link function and a gamma distribution. Our cohort consisted of 10,735 patients (59.4% women) with 594,497 mo of follow up data (50.9% of months on ART). Median baseline CD4+ cell count and viral load were 125 cells/µl and 5.16 log10 copies/ml respectively. There was a peak in costs in the period around ART initiation (from 4 mo before until 4 mo after starting ART) driven largely by hospitalisation, following which costs plateaued for 5 years. The variables associated with changes in mean total costs varied with time. Key early associations with higher costs were low baseline CD4+ cell count, high baseline HIV viral load, and shorter duration in HIV care prior to starting ART; whilst later associations with higher costs were lower ART adherence, switching to protease inhibitor-based ART, and starting ART at an older age.
Conclusions
Drivers of mean total costs changed considerably over time. Starting ART at higher CD4 counts or longer pre-ART care should reduce early costs. Monitoring ART adherence and interventions to improve it should reduce later costs. Cost models of ART should take into account these time-dependent cost drivers, and include costs before starting ART.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
About 30 million people (22 million people in sub-Saharan Africa alone) are infected with the human immunodeficiency virus (HIV), the cause of acquired immunodeficiency syndrome (AIDS). HIV destroys immune system cells (including CD4 cells, a type of lymphocyte), leaving infected individuals susceptible to other infections. Early in the AIDS epidemic, on average HIV-positive people died within 10 years of infection. Then, in 1996, highly active antiretroviral therapy (ART; combinations of powerful antiretroviral drugs) was developed. For people living in affluent, developed countries HIV/AIDS became a chronic, treatable condition, but for the millions of HIV-infected people living in low- and middle-income countries, effective treatment was unavailable and HIV/AIDS remained a fatal illness. In 2003, this situation was declared a global health emergency and governments, international agencies, and funding bodies began to implement plans to increase ART coverage in developing countries. By the end of 2008, of the 9.5 million people in need of ART in low- and middle-income countries, more than 4 million people were receiving treatment.
Why Was This Study Done?
Good progress is being made towards achieving universal access to ART, partly because the cost of antiretroviral drugs has plummeted in developing countries. But the provision of antiretroviral drugs is not the only direct cost associated with ART. General practitioner, specialist, and maternity-related care for patients receiving ART, hospital accommodation when necessary, and the investigations that are needed to monitor the progress of HIV infection such as CD4 cell counts and viral load measurements all incur considerable costs. To use their limited resources effectively, public-health officials in developing countries need to know as much as possible about the direct costs of HIV health care but few studies have investigated these costs, particularly those incurred before an individual starts taking ART. In this study, the researchers explore health care costs in a South African private-sector HIV/AIDS program and examine the variables that drive the costs of HIV health care around the time of ART initiation and during later phases of ART.
What Did the Researchers Do and Find?
The researchers analyzed the direct costs of treating more than 100,000 HIV-infected adults enrolled in a private HIV care program in South Africa from 3 years before they started ART until up to 5 years after ART initiation; within this program, individuals began to receive ART when their CD4 cell count fell below 350 cells/µl of blood. The researchers found a peak in direct health costs from 4 months before to 4 months after starting ART (the “peri-ART” period), which was driven mainly by hospital costs. After the peri-ART period, costs dropped (although not to the levels seen before this period) and stabilized at an intermediate level for the next 5 years. Detailed statistical analyses suggest that the key variables associated with higher costs in the peri-ART period were a low baseline CD4 cell count, a high baseline HIV viral load, and a shorter time in HIV care before ART initiation. The key variable associated with higher costs later in ART was lower adherence to the drug therapy. That is, costs were higher among patients who did not take their antiretroviral drugs regularly.
What Do These Findings Mean?
This study involved patients enrolled in a private health care program in which the criteria for initiating ART differed somewhat from those recommended by the World Health Organization for ART initiation in resource-limited settings. Thus, the absolute mean total costs calculated by the researchers are unlikely to be generalizable to public HIV care systems in South Africa and in other resource-poor settings. However, the finding that the drivers of mean total costs change considerably over time may be generalizable and provides some useful information for public-health planners that can now be tested in other, more resource-limited patient populations. In particular, the findings of this study suggest that the high early costs of ART programs could be reduced by starting ART at higher CD4 cell counts or by providing longer pre-ART care. In addition, the findings suggest that monitoring ART adherence and introducing interventions to improve ART adherence could reduce the later direct costs of ART programs.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000189.
Information is available from the US National Institute of Allergy and infectious diseases on HIV infection and AIDS
HIV InSite has comprehensive information on all aspects of HIV/AIDS
Information is available from Avert, an international AIDS charity on many aspects of HIV/AIDS, including information on the HIV and AIDS in Africa, and on universal access to AIDS treatment (in English and Spanish)
The World Health Organization provides information about universal access to AIDS treatment, including the September 2009 progress report (in English and French)
The US Centers for Disease Control and Prevention also provides information on global efforts to deal with the HIV/AIDS epidemic
doi:10.1371/journal.pmed.1000189
PMCID: PMC2777319  PMID: 19956658
21.  An evaluation of a morphine public health programme for cancer and AIDS pain relief in Sub-Saharan Africa 
BMC Public Health  2005;5:82.
Background
Despite growing HIV and cancer prevalence in Sub-Saharan Africa, and WHO advocacy for a public health approach to palliative care provision, opioid availability is severely limited. Uganda has achieved a morphine roll-out programme in partnership with the Ministry of Health. This study aimed to evaluate that programme by identifying challenges to implementation that may inform replication.
Methods
A multi-methods protocol appraised morphine regulation, storage, prescribing, and consumption in three phases: key informant interviews throughout the opioid supply chain, and direct observation and audit of clinical practice.
Results
Regulation had achieved its goal of preventing misuse and leakage from the supply chain. However, the Government felt that relaxation of regulation was now appropriate. Confusion and complexity in storage and authorisation rules led to discontinuation of opioid pain management at the patient level and also wasted service time in trying to obtain supplies to which they were entitled. Continued neglect to prescribe among clinicians and public fear of opioids led to under prescribing, and clinical skills showed some evidence of need for improvement with respect to physical assessment and follow-up.
Conclusion
The Ugandan programme offers a successful model for both advocacy and Governmental support in achieving opioid roll-out across health districts. Despite initial concerns, abuse of opioids has not been evident. Further work is required to ensure that available supplies of opioids are prescribed to those in need, and that clinical standards are met. However, the programme for roll-out has proved a useful model to expand opioid availability as the first step in improving patient care, and may prove a useful template for other Sub-Saharan African countries.
doi:10.1186/1471-2458-5-82
PMCID: PMC1232854  PMID: 16092958
22.  Routine HIV Testing in Botswana: A Population-Based Study on Attitudes, Practices, and Human Rights Concerns 
PLoS Medicine  2006;3(7):e261.
Background
The Botswana government recently implemented a policy of routine or “opt-out” HIV testing in response to the high prevalence of HIV infection, estimated at 37% of adults.
Methods and Findings
We conducted a cross-sectional, population-based study of 1,268 adults from five districts in Botswana to assess knowledge of and attitudes toward routine testing, correlates of HIV testing, and barriers and facilitators to testing, 11 months after the introduction of this policy. Most participants (81%) reported being extremely or very much in favor of routine testing. The majority believed that this policy would decrease barriers to testing (89%), HIV-related stigma (60%), and violence toward women (55%), and would increase access to antiretroviral treatment (93%). At the same time, 43% of participants believed that routine testing would lead people to avoid going to the doctor for fear of testing, and 14% believed that this policy could increase gender-based violence related to testing. The prevalence of self-reported HIV testing was 48%. Adjusted correlates of testing included female gender (AOR = 1.5, 95% CI = 1.1–1.9), higher education (AOR = 2.0, 95% CI = 1.5–2.7), more frequent healthcare visits (AOR = 1.9, 95% CI = 1.3–2.7), perceived access to HIV testing (AOR = 1.6, 95% CI = 1.1–2.5), and inconsistent condom use (AOR = 1.6, 95% CI = 1.2–2.1). Individuals with stigmatizing attitudes toward people living with HIV and AIDS were less likely to have been tested for HIV/AIDS (AOR = 0.7, 95% CI = 0.5–0.9) or to have heard of routine testing (AOR = 0.59, 95% CI = 0.45–0.76). While experiences with voluntary and routine testing overall were positive, 68% felt that they could not refuse the HIV test. Key barriers to testing included fear of learning one's status (49%), lack of perceived HIV risk (43%), and fear of having to change sexual practices with a positive HIV test (33%).
Conclusions
Routine testing appears to be widely supported and may reduce barriers to testing in Botswana. As routine testing is adopted elsewhere, measures should be implemented to assure true informed consent and human rights safeguards, including protection from HIV-related discrimination and protection of women against partner violence related to testing.
Editors' Summary
Background.
In 2005, there were 5 million new infections with the human immunodeficiency virus (HIV), and the disease it causes—acquired immunodeficiency syndrome (AIDS)—killed three million people. Despite the increased availability of drugs that can fight HIV (antiretrovirals), the AIDS epidemic continues to grow, particularly in sub-Saharan Africa. To halt it, more needs to be done to prevent the spread of HIV. Education about safe sex can help—HIV is most commonly spread through unprotected sex with an infected partner—but increasing HIV testing is of paramount importance. Unfortunately, the uptake of voluntary counseling and testing in sub-Saharan Africa is worryingly low. Fear of being stigmatized—socially disgraced—and discriminated against, fears about the positive result itself, and worries about access to antiretroviral drugs are all putting people off being tested.
Why Was This Study Done?
In Botswana, one in three adults is infected with HIV. Since 2002, antiretroviral drugs have been freely available but enrollment in the Botswana National Treatment Program during its first two years was slow, in part due to inadequate uptake of voluntary HIV testing. Consequently, in early 2004, the government introduced a policy of routine HIV testing in which all patients are tested for HIV when they visit their doctor unless they opt out. A major aim of this approach to HIV testing, which was formally recommended in June 2004 by UNAIDS and the World Health Organization, is to increase uptake of HIV testing and treatment, and to reduce HIV-related stigma by treating the HIV test like any other routine medical procedure. However, there are fears that the policy could back-fire—people might not visit their doctors, for example, because they are afraid of being tested and think that they will not be able to refuse the test. In this study, the researchers investigated knowledge of and attitudes to routine testing in Botswana to understand better the consequences of a routine testing policy.
What Did the Researchers Do and Find?
The researchers interviewed adults throughout Botswana about their knowledge of and attitudes to routine HIV testing 11 months after introduction of the policy. Only half of the participants had heard of routine testing before being interviewed but nearly all were in favor of routine testing. More than half thought it would reduce HIV-related stigma and the violence toward women that is associated with an HIV-positive status. However, almost half believed that routine testing might prevent people from going to the doctor because of fear of testing and a few thought the policy would increase violence against women. Nearly half of the interviewees had had an HIV test and the researchers found, for example, that women were more likely to have been tested than men and that people with stigmatizing attitudes toward people living with HIV and AIDS were less likely to be tested. Fear of learning one's HIV status, lack of perceived risk, and fear of having to change sexual practices if positive all stopped people taking the test. Finally, although experiences with testing were generally positive, approximately two-thirds of interviewees who had been tested felt that it would have been difficult to refuse the test.
What Do These Findings Mean?
These results show that there is widespread support for routine HIV testing in Botswana, a finding supported by recent increases in treatment uptake. Routine testing, write the researchers, holds significant promise for the prevention and treatment of HIV/AIDS in Botswana and elsewhere. In particular, increasing the number of people tested for HIV may reduce HIV-related stigma, which should further increase testing and hopefully slow the spread of HIV. But the results of this study also highlight some areas of concern. Whenever HIV testing policies are implemented, human rights must be protected by ensuring that patients have all the information necessary to make an informed and free decision about being tested, by providing protection for women against violence related to HIV status, and by ensuring total confidentiality. Careful monitoring of Botswana's program and similar programs will be needed to ensure that these human rights are fully met, conclude the researchers.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0030261
• US National Institute of Allergy and Infectious Diseases factsheet on HIV infection and AIDS
• US Department of Health and Human Services information on AIDS
• US Centers for Disease Control and Prevention information on HIV/AIDS
• UNAIDS and World Health Organization 2004 policy statement on HIV testing
• AVERT, a UK-based charity, provides information about HIV and AIDS in Botswana
A cross-sectional, population-based study of 1,268 adults from five districts in Botswana showed that routine HIV testing appears to be widely supported and may reduce barriers to HIV testing.
doi:10.1371/journal.pmed.0030261
PMCID: PMC1502152  PMID: 16834458
23.  Voluntary Medical Male Circumcision: Modeling the Impact and Cost of Expanding Male Circumcision for HIV Prevention in Eastern and Southern Africa 
PLoS Medicine  2011;8(11):e1001132.
Emmanuel Njeuhmeli and colleagues estimate the impact and cost of scaling up adult medical male circumcision in 13 priority countries in eastern and southern Africa, finding that reaching 80% coverage and maintaining it until 2025 would avert 3.36 million new HIV infections.
Background
There is strong evidence showing that voluntary medical male circumcision (VMMC) reduces HIV incidence in men. To inform the VMMC policies and goals of 13 priority countries in eastern and southern Africa, we estimate the impact and cost of scaling up adult VMMC using updated, country-specific data.
Methods and Findings
We use the Decision Makers' Program Planning Tool (DMPPT) to model the impact and cost of scaling up adult VMMC in Botswana, Lesotho, Malawi, Mozambique, Namibia, Rwanda, South Africa, Swaziland, Tanzania, Uganda, Zambia, Zimbabwe, and Nyanza Province in Kenya. We use epidemiologic and demographic data from recent household surveys for each country. The cost of VMMC ranges from US$65.85 to US$95.15 per VMMC performed, based on a cost assessment of VMMC services aligned with the World Health Organization's considerations of models for optimizing volume and efficiencies. Results from the DMPPT models suggest that scaling up adult VMMC to reach 80% coverage in the 13 countries by 2015 would entail performing 20.34 million circumcisions between 2011 and 2015 and an additional 8.42 million between 2016 and 2025 (to maintain the 80% coverage). Such a scale-up would result in averting 3.36 million new HIV infections through 2025. In addition, while the model shows that this scale-up would cost a total of US$2 billion between 2011 and 2025, it would result in net savings (due to averted treatment and care costs) amounting to US$16.51 billion.
Conclusions
This study suggests that rapid scale-up of VMMC in eastern and southern Africa is warranted based on the likely impact on the region's HIV epidemics and net savings. Scaling up of safe VMMC in eastern and southern Africa will lead to a substantial reduction in HIV infections in the countries and lower health system costs through averted HIV care costs.
Please see later in the article for the Editors' Summary.
Editors' Summary
Background
Every year, about 2.5 million people (mainly in sub-Saharan Africa) become infected with HIV, the virus that causes AIDS. There is no cure for HIV/AIDS. Consequently, prevention of HIV transmission is very important. Because the most common HIV transmission route is through unprotected sex with an infected partner, individuals can reduce their risk of HIV infection by abstaining from sex, by having only one or a few partners, and by using male or female condoms. There is also strong evidence that voluntary medical male circumcision (VMMC)—the removal of the foreskin, the loose fold of skin that covers the head of the penis—reduces the heterosexual acquisition of HIV in men by about 60%. In 2007, the World Health Organization (WHO) and the Joint United Nations Programme on HIV/AIDS (UNAIDS) recommended that VMMC should be offered to men as part of comprehensive HIV risk reduction programs in settings with generalized HIV epidemics and low levels of male circumcision. They also prioritized 13 countries in eastern and southern Africa for VMMC program scale-up.
Why Was This Study Done?
The impact of VMMC scale-up in terms of HIV infections and AIDS deaths averted (epidemiologic impact) is expected to be large, and the intervention should also reduce the costs associated with the treatment, care, and support of infected individuals. However, VMMC scale-up will require substantial funding and considerable effort by countries—many of which have weak health systems and limited resources—to train personnel, equip facilities, and provide the necessary commodities. To support planning for VMMC scale-up, the United States Agency for International Development Health Policy Initiative has collaborated with UNAIDS to develop the Decision Makers' Program Planning Tool (DMPPT), a mathematical model that allows analysts and decision makers to estimate the epidemiologic impact and cost of alternative VMMC scale-up programs. In this study, the researchers use DMPPT to estimate the impact and cost of scaling up adult VMMC in the 13 priority countries in eastern and southern Africa.
What Did the Researchers Do and Find?
The researchers derived VMMC unit costs for each priority country based on a cost assessment undertaken in Zimbabwe, one of the first countries to scale up VMMC services using WHO's “Models for Optimizing Volume and Efficiencies” (MOVE) guidelines. They fed these costs and recent epidemiologic data (including HIV infection rates and the effectiveness of VMMC in preventing HIV transmission) and demographic data (including the adult population size and pre-scale-up male circumcision prevalence) collected in each country into the DMPPT, together with information on the lifetime costs of HIV treatment. Results from running the DMPPT model suggest that scaling up adult VMMC to reach 80% coverage in the 13 priority countries by 2015 would require 20.33 million circumcisions to be completed between 2011 and 2015. To maintain this coverage, a further 8.42 million circumcisions would be required between 2016 and 2025. Such a scale-up would avert 3.36 million new HIV infections through 2025 and would cost US$2,000,000,000 between 2011 and 2025. However, it would result in net savings (because of averted treatment and care costs) of US$16,510,000,000.
What Do These Findings Mean?
These findings suggest that rapid VMMC scale-up in eastern and southern Africa is warranted, given its likely impact on the region's HIV epidemics and the resultant cost savings. However, the accuracy of these findings depends on the assumptions built into the DMPPT and on the data fed into it. For example, there could be risk behavior changes after circumcision. That is, risky sexual behaviors may increase in men who have been circumcised. However, the researchers show that, except in Rwanda, post-circumcision risk behavior change is unlikely to completely reverse the benefits of VMMC. These modeling results also assume that men seeking out VMMC services are typical of the general male population, but if they are actually at unusually low risk of HIV infection, then the benefits of VMMC reported here are likely to be overestimated. Finally, these findings assume 80% VMMC coverage. This may be optimistic, although results from Kenya indicate that this target is achievable. Thus, countries and their international partners must allocate sufficient resources to VMMC scale-up to achieve high coverage rates if they are to take full advantage of the benefits predicted here for VMMC scale-up.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001132.
This study is part of a PLoS Collection of articles on http://www.ploscollections.org/VMMC2011 and is further discussed in a PLoS Medicine Review Article by Hankins et al. (http://dx.doi.org/10.1371/journal.pmed.1001127)
Information is available from WHO, UNAIDS, and PEPFAR on all aspects of HIV/AIDS; the 2011WHO/UNAIDS progress report on VMMC scale-up in the 13 priority countries is available
NAM/aidsmap provides basic information about HIV/AIDS, summaries of recent research findings on HIV care and treatment, and information on male circumcision for the prevention of HIV transmission
Information is available from Avert, an international AIDS charity on many aspects of HIV/AIDS, including information on all aspects of HIV prevention, and on HIV/AIDS in Africa (in English and Spanish)
The Clearinghouse on Male Circumcision, a resource provided by WHO, UNAIDS, and other international bodies, provides information and tools for VMMC policy development and program implementation, including information on the DMPPT and the MOVE guidance
Personal stories about living with HIV/AIDS are available through Avert, through NAM/aidsmap, and through the charity website Healthtalkonline
doi:10.1371/journal.pmed.1001132
PMCID: PMC3226464  PMID: 22140367
24.  Task Shifting for Scale-up of HIV Care: Evaluation of Nurse-Centered Antiretroviral Treatment at Rural Health Centers in Rwanda 
PLoS Medicine  2009;6(10):e1000163.
Fabienne Shumbusho and colleagues evaluate a task-shifting model of nurse-centered antiretroviral treatment prescribing in rural primary health centers in Rwanda and find that nurses can effectively and safely prescribe ART when given adequate training, mentoring, and support.
Background
The shortage of human resources for health, and in particular physicians, is one of the major barriers to achieve universal access to HIV care and treatment. In September 2005, a pilot program of nurse-centered antiretroviral treatment (ART) prescription was launched in three rural primary health centers in Rwanda. We retrospectively evaluated the feasibility and effectiveness of this task-shifting model using descriptive data.
Methods and Findings
Medical records of 1,076 patients enrolled in HIV care and treatment services from September 2005 to March 2008 were reviewed to assess: (i) compliance with national guidelines for ART eligibility and prescription, and patient monitoring and (ii) key outcomes, such as retention, body weight, and CD4 cell count change at 6, 12, 18, and 24 mo after ART initiation. Of these, no ineligible patients were started on ART and only one patient received an inappropriate ART prescription. Of the 435 patients who initiated ART, the vast majority had adherence and side effects assessed at each clinic visit (89% and 84%, respectively). By March 2008, 390 (90%) patients were alive on ART, 29 (7%) had died, one (<1%) was lost to follow-up, and none had stopped treatment. Patient retention was about 92% by 12 mo and 91% by 24 mo. Depending on initial stage of disease, mean CD4 cell count increased between 97 and 128 cells/µl in the first 6 mo after treatment initiation and between 79 and 129 cells/µl from 6 to 24 mo of treatment. Mean weight increased significantly in the first 6 mo, between 1.8 and 4.3 kg, with no significant increases from 6 to 24 mo.
Conclusions
Patient outcomes in our pilot program compared favorably with other ART cohorts in sub-Saharan Africa and with those from a recent evaluation of the national ART program in Rwanda. These findings suggest that nurses can effectively and safely prescribe ART when given adequate training, mentoring, and support.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Infection with the human immunodeficiency virus (HIV) is a serious health problem in sub-Saharan Africa. The virus attacks white blood cells that protect against infection, most commonly a type of white blood cell called CD4. When a person has been infected with HIV for a long time, the number of CD4 cells they have goes down, resulting in acquired immune deficiency syndrome (AIDS), in which the person's immune system no longer functions effectively.
The World Health Organization (WHO) has divided the disease into four stages as it progresses, according to symptoms including weight loss and so-called opportunistic infections. These are known as clinical stage I, II, III, or IV but were revised and renamed 1, 2, 3, and 4 in September 2005. HIV infection and AIDS cannot be cured but they can be managed with antiretroviral treatment (ART). The WHO currently recommends that ART is begun when the CD4 count falls below 350.
Rwanda is a country situated in the central Africa with a population of around 9 million inhabitants; over 3% of the rural population and 7% of the urban population are infected with HIV. In 2007, the WHO estimated that 220,000 Rwandan children had lost one or both parents to AIDS.
Why Was This Study Done?
The WHO estimates that 9.7 million people with HIV in low- to middle-income countries need ART but at the end of 2007, only 30% of these, including in Rwanda, had access to treatment. In many low-income countries a major factor in this is a lack of doctors. Rwanda, for example, has one doctor per 50,000 inhabitants and one nurse per 3,900 inhabitants.
This situation has led the WHO to recommend “task shifting,” i.e., that the task of prescribing ART should be shifted from doctors to nurses so that more patients can be treated. This type of reorganization is well studied in high-income countries, but the researchers wanted to help develop a system for treating AIDS that would be effective and timely in a predominantly rural, low-income setting such as Rwanda.
What Did the Researchers Do and Find?
In conjunction with the Rwandan Ministry of Health, the researchers developed and piloted a task-shifting program, in which one nurse in each of three rural Rwandan primary health centers (PHCs) was trained to examine HIV patients and prescribe ART in simple cases. Nurses had to complete more than 50 consultations observed by the doctor before being permitted to consult patients independently. More complex cases were referred to a doctor. The authors developed standard checklists, instructions, and evaluation forms to guide nurses and the doctors who supervised them once a week.
The authors evaluated the pilot program by reviewing the records of 1,076 patients who enrolled on it between September 2005 and March 2008. They looked to see whether the nurses had followed guidelines and monitored the patients correctly. They also considered health outcomes for the patients, such as their death rate, their body weight, their CD4 cell count, and whether they maintained contact with caregivers.
They found that by March 2008, 451 patients had been eligible for ART. 435 received treatment and none of the patients were prescribed ART when they should not have been. Only one prescription did not follow national guidelines.
At every visit, nurses were supposed to assess whether patients were taking their drugs and to monitor side effects. They did this and maintained records correctly for the vast majority of the 435 patients who were prescribed ART. 390 patients (over 90%) of the 435 prescribed receiving ART continued to take it and maintain contact with the pilot PHC's program. 29 patients died. Only one was lost to follow up and the others transferred to another ART site. The majority gained weight in the first six months and their CD4 cell counts rose. Outcomes, including death rate, were similar to those treated on the (doctor-led) Rwandan national ART program and other sub-Saharan African national (doctor-led) programs.
What Do These Findings Mean?
The study suggests that nurses are able to prescribe ART safely and effectively in a rural sub-Saharan setting, given sufficient training, mentoring, and support. Nurse-led prescribing of ART could mean that timely, appropriate treatment reaches many more HIV patients. It would reduce the burden of HIV care for doctors, freeing their time for other duties, and the study is already being used by the Rwandan Ministry of Health as a basis for plans to adopt a task-shifting strategy for the national ART program.
The study does have some limitations. The pilot program was funded and designed as a health project to deliver ART in rural areas, rather than a research project to compare nurse-led and doctor-led ART programs. There was no group of equivalent patients treated by doctors rather than nurses for direct comparison, although the authors did compare outcomes with those achieved nationally for doctor-led ART. The most promising sites, nurses, and patients were selected for the pilot and careful monitoring may have been an additional motivation for the nurses and doctors taking part. Health professionals in a scaled-up program may not be as committed as those in the pilot, who were carefully monitored. In addition, the nature of the pilot, which lasted for under three years and recruited new patients throughout, meant that patients were followed up for relatively short periods.
The authors also warn that they did not consider in this study the changes task shifting will make to doctors' roles and the skills required of both doctors and nurses. They recommend that task shifting should be implemented as part of a wider investment in health systems, human resources, training, adapted medical records, tools, and protocols.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000163.
PLoS Medicine includes a page collecting together its recent articles on HIV infection and AIDS that includes research articles, perspectives, editorials, and policy forums
SciDev.net provides news, views, and information about science, technology, and the developing world, including a section specific to HIV/AIDs
The World Health Organization (WHO) has published a downloadable booklet Task Shifting to Tackle Health Worker Shortages
The WHO offers information on HIV and AIDS (in Arabic, Chinese, English, French, Russian, and Spanish) as well as health information and fact sheets on individual countries, including on Rwanda
The UNAIDS/WHO working group on HIV/AIDS and Sexually Transmitted Infections (STI) Surveillance gathers and publishes data on the prevalence of HIV and AIDS in individual countries, including on Rwanda
AIDS.ORG provides information to help prevent HIV infections and to improve the lives of those affected by HIV and AIDS. Factsheets on many aspects of HIV and AIDS are available. It is the official online publisher of AIDS Treatment News
doi:10.1371/journal.pmed.1000163
PMCID: PMC2752160  PMID: 19823569
25.  Associations between Mode of HIV Testing and Consent, Confidentiality, and Referral: A Comparative Analysis in Four African Countries 
PLoS Medicine  2012;9(10):e1001329.
A study carried out by Carla Obermeyer and colleagues examines whether practices regarding consent, confidentiality, and referral vary depending on whether HIV testing is provided through voluntary counseling and testing or provider-initiated testing.
Background
Recommendations about scaling up HIV testing and counseling highlight the need to provide key services and to protect clients' rights, but it is unclear to what extent different modes of testing differ in this respect. This paper examines whether practices regarding consent, confidentiality, and referral vary depending on whether testing is provided through voluntary counseling and testing (VCT) or provider-initiated testing.
Methods and Findings
The MATCH (Multi-Country African Testing and Counseling for HIV) study was carried out in Burkina Faso, Kenya, Malawi, and Uganda. Surveys were conducted at selected facilities. We defined eight outcome measures related to pre- and post-test counseling, consent, confidentiality, satisfactory interactions with providers, and (for HIV-positive respondents) referral for care. These were compared across three types of facilities: integrated facilities, where testing is provided along with medical care; stand-alone VCT facilities; and prevention of mother-to-child transmission (PMTCT) facilities, where testing is part of PMTCT services. Tests of bivariate associations and modified Poisson regression were used to assess significance and estimate the unadjusted and adjusted associations between modes of testing and outcome measures. In total, 2,116 respondents tested in 2007 or later reported on their testing experience. High percentages of clients across countries and modes of testing reported receiving recommended services and being satisfied. In the unadjusted analyses, integrated testers were less likely to meet with a counselor before testing (83% compared with 95% of VCT testers; p<0.001), but those who had a pre-test meeting were more likely to have completed consent procedures (89% compared with 83% among VCT testers; p<0.001) and pre-test counseling (78% compared with 73% among VCT testers; p = 0.015). Both integrated and PMTCT testers were more likely to receive complete post-test counseling than were VCT testers (59% among both PMTCT and integrated testers compared with 36% among VCT testers; p<0.001). Adjusted analyses by country show few significant differences by mode of testing: only lower satisfaction among integrated testers in Burkina Faso and Uganda, and lower frequency of referral among PMTCT testers in Malawi. Adjusted analyses of pooled data across countries show a higher likelihood of pre-test meeting for those testing at VCT facilities (adjusted prevalence ratio: 1.22, 95% CI: 1.07–1.38) and higher satisfaction for stand-alone VCT facilities (adjusted prevalence ratio: 1.15; 95% CI: 1.06–1.25), compared to integrated testing, but no other associations were statistically significant.
Conclusions
Overall, in this study most respondents reported favorable outcomes for consent, confidentiality, and referral. Provider-initiated ways of delivering testing and counseling do not appear to be associated with less favorable outcomes for clients than traditional, client-initiated VCT, suggesting that testing can be scaled up through multiple modes without detriment to clients' rights.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
In 2007, World Health Organization (WHO) and the Joint United Nations Programme on HIV/AIDS (UNAIDS) issued a joint guidance document on “provider-initiated” HIV testing and counseling. They noted that previous testing strategies that relied on “client-initiated” testing (also referred to as VCT, for voluntary counseling and testing) had failed to reach enough people, both in high-income and resource-constrained countries—in Africa, for example, at that time, just 12% of men and 10% of women had ever been tested. They argued that many opportunities to diagnose and counsel people that visit health facilities for other reasons are being missed, and that provider-initiated HIV testing and counseling can help expand access to HIV treatment, care, and support. They made it clear, however, that mandatory testing is not acceptable. All provider-initiated testing must therefore give individuals the option to not be tested. In addition, the guidelines stressed that all testing must continue to observe “the three Cs” (informed consent, counseling, and confidentiality) and be accompanied by an “enabling environment” including the availability of antiretroviral therapy, prevention and support services, and a supportive social, policy, and legal framework. A number of advocates have subsequently criticized the guidelines for failing to recognize that health-care services and staff in some countries do not always observe the three Cs. Critics have also questioned the appropriateness of the strategy for settings where antiretroviral therapy is not always available or where stigma and discrimination remain widespread.
Why Was This Study Done?
To inform the debate surrounding scale-up of HIV testing in general and provider-initiated testing in particular with data on “real-life” testing, researchers have since carried out a number of studies. One of them, called MATCH (for Multi-Country African Testing and Counseling for HIV), was designed to allow systematic comparisons across African countries of different ways of HIV testing. Its goal was to investigate the uptake of testing, to analyze differences in the experience of testing across countries and modes of testing, and to use the results to devise better strategies to increase knowledge of HIV status and referral to care. MATCH used different means to collect information, including surveys and interviews. People from Burkina Faso, Kenya, Malawi, and Uganda participated. Some had undergone HIV testing, others had not. This study used a subset of the survey data collected for the MATCH study and asked whether there were systematic differences depending on the type of testing people had experienced.
What Did the Researchers Do and Find?
The data the researchers used were from 2,116 people who had undergone testing in the two previous years at different facilities in the four countries. The different facilities were grouped into three “modes” of testing: VCT-only testing, integrated testing (which included hospitals and other medical facilities where provider-initiated and client-initiated testing were both available, along with other medical services), and prevention of mother-to-child transmission (PMTCT) testing at medical facilities offering services to pregnant women. Analyzing the survey responses, the researchers categorized them as related to eight different “outcomes”: pre-test meeting, pre-test counseling, consent, confidentiality, satisfaction with the person-to-person interactions, post-test meeting to receive results, post-test counseling, and referral to care.
They found that across countries and different facilities, the majority of participants reported having received most of the testing-related services. More than 90% reported having a pre-test meeting, and around 80% were satisfied with the personal interactions, with the consent process, and with confidentiality. About 50% of participants reported receiving all post-test services, and 71% of those who had tested positive for HIV reported appropriate referral to care.
When they looked for differences between different modes of testing, the researchers found that while they existed, they did not consistently favor one mode over another. Some outcomes scored higher in VCT facilities, some in PMTCT facilities, and some in integrated facilities.
What Do These Findings Mean?
While there is room for improvement in HIV testing services (especially post-test services) across the countries and facilities included, the study did not reveal major problems with consent or confidentiality. The results also suggest that services at PMTCT and integrated facilities are not any worse than those at VCT-only sites. It seems therefore reasonable to continue expanding access to HIV testing and to include all facilities in the scale-up. That said, this is only one of a number of studies examining issues surrounding HIV testing, and decisions should be based on all available evidence. The results here are consistent with some of the other studies, but there are also reports that counseling might become neglected as testing is scaled up, and that offering testing routinely at every doctor's visit makes it seem mandatory even if there is the possibility to “opt out.” Other analyses of the MATCH study use in-depth interviews to understand in more detail the feelings, experiences, and attitudes of participants who have been tested as well as those who have not been tested. It will be important to see whether their results are consistent with the ones here, which are based on a survey of people who have been tested.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001329.
WHO has published a toolkit for scaling up HIV testing and counseling services in resource-limited settings, as well as the report Service Delivery Approaches to HIV Testing and Counselling (HSC): A Strategic HTC Programme Framework
In response to reactions to the 2007 joint WHO/UNAIDS guidelines Guidance on Provider-Initiated HIV Testing and Counselling in Health Facilities, the UNAIDS Reference Group on HIV and Human Rights issued a Statement and Recommendations on Scaling up HIV Testing and Counselling
The NAM/aidsmap website has a section on HIV testing policies and guidelines.
doi:10.1371/journal.pmed.1001329
PMCID: PMC3479110  PMID: 23109914

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