Dhayendre Moodley

Pharmacokinetics and Antiretroviral Activity of Lamivudine Alone or When Coadministered with Zidovudine in Human Immunodeficiency Virus Type 1-Infected Pregnant Women and Their Offspring

The safety, pharmacokinetics, and antiretroviral activity of lamivudine alone and in combination with zidovudine was studied in pregnant women infected with human immunodeficiency virus type 1 (HIV-1) and their neonates. Women received the drugs orally from week 38 of pregnancy to 1 week after delivery. Neonate therapy began 12 h after delivery and continued for 1 week. Both treatment regimens were well-tolerated in women and newborns. Lamivudine and zidovudine pharmacokinetics in pregnant women were similar to those in nonpregnant adults. Lamivudine and zidovudine freely crossed the placenta and were secreted in breast milk. Neonatal lamivudine clearance was about half that in pediatric patients; zidovudine clearance was consistent with previous reports. HIV-1 RNA could be quantified in 17 of the 20 women. At the onset of labor/delivery, mean virus load had decreased by approximately 1.5 log10 copies/mL in both treatment cohorts. Although not definitive for HIV-1 infection status, all neonates had HIV-1 RNA levels below the limit of quantification at birth and at ages 1 and 2 weeks.

High HIV incidence during pregnancy: compelling reason for repeat HIV testing.

Objective:To determine the incidence of HIV during pregnancy as defined by seroconversion using a repeat HIV rapid testing strategy during late pregnancy. Design:Cross-sectional study nested in a prevention of mother-to-child transmission program Methods:Pregnant women were retested between 36 and 40 weeks of gestation, provided that they had been tested HIV negative at least 3 months prior. Results:Among the 2377 HIV-negative women retested, 1099 (46.2%) and 1278 (53.4%) were tested at urban and rural health facilities, respectively. Seventy-two women (3%) were HIV-positive (679 woman years of exposure) yielding a HIV incidence rate of 10.7/100 woman years [95% confidence interval (CI) 8.2–13.1]. HIV incidence in pregnancy was higher but not statistically significant at the urban facilities (12.4/100 woman years versus 9.1/100 woman years) and at least two-fold higher among the 25–29 and 30–34-year age groups (3.8 and 4.5%, respectively) as compared with the less than 20-year age group (1.9%). Single women were at 2.5 times higher risk of seroconverting during pregnancy (P = 0.017). Conclusion:HIV incidence during pregnancy is four times higher than in the nonpregnant population reported in a recent survey. Public health programs need to continue to reinforce prevention strategies and HIV retesting during pregnancy. The latter also offers an additional opportunity to prevent mother-to-child transmission and further horizontal transmission. Further research is required to understand the cause of primary HIV infection in pregnancy.

Growth in early childhood in a cohort of children born to HIV-1-infected women from Durban, South Africa.

Summary This study describes growth in a cohort of black South African children born to HIV-1-infected women in Durban. Children born to HIV-1-seropositive women were followed up from birth to early childhood. At birth and at each visit, growth parameters were measured. Mean Z-scores were calculated for weight-for-length, weight-for-age and length-for-age and, if they were low, the children were regarded as wasted, malnourished or stunted, respectively. At the end of the study, there were 48 infected and 93 uninfected children. There were no significant differences between the two groups at birth. Thereafter, the infected group was found to have early and sustained low mean Z-scores for length-for-age and weight-forage but not for weight-for-length. The means reached significance at ages 3, 6 and 12 months for length and at 3, 6 and 9 months for weight. Infected children who died early had more severe stunting, wasting and malnutrition than infected children who survived. Infected children born to HIV-positive women have early and sustained stunting and are malnourished but not wasted. Children with rapidly progressive disease have both stunting and wasting and are more severely affected. Early nutritional intervention might help prevent early progression or death in HIV-infected children, particularly in developing countries without access to anti-retroviral therapy in state hospitals.

Incident HIV Infection in Pregnant and Lactating Women and Its Effect on Mother-to-Child Transmission in South Africa

We described HIV incidence and mother-to-child transmission (MTCT) among women during pregnancy and lactation. Forty-eight (3.4%) of 1396 women seroconverted during pregnancy or <12 mo after delivery. This group of HIV-exposed children was at 2.3 times higher risk of infection (MTCT 20.5% [8 of 39] vs 9.0% (83 of 925]). An estimated 20% with CD4+ cell counts <350 would have been eligible for antiretroviral therapy (ART), yet all women with incident HIV infections are more likely to transmit HIV to their children. To ensure optimal prevention of MTCT, all women who seroconvert during pregnancy or lactation should be considered for ART for the purpose of prevention of MTCT, and women with CD4+ <350 should continue to receive ART.

Predicting perinatal human immunodeficiency virus infection by antibody patterns

The evolution of human immunodeficiency virus type 1 (HIV-1) antibody titers determined by enzyme-linked immunosorbent assay between birth and 18 months of age was investigated in 118 babies born to HIV-1-seropositive South African mothers. By 18 months 41 (34.7%) children were diagnosed as HIV-1-infected by standard criteria. All 77 uninfected babies cleared maternal antibodies by 15 months; 94.5% of these babies seroreverted by 12 months. By 9 months of age a significant difference (P < 0.05) was noted between antibody decay rates in infected and uninfected children. Of the children subsequently shown to be uninfected, 95.8% demonstrated ≶50% decay in antibody titers between 6 and 9 months; only 1 in the infected group showed a similar pattern (sensitivity, 97.8%; specificity, 93.8%). The approach of assessing the progression of antibody decay in infected and uninfected babies makes it a feasible and useful tool for estimating vertical transmission rates and diagnosis of perinatal HIV-1 infection earlier than standard practice.

Antiretroviral Drug Regimens to Prevent Mother-To-Child Transmission of HIV: A Review of Scientific, Program, and Policy Advances for Sub-Saharan Africa

Considerable advances have been made in the effort to prevent mother-to-child HIV transmission (PMTCT) in sub-Saharan Africa. Clinical trials have demonstrated the efficacy of antiretroviral regimens to interrupt HIV transmission through the antenatal, intrapartum, and postnatal periods. Scientific discoveries have been rapidly translated into health policy, bolstered by substantial investment in health infrastructure capable of delivering increasingly complex services. A new scientific agenda is also emerging, one that is focused on the challenges of effective and sustainable program implementation. Finally, global campaigns to “virtually eliminate” pediatric HIV and dramatically reduce HIV-related maternal mortality have mobilized new resources and renewed political will. Each of these developments marks a major step in regional PMTCT efforts; their convergence signals a time of rapid progress in the field, characterized by an increased interdependency between clinical research, program implementation, and policy. In this review, we take stock of recent advances across each of these areas, highlighting the challenges—and opportunities—of improving health services for HIV-infected mothers and their children across the region.

Associations Between Intimate Partner Violence and Emotional Distress Among Pregnant Women in Durban, South Africa

Intimate partner violence (IPV) during pregnancy has been associated with multiple negative health outcomes including emotional distress during pregnancy. However, little is known about IPV during pregnancy and its association with emotional distress among South African women. The objectives of this study were to determine the prevalence of both emotional distress and IPV during pregnancy, to identify whether different exposures of violence were associated with emotional distress and to assess whether social support attenuated the relationship between IPV and emotional distress. Pregnant women enrolled in the South Africa HIV Antenatal and Posttest Support Study (SAHAPS) who completed the baseline survey were included in this cross sectional analysis. We used logistic regression models to explore bivariate and multivariate relationships between the proposed covariates and emotional distress. Nearly a quarter of women experienced some type of IPV during the current pregnancy, with psychological violence being the most prevalent. The odds of emotional distress was 1.41 times (95% CI: [1.26, 1.57]) higher for each additional episode of psychological violence and 2.01 times (95% CI: [1.16, 3.77]) higher for each additional episode of sexual violence during pregnancy, adjusting for other covariates. Physical violence was only marginally associated with increased odds of emotional distress. Finally, social support was marginally significant as a main effect but did not attenuate the relationship between IPV and emotional distress. The high prevalence of IPV among South African women and its association with emotional distress during pregnancy suggest that interventions that reduce violence during or prior to pregnancy are needed.

Defining male support during and after pregnancy from the perspective of HIV-positive and HIV-negative women in Durban, South Africa.

INTRODUCTION Greater male support during pregnancy and in the postpartum period may improve health outcomes for mothers and children. To develop effective strategies to engage men, we need to first understand the ways that men are currently engaged and the barriers to their greater involvement. METHODS We conducted in-depth interviews in isiZulu with 30 HIV-positive women and 16 HIV-negative women who received prenatal care from a public clinic in Durban, South Africa. Interviews were audiotaped, transcribed, translated, and coded for analysis. RESULTS Although less than a quarter of women reported that their partners accompanied them to the clinic, they described receiving other material and psychosocial support from partners. More HIV-positive women reported that their partners were not involved or not supportive, and in some cases direct threats and experiences with violence caused them to fear partner involvement. DISCUSSION We need to broaden the lens through which we consider male support during pregnancy and in the postpartum period and acknowledge that male involvement may not always be in the best interest of women. Engaging supportive partners outside of the clinic setting and incorporating other important social network members are important next steps in the effort to increase support for women.

High prevalence and incidence of asymptomatic sexually transmitted infections during pregnancy and postdelivery in KwaZulu Natal South Africa.

Background We report the prevalence and incidence of 3 treatable sexually transmitted pathogens (Neiserria gonorrhoeae, Chlamydia trachomatis, and Trichomonas vaginalis) in women who were HIV infected or at high risk for HIV infection, in pregnancy and postpartum, respectively. Method Vulvovaginal specimens collected at the first antenatal visit and again at 14 weeks postpartum were tested for N. gonorrhoeae, C. trachomatis, and T. vaginalis in the laboratory. Women were routinely tested for HIV-1 with a point-of-care test. Results Among 1480 women, 32.3% (95% confidence interval, 29.9–34.7) tested positive for any of the sexually transmitted infections (STIs) in pregnancy and 19.2% (95% confidence interval, 16.9–21.5) were positive when retested 14 weeks postpartum (incidence rate, 79.2 per 100 person-years). The prevalence of N. gonorrhoeae and T. vaginalis infections in pregnancy and the incidence rate of any STI at 14 weeks postpartum were significantly higher in HIV-1–infected women (P < 0.0001 amd P = 0.0079). More than 50% of N. gonorrhoeae, T. vaginalis, and C. trachomatis infections in pregnancy were asymptomatic. Conclusions The high prevalence of asymptomatic STIs in pregnancy is compelling evidence that demands the development and validation of point-of-care tests for STIs be expedited. In addition, the high incidence of STIs 3 months postpartum suggests that women in this study setting resume unprotected sexual intercourse soon after delivery.

The complexity of consent: Women's experiences testing for HIV at an antenatal clinic in Durban, South Africa

Abstract Informed consent has historically been a cornerstone to ensuring autonomy during HIV testing. However, recent changes to global guidance on HIV testing have led to substantial debate on what policy provisions are necessary to ensure that consent remains meaningful in the context of testing. Despite disproportionate rates of testing during pregnancy, pregnant womens perspectives on the HIV testing process are underrepresented in the testing discourse. This study explores womens experiences with HIV testing and the consent process in a public antenatal clinic in South Africa. Qualitative interviews with 25 women were conducted at the clinic at either an antenatal visit or an infant immunization visit that followed HIV testing. Interviews were transcribed, translated, and coded for analysis. Women were categorized into one of the three groups based on their perceptions of choice in consenting for an HIV test. Matrices were used to allow for cross-category and cross-case comparison. Half of the women described having a clear choice in their decision to test. Others were less clear about their choice. Some women felt they had no choice in testing for HIV. None of the women stated that they were tested without having signed a consent form. We found that half of the womens narratives illustrated direct and indirect ways in which providers coerced them into taking an HIV test while receiving antenatal care. As the new guidance on HIV testing is implemented in different settings, it is critical to monitor womens testing experiences to ensure that a womans right to make an informed, voluntary choice is not violated. Furthermore, models of testing that allow us to meet broader public health goals while simultaneously respecting womens autonomy are needed.