Impact of six-week viral load on mortality in HIV-infected Zimbabwean infants.

Among 453 untreated HIV-infected Zimbabwean infants, 6-week viral load was the only infant factor that independently predicted mortality. Infants with viral load ≥ 1.59 million copies/mL (cohort median) had 3-fold increased mortality through 6 months (hazard ratio 3.07 [95% confidence interval: 2.16, 4.38]; P < 0.001) and 2-fold increased mortality through 12 months (hazard ratio 2.03 [95% confidence interval: 1.41, 2.91]; P < 0.001], compared with infants with viral load below the median.

Presumptive diagnosis of severe HIV infection to determine the need for antiretroviral therapy in children less than 18 months of age.

OBJECTIVE: To develop a new algorithm for the presumptive diagnosis of severe disease associated with human immunodeficiency virus (HIV) infection in children less than 18 months of age for the purpose of identifying children who require antiretroviral therapy (ART). METHODS: A conditional probability model was constructed and non-virologic parameters in various combinations were tested in a hypothetical cohort of 1000 children aged 6 weeks, 6 months and 12 months to assess the sensitivity, specificity, and positive and negative predictive values of these algorithms for identifying children in need of ART. The modelled parameters consisted of clinical criteria, rapid HIV antibody testing and CD4+ T-lymphocyte (CD4) count. FINDINGS: In children younger than 18 months, the best-performing screening algorithm, consisting of clinical symptoms plus antibody testing plus CD4 count, showed a sensitivity ranging from 71% to 80% and a specificity ranging from 92% to 99%. Positive and negative predictive values were between 61% and 97% and between 95% and 96%, respectively. In the absence of virologic tests, this alternate algorithm for the presumptive diagnosis of severe HIV disease makes it possible to correctly initiate ART in 91% to 98% of HIV-positive children who are at highest risk of dying. CONCLUSION: The algorithms presented in this paper have better sensitivity and specificity than clinical parameters, with or without rapid HIV testing, for the presumptive diagnosis of severe disease in HIV-positive children less than 18 months of age. If implemented, they can increase the number of HIV-positive children successfully initiated on ART.

Declining HIV prevalence and incidence in perinatal women in Harare, Zimbabwe.

BACKGROUND: In several recent papers it has been suggested that HIV prevalence and incidence are declining in Zimbabwe as a result of changing sexual behavior. We provide further support for these suggestions, based on an analysis of more extensive, age-stratified, HIV prevalence data from 1990 to 2009 for perinatal women in Harare, as well as data on incidence and mortality. METHODOLOGY/PRINCIPAL FINDINGS: Pooled prevalence, incidence and mortality were fitted using a simple susceptible-infected (SI) model of HIV transmission; age-stratified prevalence data were fitted using double-logistic functions. We estimate that incidence peaked at 5.5% per year in 1991 declining to 1% per year in 2010. Prevalence peaked in 1998/9 [35.9% (CI95: 31.3-40.7)] and decreased by 67% to 11.9% (CI95: 10.1-13.8) in 2009. For women <20y, 20-24y, 25-29y, 30-34y and ≥35y, prevalence peaked at 25.4%, 34.2%, 47.1%, 44.0% and 33.5% in 1993, 1996, 1997, 1998 and 1999, respectively, declining thereafter in every age group. Among women <25y, prevalence peaked in 1994 at 28.8% declining thereafter by 69% to 8.9% (CI95: 6.8-11.5) in 2009. CONCLUSION/SIGNIFICANCE: HIV prevalence declined substantially among perinatal women in Harare after 1998 consequent upon a decline in incidence starting in the early 1990s. Our model suggests that this was primarily a result of changes in behavior which we attribute to a general increase in awareness of the dangers of AIDS and the ever more apparent increases in mortality.

Predictive value of weight loss on mortality of HIV-positive mothers in a prolonged breastfeeding setting.

HIV-positive lactating women may be at high risk of weight loss due to increased caloric requirements and postpartum physiological weight loss. Ten percent weight loss is associated with a higher risk of mortality in HIV-positive patients and this alone is a criterion for highly active antiretroviral therapy (HAART) initiation where CD4 counts are not available. However, no study has investigated this association in lactating postpartum women. We investigated whether 10% weight loss predicts death in postpartum HIV-positive women. A total of 9207 HIV-negative and 4495 HIV-positive mothers were recruited at delivery. Women were weighed at 6 weeks, 3 months, and every 3 months thereafter for up to 24 months postpartum and data on mortality up to 2 years were collected. The median duration of breastfeeding was longer than 18 months. Among HIV-positive women, the independent predictors of ≥10% weight loss were CD4 cell count, body mass index, and household income. Mortality was up to 7.12 (95% CI 3.47-14.61) times higher in HIV-positive women with ≥10% weight loss than those without weight loss. Ten percent weight loss in postpartum lactating HIV-positive women was significantly predictive of death. Our findings suggest that 10% weight loss is an appropriate criterion for HAART initiation among postpartum breastfeeding women.

Morbidity among human immunodeficiency virus-exposed but uninfected, human immunodeficiency virus-infected, and human immunodeficiency virus-unexposed infants in Zimbabwe before availability of highly active antiretroviral therapy.

BACKGROUND: Human immunodeficiency virus (HIV) remains a major cause of pediatric morbidity in Africa. In addition, HIV-exposed, but uninfected (HEU) infants can comprise a substantial proportion of all infants born in high prevalence countries and may also be a vulnerable group with special health problems. METHODS: A total of 14,110 infants were recruited within 96 hours of birth between November 1996 and January 2000. Rates and causes of sick clinic visits and hospitalizations during infancy were investigated according to infant HIV infection group: infected-intrauterine, infected-intrapartum, postnatally-infected, HEU, and not-exposed (born to HIV-negative mother). RESULTS: A total of 382 infected-intrauterine, 499 infected-intrapartum, 188 postnatally-infected, 2849 HEU, and 9207 not-exposed infants were included in the analysis. Compared with not-exposed infants, HIV-infected infants made 2.8 times more all-cause sick clinic visits and required 13.3 times more hospitalizations; they had 7.2 times more clinic visits and 23.5 times more hospitalizations for lower respiratory tract infection after the neonatal period and were 159.9 times more likely to be hospitalized for malnutrition during the second half of infancy. Compared with not-exposed infants, sick clinic visits were 1.2 times more common among HEU infants, were inversely associated with maternal CD4 cell count, and were significantly higher for all HEU infants except those whose mothers had a CD4 count ≥ 800 cells/µL, which was the mean value of HIV-negative women enrolled in the trial. CONCLUSIONS: Morbidity is extremely high among HIV-infected infants. Compared with not-exposed infants, morbidity is higher among HEU infants and increases with severity of maternal disease, but is significantly higher for all mothers with CD4 cell count <800 cells/µL.

Mother to child transmission of HIV among Zimbabwean women who seroconverted postnatally: prospective cohort study.

OBJECTIVES: To estimate the rates and timing of mother to infant transmission of HIV associated with breast feeding in mothers who seroconvert postnatally, and their breast milk and plasma HIV loads during and following seroconversion, compared with women who tested HIV positive at delivery. DESIGN: Prospective cohort study. SETTING: Urban Zimbabwe. PARTICIPANTS: 14 110 women and infants enrolled in the Zimbabwe Vitamin A for Mothers and Babies (ZVITAMBO) trial (1997-2001). MAIN OUTCOME MEASURES: Mother to child transmission of HIV, and breast milk and maternal plasma HIV load during the postpartum period. RESULTS: Among mothers who tested HIV positive at baseline and whose infant tested HIV negative with polymerase chain reaction (PCR) at six weeks (n=2870), breastfeeding associated transmission was responsible for an average of 8.96 infant infections per 100 child years of breast feeding (95% CI 7.92 to 10.14) and varied little over the breastfeeding period. Breastfeeding associated transmission for mothers who seroconverted postnatally (n=334) averaged 34.56 infant infections per 100 child years (95% CI 26.60 to 44.91) during the first nine months after maternal infection, declined to 9.50 (95% CI 3.07 to 29.47) during the next three months, and was zero thereafter. Among women who seroconverted postnatally and in whom the precise timing of infection was known (≤90 days between last negative and first positive test; n=51), 62% (8/13) of transmissions occurred in the first three months after maternal infection and breastfeeding associated transmission was 4.6 times higher than in mothers who tested HIV positive at baseline and whose infant tested HIV negative with PCR at six weeks. Median plasma HIV concentration in all mothers who seroconverted postnatally declined from 5.0 log(10) copies/mL at the last negative enzyme linked immunosorbent assay (ELISA) to 4.1 log(10) copies/mL at 9-12 months after infection. Breast milk HIV load in this group was 4.3 log(10) copies/mL 0-30 days after infection, but rapidly declined to 2.0 log(10) copies/mL and <1.5 log(10) copies/mL by 31-90 days and more than 90 days, respectively. Among women whose plasma sample collected soon after delivery tested negative for HIV with ELISA but positive with PCR (n=17), 75% of their infants were infected or had died by 12 months. An estimated 18.6% to 20.4% of all breastfeeding associated transmission observed in the ZVITAMBO trial occurred among mothers who seroconverted postnatally. CONCLUSIONS: Breastfeeding associated transmission is high during primary maternal HIV infection and is mirrored by a high but transient peak in breast milk HIV load. Around two thirds of breastfeeding associated transmission by women who seroconvert postnatally may occur while the mother is still in the "window period" of an antibody based test, when she would test HIV negative using one of these tests. Trial registration Clinical trials.gov NCT00198718.

Postpartum plasma CD4 change in HIV-positive women: implications for timing of HAART initiation.

CD4 counts increase during the postpartum period and may not correctly identify HAART-eligible HIV-positive women. HAART eligibility when defined by two CD4 cutoffs (<200 and <350 cells/microl) measured at two time points (within 96 h of delivery and 6 weeks) in postpartum HIV-positive women was compared. Among HIV-positive women who had CD4 at delivery and 6 weeks (n = 423), time to Stage 3 or 4 opportunistic infection or death was compared using Cox regression between three groups of women: (1) CD4 <200 cells/microl at delivery and 6 weeks, (2) CD4 <200 cells/microl at delivery but >or=200 cells/microl at 6 weeks, and (3) CD4 >or=200 cells/microl at delivery and at 6 weeks. The analysis was repeated using the CD4 <350 cells/microl cut-off. CD4 counts increased by a median (IQR) of 70 (1-178) cells/microl between delivery and 6 weeks and decreased thereafter to approximately delivery levels at 12 months. Only 60% and 61% who had CD4 <200 cells/microl and CD4 <350 cells/microl, respectively, at delivery also had those levels at 6 weeks. Among those with CD4 <350 cells/microl at both delivery and 6 weeks, the risk of death or Stage 3 or 4 disease was 5.27 (95% CI 1.85-14.96) times higher than those with CD4 <350 at delivery but >or=350 cells/microl at 6 weeks. The use of CD4 counts immediately postpartum to define HAART eligibility may lead to substantial misclassification.

Associations between breast milk viral load, mastitis, exclusive breast-feeding, and postnatal transmission of HIV.

BACKGROUND: . Exclusive breast-feeding is protective against postnatal transmission of human immunodeficiency virus (HIV), compared with mixed breast-feeding. Accordingly, exclusive breast-feeding for 6 months is the World Health Organization's recommendation to HIV-infected mothers for whom exclusive replacement feeding is not acceptable, feasible, affordable, safe, or sustainable. The mechanism of exclusive breast-feeding protection is unknown but is hypothesized to be mediated through reduced mastitis. METHODS: We compared breast milk and plasma specimens of exclusive breast-feeding and mixed breast-feeding HIV- positive mothers archived from the ZVITAMBO trial in which mixed breast-feeding was associated with a 2-fold increased risk of postnatal transmission at 18 months. Plasma HIV load, breast milk HIV load and sodium/potassium ratio were measured as a proxy for subclinical mastitis. RESULTS: Mixed breast-feeding was not associated with mastitis or breast milk HIV load. Mastitis was associated with breast milk HIV load, and this effect increased with increasing maternal plasma HIV load; mastitis was associated with postnatal transmission only when maternal plasma HIV load was high (>3.7 log(10) copies/mL). Initiation of breast-feeding within an hour of delivery was associated with exclusive breast-feeding (adjusted odds ratio, 1.62; 95% confidence interval, 1.02-2.58). CONCLUSIONS: Exclusive breast-feeding is associated with reduced postnatal transmission of HIV from mother to child, but this protection is not mediated by reduced mastitis or breast milk HIV load. The deleterious effect of mastitis increases as the mother's plasma HIV load increases.

Effect of early exclusive breastfeeding on morbidity among infants born to HIV-negative mothers in Zimbabwe.

BACKGROUND: Early exclusive breastfeeding (EBF) is recommended by the World Health Organization, but EBF rates remain low throughout the world. For infants born to breastfeeding HIV-positive mothers, early EBF is associated with a lower risk of postnatal transmission than is feeding breast milk together with other liquids or foods. No studies conducted in Africa have reported any benefits of EBF for infants born to HIV-negative women. OBJECTIVE: The objective was to compare the rate of sick clinic visits by infants aged 43-182 d according to breastfeeding exclusivity [EBF, predominant breastfeeding (PBF), and mixed breastfeeding (MBF)]. DESIGN: We compared rates of all-cause clinic visits and clinic visits related to diarrhea and lower respiratory tract infection (LRTI) among a cohort of 9207 infants of HIV-negative mothers during 2 age intervals: 43-91 and 92-182 d according to exclusivity of breastfeeding. Breastfeeding exclusivity was defined in 2 ways ("ever since birth" and "previous 7 d") and was assessed at 43 and 91 d. RESULTS: EBF between birth and 3 mo was significantly protective against diarrhea between 3 and 6 mo of age with the "ever since birth" definition [incidence rate ratios (IRRs) of 8.83 (95% CI: 1.07, 65.53) and 8.76 (95% CI: 1.13, 68.09) for PBF and MBF, respectively] and with the "previous 7 d" definition [2.04 (95% CI: 1.11, 3.77) and 2.05 (95% CI: 1.13, 3.72) for PBF and MBF, respectively]. The adverse effect of MBF on LRTI visits was weaker, reaching borderline significance only by the "ever since birth" definition during the 43-91-d interval (IRR: 1.91; 95% CI: 0.99, 3.67). CONCLUSION: Early EBF is associated with a significant reduction in sick clinic visits, especially those due to diarrhea.

Making a working clinical diagnosis of HIV infection in infants in Zimbabwe.

OBJECTIVES: Clinical algorithms can be helpful in decisions about treatment and feeding options in infancy, but have had limited exposure to real data. This analysis uses data from a large clinical trial to test such algorithms, and thereby develop a successor which performs usefully in poor countries with high HIV-prevalence. METHODS: The ZVITAMBO trial followed 14 110 mother-baby pairs through infancy. 32% of mothers were HIV-positive. Infants were HIV tested regularly using DNA PCR. Clinical signs were evaluated in terms of identifying HIV-infection at 6 weeks, 6 and 12 months, using Zimbabwean, South African, and WHO generic adaptations of the WHO integrated management of childhood illness HIV algorithm. A modification, in which HIV-exposed infants are first divided into being at least or less than median weight-for-age, was derived and evaluated. RESULTS: At 6 weeks 65% of all infected babies are less than median weight-for-age. Adding at least two clinical signs reduces sensitivity to 20% but those identified are 1.5 (95% CI 1.1-2.1) times more likely to die by 6 months than other infected infants. At 6 months, 86% of uninfected babies of HIV-infected mothers can be identified by selecting those whose weight is greater than median or, if less than median, who exhibit <2 clinical signs. CONCLUSIONS: In poor settings a simple clinical algorithm can identify children with probable HIV infection, especially those at risk of early death, who can then be referred for further testing and care, including highly active antiretroviral therapy. Most infants who are HIV-uninfected can be identified at 6 months and provided with support to maintain infection-free survival, including focussed infant-feeding counselling.

Improved HIV-1 incidence estimates using the BED capture enzyme immunoassay.

OBJECTIVE: To validate the BED capture enzyme immunoassay for HIV-1 subtype C and to derive adjustments facilitating estimation of HIV-1 incidence from cross-sectional surveys. DESIGN: Laboratory analysis of archived plasma samples collected in Zimbabwe. METHODS: Serial plasma samples from 85 women who seroconverted to HIV-1 during the postpartum year were assayed by BED and used to estimate the window period between seroconversion and the attainment of a specified BED absorbance. HIV-1 incidences for the year prior to recruitment and for the postpartum year were calculated by applying the BED technique to HIV-1-positive samples collected at baseline and at 12 months. RESULTS: The mean window for an absorbance cut-off of 0.8 was 187 days. Among women who were HIV-1 positive at baseline and retested at 12 months, a proportion (epsilon) 5.2% (142/2749) had a BED absorbance < 0.8 at 12 months and were falsely identified as recent seroconverters. Consequently, the estimated BED annual incidence at 12 months postpartum (7.6%) was 2.2 times the contemporary prospective estimate. BED incidence adjusted for epsilon was 3.5% [95% confidence interval (CI), 2.6-4.5], close to the 3.4% estimated prospectively. Adjusted BED incidence at baseline was 6.0% (95% CI, 5.2-6.9) and, like the prospective estimates, declined with maternal age. Unadjusted BED incidence estimates were largely independent of age; the pooled estimate was 58% higher than adjusted incidence. CONCLUSION: The BED method can be used in an African setting, but further estimates of epsilon and of the window period are required, using large samples in a variety of circumstances, before its general utility can be gauged.

HIV-positive poor women may stop breast-feeding early to protect their infants from HIV infection although available replacement diets are grossly inadequate.

Little is known about mothers' perspectives and experiences of early breast-feeding cessation as a strategy to reduce postnatal HIV transmission in rural, resource-constrained settings. We conducted in-depth interviews (IDI) with 15 HIV-positive breast-feeding mothers of infants aged 3-5 mo about their plans for feeding their infants after age 6 mo. We also conducted IDI with 12 HIV-positive mothers who intended to stop breast-feeding after receiving their infant's HIV-PCR negative test result at age 6 mo. Twenty-four-hour dietary recalls were conducted with the same 12 mothers and 16 HIV-negative or status unknown mothers who were breast-feeding their 6- to 9-mo-old infants. Of the 12 mothers who intended to stop breast-feeding, 11 did so by 9 mo. Median energy intake (percent requirement) was 1382 kJ (54%) among weaned infants compared with 2234 kJ (87%) among breast-feeding infants. Median intakes were <67% of the recommended levels for 9 and 7 of the 12 micronutrients assessed for weaned and breast-feeding infants, respectively. Factors facilitating early breast-feeding cessation were mothers' knowledge about HIV transmission, family support, and disclosure of their HIV status; food unavailability was the primary barrier. HIV-positive mothers in resource-constrained settings may be so motivated to protect their child from HIV that they stop breast-feeding early even when they cannot provide an adequate replacement diet. As reflected in the new World Health Organization guidance, HIV-positive mothers should continue breastfeeding their infants beyond 6 mo if replacement feeding is still not acceptable, feasible, affordable, sustainable, and safe.

Maternal Herpes simplex virus type 2 infection, syphilis and risk of intra-partum transmission of HIV-1: results of a case control study.

BACKGROUND: Genital ulcer disease including that caused by Herpes simplex virus type 2 (HSV-2) and syphilis facilitates sexual transmission of HIV-1. The effect of these infections on intra-partum mother-to-child-transmission (MTCT) of HIV-1 is unknown. METHODS: A case-control study was conducted using archived sera from HIV-1 positive women enrolled in ZVITAMBO, an MTCT trial. Cases were 509 women who transmitted HIV-1 to their infants intra-partum; controls were 1018 women whose infants remained uninfected at 12 months. Maternal serum collected at delivery, were tested for HSV-2 antibody. The 6-week post-partum sample was also tested for syphilis by RPR and TPHA to identify women with incubating or active syphilis at delivery. Rates of prevalent and incident HSV-2 and recently acquired syphilis were compared between cases and controls. FINDINGS: Overall prevalence of maternal HSV-2 and active syphilis at delivery were 82.5% [95% confidence interval (CI), 80.6-84.5] and 4.0% (95% CI, 3.0-5.1), respectively. Prevalent HSV-2 was associated with increased intra-partum MTCT [adjusted odds ratio (OR), 1.50; 95% CI, 1.09-2.08]. The proportion of intra-partum transmissions potentially attributable to prevalent HSV-2 infection was 28.4% (95% CI, 7.3-44.7). Maternal infection with active syphilis at delivery was not associated with intra-partum MTCT (unadjusted OR, 0.89; 95%CI, 0.49-1.59; adjusted OR, 0.64; 95% CI, 0.34-1.20). INTERPRETATION: HSV-2 infection is common among HIV-1-positive women and is associated with an increased risk of intra-partum MTCT. More than 25% of intra-partum MTCT may be attributable to maternal HSV-2 co-infection. Active maternal syphilis at the time of delivery is not associated with intra-partum MTCT risk.

The impact of safer breastfeeding practices on postnatal HIV-1 transmission in Zimbabwe.

OBJECTIVES: We assessed the association between exposure to an educational intervention that emphasized safer breastfeeding practices and postnatal HIV transmission among 437 HIV-positive mothers in Zimbabwe, 365 of whom did not know their infection status. METHODS: Mothers were tested for HIV and were encouraged--but not required--to learn their HIV status. Intervention exposure was assessed by a questionnaire, Turnbull methods were used to estimate postnatal HIV transmission, and multivariate Cox proportional hazard models were constructed to assess the association between intervention exposure and postnatal HIV transmission. RESULTS: Cumulative postnatal HIV transmission was 8.2%; each additional intervention contact was associated with a 38% reduction in postnatal HIV transmission. HIV-positive mothers who were exposed to both print and video materials were 79% less likely to infect their infants compared with mothers who had no exposure. These findings were similar for mothers who did not know their HIV status. CONCLUSIONS: The promotion of exclusive breastfeeding has the potential to reduce postnatal HIV transmission among women who do not know their HIV status, and child survival and HIV prevention programs should support this practice.

Child mortality according to maternal and infant HIV status in Zimbabwe.

BACKGROUND: HIV causes substantial mortality among African children but there is limited data on how this is influenced by maternal or infant infection status and timing. METHODS: Children enrolled in the ZVITAMBO trial were divided into 5 groups: those born to HIV-negative mothers (NE, n = 9510), those born to HIV-positive mothers but noninfected (NI, n = 3135), those infected in utero (IU, n = 381), those infected intrapartum (IP, n = 508), and those infected postnatally (PN, n = 258). Their mortality was estimated. RESULTS: Two-year mortality was 2.9% (NE infants), 9.2% (NI), 67.5% (IU), 65.1% (IP), and 33.2% (PN). Between 8 weeks and 6 months, mortality in IU infants quintupled (from 309 to 1686/1000 c-y). The median time from infection to death was 208, 380, and >500 days for IU, IP, and PN infants, respectively. Among NI children, advanced maternal disease was predictive of mortality. Acute respiratory infection was the major cause of death. CONCLUSIONS: Perinatally infected infants are at particular risk of death between 2 and 6 months: cotrimoxazole prophylaxis and early pediatric HAART should be scaled up. Uninfected infants of infected mothers have at least twice the mortality risk of infants born to uninfected mothers: all HIV-exposed infants should be targeted with child survival interventions. HIV-positive mothers with more advanced disease are not only more likely to infect their infants, but their infants are more likely to die, whether infected or not: provision of antiretroviral treatment to pregnant and lactating women is an urgent need for both mothers and their children.

Effects of infant sex on mother-to-child transmission of HIV-1 according to timing of infection in Zimbabwe.

We examined the relationship between sex and the risk of intrauterine, intrapartum and postnatal HIV transmission among 4495 infants born to HIV-infected mothers in Harare, Zimbabwe. Intrauterine transmission was 8.6%, and consistent with other studies was higher among girl than boy infants (AOR 1.53; 95% CI 1.23-1.91). Unlike previous studies, we observed no independent effect of infant sex on intrapartum or breastfeeding-associated HIV transmission. Sex-specific postnatal prevention strategies are not warranted in this population.

Mortality and morbidity among postpartum HIV-positive and HIV-negative women in Zimbabwe: risk factors, causes, and impact of single-dose postpartum vitamin A supplementation.

BACKGROUND: Vitamin A deficiency is common among women in resource-poor countries and is associated with greater mortality during HIV. METHODS: Fourteen thousand one hundred ten mothers were tested for HIV and randomly administered 400,000 IU vitamin A or placebo at less than 96 hours postpartum. The effects of vitamin A and HIV status on mortality, health care utilization, and serum retinol were evaluated. RESULTS: Four thousand four hundred ninety-five (31.9%) mothers tested HIV positive. Mortality at 24 months was 2.3 per 1000 person-years and 38.3 per 1000 person-years in HIV-negative and HIV-positive women, respectively. Vitamin A had no effect on mortality. Tuberculosis was the most common cause of death, and nearly all tuberculosis-associated deaths were among HIV-positive women. Among HIV-positive women, vitamin A had no effect on rates of hospitalization or overall sick clinic visits, but did reduce clinic visits for malaria, cracked and bleeding nipples, pelvic inflammatory disease, and vaginal infection. Among HIV-negative women, serum retinol was responsive to vitamin A, but low serum retinol was rare. Among HIV-positive women, serum retinol was largely unresponsive to vitamin A, and regardless of treatment group, the entire serum retinol distribution was shifted 25% less than that of HIV-negative women 6 weeks after dosing. CONCLUSIONS: Single-dose postpartum vitamin A supplementation had no effect on maternal mortality, perhaps because vitamin A status was adequate in HIV-negative women and apparently unresponsive to supplementation in HIV-positive women.

Effect of maternal and neonatal vitamin A supplementation and other postnatal factors on anemia in Zimbabwean infants: a prospective, randomized study.

BACKGROUND: Anemia is prevalent in infants in developing countries. Its etiology is multifactorial and includes vitamin A deficiency. OBJECTIVE: Our primary aim was to measure the effect of maternal or neonatal vitamin A supplementation (or both) on hemoglobin and anemia in Zimbabwean infants. Our secondary aim was to identify the underlying causes of postnatal anemia. DESIGN: A randomized, placebo-controlled trial was conducted in 14 110 mothers and their infants; 2854 infants were randomly selected for the anemia substudy, of whom 1592 were successfully observed for 8-14 mo and formed the study sample. Infants were randomly assigned within 96 h of delivery to 1 of 4 treatment groups: mothers and infants received vitamin A; mothers received vitamin A and infants received placebo; mothers received placebo and infants received vitamin A; and mothers and infants received placebo. The vitamin A doses were 400,000 and 50,000 IU in the mothers and infants, respectively. RESULTS: Vitamin A supplementation had no effect on hemoglobin or anemia (hemoglobin <105 g/L) in unadjusted or adjusted analyses. Infant HIV infection independently increased anemia risk >6-fold. Additional predictors of anemia in HIV-negative and -positive infants were male sex and lower total body iron at birth. In addition, in HIV-positive infants, the risk of anemia increased with early infection, low maternal CD4+ lymphocyte count at recruitment, and frequent morbidity. Six-month plasma ferritin concentrations <12 microg/L were a risk factor in HIV-negative but not in HIV-positive infants. Maternal HIV infection alone did not cause anemia. CONCLUSION: Prevention of infantile anemia should include efforts to increase the birth endowment of iron and prevent HIV infection.

HIV incidence among post-partum women in Zimbabwe: risk factors and the effect of vitamin A supplementation.

OBJECTIVE: To test whether post-partum vitamin A supplementation can reduce incident HIV among post-partum women and identify risk factors for HIV incidence. DESIGN: Randomized, placebo-controlled trial METHODS: Between November 1997 and January 2001, 14,110 women were randomly administered 400,000 IU vitamin A or placebo within 96 h post-partum. HIV incidence was monitored among 9562 HIV-negative women. RESULTS: Cumulative incidence was 3.4% [95% confidence interval (CI), 3.0-3.8] and 6.5% (95% CI, 5.7-7.4) over 12 and 24 months post-partum, respectively. Vitamin A supplementation had no impact on incidence [hazard ratio (HR), 1.08; 95% CI, 0.85-1.38]. However, among 398 women for whom baseline serum retinol was measured, those with levels indicative of deficiency (< 0.7 micromol/l, 9.2% of those measured) were 10.4 (95% CI, 3.0-36.3) times more likely to seroconvert than women with higher concentrations. Furthermore, among women with low serum retinol, vitamin A supplementation tended to be protective against incidence (HR, 0.29; 95% CI, 0.03-2.60; P = 0.26), although not significantly so, perhaps due to limited statistical power. Severe anaemia (haemoglobin < 70 g/l) was associated with a 2.7-fold (95%CI, 1.2-6.1) greater incidence. Younger women were at higher risk of HIV infection: incidence declined by 5.7% (2.8-8.6) with each additional year of age. CONCLUSION: Among post-partum women, a single large-dose vitamin A supplementation had no effect on incidence, although low serum retinol was a risk factor for seroconversion. Further investigation is required to determine whether vitamin A supplementation of vitamin-A-deficient women or treatment of anaemic women can reduce HIV incidence.