PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-25 (778255)

Clipboard (0)
None

Related Articles

1.  Predictors of Delayed Antiretroviral Therapy Initiation, Mortality, and Loss to Followup in HIV Infected Patients Eligible for HIV Treatment: Data from an HIV Cohort Study in India 
BioMed Research International  2013;2013:849042.
Studies from Sub-Saharan Africa have shown that a substantial number of HIV patients eligible for antiretroviral therapy (ART) do not start treatment. However, data from other low- or middle-income countries are scarce. In this study, we describe the outcomes of 4105 HIV patients who became ART eligible from January 2007 to November 2011 in an HIV cohort study in India. After three years of ART eligibility, 78.4% started ART, 9.3% died before ART initiation, and 10.3% were lost to followup. Diagnosis of tuberculosis, being homeless, lower CD4 count, longer duration of pre-ART care, belonging to a disadvantaged community, being widowed, and not living near a town were associated with delayed ART initiation. Diagnosis of tuberculosis, being homeless, lower CD4 count, shorter duration of pre-ART care, belonging to a disadvantaged community, illiteracy, and age >45 years were associated with mortality. Being homeless, being single, not living near a town, having a CD4 count <150 cells/μL, and shorter duration of pre-ART care were associated with loss to followup. These results highlight the need to improve the timely initiation of ART in HIV programmes in India, especially in ART eligible patients with tuberculosis, low CD4 counts, living in rural areas, or having a low socioeconomic status.
doi:10.1155/2013/849042
PMCID: PMC3830789  PMID: 24288689
2.  Delays in starting antiretroviral therapy in patients with HIV-associated tuberculosis accessing non-integrated clinical services in a South African township 
BMC Infectious Diseases  2011;11:258.
Background
Delays in the initiation of antiretroviral therapy (ART) in patients with HIV-associated tuberculosis (TB) are associated with increased mortality risk. We examined the timing of ART among patients receiving care provided by non-integrated TB and ART services in Cape Town, South Africa.
Methods
In an observational cohort study, we determined the overall time delay between starting treatment for TB and starting ART in patients treated in Gugulethu township between 2002 and 2008. For patients referred from TB clinics to the separate ART clinic, we quantified and identified risk factors associated with the two component delays between starting TB treatment, enrolment in the ART clinic and subsequent initiation of ART.
Results
Among 893 TB patients studied (median CD4 count, 81 cells/μL), the delay between starting TB treatment and starting ART was prolonged (median, 95 days; IQR = 49-155). Delays were shorter in more recent calendar periods and among those with lower CD4 cell counts. However, the median delay was almost three-fold longer for patients referred from separate TB clinics compared to patients whose TB was diagnosed in the ART clinic (116 days versus 41 days, respectively; P < 0.001). In the most recent calendar period, the proportions of patients with CD4 cell counts < 50 cells/μL who started ART within 4 weeks of TB diagnosis were 11.1% for patients referred from TB clinics compared to 54.6% of patients with TB diagnosed in the ART service (P < 0.001).
Conclusions
Delays in starting ART were prolonged, especially for patients referred from separate TB clinics. Non-integration of TB and ART services is likely to be a substantial obstacle to timely initiation of ART.
doi:10.1186/1471-2334-11-258
PMCID: PMC3203070  PMID: 21957868
3.  Suboptimal patterns of provider initiated HIV testing and counselling, antiretroviral therapy eligibility assessment and referral in primary health clinic attendees in Blantyre, Malawi* 
Objective
To understand reasons for suboptimal and delayed uptake of antiretroviral therapy (ART) by describing the patterns of HIV testing and counselling (HTC) and outcomes of ART eligibility assessments in primary clinic attendees.
Methods
All clinic attendances and episodes of HTC were recorded at two clinics in Blantyre. A cohort of newly diagnosed HIV-positive adults (>15 years) was recruited and exit interviews undertaken. Logistic regression models were constructed to investigate factors associated with referral to start ART. Qualitative interviews were conducted with providers and patients.
Results
There were 2398 episodes of HTC during 18 021 clinic attendances (13.3%) between January and April 2011. The proportion of clinic attendees undergoing HTC was lowest in non-pregnant women (6.3%) and men (8.5%), compared with pregnant women (47.2%). Men had more advanced HIV infection than women (79.7% WHO stage 3 or 4 vs. 56.4%). Problems with WHO staging and access to CD4 counts affected ART eligibility assessments; only 48% completed ART eligibility assessment, and 54% of those reporting WHO stage 3/4 illnesses were not referred to start ART promptly. On multivariate analysis, HIV-positive pregnant women were significantly less likely to be referred directly for ART initiation (adjusted OR: 0.29, 95% CI: 0.13–0.63).
Conclusions
These data show that provider-initiated testing and counselling (PITC) has not yet been fully implemented at primary care clinics. Suboptimal ART eligibility assessments and referral (reflecting the difficulties of WHO staging in primary care) mean that simplified eligibility assessment tools are required to reduce unnecessary delay and attrition in the pre-ART period. Simplified initiation criteria for pregnant women, as being introduced in Malawi, should improve linkage to ART.
doi:10.1111/j.1365-3156.2011.02946.x
PMCID: PMC3378506  PMID: 22296187
HIV; provider initiated testing and counselling; WHO clinical staging; antiretroviral therapy; programmatic evaluation; primary health care; qualitative
4.  Loss to Care and Death Before Antiretroviral Therapy in Durban, South Africa 
Objective
To examine the loss to care and mortality rates before starting antiretroviral therapy (ART) among ART eligible HIV-infected patients in Durban, South Africa.
Design
Retrospective cohort study.
Methods
We reviewed data from ART eligible adults (≥18 years) at an urban HIV clinic that charges a monthly fee from July to December 2006. ART eligibility was based on CD4 count ≤200 cells per microliter or clinical criteria and a psychosocial assessment. Patients who did not start ART and were lost within 3 months were phoned. Correlates of loss to care were evaluated using logistic regression.
Results
During the study period, 501 patients registered for ART training. Mean time from initial CD4 count to first ART training was 3.6 months (interquartile range 2.3−3.9 months). Four hundred eight patients (81.4%) were in care and on ART at 3-month follow-up, and 11 (2.2%) were in care but had not initiated ART. Eighty-two ART eligible patients (16.4%) were lost before ART initiation. Of these, 28 (34.1%) had died; two thirds of deaths occurred before or within 2 months after the first ART training. Despite multiple attempts, 32 patients (39%) were unreachable by phone. Lower baseline CD4 counts (≤100 cells/μL) and unemployment were independently associated with being lost.
Conclusions
Loss to care and death occur frequently before starting ART at an HIV clinic in Durban, South Africa. This delay from CD4 count to ART training, even among those with the lowest CD4 counts, highlights the need for interventions that improve linkage to care and prioritize ART initiation for those with low baseline CD4 counts.
PMCID: PMC2747614  PMID: 19504725
Africa; HIV healthcare; linkage to care; lost to follow-up; pre-ART mortality
5.  Mother-to-child transmission of HIV in a community-based antiretroviral clinic in South Africa 
Objective
To examine the uptake of ART among pregnant women referred to an ART service and the associated rates and risk factors for vertical HIV transmission.
Method
Retrospective analysis of an observational cohort at a community ART clinic in Cape Town.
Results
Between 2002 and 2008, 367 treatment-naïve pregnant women accessed the clinic. The median age was 27.5 years, and median gestation at presentation was 28 weeks. The median baseline CD4 count and viral load were 134 cells/µl and 28 282 copies/ml. Two hundred and sixty-five women (72%) commenced ART before giving birth, 73 women (20%) were referred for prevention of mother-to-child transmission therapy (PMTCT), and 29 (8%) received no intervention. Among ART-eligible women, 13% were lost to follow-up. Of those starting ART, median duration of therapy prior to birth was 7.6 weeks (interquartile range (IQR) 4 – 11.9). The HIV transmission rate was 5.1% (95% confidence interval (CI) 2.8 – 9.0%). Factors associated with transmission were advanced maternal WHO disease stage (odds ratio (OR) 9.57, p=0.02), and follow-up viral load above 50 copies/ml (OR 3.64, p=0.03). Each additional week on ART reduced transmission by 20% (p=0.05). There was no HIV transmission among women who received more than 8 weeks’ therapy.
Conclusions
The rate of HIV transmission in this study was higher than reported in high-income countries. Prevention of vertical transmission with ART was hindered by women presenting late in pregnancy and with advanced stage of HIV disease. Interventions that facilitate earlier ART commencement and improve programmatic retention of pregnant women are required.
PMCID: PMC3954611  PMID: 21414276
6.  Suboptimal patterns of provider initiated HIV testing and counselling, ART eligibility assessment and referral in primary health clinic attendees in Blantyre, Malawi 
Objective
To understand reasons for suboptimal and delayed uptake of antiretroviral therapy (ART) by describing the patterns of HIV testing and counselling (HTC) and outcomes of ART eligibility assessments in primary clinic attendees.
Methods
All clinic attendances and episodes of HTC were recorded at two clinics in Blantyre. A cohort of newly diagnosed HIV-positive adults (>15 years) was recruited and exit interviews undertaken. Logistic regression models were constructed to investigate factors associated with referral to start ART. Qualitative interviews were conducted with providers and patients.
Findings
There were 2,398 episodes of HTC during 18,021 clinic attendances (13.3%) between January and April 2011. The proportion of clinic attendees undergoing HTC was lowest in non-pregnant women (6.3%) and men (8.5%), compared to pregnant women (47.2%). Men had more advanced HIV infection than women (79.7% WHO stage 3 or 4 vs. 56.4%). Problems with WHO staging and access to CD4 counts affected ART eligibility assessments; only 48% completed ART eligibility assessment and 54% of those reporting WHO stage 3/4 illnesses were not referred to start ART promptly. On multivariate analysis, HIV-positive pregnant women were significantly less likely to be referred directly for ART initiation (adjusted OR: 0.29, 95% CI: 0.13-0.63).
Conclusions
These data show that provider initiated testing and counselling (PITC) has not yet been fully implemented at primary care clinics. Suboptimal ART eligibility assessments and referral (reflecting the difficulties of WHO staging in primary care) mean that simplified eligibility assessment tools are required to reduce unnecessary delay and attrition in the pre-ART period. Simplified initiation criteria for pregnant women, as being introduced in Malawi, should improve linkage to ART.
doi:10.1111/j.1365-3156.2011.02946.x
PMCID: PMC3378506  PMID: 22296187
HIV; provider initiated testing and counselling; WHO clinical staging; antiretroviral therapy; programmatic evaluation; primary health care; qualitative
7.  Impact of immune reconstitution inflammatory syndrome on antiretroviral therapy adherence 
Objective
We determined the impact of immune reconstitution inflammatory syndrome (IRIS) on antiretroviral therapy (ART) adherence in a cohort of 274 human immunodeficiency virus (HIV)-infected South African adults initiating ART.
Methods
We carried out a secondary analysis of data from a randomized controlled trial of partially supervised ART in Cape Town, South Africa. Monthly pill count adherence, viral suppression (HIV viral load < 50 c/mL), and IRIS events were documented. Poisson regression was used to identify variables associated with ART adherence below the median in the first 6 months of ART.
Results
We enrolled 274 patients: 58% women, median age 34 years, median CD4 count 98 cells/μL, 46% World Health Organization clinical stage IV, and 40% on treatment for tuberculosis (TB). IRIS and TB-IRIS developed in 8.4% and 6.6% of patients, respectively. The median cumulative adherence at 6 months for those with an IRIS event vs no IRIS was 95.5% vs 98.2% (P = 0.04). Although not statistically significant, patients developing IRIS had a lower 6-month viral load suppression than those without IRIS (68% vs 80%, P = 0.32). ART adherence below the median of 98% was independently associated with alcohol abuse (relative risk [RR] 1.5; 95% confidence interval [CI] 1.2–1.9; P = 0.003) and IRIS events (RR 1.7; 95% CI 1.2–2.2; P = 0.001).
Conclusion
Although IRIS events were associated with slightly lower adherence rates, overall adherence to ART remained high in this study population. Concerns about IRIS should not deter clinicians from early ART initiation.
doi:10.2147/PPA.S38897
PMCID: PMC3526885  PMID: 23271897
ART; adherence; TB; HIV/AIDS; IRIS
8.  Integration of Antiretroviral Therapy Services into Antenatal Care Increases Treatment Initiation during Pregnancy: A Cohort Study 
PLoS ONE  2013;8(5):e63328.
Objectives
Initiation of antiretroviral therapy (ART) during pregnancy is critical to promote maternal health and prevent mother-to-child HIV transmission (PMTCT). The separation of services for antenatal care (ANC) and ART may hinder antenatal ART initiation. We evaluated ART initiation during pregnancy under different service delivery models in Cape Town, South Africa.
Methods
A retrospective cohort study was conducted using routinely collected clinic data. Three models for ART initiation in pregnancy were evaluated ART ‘integrated’ into ANC, ART located ‘proximal’ to ANC, and ART located some distance away from ANC (‘distal’). Kaplan-Meier methods and Poisson regression were used to examine the association between service delivery model and antenatal ART initiation.
Results
Among 14 617 women seeking antenatal care in the three services, 30% were HIV-infected and 17% were eligible for ART based on CD4 cell count <200 cells/µL. A higher proportion of women started ART antenatally in the integrated model compared to the proximal or distal models (55% vs 38% vs 45%, respectively, global p = 0.003). After adjusting for age and gestation at first ANC visit, women who at the integrated service were significantly more likely to initiate ART antenatally (rate ratio 1.33; 95% confidence interval: 1.09–1.64) compared to women attending the distal model; there was no difference between the proximal and distal models in antenatal ART initiation however (p = 0.704).
Conclusions
Integration of ART initiation into ANC is associated with higher levels of ART initiation in pregnancy. This and other forms of service integration may represent a valuable intervention to enhance PMTCT and maternal health.
doi:10.1371/journal.pone.0063328
PMCID: PMC3656005  PMID: 23696814
9.  Comparison of point-of-care versus laboratory-based CD4 cell enumeration in HIV-positive pregnant women 
Introduction
Early initiation of antiretroviral therapy (ART) in eligible pregnant women is a key intervention for prevention of mother-to-child transmission (PMTCT) of HIV. However, in many settings in sub-Saharan Africa where ART-eligibility is determined by CD4 cell counts, limited access to laboratories presents a significant barrier to rapid ART initiation. Point-of-care (POC) CD4 cell count testing has been suggested as one approach to overcome this challenge, but there are few data on the agreement between POC CD4 cell enumeration and standard laboratory-based testing.
Methods
Working in a large antenatal clinic in Cape Town, South Africa, we compared POC CD4 cell enumeration (using the Alere PimaTM Analyzer) to laboratory-based flow cytometry in consecutive HIV-positive pregnant women. Bland–Altman methods were used to compare the two methods, including analyses by subgroups of participant gestational age.
Results
Among the 521 women participating, the median gestational age was 23 weeks, and the median CD4 cell count according to POC and laboratory-based methods was 388 and 402 cells/µL, respectively. On average, the Pima POC test underestimated CD4 cell count relative to flow cytometry: the mean difference (laboratory test minus Pima POC) was 22.7 cells/µL (95% CI, 16.1 to 29.2), and the limits of agreement were −129.2 to 174.6 cells/µL. When analysed by gestational age categories, there was a trend towards increasing differences between laboratory and POC testing with increasing gestational age; in women more than 36 weeks’ gestation, the mean difference was 45.0 cells/µL (p=0.04).
Discussion
These data suggest reasonable overall agreement between Pima POC CD4 testing and laboratory-based flow cytometry among HIV-positive pregnant women. The finding for decreasing agreement with increasing gestational age requires further investigation, as does the operational role of POC CD4 testing to increase access to ART within PMTCT programmes.
doi:10.7448/IAS.16.1.18649
PMCID: PMC3776301  PMID: 24044627
point-of-care test; CD4 cell count; reliability; pregnancy; HIV; antiretroviral therapy; South Africa
10.  Patients’ worries before starting antiretroviral therapy and their association with treatment adherence and outcomes: a prospective study in rural Uganda, 2004 - 2009 
BMC Research Notes  2013;6:187.
Background
In HIV-infected persons, good adherence to antiretroviral therapy (ART) is essential for successful treatment outcomes. Patients’ worries before starting ART may affect their ART adherence and treatment outcomes.
Methods
Between 2004 and 2009, HIV-infected individuals in a prospective cohort study in rural Uganda were assessed for ART eligibility. A counsellor explained the ART eligibility criteria, adherence and side effects, and recorded the patients’ worries related to ART. Every quarter, patients who initiated ART had clinical, immunological (CD4 cell counts) and virological (viral loads) assessments, and data were collected on ART adherence using patients’ self-reports and pill counts. We describe the patients’ worries and examine their association with ART adherence, and immunological and virological outcomes.
Results
We assessed 421 patients, 271 (64%) were females, 318 (76%) were aged 30 years and above and 315 (75%) were eligible for ART. 277 (66%) reported any worry, and the proportions were similar by sex, age group and ART eligibility status. The baseline median CD4 counts and viral loads were similar among patients with any worry and those with no worry. The commonest worries were: fear of HIV serostatus disclosure; among 69 (16%) participants, lack of food when appetite improved after starting ART; 50 (12%), concurrent use of other medications; 33 (8%), adherence to ART; 28 (7%) and problems concerning condom use; 27 (6%). After 24 months or more on ART, patients who reported any worry had made more scheduled ART refill visits than patients who reported no worry (p<0.01), but the annual CD4 cell increases were similar (p=0.12). After one year on ART, patients who reported any worry had greater virological suppression than patients who reported no worry (p<0.05).
Conclusions
Despite the lack of significant associations of worries with unfavourable ART outcomes, physicians and counsellors should assist patients in overcoming their worries that can cause stress and discomfort. Food supplements may be desirable for some patients initiating ART.
doi:10.1186/1756-0500-6-187
PMCID: PMC3655014  PMID: 23651541
Antiretroviral therapy; Patients’ worries; Adherence; Treatment outcomes
11.  Outcomes in Patients Waiting for Antiretroviral Treatment in the Free State Province, South Africa: Prospective Linkage Study 
AIDS (London, England)  2010;24(17):2717-2725.
Objective
In South Africa, many HIV-infected patients experience delays in accessing antiretroviral therapy (ART). We examined pre-treatment mortality and access to treatment in patients waiting for ART.
Design
Cohort of HIV-infected patients assessed for ART eligibility at 36 facilities participating in the Comprehensive HIV and AIDS Management (CHAM) program in the Free State Province.
Methods
Proportion of patients initiating ART, pre-ART mortality and risk factors associated with these outcomes were estimated using competing risks survival analysis.
Results
44,844 patients enrolled in CHAM between May 2004 and December 2007, of whom 22,083 (49.2%) were eligible for ART; pre-ART mortality was 53.2 per 100 person-years (95% CI 51.8-54.7). Median CD4 count at eligibility increased from 87 cells/mm3 in 2004 to 101 cells/mm3 in 2007. Two years after eligibility an estimated 67.7% (67.1% – 68.4%) of patients had started ART, and 26.2% (25.6% - 26.9%) died before starting ART. Among patients with CD4 counts <25 cells/mm3 at eligibility, 48% died before ART and 51% initiated ART. Men were less likely to start treatment and more likely to die than women. Patients in rural clinics or clinics with low staffing levels had lower rates of starting treatment and higher mortality compared with patients in urban/ peri-urban clinics, or better staffed clinics.
Conclusions
Mortality is high in eligible patients waiting for ART in the Free State Province. The most immunocompromised patients had the lowest probability of starting ART and the highest risk of pre-ART death. Prioritization of these patients should reduce waiting times and pre-ART mortality.
doi:10.1097/QAD.0b013e32833fb71f
PMCID: PMC3235583  PMID: 20935554
HIV; ART; South Africa; waiting times; mortality; treatment access
12.  Early Mortality and AIDS Progression Despite High Initial Antiretroviral Therapy Adherence and Virologic Suppression in Botswana 
PLoS ONE  2011;6(6):e20010.
Background
Adverse outcomes occurring early after antiretroviral therapy (ART) initiation are common in sub-Saharan Africa, despite reports of high levels of ART adherence in this setting. We sought to determine the relationship between very early ART adherence and early adverse outcomes in HIV-infected adults in Botswana.
Methods
This prospective cohort study of 402 ART-naïve, HIV-infected adults initiating ART at a public HIV clinic in Gaborone, Botswana evaluated the relationship between suboptimal early ART adherence and HIV treatment outcomes in the initial months after ART initiation. Early adherence during the interval between initial ART dispensation and first ART refill was calculated using pill counts. In the primary analysis patients not returning to refill and those with adherence <0.95 were considered to have suboptimal early adherence. The primary outcome was death or loss to follow-up during the first 6 months of ART; a secondary composite outcome included the primary outcome plus incident opportunistic illness (OIs) and virologic failure. We also calculated the percent of early adverse outcomes theoretically attributable to suboptimal early adherence using the population attributable risk percent (PAR%).
Results
Suboptimal early adherence was independently associated with loss to follow-up and death (adjusted OR 2.3, 95% CI 1.1–4.8) and with the secondary composite outcome including incident OIs and virologic failure (adjusted OR 2.6, 95% CI 1.4–4.7). However, of those with early adverse outcomes, less than one-third had suboptimal adherence and approximately two-thirds achieved virologic suppression. The PAR% relating suboptimal early adherence and primary and secondary outcomes were 14.7% and 17.7%, respectively.
Conclusions
Suboptimal early adherence was associated with poor outcomes, but most early adverse outcomes occurred in patients with optimal early adherence. Clinical care and research efforts should focus on understanding early adverse outcomes that occur despite optimal adherence.
doi:10.1371/journal.pone.0020010
PMCID: PMC3115945  PMID: 21698283
13.  Economic Outcomes of Patients Receiving Antiretroviral Therapy for HIV/AIDS in South Africa Are Sustained through Three Years on Treatment 
PLoS ONE  2010;5(9):e12731.
Background
Although the medical outcomes of antiretroviral therapy (ART) for HIV/AIDS are well described, less is known about how ART affects patients' economic activities and quality of life, especially after the first year on ART. We assessed symptom prevalence, general health, ability to perform normal activities, and employment status among adult antiretroviral therapy patients in South Africa over three full years following ART initiation.
Methodology/Principal Findings
A cohort of 855 adult pre-ART patients and patients on ART for <6 months was enrolled and interviewed an average of 4.4 times each during routine clinic visits for up to three years after treatment initiation using an instrument designed for the study. The probability of pain in the previous week fell from 74% before ART initiation to 32% after three years on ART, fatigue from 66% to 12%, nausea from 28% to 4%, and skin problems from 55% to 10%. The probability of not feeling well physically yesterday fell from 46% to 23%. Before starting ART, 39% of subjects reported not being able to perform their normal activities sometime during the previous week; after three years, this proportion fell to 10%. Employment rose from 27% to 42% of the cohort. Improvement in all outcomes was sustained over 3 years and for some outcomes increased in the second and third year.
Conclusions/Significance
Improvements in adult ART patients' symptom prevalence, general health, ability to perform normal activities, and employment status were large and were sustained through the first three years on treatment. These results suggest that some of the positive economic and social externalities anticipated as a result of large-scale treatment provision, such as increases in workforce participation and productivity and the ability of patients to carry on normal lives, may indeed be accruing.
doi:10.1371/journal.pone.0012731
PMCID: PMC2939080  PMID: 20856821
14.  Design and methods of a longitudinal study investigating the impact of antiretroviral treatment on the partnerships and sexual behaviour of HIV-infected individuals in rural KwaZulu-Natal, South Africa 
BMC Public Health  2011;11:121.
Background
Diagnosed HIV-infected people form an increasingly large sub-population in South Africa, one that will continue to grow with widely promoted HIV testing and greater availability of antiretroviral therapy (ART). For HIV prevention and support, understanding the impact of long-term ART on family and sexual relationships is a health research priority. This includes improving the availability of longitudinal demographic and health data on HIV-infected individuals who have accessed ART services but who are not yet ART-eligible.
Design and methods
The aim of the study is to investigate the impact of ART on family and partner relationships, and sexual behaviour of HIV-infected individuals accessing a public HIV treatment and care programme in rural South Africa. HIV-infected men and women aged 18 years or older attending three clinics are screened. Those people initiating ART because they meet the criteria of WHO stage 4 or CD4 ≤ 200 cells/μL are assigned to an 'ART initiator' group. A 'Monitoring' group is composed of people whose most recent CD4 count was >500 cells/μL and are therefore, not yet eligible for ART. During the four-year study, data on both groups is collected every 6 months during clinic visits, or where necessary by home visits or phone. Detailed information is collected on social, demographic and health characteristics including living arrangements, past and current partnerships, sexual behaviour, HIV testing and disclosure, stigma, self-efficacy, quality of family and partner relationships, fertility and fertility intentions, ART knowledge and attitudes, and gender norms. Recruitment for both groups started in January 2009. As of October 2010, 600 participants have been enrolled; 386 in the ART initiator group (141, 37% male) and 214 in the Monitoring group (31, 14% male). Recruitment remains open for the Monitoring group.
Discussion
The data collected in this study will provide valuable information for measuring the impact of ART on sexual behaviour, and for the planning and delivery of appropriate interventions to promote family and partner support, and safe sexual behaviour for people living with HIV in this setting and elsewhere in sub-Saharan Africa.
doi:10.1186/1471-2458-11-121
PMCID: PMC3049146  PMID: 21333022
15.  Introduction and evaluation of a ‘pre-ART care’ service in Swaziland: an operational research study 
BMJ Open  2012;2(2):e000195.
Objective
To implement and evaluate a formal pre-antiretroviral therapy (ART) care service at a district hospital in Swaziland.
Design
Operational research.
Setting
District hospital in Southern Africa.
Participants
1171 patients with a previous diagnosis of HIV. A baseline patient group consisted of the first 200 patients using the service. Two follow-up groups were defined: group 1 was all patients recruited from April to June 2009 and group 2 was 200 patients recruited in February 2010.
Intervention
Introduction of pre-ART care—a package of interventions, including counselling; regular review; clinical staging; timely initiation of ART; social and psychological support; and prevention and management of opportunistic infections, such as tuberculosis.
Primary and secondary outcome measures
Proportion of patients assessed for ART eligibility, proportion of eligible patients who were started on ART and proportion receiving defined evidence-based interventions (including prophylactic co-trimoxazole and tuberculosis screening).
Results
Following the implementation of the pre-ART service, the proportion of patients receiving defined interventions increased; the proportion of patient being assessed for ART eligibility significantly increased (baseline: 59%, group 1: 64%, group 2: 76%; p=0.001); the proportion of ART-eligible patients starting treatment increased (baseline: 53%, group 1: 81%, group: 2, 81%; p<0.001) and the median time between patients being declared eligible for ART and initiation of treatment significantly decreased (baseline: 61 days, group 1: 39 days, group 2: 14 days; p<0.001).
Conclusions
This intervention was part of a shift in the model of care from a fragmented acute care model to a more comprehensive service. The introduction of structured pre-ART was associated with significant improvements in the assessment, management and timeliness of initiation of treatment for patients with HIV.
Article summary
Article focus
Impact of pre-ART care on the quality of care in a district hospital in Southern Africa.
Key messages
After introduction of a pre-ART care service, a higher proportion of patients were assessed for ART, a higher proportion of those eligible started on ART and a higher proportion received key interventions.
Strengths and limitations of this study
This was a pragmatic evaluation in a routine service setting.
The intervention was implemented as part of routine health service delivery by existing clinical staff.
Routine data collection systems do not link testing and HIV care data, preventing an evaluation from testing to initiation.
The evaluation focuses on those with a known status, rather than new testers, those with tuberculosis or those who are pregnant.
The evaluation relies on intermediate outcomes, that is, initiation on ART, rather than long-term outcomes, such as mortality.
There is a lack of information on those requiring long-term follow-up but not ART.
doi:10.1136/bmjopen-2011-000195
PMCID: PMC3307034  PMID: 22422913
16.  Pre-treatment mortality and loss-to-follow-up in HIV-1, HIV-2 and HIV-1/HIV-2 dually infected patients eligible for antiretroviral therapy in The Gambia, West Africa 
Background
High early mortality rate among HIV infected patients following initiation of antiretroviral therapy (ART) in resource limited settings may indicate high pre-treatment mortality among ART-eligible patients. There is dearth of data on pre-treatment mortality in ART programmes in sub-Sahara Africa. This study aims to determine pre-treatment mortality rate and predictors of pre-treatment mortality among ART-eligible adult patients in a West Africa clinic-based cohort.
Methods
All HIV-infected patients aged 15 years or older eligible for ART between June 2004 and September 2009 were included in the analysis. Assessment for eligibility was based on the Gambia ART guideline. Survival following ART-eligibility was determined by Kaplan-Meier estimates and predictors of pre-treatment mortality determined by Cox proportional hazard models.
Result
Overall, 790 patients were assessed as eligible for ART based on their clinical and/or immunological status among whom 510 (64.6%) started treatment, 26 (3.3%) requested transfer to another health facility, 136 (17.2%) and 118 (14.9%) were lost to follow-up and died respectively without starting ART. ART-eligible patients who died or were lost to follow-up were more likely to be male or to have a CD4 T-cell count < 100 cells/μL, while patients in WHO clinical stage 3 or 4 were more likely to die without starting treatment. The overall pre-treatment mortality rate was 21.9 deaths per 100 person-years (95% CI 18.3 - 26.2) and the rate for the composite end point of death or loss to follow-up was 47.1 per 100 person-years (95% CI 41.6 - 53.2). Independent predictors of pre-treatment mortality were CD4 T-cell count <100 cells/μL (adjusted Hazard ratio [AHR] 3.71; 95%CI 2.54 - 5.41) and WHO stage 3 or 4 disease (AHR 1.91; 95% CI 1.12 - 3.23). Forty percent of ART-eligible patients lost to follow-up seen alive at field visit cited difficulty with the requirement of disclosing their HIV status as reason for not starting ART.
Conclusion
Approximately one third of ART-eligible patients did not start ART and pre-treatment mortality rate was found high among HIV infected patients in our cohort. CD4 T-cell count <100 cells/μL is the strongest independent predictor of pre-treatment mortality. The requirement to disclose HIV status as part of ART preparation counselling constitutes a huge barrier for eligible patients to access treatment.
doi:10.1186/1742-6405-8-24
PMCID: PMC3152879  PMID: 21774813
17.  Health system weaknesses constrain access to PMTCT and maternal HIV services in South Africa: a qualitative enquiry 
Background
HIV remains responsible for an estimated 40% of mortality in South African pregnant women and their children. To address these avoidable deaths, eligibility criteria for antiretroviral therapy (ART) in pregnant women were revised in 2010 to enhance ART coverage. With greater availability of HIV services in public health settings and increasing government attention to poor maternal-child health outcomes, this study used the patient's journey through the continuum of maternal and child care as a framework to track and document women's experiences of accessing ART and prevention of mother-to-child HIV transmission (PMTCT) programmes in the Eastern Cape (three peri-urban facilities) and Gauteng provinces (one academic hospital).
Results
In-depth interviews identified considerable weaknesses within operational HIV service delivery. These manifested as missed opportunities for HIV testing in antenatal care due to shortages of test kits; insufficient staff assigned to HIV services; late payment of lay counsellors, with consequent absenteeism; and delayed transcription of CD4 cell count results into patient files (required for ART initiation). By contrast, individual factors undermining access encompassed psychosocial concerns, such as fear of a positive test result or a partner's reaction; and stigma. Data and information systems for monitoring in the three peri-urban facilities were markedly inadequate.
Conclusions
A single system- or individual-level delay reduced the likelihood of women accessing ART or PMTCT interventions. These delays, when concurrent, often signalled wholesale denial of prevention and treatment. There is great scope for health systems' reforms to address constraints and weaknesses within PMTCT and ART services in South Africa. Recommendations from this study include: ensuring autonomy over resources at lower levels; linking performance management to facility-wide human resources interventions; developing accountability systems; improving HIV services in labour wards; ensuring quality HIV and infant feeding counselling; and improved monitoring for performance management using robust systems for data collection and utilisation.
doi:10.1186/1742-6405-8-10
PMCID: PMC3058008  PMID: 21371301
18.  Barriers to Initiation of Antiretrovirals during Antituberculosis Therapy in Africa 
PLoS ONE  2011;6(5):e19484.
Background
In the developing world, the principal cause of death among HIV-infected patients is tuberculosis (TB). The initiation of antiretroviral therapy (ART) during TB therapy significantly improves survival, however it is not known which barriers prevent eligible TB patients from initiating life-saving ART.
Method
Setting. A South African township clinic with integrated tuberculosis and HIV services. Design. Logistic regression analyses of a prospective cohort of HIV-1 infected adults (≥18 years) who commenced TB therapy, were eligible for ART, and were followed for 6 months.
Findings
Of 100 HIV-1 infected adults eligible for ART during TB therapy, 90 TB patients presented to an ART clinic for assessment, 66 TB patients initiated ART, and 15 TB patients died. 34% of eligible TB patients (95%CI: 25–43%) did not initiate ART. Male gender and younger age (<36 years) were associated with failure to initiate ART (adjusted odds ratios of 3.7 [95%CI: 1.25–10.95] and 3.3 [95%CI: 1.12–9.69], respectively). Death during TB therapy was associated with a CD4+ count <100 cells/µL.
Conclusion
In a clinic with integrated services for tuberculosis and HIV, one-third of eligible TB patients – particularly young men – did not initiate ART. Strategies are needed to promote ART initiation during TB therapy, especially among young men.
doi:10.1371/journal.pone.0019484
PMCID: PMC3093394  PMID: 21589868
19.  Acceptance of Voluntary Counselling, Testing and Treatment for HIV Among Pregnant Women in Kumasi, Ghana 
Ghana Medical Journal  2008;42(1):8-15.
Summary
Background
Voluntary counselling and testing (VCT) for human immunodeficiency virus (HIV) and treatment of positive pregnant women can reduce mother to child transmission (MTCT) of HIV.
Objective
This study was conducted to assess acceptance of HIV VCT and antiretroviral therapy (ART) by pregnant women in Kumasi, Ghana, before and after VCT and ART were available.
Methods
Two cross-sectional studies were conducted among women in antenatal clinics. The first, in 2003 among 501 women, before VCT and ART were available in Kumasi. Women who were willing were counselled and tested for HIV. In 2005, after the introduction of VCT and ART by the Ghana Health Service, 675 pregnant women were surveyed regarding HIV/VCT acceptance and uptake.
Results
In 2003, 98% of women accepted counselling and 97% accepted testing; 3.3% tested HIV positive. Multivariate analysis showed that women with secondary education were 88% less likely than those with no/primary education to accept testing (OR=0.12, CI=0.03–0.54,p=0.006). Women who had prior HIV testing were 95% less likely to accept testing (OR=0.05, CI=0.01–0.19, p=0.0001). Women who reported two sexual partners in the past year were 6 times as likely to be HIV positive than those reporting one sexual partner (OR=5.76. CI=1.53 – 21.69, p=>0.05). In 2005, 76% of women reported no prior HIV counselling and 78% no testing.
Conclusions
In 2003, there was wide uptake of VCT by prenatal women. However, in 2005 the majority of pregnant women were not accessing the available VCT services.
PMCID: PMC2423339  PMID: 18560557
HIV; voluntary counselling and testing (VCT); pregnant women; Ghana
20.  HIV-Infected Children in Rural Zambia Achieve Good Immunologic and Virologic Outcomes Two Years after Initiating Antiretroviral Therapy 
PLoS ONE  2011;6(4):e19006.
Background
Many HIV-infected children in sub-Saharan Africa reside in rural areas, yet most research on treatment outcomes has been conducted in urban centers. Rural clinics and residents may face unique barriers to care and treatment.
Methods
A prospective cohort study of HIV-infected children was conducted between September 2007 and September 2010 at the rural HIV clinic in Macha, Zambia. HIV-infected children younger than 16 years of age at study enrollment who received antiretroviral therapy (ART) during the study were eligible. Treatment outcomes during the first two years of ART, including mortality, immunologic status, and virologic suppression, were assessed and risk factors for mortality and virologic suppression were evaluated.
Results
A total of 69 children entered the study receiving ART and 198 initiated ART after study enrollment. The cumulative probabilities of death among children starting ART after study enrollment were 9.0% and 14.4% at 6 and 24 months after ART initiation. Younger age, higher viral load, lower CD4+ T-cell percentage and lower weight-for-age z-scores at ART initiation were associated with higher risk of mortality. The mean CD4+ T-cell percentage increased from 16.3% at treatment initiation to 29.3% and 35.0% at 6 and 24 months. The proportion of children with undetectable viral load increased to 88.5% and 77.8% at 6 and 24 months. Children with longer travel times (≥5 hours) and those taking nevirapine at ART initiation, as well as children who were non-adherent, were less likely to achieve virologic suppression after 6 months of ART.
Conclusions
HIV-infected children receiving treatment in a rural clinic experienced sustained immunologic and virologic improvements. Children with longer travel times were less likely to achieve virologic suppression, supporting the need for decentralized models of ART delivery.
doi:10.1371/journal.pone.0019006
PMCID: PMC3084269  PMID: 21552521
21.  Sex differences in responses to antiretroviral treatment in South African HIV-infected children on ritonavir-boosted lopinavir- and nevirapine-based treatment 
BMC Pediatrics  2014;14:39.
Background
While studies of HIV-infected adults on antiretroviral treatment (ART) report no sex differences in immune recovery and virologic response but more ART-associated complications in women, sex differences in disease progression and response to ART among children have not been well assessed. The objective of this study was to evaluate for sex differences in response to ART in South African HIV-infected children who were randomized to continue ritonavir-boosted lopinavir (LPV/r)-based ART or switch to nevirapine-based ART.
Methods
ART outcomes in HIV-infected boys and girls in Johannesburg, South Africa from 2005–2010 were compared. Children initiated ritonavir-boosted lopinavir (LPV/r)-based ART before 24 months of age and were randomized to remain on LPV/r or switch to nevirapine-based ART after achieving viral suppression. Children were followed for 76 weeks post-randomization and then long-term follow up continued for a minimum of 99 weeks and maximum of 245 weeks after randomization. Viral load, CD4 count, lipids, anthropometrics, drug concentrations, and adherence were measured at regular intervals. Outcomes were compared between sexes within treatment strata.
Results
A total of 323 children (median age 8.8 months, IQR 5.1-13.5), including 168 boys and 155 girls, initiated LPV/r-based ART and 195 children were randomized. No sex differences in risk of virological failure (confirmed viral load >1000 copies/mL) by 156 weeks post-randomization were observed within either treatment group. Girls switched to nevirapine had more robust CD4 count improvement relative to boys in this group through 112 weeks post-randomization. In addition, girls remaining on LPV/r had higher plasma concentrations of ritonavir than boys during post-randomization visits. After a mean of 3.4 years post-randomization, girls remaining on LPV/r also had a higher total cholesterol:HDL ratio and lower mean HDL than boys on LPV/r.
Conclusions
Sex differences are noted in treated HIV-infected children even at a young age, and appear to depend on treatment regimen. Future studies are warranted to determine biological mechanisms and clinical significance of these differences.
Trial registration
ClinicalTrials.gov Identifier: NCT00117728
doi:10.1186/1471-2431-14-39
PMCID: PMC3927631  PMID: 24521425
HIV; Children; Sex differences; Antiretroviral treatment outcomes; Pharmacokinetics
22.  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
23.  Who starts antiretroviral therapy in Durban, South Africa?… not everyone who should 
AIDS (London, England)  2010;24(Suppl 1):S37-S44.
Objective
To evaluate rates of antiretroviral therapy (ART) initiation within 12 months of a new HIV diagnosis in Durban, South Africa.
Design
Prospective observational cohort.
Methods
Adults (≥18 years) were enrolled before HIV testing at two outpatient clinics into the South African Test, Identify and Link cohort. Both sites offer comprehensive HIV care. HIV test results, CD4 cell counts, dates of ART initiation and dates of death were collected from medical records and 12-month patient/family interviews were conducted. ART eligibility was defined as a CD4 cell count less than 200 cells/μl within 90 days of HIV diagnosis. The primary endpoint was ART initiation within 12 months for ART-eligible subjects.
Results
From November 2006 to October 2008, 1474 newly diagnosed HIV-infected outpatients were enrolled, 1012 (69%) of whom underwent CD4 cell count testing within 90 days. The median CD4 cell count was 159 cells/μl (interquartile range 65–299). Of those who underwent CD4 cell count testing, 538 (53%) were ART-eligible. Only 210 (39%) eligible enrollees were known to have initiated ART within 12 months. Among ART-eligible subjects, there were 108 known deaths; 82% occurred before ART initiation or with unknown ART initiation status. Men [rate ratio (RR) 1.3, 95% confidence interval (CI) 1.1–1.5] and subjects without an HIV-infected family member/friend (RR 1.3, 95% CI 1.1–1.7) were more likely not to start ART.
Conclusion
Less than half of ART-eligible subjects started ART within 12 months. Substantial attrition and mortality follow HIV diagnosis before ART initiation in Durban, South Africa. Major efforts directed towards earlier HIV diagnosis, effective linkage to care and timely ART initiation are urgently needed.
doi:10.1097/01.aids.0000366081.91192.1c
PMCID: PMC3521614  PMID: 20023438
HIV-1; HIV testing; linkage to care; loss to care; South Africa
24.  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
25.  Patient retention from HIV diagnosis through one year on antiretroviral therapy at a primary healthcare clinic in Johannesburg, South Africa 
Objective
To compare patient retention at three stages of pre-antiretroviral (ART) care and two stages of post-ART care to identify when greatest attrition occurs.
Design
An observational cohort study.
Methods
We reviewed files of all adult, non-pregnant individuals testing HIV-positive January 1 – June 30, 2010, at a primary health clinic in Johannesburg, South Africa (N=842). We classified retention in pre-ART stage 1 (HIV diagnosis to CD4 results notification in ≤3 months), pre-ART stage 2 (initially ineligible for ART with repeat CD4 test ≤1 year of prior CD4), pre-ART stage 3 (initiating ART ≤3 months after first eligible CD4 result), as well as at 0–6 and 6–12 months post-ART.
Results
Retention among all patients during pre-ART stage 1 was 69.8% (95%CI 66.7–72.9%). For patients initially ART-ineligible (n=221), 57.4% (95%CI 49.5–65.0%) returned for a repeat CD4 during pre-ART stage 2. Among those ART-eligible (n=589), 73.5% (95%CI 69.0–77.6%) were retained during pre-ART stage 3. Retention increased with time on ART, from 80.2% (95%CI 75.3–84.5%) at 6 months to 95.3% (95%CI 91.7–97.6%) between 6–12 months. Cumulative retention from diagnosis to 12 months on ART was 36.9% (95%CI 33.0–41.1%) for those ART-eligible and 43.0% (95%CI 36.4–49.8%) from diagnosis to repeat CD4 testing within one year among those ART-ineligible.
Conclusions
Patient attrition in the first year following HIV diagnosis was greatest prior to ART initiation: over 25% at each of three pre-ART stages. As countries expand HIV testing and ART programs, success will depend on linkage to care, especially prior to ART eligibility and initiation.
doi:10.1097/QAI.0b013e318273ac48
PMCID: PMC3548953  PMID: 23011400
HIV/AIDS; antiretroviral therapy (ART); retention; attrition; linkage to care; South Africa

Results 1-25 (778255)