Heena Brahmbhatt

Increased risk of incident HIV during pregnancy in Rakai, Uganda: a prospective study

BACKGROUND HIV acquisition is significantly higher during pregnancy than in the postpartum period. We did a prospective study to estimate HIV incidence rates during pregnancy and lactation. METHODS We assessed 2188 HIV-negative sexually active women with 2625 exposure intervals during pregnancy and 2887 intervals during breastfeeding, and 8473 non-pregnant and non-lactating women with 24,258 exposure intervals. Outcomes were HIV incidence rates per 100 person years and incidence rate ratios estimated by Poisson multivariate regression, with the non-pregnant or non-lactating women as the reference group. We also assessed the husbands of the married women to study male risk behaviours. FINDINGS HIV incidence rates were 2.3 per 100 person years during pregnancy, 1.3 per 100 person years during breastfeeding, and 1.1 per 100 person years in the non-pregnant and non-lactating women. The adjusted incidence rate ratios were 2.16 (95% CI 1.39-3.37) during pregnancy and 1.16 (0.82-1.63) during breastfeeding. Pregnant women and their male partners reported significantly fewer external sexual partners than did the other groups. In married pregnant women who had a sexual relationship with their male spouses, the HIV incidence rate ratio was 1.36 (0.63-2.93). In married pregnant women in HIV-discordant relationships (ie, with HIV-positive men) the incidence rate ratio was 1.76 (0.62-4.03). INTERPRETATION The risk of HIV acquisition rises during pregnancy. This change is unlikely to be due to sexual risk behaviours, but might be attributable to hormonal changes affecting the genital tract mucosa or immune responses. HIV prevention efforts are needed during pregnancy to protect mothers and their infants.

Child mortality and HIV infection in Africa: a review.

Objectives: To review the available data relating to child mortality in Africa by the HIV infection status of mothers and children. Results: Child survival is influenced by the HIV epidemic through several mechanisms. Mother-to-child transmission of HIV ranges from 15 to 45%, with up to 15–20% resulting from breastfeeding. HIV-infected children have high mortality rates. For example, a recent community-based study in Rakai, Uganda, showed 2-year mortality rates of 547, 166 and 128 per thousand among HIV-infected children, HIV-negative children of HIV-positive mothers, and HIV-negative children of HIV-negative women, respectively. Child mortality estimates from community-based cohorts demonstrate that the children of HIV-infected mothers have higher mortality rates than the children of uninfected mothers, and that child mortality is closely linked with maternal health status, but because the proportion of vertically infected children is unknown, the value of these studies is limited. Models that use HIV surveillance data together with a set of assumptions indicate that child mortality caused by HIV/AIDS has increased throughout the 1990s to reach close to 10% by 2002. Conclusion: Both disparate trends in HIV prevalence and varying levels of non-HIV-associated child mortality will ensure very different impacts in different countries. To improve the projections of the overall effect that the HIV epidemic will have on child mortality at the population level in countries with generalized epidemics, reliable age-specific mortality rates in infected and uninfected children are needed.

Mortality in HIV-infected and uninfected children of HIV-infected and uninfected mothers in rural Uganda

Objective: To estimate 2-year mortality rates in HIV-1-infected and uninfected infants born to HIV+ and HIV− mothers. Methods: Data are from a prospective study in rural Rakai District, Uganda. Infant HIV status (determined by polymerase chain reaction) was evaluated at 1 to 6 weeks postpartum and during breast-feeding, and maternal HIV viral load and CD4 levels were measured at the postpartum visit. Multivariate Cox proportional hazards models and Kaplan-Meier survival analysis were used to assess survival of infants by maternal and infant HIV status and by quartiles of viral load. Log-rank tests were used to test the equality of survival functions. Results: Of the 4604 pregnant women, 16.9% were HIV+, and the proportion of children infected was 20.9%. Median survival of HIV-infected infants was 23 months. Two-year child mortality rates were 128 of 1000 children born to HIV− mothers, 165.5 of 1000 uninfected children born to HIV+ mothers, and 540.1 of 1000 HIV-infected children (P < 0.0001). Compared with children of HIV− mothers, the hazard of child mortality was 2.04 (P < 0.001) if the mother was HIV+and 3.78 (P < 0.001) if the infant was also infected. In the adjusted model, the highest quartiles of log10 HIV viral load in infants and mothers were associated with significantly increased hazard of child mortality (hazard ratio [HR] = 8.54 and HR = 2.50, respectively). Maternal CD4 counts <200 cells/mL were also significant predictors of child mortality (HR = 2.61). A total of 67.6% of HIV-infected children with viral loads above the median died by the age of 2 years and are in need of early antiretroviral therapy (ART). Conclusions: More than half of HIV-infected infants died at less than 2 years of age. Therefore, ART may need to be initiated earlier in HIV-infected African children.

Effectiveness of an integrated intimate partner violence and HIV prevention intervention in Rakai, Uganda: analysis of an intervention in an existing cluster randomised cohort.

BACKGROUND Intimate partner violence (IPV) is associated with HIV infection. We aimed to assess whether provision of a combination of IPV prevention and HIV services would reduce IPV and HIV incidence in individuals enrolled in the Rakai Community Cohort Study (RCCS), Rakai, Uganda. METHODS We used pre-existing clusters of communities randomised as part of a previous family planning trial in this cohort. Four intervention group clusters from the previous trial were provided standard of care HIV services plus a community-level mobilisation intervention to change attitudes, social norms, and behaviours related to IPV, and a screening and brief intervention to promote safe HIV disclosure and risk reduction in women seeking HIV counselling and testing services (the Safe Homes and Respect for Everyone [SHARE] Project). Seven control group clusters (including two intervention groups from the original trial) received only standard of care HIV services. Investigators for the RCCS did a baseline survey between February, 2005, and June, 2006, and two follow-up surveys between August, 2006, and April, 2008, and June, 2008, and December, 2009. Our primary endpoints were self-reported experience and perpetration of past year IPV (emotional, physical, and sexual) and laboratory-based diagnosis of HIV incidence in the study population. We used Poisson multivariable regression to estimate adjusted prevalence risk ratios (aPRR) of IPV, and adjusted incidence rate ratios (aIRR) of HIV acquisition. This study was registered with ClinicalTrials.gov, number NCT02050763. FINDINGS Between Feb 15, 2005, and June 30, 2006, we enrolled 11 448 individuals aged 15-49 years. 5337 individuals (in four intervention clusters) were allocated into the SHARE plus HIV services group and 6111 individuals (in seven control clusters) were allocated into the HIV services only group. Compared with control groups, individuals in the SHARE intervention groups had fewer self-reports of past-year physical IPV (346 [16%] of 2127 responders in control groups vs 217 [12%] of 1812 responders in intervention groups; aPRR 0·79, 95% CI 0·67-0·92) and sexual IPV (261 [13%] of 2038 vs 167 [10%] of 1737; 0·80, 0·67-0·97). Incidence of emotional IPV did not differ (409 [20%] of 2039 vs 311 [18%] of 1737; 0·91, 0·79-1·04). SHARE had no effect on male-reported IPV perpetration. At follow-up 2 (after about 35 months) the intervention was associated with a reduction in HIV incidence (1·15 cases per 100 person-years in control vs 0·87 cases per 100 person-years in intervention group; aIRR 0·67, 95% CI 0·46-0·97, p=0·0362). INTERPRETATION SHARE could reduce some forms of IPV towards women and overall HIV incidence, possibly through a reduction in forced sex and increased disclosure of HIV results. Findings from this study should inform future work toward HIV prevention, treatment, and care, and SHAREs ecological approach could be adopted, at least partly, as a standard of care for other HIV programmes in sub-Saharan Africa. FUNDING Bill & Melinda Gates Foundation, US National Institutes of Health, WHO, Presidents Emergency Plan for AIDS Relief, Fogarty International Center.

The effects of placental malaria on mother-to-child HIV transmission in Rakai, Uganda.

We examined the association of placental malaria and mother-to-child transmission (MTCT) of HIV in a prospective community-randomized trial in Rakai District, Uganda. In the 746 HIV-positive mother-infant pairs, the MTCT rate was 20.4%. Placental malaria was more common in HIV-positive than HIV-negative women. After multivariate adjustment for HIV viral load, the risk of MTCT associated with placental malaria was 2.89 and with HIV viral load the risk was 2.85. Interventions to prevent malaria during pregnancy could potentially reduce MTCT.

Estimating the net effect of HIV on child mortality in African populations affected by generalized HIV epidemics

Summary:For a given prevalence, HIV has a relatively higher impact on child mortality when mortality from other causes is low. To project the effect of the epidemic on child mortality, it is necessary to estimate a realistic schedule of “net” age-specific mortality rates that would operate if HIV were the only cause of child death observable. We assume that this net pattern would be independent of mortality from other causes. We used African studies that measured the survival of HIV-infected children (direct data) or survival of children of HIV-infected mothers (indirect data). We developed a mathematic procedure to estimate the mortality of infected children from indirect data sources and obtained net HIV mortality patterns for each study population. The net age-specific HIV mortality pattern for infected children can be described by a double Weibull curve fitted to empiric data; this gives a functional representation of age-specific mortality rates that decline after infancy and rise in the preteens. The fitted curve that we would expect if HIV were the only effective cause of death shows 67% net survival at 1 year and 39% at 5 years. The curve also predicts 13% net survival at 10 years using constraints based on survival of infected adults.

Treatment of Trichomonas in pregnancy and adverse outcomes of pregnancy: A subanalysis of a randomized trial in Rakai, Uganda

OBJECTIVE The purpose of this study was to assess the association of presumptive Trichomonas vaginalis treatment during pregnancy and birth outcomes. STUDY DESIGN A community-randomized trial of presumptive sexually transmitted disease treatment during pregnancy was conducted between 1994 and 1999 in Rakai district, Uganda. A subanalysis of a trial of presumptive therapy with azithromycin, cefixime, and metronidazole assessed Trichomonas vaginalis treatment in pregnant women. RESULTS Children of 94 women with Trichomonas who were treated had increased low birth weight (relative risk, 2.49; 95% CI, 1.12-5.50), preterm birth rate (relative risk, 1.28; 95% CI, 0.81-2.02), and 2-year mortality rate (relative risk, 1.58; 95% CI, 0.99-2.52), compared with children of 112 women with Trichomonas who were not treated. CONCLUSION Treatment of Trichomonas vaginalis during pregnancy may be deleterious, and we infer that this may be due to metronidazole. This is consistent with a National Institute for Child Health and Human Development trial that found an excess of preterm births in children of women with Trichomonas vaginalis infection who were treated with metronidazole.

Survival of infants born to HIV-positive mothers by feeding modality in Rakai Uganda.

Background Data comparing survival of formula-fed to breast-fed infants in programmatic settings are limited. We compared mortality and HIV-free of breast and formula-fed infants born to HIV-positive mothers in a program in rural, Rakai District Uganda. Methodology/Principal Findings One hundred eighty two infants born to HIV-positive mothers were followed at one, six and twelve months postpartum. Mothers were given infant-feeding counseling and allowed to make informed choices as to whether to formula-feed or breast-feed. Eligible mothers and infants received antiretroviral therapy (ART) if indicated. Mothers and their newborns received prophylaxis for prevention of mother-to-child HIV transmission (pMTCT) if they were not receiving ART. Infant HIV infection was detected by PCR (Roche Amplicor 1.5) during the follow-up visits. Kaplan Meier time-to-event methods were used to compare mortality and HIV-free survival. The adjusted hazard ratio (Adjusted HR) of infant HIV-free survival was estimated by Cox regression. Seventy-five infants (41%) were formula-fed while 107 (59%) were breast-fed. Exclusive breast-feeding was practiced by only 25% of breast-feeding women at one month postpartum. The cumulative 12-month probability of infant mortality was 18% (95% CI = 11%–29%) among the formula-fed compared to 3% (95% CI = 1%–9%) among the breast-fed infants (unadjusted hazard ratio (HR)  = 6.1(95% CI = 1.7–21.4, P-value<0.01). There were no statistically significant differentials in HIV-free survival by feeding choice (86% in the formula-fed compared to 96% in breast-fed group (Adjusted RH = 2.8[95%CI = 0.67–11.7, P-value = 0.16] Conclusions/Significance Formula-feeding was associated with a higher risk of infant mortality than breastfeeding in this rural population. Our findings suggest that formula-feeding should be discouraged in similar African settings.

HIV knowledge and risk behaviors among Pakistani and Afghani drug users in Quetta, Pakistan.

Situated on the Pakistan-Afghan border, Quetta is home to growing numbers of Afghan refugees. We studied HIV knowledge and risk behaviors among Pakistani and Afghani drug users between July 2001 and November 2001. Of 959 drug users, all were male and the majority used heroin. Most were Pakistani (84.8%), 14.9% were Afghani, and 0.3% were Iranian. Relative to Pakistani drug users, a higher proportion of Afghanis reported no formal education, homelessness, and unemployment ( p <.001). Afghanis were more likely to have used an opiate as their first illicit drug (16% vs. 7%, p <.001), to have ever injected (18.8% vs. 12.3%, p =.04), to report needle sharing (72.2% vs. 48.2%, p =.08), or to report a drug user in their family ( p =.08). None of sexually active Afghanis had ever used a condom compared with 5.0% of the Pakistanis ( p =.01). Only 4.3% of Afghans had ever heard of HIV/AIDS compared with 18.3% of Pakistanis ( p <.001). Extremely low levels of HIV/AIDS awareness and high HIV risk behaviors were evident among drug users in Quetta, among whom Afghanis were especially vulnerable. Interventions to prevent transition to injection, needle exchange, and drug treatment are urgently required to prevent blood-borne infections.

Association of HIV and Malaria With Mother-to-Child Transmission, Birth Outcomes, and Child Mortality

Objective:To assess the impact of HIV and malaria coinfection on mother-to-child HIV transmission (MTCT) and adverse birth outcomes. Methods:One hundred nine HIV-positive mother-infant pairs with a malaria diagnosis were identified in a community cohort and followed up postpartum. Maternal malaria was diagnosed by a rapid immunochromatographic test (ICT) on sera and histopathologic examination of placenta. Infant HIV was diagnosed within 6 weeks of birth using polymerase chain reaction (PCR) to capture in-utero and intrapartum HIV transmission. Log binomial models were used to assess the relative risk of MTCT, low birth weight, and preterm birth associated with malaria. Results:Approximately 17.4% of infants were HIV positive at or around birth, and the prevalence of serologic and placental malaria were 31% and 32%, respectively. HIV-positive mothers with serological ICT malaria were significantly more likely to have low-birth-weight infants, and low-birth-weight infants had significantly higher risk of MTCT compared with infants of normal birth weight. Although placental and serologic ICT malaria were significantly associated with MTCT, after adjusting for maternal HIV viral load, the risk of MTCT was significantly increased only for mothers coinfected with placental malaria (relative risk [RR] = 7.9, P = 0.025). Conclusions:Placental malaria increases the risk of MTCT after adjustment for viral load. Programs should focus on enhanced malaria prevention during pregnancy to decrease the risk of adverse birth outcomes and MTCT.