Chiwawa Nkhoma

Short postexposure prophylaxis in newborn babies to reduce mother-to-child transmission of HIV-1: NVAZ randomised clinical trial

BACKGROUND In sub-Saharan Africa, most women present late for delivery with unknown HIV status, which limits the use of intrapartum nevirapine to prevent mother-to-child transmission of HIV. We aimed to determine whether post-exposure prophylaxis of nevirapine plus zidovudine given to babies only reduced transmission of HIV more than did a regimen of nevirapine alone. METHODS We randomly assigned 1119 babies of Malawian women with HIV-1 who presented late (ie, within 2 h of expected delivery) to either nevirapine alone or nevirapine and zidovudine. Both drugs were given immediately after birth: one dose of nevirapine (2 mg/kg weight) was given as a single dose; babies in the nevirapine plus zidovudine group also received zidovudine twice daily for 1 week (4 mg/kg weight). Infant HIV infection was determined at birth and at 6-8 weeks. Primary outcome was HIV infection in babies at 6-8 weeks in those not infected at birth. Analysis was by intention to treat. FINDINGS The overall rate of mother-to-child transmission at 6-8 weeks was 15.3% in 484 babies who received nevirapine and zidovudine and 20.9% in 468 babies who received nevirapine only (p=0.03). At 6-8 weeks, in babies who were HIV negative at birth, 34 (7.7%) babies who had nevirapine and zidovudine and 51 (12.1%) who received nevirapine only were infected (p=0.03)-a protective efficacy of 36%. This finding remained after controlling for maternal viral load and other factors at baseline. Adverse events were mild and of similar frequency in the two groups. INTERPRETATION Postexposure prophylaxis can offer protection against HIV infection to babies of women who missed opportunities to be counselled and tested before or during pregnancy. The nevirapine and zidovudine regimen is safe and easy to implement.

The impact of breastfeeding on the health of HIV-positive mothers and their children in sub-Saharan Africa.

OBJECTIVE We assessed the impact of breastfeeding by women infected with human immunodeficiency virus (HIV)-1 on their morbidity and risk of mortality and on the mortality of their children. METHODS We analysed longitudinal data from two previous randomized clinical trials of mother-to-child transmission of HIV conducted between April 2000 and March 2003 in the Republic of Malawi, Africa. Mothers infected with HIV, and their newborns, were enrolled at the time of their childs birth; they then returned for follow-up visits when the child was aged 1 week, 6-8 weeks and then 3, 6, 9, 15, 18, 21 and 24 months. Patterns of breastfeeding (classified as exclusive, mixed or no breastfeeding), maternal morbidity and mortality, and mortality among their children were assessed at each visit. Descriptive and multivariate analyses were performed to determine the association between breastfeeding and maternal and infant outcomes. FINDINGS A total of 2000 women infected with HIV were enrolled in the original studies. During the 2 years after birth, 44 (2.2%) mothers and 310 (15.5%) children died. (Multiple births were excluded.) The median duration of breastfeeding was 18 months (interquartile range (IQR)=9.0-22.5), exclusive breastfeeding 2 months (IQR=2-3) and mixed feeding 12 months (IQR=6-18). Breastfeeding patterns were not significantly associated with maternal mortality or morbidity after adjusting for maternal viral load and other covariates. Breastfeeding was associated with reduced mortality among infants and children: the adjusted hazard ratio for overall breastfeeding was 0.44 (95% confidence interval (CI)=0.28-0.70), for mixed feeding 0.45 (95% CI=0.28-0.71) and for exclusive breastfeeding 0.40 (95% CI=0.22-0.72). These protective effects were seen both in infants who were infected with HIV and those who were not. CONCLUSION Breastfeeding by women infected with HIV was not associated with mortality or morbidity; it was associated with highly significant reductions in mortality among their children.

Late Postnatal Transmission of HIV-1 and Associated Factors

BACKGROUND The present study was undertaken to determine the risk and timing of late postnatal transmission (LPT) of human immunodeficiency virus type 1 (HIV-1). METHODS Breast-fed infants previously enrolled in 2 trials of antiretroviral prophylaxis were monitored in Malawi. Kaplan-Meier and proportional hazard models assessed cumulative incidence and association of factors with LPT. RESULTS Overall, 98 infants were HIV infected, and 1158 were uninfected. The cumulative risk of LPT at age 24 months was 9.68% (95% confidence interval, 7.80%-11.56%). The interval hazards at 1.5-6, 6-12, 12-18, and 18-24 months were 1.22%, 4.05%, 3.48%, and 1.27%, respectively. CONCLUSIONS The risk of LPT beyond 6 months is substantial. Weaning at 6 months could prevent >85% of LPT.

Gender Differences in Perinatal HIV Acquisition Among African Infants

Objective. We investigated gender-specific risks of mother-to-child transmission (MTCT) at birth and at 6 to 8 weeks among infants born to HIV-infected African women. Design. Follow-up study of infants enrolled in 2 randomized, phase III, clinical trials to prevent MTCT, conducted in Blantyre, Malawi, in southeast Africa. Methods. Infants were enrolled at birth and monitored postnatally, and their HIV status was assessed at birth and at 6 to 8 weeks (assessment beyond 6–8 weeks is ongoing). Statistical analyses were stratified according to gender, and comparisons were made with descriptive, univariate, and multivariate statistical tests. MTCT was estimated at birth and at 6 to 8 weeks among infants who were not infected at birth. Results. Overall, 966 boys and 998 girls were enrolled. The rate of HIV transmission at birth was 9.5% (187 of 1964 infants). However, at birth significantly more girls (12.6%) than boys (6.3%) were infected with HIV. This association remained significant after controlling for maternal viral load and other factors. Among infants who were uninfected at birth, 8.7% (135 of 1554 infants) acquired HIV by 6 to 8 weeks; of these infants, more girls acquired HIV (10.0%), compared with boys (7.4%). Conclusions. Female infants may be more susceptible to HIV infection before birth and continuing after birth. Alternatively, in utero mortality rates of HIV-infected male infants may be disproportionately higher and thus more HIV-infected female infants are born. In areas of sub-Saharan Africa, where HIV infection rates are high among women of reproductive age, the magnitude of the gender transmission differences observed in this study could have clinical, preventive, and demographic implications.

Natural History and Risk Factors Associated with Early and Established HIV Type 1 Infection among Reproductive-Age Women in Malawi

BACKGROUND Data evaluating the biological events and determinants of early human immunodeficiency virus type 1 (HIV-1) infection are limited in sub-Saharan Africa. We examined plasma viral levels and trends during early and established HIV-1 infection among reproductive-age women who participated in a randomized trial to treat genital tract infection in Malawi. We also assessed the association of injectable hormonal contraceptive use with HIV-1 infection. METHODS We studied 3 groups of women who were infected or uninfected with HIV-1: seroconverters, seroprevalent women, and seronegative women. Questionnaires and blood samples were collected at baseline and every 3 months for 1 year. The virus set point in seroconverters and levels and trends of viral load over time were determined. The associations of injectable hormonal contraceptive use with HIV-1 infection and viral load were assessed using conditional logistic regression and mixed-effect models, respectively. RESULTS In the original clinical trial, 844 women infected with HIV-1 and 842 women not infected with HIV-1 were enrolled. Of 31 women who experienced seroconversion during 12 months, 27 were matched with 54 seroprevalent and 54 seronegative women. The estimated median plasma virus set point was 4.45 log(10) copies/mL (interquartile range, 4.32-5.14 log(10) copies/mL). Injectable hormonal contraceptive use was significantly associated with HIV-1 seroconversion (adjusted odds ratio, 10.42; P = .03) but not with established HIV-1 infection. Among the seroconverters, a statistically significant interaction was found between the linear association of viral load and time of injectable hormonal contraceptive use (regression coefficient, -0.14; P = .02). CONCLUSION Knowledge of virus set point and trends of viral load in HIV-1 seroincident and seroprevalent asymptomatic women could assist in antiretroviral treatment management.

Intermittent Intravaginal Antibiotic Treatment of Bacterial Vaginosis in HIV-Uninfected and -Infected Women: A Randomized Clinical Trial

Objective: Assess efficacy of intermittent intravaginal metronidazole gel treatment in reducing frequency of bacterial vaginosis (BV). Design: Randomized, double-masked, placebo-controlled phase 3 trial. Setting: Postnatal and family planning clinics of the Queen Elizabeth Central Hospital and two health centers in Blantyre, Malawi. Participants: Nonpregnant HIV-uninfected and -infected women. Intervention: Intravaginal metronidazole treatment and placebo gels provided at baseline and every 3 mo for 1 y. Outcome measures: Primary: Cross-sectional and longitudinal comparisons of BV frequency at baseline, 1 mo after product dispensation (post-treatment evaluation [PTE]), and every quarterly visit. Secondary: Effect of treatment on BV clearance and recurrence. Results: Baseline: 842 HIV-uninfected and 844 HIV-infected women were enrolled. The frequency of BV at baseline in treatment and placebo arms, respectively, was 45.9% and 46.8% among HIV-uninfected women, and 60.5% and 56.9% among HIV-infected women. Primary outcomes: At the PTEs the prevalence of BV was consistently lower in treatment than placebo arms irrespective of HIV status. The differences were statistically significant mainly in HIV-uninfected women. Prevalence of BV was also reduced over time in both treatment and placebo arms. In a multivariable analysis that controlled for other covariates, the effect of intravaginal metronidazole treatment gel compared with placebo was not substantial: adjusted relative risk (RR) 0.90, 95% confidence interval (CI) 0.83–0.97 in HIV-uninfected women and adjusted RR 0.95, 95% CI 0.89–1.01 in HIV-infected women. Secondary outcomes: Intravaginal metronidazole treatment gel significantly increased BV clearance (adjusted hazard ratio [HR] 1.34, 95% CI 1.07–1.67 among HIV-uninfected women and adjusted HR 1.29, 95% CI 1.06–1.58 among HIV-infected women) but was not associated with decreased BV recurrence. Safety: No serious adverse events were related to use of intravaginal gels. Conclusion: Intermittent microbicide treatment with intravaginal gels is an innovative approach that can reduce the frequency of vaginal infections such as BV.

HIV-1 incidence among women of reproductive age in Malawi

The aim of this study was to determine HIV-1 incidence among women of reproductive age in Malawi. A prospective study design was followed. HIV-1 uninfected women were followed up for nine visits during a period of 12 months. At baseline, women received HIV-1 counselling and testing. At each visit, venous blood was collected for HIV-1 testing. Incidence rate for HIV-1 was estimated using person-years of follow up (PYFU). Risk factors for HIV acquisition were assessed using Cox proportional hazard models. A total of 842 HIV-1 negative women were enrolled in the study. Of these, 787 had subsequent HIV testing and 31 were found HIV-1 infected; an overall incidence rate of 4.51 (95% confidence interval: 2.96–6.06) per 100 PYFU was obtained. Young age, using hormonal injectable contraceptives and bacterial vaginosis were the main predictors of HIV acquisition. The incidence of HIV continues to be high among women in Malawi, and young women appear to be at higher risk.

The effect of human immunodeficiency virus and breastfeeding on the nutritional status of African children.

Background: The risk of HIV-1 infection is high among breast-fed children in sub-Saharan Africa. Monitoring the nutritional status can provide useful information to determine the effect of HIV infection and breast-feeding on child growth and development. We longitudinally assessed the nutritional status and determined its association with HIV infection and breast-feeding among Malawian children. Methods: We analyzed data from 2 clinical trials to prevent mother-to-child transmission of HIV in Malawi. These trials were conducted during 2000–2003 before the current guidelines were implemented to breast-feed exclusively during the first 6 months and wean thereafter. The nutritional status of children was measured up to age 24 months, using z-scores. Age-specific differences in length-for-age (L/A), weight-for-age (W/A), and weight-for-length (W/L) were compared stratifying by gender and HIV infection status. Multivariable models examined the mean change in z-scores controlling for breast-feeding and other factors. Results: In this analysis, 1589 children were included. Boys had significantly lower L/A scores and became stunted (z-score −<2 standard deviations) earlier than girls. HIV-infected children had significantly lower mean L/A and W/A z-scores than HIV-uninfected children and became stunted and underweight at an earlier age. In multivariable analysis not being breast-fed and being HIV infected were significantly (P < 0.001) associated with decreases in mean L/A, W/A, and W/L z-scores. Conclusions: This study shows the impact of infant HIV infection on growth and supports the critical importance of breast-feeding. Mother-to-child transmission of HIV programs should endeavor to preserve breast-feeding and find alternative measures to prevent postnatal HIV transmission.

Impacto de la lactancia materna en la salud de las madres VIH-positivas y en sus hijos en el África subsahariana

Introduction In sub-Saharan Africa, women infected with human immunondeficiency virus (HIV)-1 continue to breastfeed their infants for several reasons. Breastfeeding satisfies the nutritional needs of an infant and is frequently encouraged by other family members as a cultural norm. Women who do not initiate and maintain breastfeeding raise suspicion in the community about their HIV status, and this may lead to discrimination. Furthermore, substitutes for breast milk are either expensive or not safe to use owing to a lack of safe water, and containers for feeding the infant are easily contaminated. (1) Breastfeeding protects the infant against diarrhoeal and upper respiratory diseases, and has many other well documented biological benefits. (2-6) However, breastfeeding is the most important route of postnatal HIV transmission to the infant. (7) To counterbalance the benefits and risks of breastfeeding when the mother is infected with HIV, WHO, UNICEF and others have developed guidelines to assist women in making an informed decision about whether to breastfeed. (8) In settings where formula feeding is not affordable, it is generally recognized that women infected with HIV should continue to exclusively breastfeed their infants until they are aged 6 months and then abruptly wean them. The adverse effect of breastfeeding on the health of mothers has appeared minimal in settings where HIV is not a major problem. (9) However, the impact of breastfeeding on the health of women infected with HIV is not well understood. Several studies from sub-Saharan Africa have reported the effects of breastfeeding on the health of mothers. A randomized trial conducted in Kenya compared breastfeeding to formula feeding and reported there was an increased risk of maternal death among women who breastfed their infants. (10) However, the number of events in this secondary analysis was small (24 deaths). Two subsequent observational studies from South Africa and the United Republic of Tanzania found no association between breastfeeding and maternal mortality among women infected with HIV. (11,12) A randomized study in Zambia of women infected with HIV that compared those who abruptly ceased breastfeeding at 4 months with those who engaged in prolonged breastfeeding reported no difference in mortality based on duration of breastfeeding. (13) Additionally, a meta-analysis that used data from several clinical trials conducted in Africa found that the risk of mortality among women infected with HIV did not differ according to how the child was fed. (14) In this study from the Republic of Malawi, we examined the impact of breastfeeding by women infected with HIV-1 on both their and their childrens mortality and on several indicators of maternal morbidity. Methods The data for the present analysis were Originally obtained as part of two clinical trials (the Nevirapine/AZT (NVAZ) Studies) seeking to prevent mother-to-child transmission of HIV through the use of short-course antiretroviral postexposure prophylaxis given immediately after birth. (15,16) Women were enrolled in the NVAZ studies based on their time of presentation for delivery. The HIV status of these women was not known on their arrival at the participating health centres. After obtaining informed consent for HIV counselling and testing, and after being enrolled in these trials, women who presented early (with an approximate time of [greater than or equal to] 4 hours from arrival to delivery, known as early presenters) were provided with a single dose of nevirapine intrapartum if they were found to be infected with HIV. The babies of early presenters were randomized to receive orally either a standard single dose of nevirapine only or the same dose of nevirapine plus zidovudine twice daily for 1 week. Women who presented late (with an approximate time