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1.  Maternal post-traumatic stress disorder, depression and alcohol dependence and child behaviour outcomes in mother–child dyads infected with HIV: a longitudinal study 
BMJ Open  2013;3(12):e003638.
Objectives
HIV and psychiatric disorders are prevalent and often concurrent. Childbearing women are at an increased risk for both HIV and psychiatric disorders, specifically depression and post-traumatic stress disorder (PTSD). Poor mental health in the peripartum period has adverse effects on infant development and behaviour. Few studies have investigated the relationship between maternal PTSD and child behaviour outcomes in an HIV vertically infected sample. The aim of this study was to investigate whether maternal postpartum trauma exposure and PTSD were risk factors for child behaviour problems. In addition, maternal depression, alcohol abuse and functional disability were explored as cofactors.
Setting
The study was conducted in Cape Town, South Africa.
Participants
70 mother–child dyads infected with HIV were selected from a group of participants recruited from community health centres.
Design
The study followed a longitudinal design. Five measures were used to assess maternal trauma exposure, PTSD, depression, alcohol abuse and functional disability at 12 months postpartum: Life Events Checklist (LEC), Harvard Trauma Scale (HTS), Alcohol Use Disorders Identification Test (AUDIT), Center for Epidemiological Studies Depression (CESD) Scale and the Sheehan Disability Scale (SDS). Child behaviour was assessed at 42 months with the Child Behaviour Checklist (CBCL).
Results
The rate of maternal disorder was high with 50% scoring above the cut-off for depression, 22.9% for PTSD and 7% for alcohol abuse. Half of the children scored within the clinical range for problematic behaviour. Children of mothers with depression were significantly more likely to display total behaviour problems than children of mothers without depression. Maternal PTSD had the greatest explanatory power for child behaviour problems, although it did not significantly predict child outcomes.
Conclusions
This study highlights the importance of identifying and managing maternal PTSD and depression in mothers of children infected with HIV. The relationship between maternal PTSD and child behaviour warrants further investigation.
doi:10.1136/bmjopen-2013-003638
PMCID: PMC3863126  PMID: 24334155
Maternal mental health; Child behaviour and development; Posttraumatic Stress Disorder; Depression; Alcohol abuse; HIV/AIDS
2.  Cofactors for HIV-1 Incidence during Pregnancy and Postpartum Period 
Current HIV Research  2010;8(7):510-514.
Objectives
To estimate HIV-1 incidence and cofactors for HIV-1 incidence during pregnancy and postpartum.
Design
Retrospective study among women who were HIV seronegative during pregnancy.
Methods
Mothers accompanying their infants for routine 6-week immunizations at 6 maternal child health clinics in Nairobi and Western Kenya were tested for HIV-1 after completing a questionnaire that included assessment of sociodemographics, obstetric history and HIV-1 risk perception.
Results
Of 2,135 mothers who had tested HIV-1 seronegative antenatally, 2,035 (95.3%) accepted HIV-1 re-testing at 6 weeks postpartum. Of these, 53 (2.6%) were HIV-1 seropositive yielding an estimated HIV-1 incidence of 6.8 (95% CI: 5.1-8.8) per 100 woman-years). Mothers who seroconverted were more likely to be employed (45.3% vs 29.0%, p=0.01), married (96.2 vs 86.6%, p=0.04) and from a higher HIV-1 prevalence region (60.4% in Western Kenya vs 28.8% in Nairobi, p<0.001). Among married women, those in polygamous relationship were significantly more likely to seroconvert (19.6% vs 6.7%, p<0.001). In multivariate analysis, region and employment independently predicted seroconversion.
Conclusions
Repeat HIV-1 testing in early postpartum was highly acceptable and resulted in detection of substantial HIV-1 incidence during pregnancy and postpartum period. Within prevention of mother-to-child HIV-1 transmission programs strategic approaches to prevent maternal HIV-1 acquisition during pregnancy are urgently needed.
PMCID: PMC3372399  PMID: 20946093
Seroconversion; pregnancy; incidence; sub Saharan Africa; risk factors; heterosexual transmission
3.  Mortality and Health Outcomes in HIV-Infected and HIV-Uninfected Mothers at 18–20 Months Postpartum in Zomba District, Malawi 
PLoS ONE  2012;7(9):e44396.
Background
Maternal morbidity and mortality among HIV-infected women is a global concern. This study compared mortality and health outcomes of HIV-infected and HIV-uninfected mothers at 18–20 months postpartum within routine prevention of mother-to-child transmission of HIV (PMTCT) services in a rural district in Malawi.
Methods
A retrospective cohort study of mother-child dyads at 18–20 months postpartum in Zomba District. Data on socio-demographic characteristics, service uptake, maternal health outcomes and biometric parameters were collected.
Results
173 HIV-infected and 214 HIV-uninfected mothers were included. HIV-specific cohort mortality at 18–20 months postpartum was 42.4 deaths/1000 person-years; no deaths occurred among HIV-uninfected women. Median time to death was 11 months post-partum (range 3–19). Women ranked their health on a comparative qualitative scale; HIV-infected women perceived their health to be poorer than did HIV-uninfected women (RR 2.4; 95% CI 1.6–3.7). Perceived maternal health status was well correlated with an objective measure of functional status (Karnofsky scale; p<0.001). HIV-infected women were more likely to report minor (RR 3.8; 95% CI 2.3–6.4) and major (RR 6.2; 95% CI 2.2–17.7) signs or symptoms of disease. In multivariable analysis, HIV-infected women remained twice as likely to report poorer health [adjusted OR (aOR) 2.3; 95% CI 1.4–3.6], as did women with low BMI (aOR 2.1; 95% CI 1.1–4.0) and scoring lowest on the welfare scale (aOR 2.0; 95% CI 1.1–3.8).
Conclusions
HIV-infected women show increased mortality and morbidity at 18–20 months postpartum. In our rural Malawian operational setting, where there is documented under-application of ART and poor adherence to PMTCT services, these results support attention to optimizing maternal participation in PMTCT programs.
doi:10.1371/journal.pone.0044396
PMCID: PMC3433431  PMID: 22973443
4.  Incident HIV during Pregnancy and Postpartum and Risk of Mother-to-Child HIV Transmission: A Systematic Review and Meta-Analysis 
PLoS Medicine  2014;11(2):e1001608.
Alison Drake and colleagues conduct a systematic review and meta-analysis to estimate maternal HIV incidence during pregnancy and the postpartum period and to compare mother-to-child HIV transmission risk among women with incident versus chronic infection.
Please see later in the article for the Editors' Summary
Background
Women may have persistent risk of HIV acquisition during pregnancy and postpartum. Estimating risk of HIV during these periods is important to inform optimal prevention approaches. We performed a systematic review and meta-analysis to estimate maternal HIV incidence during pregnancy/postpartum and to compare mother-to-child HIV transmission (MTCT) risk among women with incident versus chronic infection.
Methods and Findings
We searched PubMed, Embase, and AIDS-related conference abstracts between January 1, 1980, and October 31, 2013, for articles and abstracts describing HIV acquisition during pregnancy/postpartum. The inclusion criterion was studies with data on recent HIV during pregnancy/postpartum. Random effects models were constructed to pool HIV incidence rates, cumulative HIV incidence, hazard ratios (HRs), or odds ratios (ORs) summarizing the association between pregnancy/postpartum status and HIV incidence, and MTCT risk and rates. Overall, 1,176 studies met the search criteria, of which 78 met the inclusion criterion, and 47 contributed data. Using data from 19 cohorts representing 22,803 total person-years, the pooled HIV incidence rate during pregnancy/postpartum was 3.8/100 person-years (95% CI 3.0–4.6): 4.7/100 person-years during pregnancy and 2.9/100 person-years postpartum (p = 0.18). Pooled cumulative HIV incidence was significantly higher in African than non-African countries (3.6% versus 0.3%, respectively; p<0.001). Risk of HIV was not significantly higher among pregnant (HR 1.3, 95% CI 0.5–2.1) or postpartum women (HR 1.1, 95% CI 0.6–1.6) than among non-pregnant/non-postpartum women in five studies with available data. In African cohorts, MTCT risk was significantly higher among women with incident versus chronic HIV infection in the postpartum period (OR 2.9, 95% CI 2.2–3.9) or in pregnancy/postpartum periods combined (OR 2.3, 95% CI 1.2–4.4). However, the small number of studies limited power to detect associations and sources of heterogeneity.
Conclusions
Pregnancy and the postpartum period are times of persistent HIV risk, at rates similar to “high risk” cohorts. MTCT risk was elevated among women with incident infections. Detection and prevention of incident HIV in pregnancy/postpartum should be prioritized, and is critical to decrease MTCT.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Worldwide, about 3.4 million children younger than 15 years old (mostly living in sub-Saharan Africa) are infected with HIV, the virus that causes AIDS by gradually destroying immune system cells, thereby leaving infected individuals susceptible to other serious infections. In 2012 alone, 230,000 children (more than 700 every day) were newly infected with HIV. Most HIV infections among children are the result of mother-to-child HIV transmission (MTCT) during pregnancy, delivery, or breastfeeding. The rate of MTCT (and deaths among HIV-positive pregnant women from complications related to HIV infection) can be greatly reduced by testing women for HIV infection during pregnancy (antenatal HIV testing), treating HIV-positive women with antiretroviral drugs (ARVs, powerful drugs that control HIV replication and allow the immune system to recover) during pregnancy, delivery, and breastfeeding, and giving ARVs to their newborn babies.
Why Was This Study Done?
The World Health Organization and the Joint United Nations Programme on HIV/AIDS (UNAIDS) have developed a global plan that aims to move towards eliminating new HIV infections among children by 2015 and towards keeping their mothers alive. To ensure the plan's success, the incidence of HIV (the number of new infections) among women and the rate of MTCT must be reduced by increasing ARV uptake by mothers and their infants for the prevention of MTCT. However, the risk of HIV infection among pregnant women and among women who have recently given birth (postpartum women) is poorly understood because, although guidelines recommend repeat HIV testing during late pregnancy or at delivery in settings where HIV infection is common, pregnant women are often tested only once for HIV infection. The lack of retesting represents a missed opportunity to identify pregnant and postpartum women who have recently acquired HIV and to prevent MTCT by initiating ARV therapy. In this systematic review (a study that uses predefined criteria to identify all the research on a given topic) and meta-analysis (a study that uses statistical methods to combine the results of several studies), the researchers estimate maternal HIV incidence during pregnancy and the postpartum period, and compare the risk of MTCT among women with incident (new) and chronic (long-standing) HIV infection.
What Did the Researchers Do and Find?
The researchers identified 47 studies (35 undertaken in Africa) that examined recent HIV acquisition by women during pregnancy and the 12-month postpartum period. They used random effects statistical models to estimate the pooled HIV incidence rate and cumulative HIV incidence (the number of new infections per number of people at risk), and the association between pregnancy/postpartum status and HIV incidence and MTCT risk and rates. The pooled HIV incidence rate among pregnant/postpartum women estimated from 19 studies (all from sub-Saharan Africa) that reported HIV incidence rates was 3.8/100 person-years. The pooled cumulative HIV incidence was significantly higher in African countries than in non-African countries (3.6% and 0.3%, respectively; a “significant” difference is one that is unlikely to arise by chance). In the five studies that provided suitable data, the risk of HIV acquisition was similar in pregnant, postpartum, and non-pregnant/non-postpartum women. Finally, among African women, the risk of MTCT was 2.9-fold higher during the postpartum period among those who had recently acquired HIV than among those with chronic HIV infection, and 2.3-fold higher during the pregnancy/postpartum periods combined.
What Do These Findings Mean?
These results suggest that women living in regions where HIV infection is common are at high risk of acquiring HIV infection during pregnancy and the postpartum period and that mothers who acquire HIV during pregnancy or postpartum are more likely to pass the infection on to their offspring than mothers with chronic HIV infections. However, the small number of studies included in this meta-analysis and the use of heterogeneous research methodologies in these studies may limit the accuracy of these findings. Nevertheless, these findings have important implications for the global plan to eliminate HIV infections in children. First, they suggest that women living in regions where HIV infection is common should be offered repeat HIV testing (using sensitive methods to enhance early detection of infection) during pregnancy and in the postpartum period to detect incident HIV infections, and should be promptly referred to HIV care and treatment. Second, they suggest that prevention of HIV transmission during pregnancy and postpartum should be prioritized, for example, by counseling women about the need to use condoms to prevent transmission during this period of their lives.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001608.
Information is available from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS
NAM/aidsmap provides basic information about HIV/AIDS and summaries of recent research findings on HIV care and treatment
Information is available from Avert, an international AIDS charity, on many aspects of HIV/AIDS, including information on children and HIV/AIDS and on the prevention of mother-to-child transmission of HIV (in English and Spanish)
The 2013 UNAIDS World AIDS Day Report provides information about the AIDS epidemic and efforts to halt it; the 2013 UNAIDS Progress Report on the Global Plan provides information on progress towards eliminating new HIV infections among children; the UNAIDS Believe it. Do it website provides information about the campaign to support the UNAIDS global plan
Personal stories about living with HIV/AIDS, including stories from young people infected with HIV, are available through Avert, NAM/aidsmap, and Healthtalkonline
doi:10.1371/journal.pmed.1001608
PMCID: PMC3934828  PMID: 24586123
5.  'My dreams are shuttered down and it hurts lots’–a qualitative study of palliative care needs and their management by HIV outpatient services in Kenya and Uganda 
BMC Palliative Care  2013;12:35.
Background
Despite the huge burden of HIV in sub-Saharan Africa, there is little evidence of the multidimensional needs of patients with HIV infection to inform the person-centred care across physical, psychological, social and spiritual domains stipulated in policy guidance. We aimed to describe the problems experienced by people with HIV in Kenya and Uganda and the management of these problems by HIV outpatient services.
Methods
Local researchers conducted in depth qualitative interviews with HIV patients, caregivers and service staff at 12 HIV outpatient facilities (6 in Kenya, 6 in Uganda). Interview data were analysed thematically.
Results
189 people were interviewed (83 patients, 47 caregivers, 59 staff). The impact of pain and symptoms and their causes (HIV, comorbidities, treatment side-effects) were described. Staff reported that effective pain relief was not always available, particularly in Kenya. Psychosocial distress (isolation, loneliness, worry) was exacerbated by stigma and poverty, and detrimentally affected adherence. Illness led to despair and hopelessness. Provision of counselling was reported, but spiritual support appeared to be less common. Neither pain nor psychosocial problems were routinely reported to service staff. Collaboration with local hospices and income-generation activities for patients were highlighted as useful.
Conclusions
The findings demonstrate the multiple and interrelated problems associated with living with HIV and how psychosocial and spiritual distress can contribute to 'total pain’ in this population. In line with the palliative care approach, HIV care requires holistic care and assessment that take into account psychological, socioeconomic and spiritual distress alongside improved access to pain-relieving drugs, including opioids.
doi:10.1186/1472-684X-12-35
PMCID: PMC3851824  PMID: 24098941
Kenya; Uganda; HIV; Distress; Experience; Pain; Drug availability; Qualitative research
6.  Trends and determinants of Comprehensive HIV and AIDS knowledge among urban young women in Kenya 
Background
Sub-Saharan Africa remains the region most heavily affected by HIV. In 2008, the region accounted for 67% of HIV infections worldwide, the region also accounted for 72% of the world's AIDS-related deaths in 2008. Young people aged 15-24 years accounted for an estimated 45% of the new HIV infections. In sub-Saharan Africa, Kenya is among countries affected by the HIV and AIDS pandemic which led to the declaration of AIDS as a national disaster in 1999. Given these scenario the study was undertaken to examine trends in HIV and AIDS comprehensive knowledge and identify the main correlates of comprehensive HIV and AIDS knowledge among Kenyan urban young women.
Methods
Data used was drawn from the 1993, 1998, 2003 and 2008/09 Kenya Demographic & Health Surveys. Logistic regression was used for analysis.
Results
While comprehensive HIV and AIDS knowledge is low among urban young women in Kenya, the results show a significant increase in comprehensive knowledge from 9% in 1993 to 54% in 2008/09. The strongest predictors for having comprehensive knowledge were found to be 1) education; 2) having tested for HIV; 3) knowing someone with HIV, and/or 4) having a small or moderate to great risk perception.
Conclusion
The response to HIV and AIDS can only be successful if individuals adopt behaviours that will protect against infection. Currently, efforts are underway in Kenya to ensure that young people have comprehensive knowledge. As evident from the results, comprehensive HIV and AIDS knowledge has increased over the 15 year period among urban young women from 9% in 1993 to 54% in 2008/09. Despite this improvement, a lot more needs to be done to attain the target of 90% threshold set by UNGASS. While both young women and men should be targeted with education on HIV prevention, concerted efforts should be directed at young women as many continue to get infected due to low levels of comprehensive HIV knowledge.
doi:10.1186/1742-6405-8-11
PMCID: PMC3060857  PMID: 21375746
7.  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
8.  Male Antenatal Attendance and HIV Testing Are Associated with Decreased Infant HIV Infection and Increased HIV Free Survival 
Objective
To investigate the relationship between male involvement in prevention of mother-to-child HIV transmission (PMTCT) services and infant HIV acquisition and mortality a prospective cohort study was undertaken between 1999 and 2005 in Nairobi, Kenya.
Methods
HIV-infected pregnant women were enrolled and followed with their infants for 1 year with infant HIV DNA testing at birth, 1, 3, 6, 9 and 12 months postpartum. Women were encouraged to invite male partners for prevention counseling and HIV testing.
Findings
Among 456 female participants, 140 (31%) partners attended the antenatal clinic. Eighty-two (19%) of 441 infants tested were HIV infected by one year of age. Adjusting for maternal viral load, vertical transmission risk was lower among women with partner attendance compared to those without (Adjusted hazard ratio [aHR]=0.56, 95% CI 0.33–0.98; P=0.042) and among women reporting versus not reporting previous partner HIV testing (aHR=0.52, 95% CI 0.32–0.84; P=0.008). The combined risk of HIV acquisition or infant mortality was lower with male attendance (aHR=0.55, 95% CI 0.35–0.88; P=0.012) and report of prior male HIV testing (aHR=0.58, 95% CI 0.34–0.88; P=0.01) when adjusting for maternal viral load and breastfeeding.
Conclusion
Including men in antenatal PMTCT services with HIV testing may improve infant health outcomes.
doi:10.1097/QAI.0b013e3181fdb4c4
PMCID: PMC3005193  PMID: 21084999
male partners; PMTCT; vertical transmission of HIV; infant mortality; Kenya
9.  HIV Infection and Fertility Preferences in Rural Malawi 
Studies in family planning  2009;40(4):261-276.
Although HIV-prevalence and fertility rates in sub-Saharan Africa are among the highest in the world, little is known about how HIV infection affects the fertility preferences of men and women in the region. A quasi-experimental design and in-depth interviews conducted in rural Malawi are employed to examine how and through what pathways learning that one is HIV positive alters a person’s childbearing desires. Among rural Malawians, particularly men, the desire to have more children decreases after receiving a positive HIV-test result. The motivations underlying this effect are greatly influenced by gender: women fear the physical health consequences of HIV-positive pregnancies and childbearing, whereas men see childbearing as futile because they anticipate their own early death and the deaths of their future children. Considerable ambivalence remains, nevertheless, particularly among women who strategize to live normal lives in spite of their infection, but whose definitions of “normal” vary.
doi:10.1111/j.1728-4465.2009.00210.x
PMCID: PMC2998897  PMID: 21151844
10.  Morbidity and Mortality Among a Cohort of Human Immunodeficiency Virus Type 1-Infected and Uninfected Pregnant Women and Their Infants From Malawi, Zambia, and Tanzania 
Background:
Morbidity and mortality patterns among pregnant women and their infants (before antiretroviral therapy was widely available) determines HIV-1 diagnostic, monitoring, and care interventions.
Methods:
Data from mothers and their infants enrolled in a trial of antibiotics to reduce mother-to-child-transmission of HIV-1 at 4 sub-Saharan African sites were analyzed. Women were enrolled during pregnancy and follow-up continued until the infants reached 12 months of age. We describe maternal and infant morbidity and mortality in a cohort of HIV-1-infected and HIV-1-uninfected mothers. Maternal and infant factors associated with mortality risk in the infants were assessed using Cox proportional hazard modeling.
Results:
Among 2292 HIV-1-infected mothers, 166 (7.2%) had a serious adverse event (SAE) and 42 (1.8%) died, whereas no deaths occurred among the 331 HIV-1 uninfected mothers. Four hundred twenty-four (17.8%) of 2383 infants had an SAE and 349 (16.4%) died before the end of follow-up. Infants with early HIV-1 infection (birth to 4 – 6 weeks) had the highest mortality. Among infants born to HIV-1-infected women, maternal morbidity and mortality (P = 0.0001), baseline CD4 count (P = 0.0002), and baseline plasma HIV-1 RNA concentration (P < 0.0001) were significant predictors of infant mortality in multivariate analyses.
Conclusions:
The high mortality among infants with early HIV-1 infection supports access to HIV-1 diagnostics and appropriate early treatment for all infants of HIV-1-infected mothers. The significant association between stage of maternal HIV-1 infection and infant mortality supports routine CD4 counts at the time of prenatal HIV-1 testing.
doi:10.1097/INF.0b013e31817109a4
PMCID: PMC2739309  PMID: 18679152
HIV-1 infection; infant mortality; maternal morbidity and mortality; sub-Saharan Africa; pregnant women
11.  Is 'Opt-Out HIV Testing' a real option among pregnant women in rural districts in Kenya? 
BMC Public Health  2011;11:151.
Background
An 'opt-out' policy of routine HIV counseling and testing (HCT) is being implemented across sub-Saharan Africa to expand prevention of mother-to-child transmission (PMTCT). Although the underlying assumption is that pregnant women in rural Africa are able to voluntarily consent to HIV testing, little is known about the reality and whether 'opt-out' HCT leads to higher completion rates of PMTCT. Factors associated with consent to HIV testing under the 'opt-out' approach were investigated through a large cross-sectional study in Kenya.
Methods
Observations during HIV pre-test information sessions were followed by a cross-sectional survey of 900 pregnant women in three public district hospitals carrying out PMTCT in the Busia district. Women on their first antenatal care (ANC) visit during the current pregnancy were interviewed after giving blood for HIV testing but before learning their test results. Descriptive statistics and multivariate regression analysis were performed.
Results
Of the 900 women participating, 97% tested for HIV. Lack of testing kits was the only reason for women not being tested, i.e. nobody declined HIV testing. Despite the fact that 96% had more than four earlier pregnancies and 37% had been tested for HIV at ANC previously, only 17% of the women surveyed knew that testing was optional. Only 20% of those surveyed felt they could make an informed decision to decline HIV testing. Making an informed decision to decline HIV testing was associated with knowing that testing was optional (OR = 5.44, 95%CI 3.44-8.59), not having a stable relationship with the child's father (OR = 1.76, 95%CI 1.02-3.03), and not having discussed HIV testing with a partner before the ANC visit (OR = 2.64 95%CI 1.79-3.86).
Conclusion
High coverage of HIV testing appears to be achieved at the cost of pregnant women not understanding that testing is optional. Good quality HIV pre-test information is central to ensure that pregnant women understand and accept the reasons for testing and will thus come back to collect their test results, an important prerequisite for completing PMTCT for those who test HIV-positive.
doi:10.1186/1471-2458-11-151
PMCID: PMC3061915  PMID: 21385423
12.  Field effectiveness of combination antiretroviral prophylaxis for the prevention of mother-to-child HIV transmission in rural Zambia 
AIDS (London, England)  2013;27(8):10.1097/QAD.0b013e32835e3937.
Objective
To evaluate the effectiveness of maternal combination antiretroviral prophylaxis for prevention of mother-to-child transmission of HIV (PMTCT) in a program setting
Design
Prospective cohort study
Setting
Nine primary care clinics in rural Zambia
Participants
284 HIV-infected pregnant women at ≥28 weeks gestation initiating PMTCT services between April 2009 and January 2011 and their newborn infants
Intervention
In four “intervention” sites, PMTCT comprised universal combination antiretroviral prophylaxis (i.e., irrespective of CD4 count) from pregnancy until the cessation of breastfeeding. In five “control” sites, women received antenatal zidovudine and peripartum nevirapine, the standard of care at the time. Prophylaxis during breastfeeding was not available in control sites.
Main outcome measure
Cumulative infant HIV infection and death at 12 months postpartum
Results
At 12 month postpartum, 1 of 104 (1.0%) infants born to mothers at the intervention sites were HIV-infected, compared to 14 of 116 (12.1%) receiving care in the control sites (relative risk [RR]: 12.6, 95%CI: 2.2-73.1; P=0.005). When we considered the composite outcome of HIV infection or death, similar trends were observed in the overall study population (RR: 3.4, 95%CI: 1.6-7.6; P=0.002) and in a sub-analysis of women with CD4 >350 cells/μL (RR: 3.2; 95%CI: 1.1-9.6; P=0.04).
Conclusions
When compared to PMTCT services based on antenatal zidovudine and peripartum nevirapine, the provision of maternal combination prophylaxis imparted measurable health benefits to HIV-exposed infants. Implementation research is needed to further tailor and optimize these strategies for similar field settings.
doi:10.1097/QAD.0b013e32835e3937
PMCID: PMC3836017  PMID: 23324656
HIV; prevention of mother to child transmission; antiretroviral therapy; breastfeeding; Zambia
13.  Systematic cultural adaptation of cognitive-behavioral therapy to reduce alcohol use among HIV-infected outpatients in western Kenya 
AIDS and behavior  2010;14(3):669-678.
Two-thirds of those with HIV worldwide live in sub-Saharan Africa. Alcohol use is associated with the HIV epidemic through risky sex and suboptimal ARV adherence. In western Kenya, hazardous drinking was reported by HIV (53%) and general medicine (68%) outpatients. Cognitive behavioral treatment (CBT) has demonstrated strong efficacy to reduce alcohol use. This article reports on a systematic cultural adaptation and pilot feasibility study of group paraprofessional-delivered CBT to reduce alcohol use among HIV-infected outpatients in Eldoret, Kenya. Following adaptation and counselor training, five pilot groups were run (n=27). Overall attendance was 77%. Percent days abstinent from alcohol (PDA) before session 1 was 52%–100% (women) and 21–36% (men), and by session 6 was 96%–100% (women) and 89%–100% (men). PDA effect sizes (Cohen’s d) between first and last CBT session were 2.32 (women) and 2.64 (men). Participants reported treatment satisfaction. Results indicate feasibility, acceptability and preliminary efficacy for CBT in Kenya.
doi:10.1007/s10461-009-9647-6
PMCID: PMC2949418  PMID: 19967441
alcohol; cognitive behavioral therapy; cultural adaptation; HIV; Kenya
14.  Preexposure Prophylaxis for HIV Infection among African Women 
The New England journal of medicine  2012;367(5):411-422.
BACKGROUND
Preexposure prophylaxis with antiretroviral drugs has been effective in the prevention of human immunodeficiency virus (HIV) infection in some trials but not in others.
METHODS
In this randomized, double-blind, placebo-controlled trial, we assigned 2120 HIV-negative women in Kenya, South Africa, and Tanzania to receive either a combination of tenofovir disoproxil fumarate and emtricitabine (TDF–FTC) or placebo once daily. The primary objective was to assess the effectiveness of TDF–FTC in preventing HIV acquisition and to evaluate safety.
RESULTS
HIV infections occurred in 33 women in the TDF–FTC group (incidence rate, 4.7 per 100 person-years) and in 35 in the placebo group (incidence rate, 5.0 per 100 person-years), for an estimated hazard ratio in the TDF-FTC group of 0.94 (95% confidence interval, 0.59 to 1.52; P = 0.81). The proportions of women with nausea, vomiting, or elevated alanine aminotransferase levels were significantly higher in the TDF–FTC group (P = 0.04, P<0.001, and P = 0.03, respectively). Rates of drug discontinuation because of hepatic or renal abnormalities were higher in the TDF–FTC group (4.7%) than in the placebo group (3.0%, P = 0.051). Less than 40% of the HIV-uninfected women in the TDF–FTC group had evidence of recent pill use at visits that were matched to the HIV-infection window for women with seroconversion. The study was stopped early, on April 18, 2011, because of lack of efficacy.
CONCLUSIONS
Prophylaxis with TDF–FTC did not significantly reduce the rate of HIV infection and was associated with increased rates of side effects, as compared with placebo. Despite substantial counseling efforts, drug adherence appeared to be low. (Supported by the U.S. Agency for International Development and others; FEM-PrEP ClinicalTrials.gov number, NCT00625404.)
doi:10.1056/NEJMoa1202614
PMCID: PMC3687217  PMID: 22784040
15.  Child Mortality Levels and Trends by HIV Status in Blantyre, Malawi: 1989-2009 
Introduction
Continuous evaluation of child survival is needed in sub-Saharan Africa where HIV prevalence among women of reproductive age continues to be high. We examined mortality levels and trends over a period of ~20 years among HIV-unexposed and exposed children in Blantyre, Malawi.
Methods
Data from five prospective cohort studies conducted at a single research site from 1989-2009 were analyzed. In these studies, children born to HIV-infected and uninfected mothers were enrolled at birth and followed longitudinally for at least two years. Information on socio-demographic, HIV infection status, survival and associated risk factors was collected in all studies. Mortality rates were estimated using birth-cohort analyses stratified by maternal and infant HIV status. Multivariate Cox regression models were used to determine risk factors associated with mortality.
Results
The analysis included 8,286 children. From 1989-1995, overall mortality rates (per 100 person-years) in these clinic-based cohorts remained comparable among HIV-uninfected children born to HIV-uninfected mothers (range 3.3-6.9) or to HIV-infected mothers (range 2.5-7.5). From 1989-2009, overall mortality remained high among all children born to HIV-infected mothers (range 6.3-19.3), and among children who themselves became infected (range 15.6-57.4, 1994-2009). Only lower birth weight was consistently and significantly (P<0.05) associated with higher child mortality.
Conclusions
HIV infection among mothers and children contributed to high levels of child mortality in the African setting in the pre-treatment era. In addition to services that prevent mother-to-child transmission of HIV, other programs are needed to improve child survival by lowering HIV-unrelated mortality through innovative interventions that strengthen health infrastructure.
doi:10.1097/QAI.0b013e3182618eea
PMCID: PMC3458133  PMID: 22692091
birth weight; child mortality; cohort effect; HIV; Malawi; Sub-Saharan Africa
16.  Incidence of malaria-related fever and morbidity due to Plasmodium falciparum among HIV1-infected pregnant women: a prospective cohort study in South Benin 
Malaria Journal  2014;13:255.
Background
Malaria and HIV are two major causes of morbidity and mortality among pregnant women in sub-Saharan Africa. Foetal and neonatal outcomes of this co-infection have been extensively studied. However, little is known about maternal morbidity due to clinical malaria in pregnancy, especially malaria-related fever, in the era of generalized access to antiretroviral therapy and anti-malarial preventive strategies.
Methods
A cohort study was conducted in order to estimate the incidence rate and to determine the factors associated with malaria-related fever, as well as the maternal morbidity attributable to malaria in a high-transmission setting of South Benin among HIV-infected pregnant women. Four-hundred and thirty-two women who participated in a randomized trial testing strategies to prevent malaria in pregnancy were included and followed until delivery, with at least three scheduled visits during pregnancy. Confirmed malaria-related fever was defined as axillary temperature >37.5°C and a concomitant, positive, thick blood smear or rapid diagnostic test for Plasmodium falciparum. Suspected malaria-related fever was defined as an axillary temperature >37.5°C and the concomitant administration of an anti-malarial treatment in the absence of parasitological investigation.
Results
Incidence rate for confirmed malaria-related fever was of 127.9 per 1,000 person-year (PY) (95% confidence interval (CI): 77.4-211.2). In multivariate analysis, CD4 lymphocytes (Relative Risk (RR) for a 50 cells/mm3 variation = 0.82; CI: 0.71-0.96), antiretroviral treatment started before inclusion (RR = 0.34; CI: 0.12-0.98) and history of symptomatic malaria in early pregnancy (RR = 7.10; CI: 2.35-22.49) were associated with the incidence of confirmed or suspected malaria-related fever. More than a half of participants with parasitaemia were symptomatic, with fever being the most common symptom. The crude fraction of febrile episodes attributable to malaria was estimated at 91%.
Conclusions
This work highlights that malaria is responsible for a substantial morbidity in HIV-infected pregnant women, with cellular immunodepression as a major determinant, and establishes the possible advantage offered by the early initiation of antiretroviral treatment.
Trial registration
PACOME Study has been registered under the number NCT00970879.
doi:10.1186/1475-2875-13-255
PMCID: PMC4089929  PMID: 24996807
Malaria; Pregnancy; HIV; Fever; Incidence rate; Attributable fraction; Morbidity
17.  Early adolescent pregnancy increases risk of incident HIV infection in the Eastern Cape, South Africa: a longitudinal study 
Introduction
Adolescents having unprotected heterosexual intercourse are at risk of HIV infection and unwanted pregnancy. However, there is little evidence to indicate whether pregnancy in early adolescence increases the risk of subsequent HIV infection. In this paper, we tested the hypothesis that adolescent pregnancy (aged 15 or younger) increases the risk of incident HIV infection in young South African women.
Methods
We assessed 1099 HIV-negative women, aged 15–26 years, who were volunteer participants in a cluster-randomized, controlled HIV prevention trial in the predominantly rural Eastern Cape province of South Africa. All of these young women had at least one additional HIV test over two years of follow-up. Outcomes were HIV incidence rates per 100 person years and HIV incidence rate ratios (IRRs) estimated by Poisson multivariate models. Three pregnancy categories were created for the Poisson model: early adolescent pregnancy (a first pregnancy at age 15 years or younger); later adolescent pregnancy (a first pregnancy at age 16 to 19 years); and women who did not report an adolescent pregnancy. Models were adjusted for study design, age, education, time since first sexual experience, socio-economic status, childhood trauma and herpes simplex virus type 2 infection.
Results
HIV incidence rates were 6.0 per 100 person years over two years of follow-up. The adjusted IRR was 3.02 (95% CI 1.50–6.09) for a pregnancy occurring at age 15 or younger. Women with pregnancies occurring between 16 and 19 years of age did not have a higher incidence of HIV (IRR 1.08; 95% CI 0.64–1.84). Early adolescent pregnancies were associated with higher partner numbers and a greater age difference with partners.
Conclusions
Early adolescent pregnancies increase the incidence of HIV among South African women. The higher risk is associated with sexual risk behaviours such as higher partner numbers and a greater age difference with partners rather than a biological explanation of hormonal changes during pregnancy.
doi:10.7448/IAS.17.1.18585
PMCID: PMC3962027  PMID: 24650763
HIV/AIDS; adolescent pregnancy; South Africa; longitudinal data; sexual risk behaviour
18.  Family planning practices and pregnancy intentions among HIV-positive and HIV-negative postpartum women in Swaziland: a cross sectional survey 
Background
In settings where sexually transmitted infection (STI) and HIV prevalence is high, the postpartum period is a time of increased biological susceptibility to pregnancy related sepsis. Enabling women living with HIV to avoid unintended pregnancies during the postpartum period can reduce vertical transmission and maternal mortality associated with HIV infection. We describe family planning (FP) practices and fertility desires of HIV-positive and HIV-negative postpartum women in Swaziland.
Methods
Data are drawn from a baseline survey of a four-year multi country prospective cohort study under the Integra Initiative, which is measuring the benefits and costs of providing integrated HIV and sexual and reproductive health (SRH) services in Kenya and Swaziland. We compare data from 386 HIV-positive women and 483 HIV-negative women recruited in Swaziland between February and August 2010. Data was collected on hand-held personal digital assistants (PDAs) covering fertility desires, mistimed or unwanted pregnancies and contraceptive use prior to their most recent pregnancy. Data were analysed using Stata 10.0. Descriptive statistics were conducted using the chi square test for categorical variables. Measures of effect were assessed using multivariate fixed effects logistic regression model accounting for clustering at facility level and the results are presented as adjusted odds ratios.
Results
Majority (69.2%) of postpartum women reported that their most recent pregnancy was unintended with no differences between HIV-positive and HIV-negative women: OR: 0.96 (95% CI) (0.70, 1.32). Although, there were significant differences between HIV-positive and HIV-negative women who reported that their previous pregnancy was unwanted, (20.7% vs. 13.5%, p = 0.004), when adjusted this was not significant OR: 1.43 (0.92, 1.91). 47.2% of HIV-positive women said it was mistimed compared to 52.5%, OR: 0.79 (0.59, 1.06). 37.9% of all women said they do not want another child. Younger women were more likely to have unwanted pregnancies: OR: 1.12 (1.07, 1.12), while they were less likely to have mistimed births; OR: 0.82 (0.70, 0.97). Those with tertiary education were less likely to have unwanted or mistimed pregnancies OR: 0.30 (0.11, 0.86). Half of HIV-positive women and more than a third of HIV-negative women reported that they had been using a FP method when they became pregnant with no differences between the groups: OR: 1.61 (0.82,3.41). Only short-acting methods were available to these women before the most recent pregnancy; and available during the postpartum visit. One fifth of all women received an FP method during the current visit. Among the four fifths who did not receive a method 17.3% reported they were already using a method or were breastfeeding. HIV-positive women were more likely to have already started a method than HIV-negative women (20% vs. 15%, p = 0.089).
Conclusion
There are few differences overall between the experiences of both HIV-positive and negative women in terms of FP experiences, unintended pregnancy and services received during the early postpartum period in Swaziland. Women attending postpartum facilities are receiving satisfactory care. Access to a wider range of effective methods is urgently needed if high levels of unintended pregnancy are to be reduced among HIV-positive and HIV-negative women living in Swaziland.
doi:10.1186/1471-2393-13-150
PMCID: PMC3720191  PMID: 23855776
Pregnancy; Fertility desires; Postpartum care; Family planning; HIV
19.  Changes in Maternal Depressive Symptoms Across the Postpartum Year at Well Childcare Visits 
Background:
Postpartum depression, which affects 10-15% of childbearing women, can have detrimental effects on child development. Despite clinicians’ need to understand the course of postpartum depressive symptoms to incorporate optimal screening protocols, little is known about changes in symptoms across the postpartum year, particularly among low-income, minority women.
Objective:
To describe the incidence, continuation, and resolution of symptoms during the postpartum year in urban women experiencing high depressive symptom levels at one or more well childcare visits.
Design:
As part of a prior study of postpartum depressive symptoms, demographic data and the Edinburgh Postnatal Depression Scale (EPDS) were systematically collected from pediatric records of a clinic that routinely screens mothers with the EPDS at each first year well childcare visit. To explore the course of depressive symptoms throughout the postpartum year in this pilot study, we included only data from the records that had at least one EPDS ≥ 10 (N=100), a score indicating a high likelihood for clinically significant depressive symptoms.
Results:
Among 49 women who completed the EPDS at least once before 3 months and between 3 and 11 months postpartum, 33% had high symptom levels throughout the year, 41% improved after the first three months, and 26% developed high symptom levels after the first three months.
Conclusions:
Postpartum depressive symptoms persist in many women throughout the postpartum year. Routine screening throughout the year might better identify both a subgroup of women who develop new symptoms during the year, as well as the women whose symptoms persist.
doi:10.1016/j.ambp.2006.04.003
PMCID: PMC1781518  PMID: 16843254
postpartum depression; maternal depression; screening
20.  Women and HIV in Sub-Saharan Africa 
Thirty years since the discovery of HIV, the HIV pandemic in sub-Saharan Africa accounts for more than two thirds of the world’s HIV infections. Southern Africa remains the region most severely affected by the epidemic. Women continue to bear the brunt of the epidemic with young women infected almost ten years earlier compared to their male counterparts. Epidemiological evidence suggests unacceptably high HIV prevalence and incidence rates among women. A multitude of factors increase women’s vulnerability to HIV acquisition, including, biological, behavioral, socioeconomic, cultural and structural risks. There is no magic bullet and behavior alone is unlikely to change the course of the epidemic. Considerable progress has been made in biomedical, behavioral and structural strategies for HIV prevention with attendant challenges of developing appropriate HIV prevention packages which take into consideration the socioeconomic and cultural context of women in society at large.
doi:10.1186/1742-6405-10-30
PMCID: PMC3874682  PMID: 24330537
HIV incidence; Sub-Saharan Africa; Adherence; Prevention
21.  HIV serostatus and disclosure: implications for infant feeding practice in rural south Nyanza, Kenya 
BMC Public Health  2014;14:390.
Background
The World Health Organization (WHO) recommends that HIV-infected women practice exclusive breastfeeding (EBF) for the first 6 months postpartum to reduce HIV transmission. The aim of this study was to determine the effects of HIV/AIDS knowledge and other psychosocial factors on EBF practice among pregnant and postpartum women in rural Nyanza, Kenya, an area with a high prevalence of HIV.
Methods
Data on baseline characteristics and knowledge during pregnancy, as well as infant feeding practices 4–8 weeks after the birth were obtained from 281 pregnant women recruited from nine antenatal clinics. Factors examined included: fear of HIV/AIDS stigma, male partner reactions, lack of disclosure to family members, knowledge of prevention of mother-to-child transmission (PMTCT) and mental health. In the analysis, comparisons were made using chi-squared and t-test methods as well as logistic multivariate regression models.
Results
There were high levels of anticipated stigma 171(61.2%), intimate partner violence 57(20.4%) and postpartum depression 29(10.1%) and low levels of disclosure among HIV positive women 30(31.3%). The most significant factors determining EBF practice were hospital delivery (aOR = 2.1 95% CI 1.14-3.95) HIV positive serostatus (aOR 2.5 95% CI 1.23-5.27), and disclosure of HIV-positive serostatus (aOR 2.9 95% CI 1.31-6.79). Postpartum depression and PMTCT knowledge were not associated with EBF (aOR 1.1 95% CI 0.47-2.62 and aOR 1.2 95% CI 0.64-2.24) respectively.
Conclusions
Health care workers and counselors need to receive support in order to improve skills required for diagnosing, monitoring and managing psychosocial aspects of the care of pregnant and HIV positive women including facilitating disclosure to male partners in order to improve both maternal and child health outcomes.
doi:10.1186/1471-2458-14-390
PMCID: PMC4041135  PMID: 24754975
Infant feeding choices; Breastfeeding; PMTCT; Disclosure; Mental health; Kenya; HIV
22.  Eliminating paediatric infections and keeping mothers alive 
The global plan of reducing the number of new child HIV infections and a reduction in the number of HIV-related maternal deaths by 2015 will require inordinate political commitment and strengthening of health systems in Sub-Saharan Africa where the burden of HIV infections in pregnant women is the highest. Preventing HIV infection in women of child-bearing age and unwanted pregnancies in HIV-positive women forms the cornerstone of long-term control of paediatric HIV infections. To achieve the goal of eliminating paediatric HIV infection by 2015, health systems strengthening to address prevention of mother-to-child HIV transmission cascade attrition and focusing on the elimination of breastmilk transmission is critical. Understanding the pathogenesis of breastmilk transmission and the mechanisms by which antiretroviral therapy impacts on transmission through this compartment will drive future interventions. Identifying and retaining HIV-positive pregnant women in care and committed to long-term antiretroviral therapy will improve maternal outcomes and concomitant reductions in maternal mortality. Research assessing the natural history of HIV infection and long-term outcomes in women who interrupt antiretroviral therapy post-weaning is urgently required. Data on the outcome of women who opt to continue the long-term use of antiretroviral therapy after initiating therapy during pregnancy will determine future policy in countries considering option B+. The prevalence of antiretroviral resistance and impact on survival in infants who sero-convert whilst receiving neonatal prophylaxis, or are exposed to maternal HAART through breastmilk at a population level, are currently unknown. In addition to the provision of biomedical interventions, healthcare workers and policy makers must address the structural, cultural and community issues that impact on treatment uptake, adherence to medication and retention in care.
doi:10.7448/IAS.15.6.18082
PMCID: PMC3512517
23.  Hormonal contraceptive use and risk of HIV-1 disease progression 
AIDS (London, England)  2013;27(2):261-267.
Background
For HIV-1 infected women, hormonal contraception prevents unintended pregnancy, excess maternal morbidity, and vertical HIV-1 transmission. Hormonal contraceptives are widely used but their effects on HIV-1 disease progression are unclear.
Methods
In a prospective study among 2269 chronically HIV-1 infected women from 7 countries in East and southern Africa and with enrollment CD4 counts ≥250 cells/mm3, we compared rates of HIV-1 disease progression among those using and not using hormonal contraception (i.e. oral or injectable methods). The primary outcome was a composite endpoint of CD4 decline to <200 cells/mm3, initiation of antiretroviral therapy, or death.
Results
372 women experienced HIV-1 disease progression during 3242 years of follow up (incidence rate=11.5 events per 100 person-years). Rates of HIV-1 disease progression among women who were currently using and not using hormonal contraception were 8.54 and 12.31 per 100 person-years, respectively (adjusted hazard ratio [HR] 0.74, 95% CI 0.56–0.98, p=0.04). Rates were 8.58 and 8.39 per 100 person-years for the subsets using injectable and oral contraception (adjusted HR=0.72, p=0.04 for injectable users and adjusted HR=0.83, p=0.5 for oral users compared to women not using hormonal contraception). Sensitivity analyses assessing enrollment or cumulative contraceptive use during the study demonstrated risk estimates closer to 1.0 with no evidence for accelerated disease progression.
Conclusions
Among African women with chronic HIV-1 infection, use of hormonal contraception was not associated with deleterious consequences for HIV-1 disease progression.
doi:10.1097/QAD.0b013e32835ad473
PMCID: PMC3740957  PMID: 23079806
HIV-1; women; hormonal contraception; death; CD4 count; antiretroviral therapy
24.  The association between malnutrition and the incidence of malaria among young HIV-infected and -uninfected Ugandan children: a prospective study 
Malaria Journal  2012;11:90.
Background
In sub-Saharan Africa, malnutrition and malaria remain major causes of morbidity and mortality in young children. There are conflicting data as to whether malnutrition is associated with an increased or decreased risk of malaria. In addition, data are limited on the potential interaction between HIV infection and the association between malnutrition and the risk of malaria.
Methods
A cohort of 100 HIV-unexposed, 203 HIV-exposed (HIV negative children born to HIV-infected mothers) and 48 HIV-infected children aged 6 weeks to 1 year were recruited from an area of high malaria transmission intensity in rural Uganda and followed until the age of 2.5 years. All children were provided with insecticide-treated bed nets at enrolment and daily trimethoprim-sulphamethoxazole prophylaxis (TS) was prescribed for HIV-exposed breastfeeding and HIV-infected children. Monthly routine assessments, including measurement of height and weight, were conducted at the study clinic. Nutritional outcomes including stunting (low height-for-age) and underweight (low weight-for-age), classified as mild (mean z-scores between -1 and -2 during follow-up) and moderate-severe (mean z-scores < -2 during follow-up) were considered. Malaria was diagnosed when a child presented with fever and a positive blood smear. The incidence of malaria was compared using negative binomial regression controlling for potential confounders with measures of association expressed as an incidence rate ratio (IRR).
Results
The overall incidence of malaria was 3.64 cases per person year. Mild stunting (IRR = 1.24, 95% CI 1.06-1.46, p = 0.008) and moderate-severe stunting (IRR = 1.24, 95% CI 1.03-1.48, p = 0.02) were associated with a similarly increased incidence of malaria compared to non-stunted children. Being mildly underweight (IRR = 1.09, 95% CI 0.95-1.25, p = 0.24) and moderate-severe underweight (IRR = 1.12, 95% CI 0.86-1.46, p = 0.39) were not associated with a significant difference in the incidence of malaria compared to children who were not underweight. There were no significant interactions between HIV-infected, HIV-exposed children taking TS and the associations between malnutrition and the incidence of malaria.
Conclusions
Stunting, indicative of chronic malnutrition, was associated with an increased incidence of malaria among a cohort of HIV-infected and -uninfected young children living in an area of high malaria transmission intensity. However, caution should be made when making causal inferences given the observational study design and inability to disentangle the temporal relationship between malnutrition and the incidence of malaria.
Trial Registration
ClinicalTrials.gov: NCT00527800.
doi:10.1186/1475-2875-11-90
PMCID: PMC3337276  PMID: 22453048
25.  SAVVY® (C31G) Gel for Prevention of HIV infection in Women: A Phase 3, Double-Blind, Randomized, Placebo-Controlled Trial in Ghana 
PLoS ONE  2007;2(12):e1312.
Objective
The objective of this trial was to determine the effectiveness of 1.0% C31G (SAVVY) in preventing male-to-female vaginal transmission of HIV infection among women at high risk.
Methodology/Principal Findings
This was a Phase 3, double-blind, randomized, placebo-controlled trial. Participants made up to 12 monthly visits for HIV testing, adverse event reporting, and study product supply. The study was conducted between March 2004 and February 2006 in Accra and Kumasi, Ghana. We enrolled 2142 HIV-negative women at high risk of HIV infection, and randomized them to SAVVY or placebo gel. Main outcome measures were the incidence of HIV-1 and HIV-2 infection as determined by detection of HIV antibodies from oral mucosal transudate specimens and adverse events. We accrued 790 person-years of follow-up in the SAVVY group and 772 person-years in the placebo group. No clinically significant differences in the overall frequency of adverse events, abnormal pelvic examination findings, or abnormal laboratory results were seen between treatment groups. However, more participants in the SAVVY group reported reproductive tract adverse events than in the placebo group (13.0% versus 9.4%). Seventeen HIV seroconversions occurred; eight in participants randomized to SAVVY and nine in participants receiving placebo. The Kaplan-Meier estimates of the cumulative probability of HIV infection through 12 months were 0.010 in the SAVVY group and 0.011 in the placebo group (p = 0.731), with a hazard ratio (SAVVY versus placebo) of 0.88 (95% confidence interval 0.33, 2.27). Because of a lower-than-expected HIV incidence, we were unable to achieve the required number of HIV infections (66) to obtain the desired study power.
Conclusions/Significance
SAVVY was not associated with increased adverse events overall, but was associated with higher reporting of reproductive adverse events. Our data are insufficient to conclude whether SAVVY is effective at preventing HIV infection relative to placebo.
Trial Registration
ClinicalTrials.gov NCT00129532
doi:10.1371/journal.pone.0001312
PMCID: PMC2129116  PMID: 18091987

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