Lucie C. Malaba

Effects of a Single Large Dose of Vitamin A, Given during the Postpartum Period to HIV-Positive Women and Their Infants, on Child HIV Infection, HIV-Free Survival, and Mortality

BACKGROUND Low maternal serum retinol level is a risk factor for mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV). Multiple-large-dose vitamin A supplementation of HIV-positive children reduces mortality. The World Health Organization recommends single-large-dose vitamin A supplementation for postpartum women in areas of prevalent vitamin A deficiency; neonatal dosing is under consideration. We investigated the effect that single-large-dose maternal/neonatal vitamin A supplementation has on MTCT, HIV-free survival, and mortality in HIV-exposed infants. METHODS A total of 14,110 mother-infant pairs were enrolled < or =96 h after delivery, and both mother and infant, mother only, infant only, or neither received vitamin A supplementation in a randomized, placebo-controlled trial with a 2 x 2 factorial design. All but 4 mothers initiated breast-feeding. A total of 4495 infants born to HIV-positive women were included in the present analysis. RESULTS Neither maternal nor neonatal vitamin A supplementation significantly affected postnatal MTCT or overall mortality between baseline and 24 months. However, the timing of infant HIV infection modified the effect that supplementation had on mortality. Vitamin A supplementation had no effect in infants who were polymerase chain reaction (PCR) positive [corrected] for HIV at baseline. In infants who were PCR negative at baseline and PCR positive at 6 weeks, neonatal supplementation reduced mortality by 28% (P=.01), but maternal supplementation had no effect. In infants who were PCR negative at 6 weeks, all 3 vitamin A regimens were associated with ~2-fold higher mortality (P< or =.05). CONCLUSIONS Targeted vitamin A supplementation of HIV-positive children prolongs their survival. However, postpartum maternal and neonatal vitamin A supplementation may hasten progression to death in breast-fed children who are PCR negative at 6 weeks. These findings raise concern about universal maternal or neonatal vitamin A supplementation in HIV-endemic areas.

Neonatal erythropoiesis and subsequent anemia in HIV-positive and HIV-negative Zimbabwean babies during the first year of life: a longitudinal study

BackgroundAnemia is common in HIV infection and independently associated with disease progression and mortality. The pathophysiology of HIV-related anemia is not well understood especially in infancy.MethodsWe conducted a longitudinal cohort study nested within the Zimbabwe Vitamin A for Mothers and Babies Project. We measured hemoglobin, erythropoietin (EPO), serum transferrin receptor (TfR) and serum ferritin at 6 weeks, 3 and 6 months of age and hemoglobin at 9 and 12 months in 3 groups of randomly selected infants: 136 born to HIV-negative mothers, and 99 born to HIV-positive mothers and who were infected themselves by 6 weeks of age, and 324 born to HIV-positive mothers but who did not become infected in the 6 months following birth.ResultsAt one year of age, HIV-positive infants were 5.26 (adjusted odds ratio, P < 0.001) times more likely to be anemic compared to HIV-negative infants. Among, HIV-negative infants, EPO was or tended to be inversely associated with hemoglobin and was significantly positively associated with TfR throughout the first 6 months of life; TfR was significantly inversely associated with ferritin at 6 months; and EPO explained more of the variability in TfR than did ferritin. Among infected infants, the inverse association of EPO to hemoglobin was attenuated during early infancy, but significant at 6 months. Similar to HIV-negative infants, EPO was significantly positively associated with TfR throughout the first 6 months of life. However, the inverse association between TfR and ferritin observed among HIV-negative infants at 6 months was not observed among infected infants. Between birth and 6 months, mean serum ferritin concentration declined sharply (by ~90%) in all three groups of babies, but was significantly higher among HIV-positive compared to HIV-negative babies at all time points.ConclusionHIV strongly increases anemia risk and confounds interpretation of hematologic indicators in infants. Among HIV-infected infants, the EPO response to anemia is attenuated near the time of infection in the first weeks of life, but normalizes by 6 months.

Timing of mother-to-child transmission of HIV-1 and infant mortality in the first 6 months of life in Harare, Zimbabwe.

Objectives: To examine the risks of intra-uterine (IU), intra- and early post-partum (IP/ePP) and late post-partum (LPP) mother-to-child transmission (MTCT) of HIV-1 and infant mortality in the first 6 months of life. Methods: Whole blood was collected in ethylenediaminetetra-acetic acid at birth, 6 weeks, 3 and 6 months from 996 infants born to HIV-1 seropositive mothers. Polymerase chain reaction using Roche DNA amplification assay, version 1.5 (Roche Diagnostics Incorporation, Alameda, California, USA) was used to determine timing of MTCT. Logistic regression models determined risk factors for HIV-1 transmission and survival analyses examined mortality by timing of transmission. Results: Two hundred and forty-nine mothers (30.7%) transmitted HIV-1 infection to their infants by 6 months of age. Eighty-nine infants [9.4%; 95% confidence interval (CI), 7.7–11.5], 104 infants (16.0%; 95% CI, 10.8–21.2) and 21 infants (5.3%; 95% CI, 1.6–12.2) were infected IU, IP/ePP and LPP respectively. Low maternal CD4 cell count and arm circumference were risk factors for IP/ePP transmission. Infant mortality was higher among infected infants than uninfected (P < 0.001, log rank test). Timing of infection, birth weight and maternal CD4 cell counts were important factors in predicting infant death. Conclusion: In the first 6 months of life, IU and IP/ePP transmission contributed more than three-quarters of the 30.7% MTCT. Our data, in addition to serving as a historical comparison, may be useful in designing and evaluating the efficacy of short course antiretroviral trials aimed at reducing MTCT in developing countries.

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 μmol/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.

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.

HIV-1 and HIV-2 prevalence and associated risk factors among postnatal women in Harare, Zimbabwe

Studies of antenatal women form the predominant source of data on HIV-1 prevalence in Africa. Identifying factors associated with prevalent HIV is important in targeting diagnostic services and care. Between November 1997 and January 2000, 14,110 postnatal women from Harare, Zimbabwe were tested by ELISAs reactive to both HIV-1 and HIV-2; a subset of positive samples was confirmed with assays specific for HIV-1 and HIV-2. Baseline characteristics were elicited and modelled to identify risk factors for prevalent HIV infection. HIV-1 and HIV-2 prevalences were 32.0% (95% CI 31.2-32.8) and 1.3% (95% CI 1.1-1.5), respectively; 4% of HIV-1-positive and 99% of HIV-2-positive women were co-infected. HIV-1 prevalence increased from 0% among 14-year-olds to >45% among women aged 29-31 years, then fell to <20% among those aged>40 years. In multivariate analyses, prevalence increased with parity, was lower in married women than in single women, divorcees and widows, and higher in women with the lowest incomes and those professing no religion. Adjusted HIV-1 prevalence increased during 1998 and decreased during 1999. Age modified the effects of parity, home ownership and parental education. Among older women, prevalence was greater for women who were not homeowners. Among younger women, prevalence increased with parity and low parental education. None of these factors distinguished women co-infected with HIV-2 from those infected with HIV-1 alone. Prevalent HIV-1 infection is associated with financial insecurity and weak psychosocial support. The ZVITAMBO study apparently spanned the peak of the HIV-1 epidemic among reproductive women in Harare.

Complex formation between transketolase, transaldolase, and glyceraldehyde phosphate dehydrogenase

1. 1. The existence of complexes between transketolase, transaldolase, and glyceraldehyde phosphate dehydrogenase from Candida utilis was investigated. 2. 2. Evidence of complex formation was obtained by gel filtration, chromatography on DEAE-Sephadex, and gel electrophoresis. 3. 3. The complexes were fairly stable at pH 6.0 but dissociated slowly in the pH range 7.4–8.5 with a concomitant increase in the activities of transaldolase and glyceraldehyde phosphate dehydrogenase. 4. 4. The partial purification of glyceraldehyde phosphate dehydrogenase from Candida utilis is described. 5. 5. Incubation of the above preparation with pure transketolase and transaldolase at pH 6.4 led to the formation of binary complexes of transketolase with transaldolase, of transketolase with glyceraldehyde phosphate dehydrogenase, and of a ternary complex. 6. 6. The function of the ternary complex was suggested to be the coupled conversion of 1,3-bisphosphoglycerate and fructose 6-phosphate to pentose phosphate and experimental evidence was obtained for the feasibility of the reaction.