Prisca Kasonde

Effects of early, abrupt weaning on HIV-free survival of children in Zambia.

BACKGROUND In low-resource settings, many programs recommend that women who are infected with the human immunodeficiency virus (HIV) stop breast-feeding early. We conducted a randomized trial to evaluate whether abrupt weaning at 4 months as compared with the standard practice has a net benefit for HIV-free survival of children. METHODS We enrolled 958 HIV-infected women and their infants in Lusaka, Zambia. All the women planned to breast-feed exclusively to 4 months; 481 were randomly assigned to a counseling program that encouraged abrupt weaning at 4 months, and 477 to a program that encouraged continued breast-feeding for as long as the women chose. The primary outcome was either HIV infection or death of the child by 24 months. RESULTS In the intervention group, 69.0% of the mothers stopped breast-feeding at 5 months or earlier; 68.8% of these women reported the completion of weaning in less than 2 days. In the control group, the median duration of breast-feeding was 16 months. In the overall cohort, there was no significant difference between the groups in the rate of HIV-free survival among the children; 68.4% and 64.0% survived to 24 months without HIV infection in the intervention and control groups, respectively (P=0.13). Among infants who were still being breast-fed and were not infected with HIV at 4 months, there was no significant difference between the groups in HIV-free survival at 24 months (83.9% and 80.7% in the intervention and control groups, respectively; P=0.27). Children who were infected with HIV by 4 months had a higher mortality by 24 months if they had been assigned to the intervention group than if they had been assigned to the control group (73.6% vs. 54.8%, P=0.007). CONCLUSIONS Early, abrupt cessation of breast-feeding by HIV-infected women in a low-resource setting, such as Lusaka, Zambia, does not improve the rate of HIV-free survival among children born to HIV-infected mothers and is harmful to HIV-infected infants.(ClinicalTrials.gov number, NCT00310726.)

Women in couples antenatal HIV counseling and testing are not more likely to report adverse social events

Background: Couple counseling has been promoted as a strategy to improve uptake of interventions to prevent mother-to-child HIV transmission (pMTCT) and to minimize adverse social outcomes associated with disclosure of HIV status. Objectives: We tested whether women counseled antenatally as part of a couple were more likely to accept HIV testing and nevirapine in a pMTCT program, and whether they would be less likely to experience later adverse social events than women counseled alone. Methods: A pMTCT program that included active community education and outreach to encourage couple counseling and testing was implemented in two antenatal clinics in Lusaka, Zambia. A subset of HIV-positive women was asked to report their experience of adverse social events 6 months after delivery. Couple-counseled women were compared with individual-counseled women stratified by whether or not they had disclosed their HIV status to their partners. Results: Nine percent (868) of 9409 women counseled antenatally were counseled with their husband. Couple-counseled women were more likely to accept HIV testing (96%) than women counseled alone (79%); however uptake of nevirapine was not improved. Six months after delivery, 28% of 324 HIV-positive women reported at least one adverse social event (including physical violence, verbal abuse, divorce or separation). There were no significant differences in reported adverse social events between couple- and individual-counseled women. Conclusions: Couple counseling did not increase the risk of adverse social events associated with HIV disclosure. Support services and interventions to improve social situations for people living with HIV need to be further evaluated.

Does Severity of HIV Disease in HIV-Infected Mothers Affect Mortality and Morbidity among Their Uninfected Infants?

BACKGROUND Rates of perinatal human immunodeficiency virus (HIV) transmission are higher among HIV-infected mothers with more advanced disease, but effects of maternal disease on HIV-uninfected offspring are unclear. We investigated the hypothesis that the severity of HIV disease and immune dysfunction among mothers is associated with increased morbidity and mortality among their uninfected infants. METHODS In a birth cohort of 620 HIV-uninfected infants born to HIV-infected mothers in Lusaka, Zambia, we investigated associations between markers of more advanced maternal HIV disease and child mortality, hospital admissions, and infant weight through 4 months of age. RESULTS Mortality in the cohort of uninfected infants was 4.6% (95% confidence interval [CI], 2.8-6.3) through 4 months of age. Infants of mothers with CD4+ T cell counts of <350 cells/microL were more likely to die (hazard ratio [HR], 2.87; 95% CI, 1.03-8.03) and were more likely to be hospitalized (HR, 2.28; 95% CI, 1.17-4.45), after adjusting for other factors, including maternal death and low birth weight. The most common cause of infant death and hospitalization was pneumonia and/or sepsis. A maternal viral load of >100,000 copies/mL was associated with significantly lower child weight through 4 months of age. CONCLUSION Children born to HIV-infected mothers with advanced disease who escaped perinatal or early breastfeeding-related HIV infection are nonetheless at high risk of mortality and morbidity during the first few months of life. HIV-related immunosuppression appears to have adverse consequences for the health of infants, in addition to risks of vertical transmission.

High uptake of exclusive breastfeeding and reduced early post-natal HIV transmission.

Background Empirical data showing the clear benefits of exclusive breastfeeding (EBF) for HIV prevention are needed to encourage implementation of lactation support programs for HIV-infected women in low resource settings among whom replacement feeding is unsafe. We conducted a prospective, observational study in Lusaka, Zambia, to test the hypothesis that EBF is associated with a lower risk of postnatal HIV transmission than non-EBF. Methods and Results As part of a randomized trial of early weaning, 958 HIV-infected women and their infants were recruited and all were encouraged to breastfeed exclusively to 4 months. Single-dose nevirapine was provided to prevent transmission. Regular samples were collected from infants to 24 months of age and tested by PCR. Detailed measurements of actual feeding behaviors were collected to examine, in an observational analysis, associations between feeding practices and postnatal HIV transmission. Uptake of EBF was high with 84% of women reporting only EBF cumulatively to 4 months. Post-natal HIV transmission before 4 months was significantly lower (p = 0.004) among EBF (0.040 95% CI: 0.024–0.055) than non-EBF infants (0.102 95% CI: 0.047–0.157); time-dependent Relative Hazard (RH) of transmission due to non-EBF = 3.48 (95% CI: 1.71–7.08). There were no significant differences in the severity of disease between EBF and non-EBF mothers and the association remained significant (RH = 2.68 95% CI: 1.28–5.62) after adjusting for maternal CD4 count, plasma viral load, syphilis screening results and low birth weight. Conclusions Non-EBF more than doubles the risk of early postnatal HIV transmission. Programs to support EBF should be expanded universally in low resource settings. EBF is an affordable, feasible, acceptable, safe and sustainable practice that also reduces HIV transmission providing HIV-infected women with a means to protect their childrens lives. Trial Registration ClinicalTrials.gov NCT00310726

Elevations in Mortality Associated with Weaning Persist into the Second Year of Life among Uninfected Children Born to HIV-Infected Mothers

BACKGROUND Early weaning has been recommended to reduce postnatal human immunodeficiency virus (HIV) transmission. We evaluated the safety of stopping breast-feeding at different ages for mortality of uninfected children born to HIV-infected mothers. METHODS During a trial of early weaning, 958 HIV-infected mothers and their infants were recruited and followed up from birth to 24 months postpartum in Lusaka, Zambia. One-half of the cohort was randomized to wean abruptly at 4 months, and the other half of the cohort was randomized to continue breast-feeding. We examined associations between uninfected child mortality and actual breast-feeding duration and investigated possible confounding and effect modification. RESULTS The mortality rate among 749 uninfected children was 9.4% by 12 months of age and 13.6% by 24 months of age. Weaning during the interval encouraged by the protocol (4-5 months of age) was associated with a 2.03-fold increased risk of mortality (95% confidence interval [CI], 1.13-3.65), weaning at 6-11 months of age was associated with a 3.54-fold increase (95% CI, 1.68-7.46), and weaning at 12-18 months of age was associated with a 4.22-fold increase (95% CI, 1.59-11.24). Significant effect modification was detected, such that risks associated with weaning were stronger among infants born to mothers with higher CD4(+) cell counts (>350 cells/microL). CONCLUSION Shortening the normal duration of breast-feeding for uninfected children born to HIV-infected mothers living in low-resource settings is associated with significant increases in mortality extending into the second year of life. Intensive nutritional and counseling interventions reduce but do not eliminate this excess mortality.

Predictors of nonadherence to single-dose nevirapine therapy for the prevention of mother-to-child HIV transmission.

Background:Adequate adherence is required for prevention of mother-to-child transmission of HIV (pMTCT) programs to be effective. We investigated predictors and extent of nonadherence to single-dose nevirapine. Methods:Data on nevirapine intake and possible predictors were collected among 760 HIV-positive women with liveborn babies enrolled in a study in Lusaka, Zambia. Results:Most (94%) women took nevirapine before delivery, and most (91%) newborns received it soon after delivery. Maternal nonadherence was associated with home births (odds ratio [OR]: 3.2; 95% confidence interval [CI]: 1.3 to 7.4), no high school education (OR: 2.4; 95% CI: 1.1 to 5.3), and low newborn birth weight (OR: 4.6; 95% CI: 1.3 to 20.1). Disclosure of HIV status and couples counseling was only associated with adherence among home births. Failure to administer nevirapine to the newborn was associated with birth at the tertiary hospital (OR: 7.2; 95% CI: 3.7 to 13.8), lower 5-minute Apgar scores (OR: 0.5; 95% CI: 0.4 to 0.7), and neonatal death (OR: 5.8; 95% CI: 2.0 to 16.3). Conclusions:Excellent adherence to single-dose nevirapine for pMTCT can be achieved. Nonadherence seems to be affected by place of birth and by poor health status of the newborn. Procedures to ensure that viable yet ill neonates receive nevirapine should be part of clinical protocols and training within pMTCT programs.

Reduction in Preterm Delivery and Neonatal Mortality after the Introduction of Antenatal Cotrimoxazole Prophylaxis among HIV-Infected Women with Low CD4 Cell Counts

BACKGROUND Cotrimoxazole prophylaxis is recommended for subgroups of human immunodeficiency virus (HIV)-infected adults and children to reduce all-cause morbidity and mortality. We investigated whether antenatal cotrimoxazole prophylaxis begun during pregnancy for HIV-infected pregnant women with low CD4 cell counts would affect birth outcomes. METHODS Cotrimoxazole prophylaxis was introduced as a routine component of antenatal care for HIV-infected women with CD4 cell counts <200 cells/ micro L during the course of a trial of mother-to-child HIV transmission in Lusaka, Zambia. Rates of preterm delivery, low birth weight, and neonatal mortality were compared for women with low CD4 cell counts before and after its introduction. RESULTS Among 255 women with CD4 cell counts <200 cells/ micro L, the percentage of preterm births (< or =34 weeks of gestation) was lower (odds ratio [OR], 0.49 [95% confidence interval {CI}, 0.24-0.98]) after cotrimoxazole prophylaxis was introduced than before; there was a significant decrease in neonatal mortality (9% to 0%; P=.01) and a trend toward increased birth weight ( beta =114 g [95% CI, -42 to 271 g]). In contrast, there were no significant changes in these parameters over the same time interval among women with CD4 cell counts > or =200 cells/ micro L.Conclusion. Antenatal provision of cotrimoxazole for HIV-infected pregnant women with low CD4 cell counts may have indirect benefits for neonatal health.

Post-weaning breast milk HIV-1 viral load, blood prolactin levels and breast milk volume.

Background:The effect of abrupt weaning, advocated as a safe transition from exclusive breastfeeding in HIV-exposed children, on the quantity of HIV viral load in breast milk (BMVL) is not known. Objectives:To determine the effect of abrupt cessation of breastfeeding on serum prolactin, pumped breast milk volume and BMVL obtained 2 weeks after rapid weaning in HIV-infected women. Methods:Women enrolled in a prospective study (ZEBS) were randomized to abruptly wean at 20 weeks postpartum or continue exclusive breastfeeding. Breast milk was obtained at 22 weeks by electric breast pump over 10 min from 222 women who had either weaned or continued to breastfeed. Pre- and post-pumping prolactin was measured. BMVL was measured at 20 and 22 weeks in 71 randomly selected women from both groups. Results:Baseline prolactin and breast milk volume was significantly lower among women who had weaned. Detectable (68 versus 42%; P = 0.03) and median BMVL (448 versus < 50 copies/ml; P = 0.005) was significantly higher among those who had weaned in comparison with those who were still breastfeeding and was significantly higher in the same women after weaning compared with 2 weeks earlier (P = 0.001). Conclusions:BMVL is substantially higher after rapid weaning and this may pose an increased risk of HIV transmission if children resume breastfeeding after a period of cessation. Increases in BMVL with differing degrees of mixed feeding needs to be assessed.

Prolonged breast-feeding and mortality up to two years post-partum among HIV-positive women in Zambia.

Background:A previously reported association between prolonged lactation and maternal mortality has generated concern that breast-feeding may be detrimental for HIV-positive women. Methods:As part of a trial conducted in Lusaka, Zambia, 653 HIV-positive women were randomly assigned either to a counseling program that encouraged abrupt cessation of breast-feeding at 4 months (group A) or to a program that encouraged prolonged breast-feeding for the duration of the womans own informed choice (group B). We examined whether mortality up to 2 years post-partum increased with breast-feeding for a longer duration. Results:There was no difference in mortality 12 months after delivery between 326 HIV-positive women randomly assigned to short breast-feeding [group A: 4.93%; 95% confidence interval (CI), 2.42–7.46] versus 327 women assigned to long breast-feeding (group B: 4.89%; 95% CI, 2.38–7.40). Analysis based on actual practice, rather than random assignment, also demonstrated no increased mortality due to breast-feeding. Conclusions:Although HIV-related mortality was high in this cohort of untreated HIV-positive women, prolonged lactation was not associated with increased mortality.

Differential Effects of Early Weaning for HIV-Free Survival of Children Born to HIV-Infected Mothers by Severity of Maternal Disease

Background We previously reported no benefit of early weaning for HIV-free survival of children born to HIV-infected mothers in intent-to-treat analyses. Since early weaning was poorly accepted, we conducted a secondary analysis to investigate whether beneficial effects may have been hidden. Methods 958 HIV-infected women in Lusaka, Zambia, were randomized to abrupt weaning at 4 months (intervention) or to continued breastfeeding (control). Children were followed to 24 months with regular HIV PCR tests and examinations to determine HIV infection or death. Detailed behavioral data were collected on when all breastfeeding ended. Most participants were recruited before antiretroviral treatment (ART) became available. We compared outcomes among mother-child pairs who weaned earlier or later than intended by study design adjusting for potential confounders. Results Of infants alive, uninfected and still breastfeeding at 4 months in the intervention group, 16.1% who weaned as instructed acquired HIV or died by 24 months compared to 16.0% who did not comply (p = 0.98). Children of women with less severe disease during pregnancy (not eligible for ART) had worse outcomes if their mothers weaned as instructed (RH = 2.60 95% CI: 1.06–6.36) compared to those who continued breastfeeding. Conversely, children of mothers with more severe disease (eligible for ART but did not receive it) who weaned early had better outcomes (p-value interaction = 0.002). In the control group, weaning before 15 months was associated with 3.94-fold (95% CI: 1.65–9.39) increase in HIV infection or death among infants of mothers with less severe disease. Conclusion Incomplete adherence did not mask a benefit of early weaning. On the contrary, for women with less severe disease, early weaning was harmful and continued breastfeeding resulted in better outcomes. For women with more advanced disease, ART should be given during pregnancy for maternal health and to reduce transmission, including through breastfeeding. Trial Registration Clinical trials.gov NCT00310726