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1.  Pre-exposure prophylaxis in Southern Africa: feasible or not? 
Journal of the International AIDS Society  2015;18(4Suppl 3):19979.
Southern and Eastern Africa bear the brunt of the AIDS epidemic, and current prevention interventions remain inadequate. Antiretroviral-based pre-exposure prophylaxis (PrEP) is gaining momentum as an effective prevention intervention.
Discussions have been started on how this strategy could be employed in Africa such that the populations most in need can be reached urgently for the greatest impact. This requires the selection of specific risk groups and service environments in which PrEP can be distributed safely and cost effectively while being mindful of any ethical issues.
Given the need for an integrated public health approach to this, a number of potential populations and opportunities for PrEP distribution exist and are discussed in this commentary.
PMCID: PMC4509894  PMID: 26198344
PrEP; HIV; AIDS; South Africa
2.  Timing of maternal HIV testing and uptake of Prevention of Mother-to-Child Transmission interventions among women and their infected infants in Johannesburg, South Africa 
By 2011, South African prevention of mother-to-child transmission of HIV (PMTCT) programmes had reduced perinatal HIV transmission at 6-weeks of age to 2.7%. We investigated the profile of newly-diagnosed vertically-infected children and their mothers to identify short-falls in the PMTCT programme.
In this operational follow-up study, fieldworkers enrolled mothers of newly-diagnosed HIV-infected children up to 2 years of age at 5 major healthcare facilities in Johannesburg. Structured questionnaires and clinical record reviews were conducted and analysed to describe the population and assess factors associated with PMTCT uptake.
289 mother-child pairs were enrolled. Timing of maternal HIV diagnosis influenced PMTCT access and feeding choices, and was associated with infants’ age at HIV diagnosis (7 weeks vs. 11 weeks vs. 31 weeks where mothers tested before, during or after the pregnancy respectively; p <0.0001). Women diagnosed before pregnancy (12%) were older (median 31 years) than those diagnosed during the index pregnancy (53% - median 27 years). Women diagnosed after delivery (35%) were younger (median 25 years, p<0.0001), of lower parity, and less likely to be South African citizens. In 81 cases (29%) late maternal diagnosis precluded any PMTCT access. Where women were diagnosed during or before pregnancy, the recommended PMTCT guidelines for mother and infant were followed in 86 (61%) pairs.
Failure to diagnose maternal HIV infection before delivery was the main reason for missing PMTCT prophylaxis and early infant testing. Timely maternal diagnosis enables PMTCT uptake, but implementation and follow-up gaps require attention to improve infant outcomes.
PMCID: PMC3999509  PMID: 24759066
HIV infection; pregnancy; vertical transmission; children; maternal diagnosis
3.  Efavirenz Conceptions and Regimen Management in a Prospective Cohort of Women on Antiretroviral Therapy 
Use of the antiretroviral drug efavirenz (EFV) is not recommended by the WHO or South African HIV treatment guidelines during the first trimester of pregnancy due to potential fetal teratogenicity; there is little evidence of how clinicians manage EFV-related fertility concerns. Women on antiretroviral therapy (ART) were enrolled into a prospective cohort in four public clinics in Johannesburg, South Africa. Fertility intentions, ART regimens, and pregnancy testing were routinely assessed during visits. Women reporting that they were trying to conceive while on EFV were referred for regimen changes. Kaplan-Meier estimators were used to assess incidence across ART regimens. From the 822 women with followup visits between August 2009–March 2011, 170 pregnancies were detected during study followup, including 56 EFV conceptions. Pregnancy incidence rates were comparable across EFV, nevirapine, and lopinavir/ritonavir person-years (95% 100/users (P = 0.25)); incidence rates on EFV were 18.6 Confidence Interval: 14.2–24.2). Treatment substitution from EFV was made for 57 women, due to pregnancy intentions or actual pregnancy; however, regimen changes were not systematically applied across women. High rates of pregnancy on EFV and inconsistencies in treatment management suggest that clearer guidelines are needed regarding how to manage fertility-related issues in. women on EFV-based regimens.
PMCID: PMC3384948  PMID: 22778534
4.  High Incidence of Unplanned Pregnancy after Antiretroviral Therapy Initiation: Findings from a Prospective Cohort Study in South Africa 
PLoS ONE  2012;7(4):e36039.
Increased fertility rates in HIV-infected women receiving antiretroviral therapy (ART) have been attributed to improved immunological function; it is unknown to what extent the rise in pregnancy rates is due to unintended pregnancies.
Non-pregnant women ages 18–35 from four public-sector ART clinics in Johannesburg, South Africa, were enrolled into a prospective cohort and followed from August 2009–March 2011. Fertility intentions, contraception and pregnancy status were measured longitudinally at participants' routine ART clinic visits.
Of the 850 women enrolled, 822 (97%) had at least one follow-up visit and contributed 745.2 person-years (PY) at-risk for incident pregnancy. Overall, 170 pregnancies were detected in 161 women (incidence rate [IR]: 21.6/100 PY [95% confidence interval (CI): 18.5–25.2]). Of the 170 pregnancies, 105 (62%) were unplanned. Unmet need for contraception was 50% higher in women initiating ART in the past year as compared to women on ART>1 year (prevalence ratio 1.5 [95% CI: 1.1–2.0]); by two years post-ART initiation, nearly one quarter of women had at least one unplanned pregnancy. Cumulative incidence of pregnancy was equally high among recent ART initiators and ART experienced participants: 23.9% [95% CI: 16.4–34.1], 15.9% [12.0–20.8], and 21.0% [16.8–26.1] for women on ART 0–1 yr, >1 yr–2 yrs, and >2 yrs respectively (log-rank, p = 0.54). Eight hormonal contraceptive failures were detected [IR: 4.4 [95% CI: 2.2–8.9], 7/8 among women using injectable methods. Overall 47% (80/170) of pregnancies were not carried to term.
Rates of unintended pregnancies among women on ART are high, including women recently initiating ART with lower CD4 counts and higher viral loads. A substantial burden of pregnancy loss was observed. Integration of contraceptive services and counselling into ART care is necessary to reduce maternal and child health risks related to mistimed and unwanted pregnancies. Further research into injectable contraceptive failures on ART is warranted.
PMCID: PMC3338622  PMID: 22558319
5.  “They Told Me to Come Back”: Women’s Antenatal Care Booking Experience in Inner-City Johannesburg 
Maternal and Child Health Journal  2012;17(2):359-367.
To assess women’s experience of public antenatal care (ANC) services and reasons for late antenatal care attendance in inner-city Johannesburg, South Africa. This cross-sectional study was conducted at three public labour wards in Johannesburg. Interviews were conducted with 208 women who had a live-birth in October 2009. Women were interviewed in the labour wards post-delivery about their ANC experience. Gestational age at first clinic visit was compared to gestational age at booking (ANC service provided). ANC attendance was high (97.0 %) with 46.0 % seeking care before 20 weeks gestation (early). Among the 198 women who sought care, 19.2 % were asked to return more than a month later, resulting in a 3-month delay in being booked into the clinic for these women. Additionally 49.0 % of women reported no antenatal screening being conducted when they first sought care at the clinic. Delay in recognizing pregnancy (21.7 %) and lack of time (20.8 %) were among the reasons women gave for late attendance. Clinic booking procedures and delays in diagnosing pregnancy are important factors causing women to access antenatal care late. In a country where a third of pregnant women are HIV infected, early ANC is vital in order to optimise ART initiation and thereby reduce maternal mortality and paediatric HIV infection. It is therefore imperative that existing antenatal care policies are implemented and reinforced and that women are empowered to demand better services.
PMCID: PMC3587683  PMID: 22527767
Antenatal care; South Africa; Late ANC access; ANC booking experience; PMTCT; HIV
6.  Birth outcomes in South African women receiving highly active antiretroviral therapy: a retrospective observational study 
Use of highly active antiretroviral therapy (HAART), a triple-drug combination, in HIV-infected pregnant women markedly reduces mother to child transmission of HIV and decreases maternal morbidity. However, there remains uncertainty about the effects of in utero exposure to HAART on foetal development.
Our objectives were to investigate whether in utero exposure to HAART is associated with low birth weight and/or preterm birth in a population of South African women with advanced HIV disease. A retrospective observational study was performed on women with CD4 counts ≤250 cells/mm3 attending antenatal antiretroviral clinics in Johannesburg between October 2004 and March 2007. Low birth weight (<2.5 kg) and preterm birth rates (<37 weeks) were compared between those exposed and unexposed to HAART during pregnancy. Effects of different HAART regimen and duration were assessed.
Among HAART-unexposed infants, 27% (60/224) were low birth weight compared with 23% (90/388) of early HAART-exposed (exposed <28 weeks gestation) and 19% (76/407) of late HAART-exposed (exposed ≥28 weeks) infants (p = 0.05). In the early HAART group, a higher CD4 cell count was protective against low birth weight (AOR 0.57 per 50 cells/mm3 increase, 95% CI 0.45-0.71, p < 0.001) and preterm birth (AOR 0.68 per 50 cells/mm3 increase, 95% CI 0.55-0.85, p = 0.001). HAART exposure was associated with an increased preterm birth rate (15%, or 138 of 946, versus 5%, or seven of 147, in unexposed infants, p = 0.001), with early nevirapine and efavirenz-based regimens having the strongest associations with preterm birth (AOR 5.4, 95% CI 2.1-13.7, p < 0.001, and AOR 5.6, 95% CI 2.1-15.2, p = 0.001, respectively).
In this immunocompromised cohort, in utero HAART exposure was not associated with low birth weight. An association between NNRTI-based HAART and preterm birth was detected, but residual confounding is plausible. More advanced immunosuppression was a risk factor for low birth weight and preterm birth, highlighting the importance of earlier HAART initiation in women to optimize maternal health and improve infant outcomes.
PMCID: PMC3163172  PMID: 21843356
7.  Effects of Highly Active Antiretroviral Therapy Duration and Regimen on Risk for Mother-to-Child Transmission of HIV in Johannesburg, South Africa 
Limited information exists about effects of different highly active antiretroviral therapy (HAART) regimens and duration of regimens on mother-to-child transmission (MTCT) of HIV among women in Africa who start treatment for advanced immunosuppression.
Between January 2004 to August 2008, 1,142 women were followed at antenatal antiretroviral clinics in Johannesburg. Predictors of MTCT (positive infant HIV DNA PCR at 4-6 weeks) were assessed with multivariate logistic regression.
Mean age was 30.2 years (SD=5.0) and median baseline CD4 count was 161 cells/mm3 (SD=84.3). HAART duration at time of delivery was a mean 10.7 weeks (SD=7.4) for the 85% of women who initiated treatment during pregnancy and 93.4 weeks (SD=37.7) for those who became pregnant on HAART. Overall MTCT rate was 4.9% (43/874), with no differences detected between HAART regimens. MTCT rates were lower in women who became pregnant on HAART than those initiating HAART during pregnancy (0.7% versus 5.7%; p=0.01). In the latter group, each additional week of treatment reduced odds of transmission by 8% (95% CI: 0.87-0.99, p=0.02).
Late initiation of HAART is associated with increased risk of MTCT. Strategies are needed to facilitate earlier identification of HIV-infected women.
PMCID: PMC2880466  PMID: 20216425
HIV/AIDS; pregnancy; highly active antiretroviral therapy; mother-to-child transmission; integration; South Africa
8.  Health system weaknesses constrain access to PMTCT and maternal HIV services in South Africa: a qualitative enquiry 
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).
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.
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.
PMCID: PMC3058008  PMID: 21371301
9.  Safety and Efficacy of Initiating Highly Active Antiretroviral Therapy in an Integrated Antenatal and HIV Clinic in Johannesburg, South Africa 
To describe the safety and efficacy of highly active antiretroviral therapy (HAART) in pregnant women treated in an integrated antenatal antiretroviral programme (ANC ARV).
A retrospective analysis was performed on patients attending the ANC ARV from August 2004 through February 2007.
Data was collected on 689 treatment-naïve pregnant women initiated on HAART. The mean age was 29.2 years. The mean baseline CD4+ count was 154 cells/uL and mean baseline HIV viral load was 101,561 copies/ml. Tuberculosis was the most prevalent presenting opportunistic infection (7.7%). Stavudine, lamivudine, and nevirapine were initiated in 82% of women with the most frequent adverse drug reaction being nevirapine-associated skin rash (3.5%). Mean gestational age at HAART initiation was 27 weeks. Among women with follow-up data, 80% gained 50 or more CD4 cells/uL, and 80.5% achieved viral suppression to <1000 copies/ml. Of 302 mother/infant pairs who completed postnatal follow-up, the HIV transmission rate was 5%. In women who received more than seven weeks of HAART during pregnancy, transmission was 0.3%.
Within the ANC ARV programme, initiating pregnant women on HAART was feasible, safe, and effective. Advanced gestational age at treatment initiation and loss to follow-up emerge as important challenges in this population.
PMCID: PMC2893046  PMID: 18845949
HIV/AIDS; pregnancy; high active antiretroviral therapy (HAART); prevention of mother-to-child transmission (PMTCT)

Results 1-9 (9)