Mwiya

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.)

Effect of nitazoxanide on morbidity and mortality in Zambian children with cryptosporidiosis: a randomised controlled trial

BACKGROUND Cryptosporidiosis in children in developing countries causes persistent diarrhoea and malnutrition and is associated with increased mortality, but there is no effective treatment. We aimed to assess the effect of nitazoxanide-a new broad-spectrum antiparasitic drug-on morbidity and mortality in Zambian children with diarrhoea due to Cryptosporidium parvum. METHODS Children with cryptosporidial diarrhoea who were admitted to the University Teaching Hospital, Lusaka, Zambia, between November, 2000, and July, 2001, and whose parents consented to their having an HIV test were randomly assigned nitazoxanide (100 mg twice daily orally for 3 days) or placebo. The primary endpoint was clinical response on day 7 after the start of treatment. Secondary endpoints included parasitological response by day 10 and mortality at day 8. Analysis was by intention to treat, with exclusion of patients subsequently found to be negative for C parvum or co-infected at baseline. The trial was stratified by HIV serology. FINDINGS 50 HIV-seropositive and 50 HIV-seronegative children were recruited for the study, four of whom were subsequently excluded. In HIV-seronegative children, diarrhoea resolved in 14 (56%) of 25 receiving nitazoxanide and 5 (23%) of 22 receiving placebo (difference 33%, 95% CI 7-59; p=0.037). C parvum was eradicated from stool in 13 (52%) of 25 receiving nitazoxanide and three (14%) of 22 receiving placebo (38%, 95% CI 14-63; p=0.007). Four children (18%) of 22 in the placebo group had died by day 8, compared with none of 25 in the nitazoxanide group (-18%, -34 to 2; p=0.041). HIV-seropositive children did not benefit from nitazoxanide. Nitazoxanide was not significantly associated with adverse events in either stratum. INTERPRETATION A 3-day course of nitazoxanide significantly improved the resolution of diarrhoea, parasitological eradication, and mortality in HIV-seronegative, but not HIV-seropositive, children.

Barriers to acceptance and adherence of antiretroviral therapy in urban Zambian women: a qualitative study

Abstract Sub-Saharan Africa contains over 60% of the worlds HIV infections and Zambia is among the most severely affected countries in the region. As antiretroviral programs have been rapidly expanding, the long-term success of these programs depends on a good understanding of the behavioral determinants of acceptance and adherence to antiretroviral therapy (ART). The study used qualitative methods to gain local insight into potentially important factors affecting HIV-infected womens decision to accept or continue with ART. Some of the barriers identified by this study are consistent with factors cited in the existing adherence literature from both developed and developing nations such as side effects, hunger and stigma; other factors have not been previously reported. One major theme was unfamiliarity with the implications of having a chronic, potentially deadly disease. Other emerging themes from this study include the complicated effect of ART on interpersonal relationship, particularly between husbands and wives, the presence of depression and hopelessness, and lack of accurate information. The results suggest that the reasons for non-uptake of treatment include issues related to local cultural frameworks (e.g., illness ideology), mental and behavioral health (e.g., depression and/or interpersonal challenges), stigma, and motivating factors (e.g., values of church or marriage) of different cultures that affect the ability and willingness to take life-saving medicine for a long period of time. Qualitative studies are critical to better understand why ART eligible individuals are choosing not to initiate or continue treatment to achieve needed adherence levels.

Intestinal and systemic infection, HIV, and mortality in Zambian children with persistent diarrhea and malnutrition.

Background Persistent diarrhea–malnutrition syndrome is a complex of infection and immune failure that involves protein, calorie and micronutrient depletion, and metabolic disturbances. We report an analysis of the impact of HIV infection on infectious disease, clinical presentation, and mortality in Zambian children with persistent diarrhea and malnutrition. Methods Two hundred children (94 boys and 106 girls, 6–24 months old) were examined on admission to the malnutrition ward of University Teaching Hospital in Lusaka, Zambia. There was then 1 month of follow-up. Results Antibodies to HIV were found in 108 of the children (54%). The common intestinal infections (Cryptosporidium parvum [26%] and nontyphoid Salmonella spp [18%]), septicemia (17%), and pulmonary tuberculosis confirmed by gastric lavage (13.5%) were not significantly more common in HIV-seropositive than in HIV-seronegative children. HIV-seropositive children were more likely to have marasmus whereas HIV-seronegative children were more likely to have kwashiorkor. Weight-for-age z scores at nadir (postedema) were lower in HIV-seropositive children (median, -4.4; interquartile range [IQR], −5.0 to −3.8) than in HIV-seronegative children (median, −3.7; IQR, -4.2 to -3.1;P < 0.0001). Height-for-age and weight-for-height z scores and mid-upper arm circumference showed a similar difference. Of the 200 children, 39 (19.5%) died within 28 days; cryptosporidiosis and marasmus were the only independent predictors of death. Conclusions Although intestinal and systemic infections did not differ for HIV-seropositive and HIV-seronegative children, HIV influenced nutritional states of all children. Cryptosporidiosis and marasmus were associated with higher mortality.

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

Growth faltering due to breastfeeding cessation in uninfected children born to HIV-infected mothers in Zambia

BACKGROUND The effect of breastfeeding on growth in HIV-exposed infants is not well described. OBJECTIVE The objective was to evaluate the effect of early breastfeeding cessation on growth. DESIGN In a trial conducted in Lusaka, Zambia, HIV-infected mothers were randomly assigned to exclusive breastfeeding for 4 mo followed by rapid weaning to replacement foods or exclusive breastfeeding for 6 mo followed by introduction of complementary foods and continued breastfeeding for a duration of the mothers choice. Weight-for-age z score (WAZ), length-for-age z score (LAZ), and weight-for-length z score (WLZ) and the self-reported breastfeeding practices of 593 HIV-uninfected singletons were analyzed. Generalized estimating equations were used to adjust for confounders. RESULTS WAZ scores declined precipitously between 4.5 and 15 mo. The decline was slower in the breastfed infants. At 9, 12, and 15 mo, mean WAZs were, respectively, -0.74, -0.92, and -1.06 in infants who were reportedly breastfed and were -1.07, -1.20, and -1.31 in the weaned infants (P = 0.003, 0.007, and 0.02, respectively). No differences were observed past 15 mo. Breastfeeding practice was not associated with LAZ, which declined from -0.98 to -2.24 from 1 to 24 mo. After adjustment for birth weight, maternal viral load, body mass index, education, season, and marital and socioeconomic status, not breastfeeding was associated with a 0.28 decline in WAZ between 4.5 and 15 mo (P < 0.0001). During the rainy season, not breastfeeding was associated with a larger WAZ decline (0.33) than during the dry season (0.22; P for interaction = 0.02). CONCLUSIONS Early growth is compromised in uninfected children born to HIV-infected Zambian mothers. Continued breastfeeding partially mitigates this effect through 15 mo. Nutritional interventions to complement breastfeeding after 6 mo are urgently needed. This trial was registered at clinicaltrials.gov as 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.

Early Weaning Increases Diarrhea Morbidity and Mortality Among Uninfected Children Born to HIV-infected Mothers in Zambia

BACKGROUND Early weaning may reduce human immunodeficiency virus (HIV) transmission but may have deleterious consequences for uninfected children. Here we evaluate effects of early weaning on diarrhea morbidity and mortality of uninfected children born to HIV-infected mothers. METHODS HIV-infected women in Lusaka, Zambia, were randomly assigned to breastfeeding for 4 months only or to continue breastfeeding until the mother decided to stop. Replacement and complementary foods were provided and all women were counseled around feeding and hygiene. Diarrhea morbidity and mortality were assessed in 618 HIV-uninfected singletons alive and still breastfeeding at 4 months. Intent-to-treat analyses and comparisons based on actual feeding practices were conducted using regression methods. RESULTS Between 4 and 6 months, diarrheal episodes were 1.8-fold (95% confidence interval (CI), 1.3-2.4) higher in the short compared with long breastfeeding group. Associations were stronger based on actual feeding practices and persisted after adjustment for confounding. At older ages, only more severe outcomes, including diarrhea-related hospitalization or death (relative hazard [RH], 3.2, 95% CI, 2.1-5.1 increase 4-24 months), were increased among weaned children. CONCLUSIONS Continued breastfeeding is associated with reduced risk of diarrhea-related morbidity and mortality among uninfected children born to HIV-infected mothers in this low-resource setting despite provision of replacement and complementary food and counseling. CLINICAL TRIALS REGISTRATION NCT00310726.

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.

Dendritic Cell Anergy Results from Endotoxemia in Severe Malnutrition

Malnutrition predicts an increased risk of morbidity and mortality from infection. Defects in cell-mediated immunity, such as thymic atrophy, impaired cutaneous tuberculin responses, and reduced T cell mitogenesis in vitro, are well characterized. There has been no convincing mechanism proposed for these T cell defects. However, as T cell responses rely on signals received from APCs, this study evaluates dendritic cell (DC) function in children with severe malnutrition. Repeated sampling of peripheral blood from 81 severely malnourished children at the University Teaching Hospital, Lusaka, Zambia, demonstrated for the first time a defect in DC numbers in children with malnutrition (28 per microliter) and a recovery in cell number (48 per microliter; p < 0.01) with standard treatment. We describe normal DC maturation in the majority of malnourished children. However, in 17% of our study patients, in association with endotoxemia we describe the novel finding of DC maturation failure (down-regulation rather than up-regulation of HLA-DR). There was a strong correlation between the strength of HLA-DR up or down-regulation and the generation of IL-10 (r = −0.481; p = 0.003). These “anergic” DCs failed to support T cell proliferation. Defects in DC number and the immunosuppressive phenotype of DCs from severely malnourished children with endotoxemia provide a rational basis for the anergy found in severe malnutrition.