Anna Coutsoudis

Influence of infant-feeding patterns on early mother-to-child transmission of HIV-1 in Durban, South Africa: a prospective cohort study

Summary Background The observation that mother-to-child transmission of HIV-1 can occur through breastfeeding has resulted in policies that recommend avoidance of breastfeeding by HIV-1-infected women in the developed world and under specific circumstances in developing countries. We compared transmission rates in exclusively breastfed, mixedfed, and formula-fed (never breastfed) infants to assess whether the pattern of breastfeeding is a critical determinant of early mother-to-child transmission of HIV-1. Methods We prospectively assessed infant-feeding practices of 549 HIV-1-infected women who were part of a vitamin A intervention trial in Durban, South Africa. The proportions of HIV-1-infected infants at 3 months (estimated by use of Kaplan-Meier life tables) were compared in the three different feeding groups. HIV-1 infection was defined by a positive RNA-PCR test. Findings At 3 months, 18·8% (95% CI 12·6–24·9) of 156 never-breastfed children were estimated to be HIV-1 infected compared with 21·3% (17·2–25·5) of 393 breastfed children (p=0·5). The estimated proportion (Kaplan-Meier) of infants HIV-1 infected by 3 months was significantly lower for those exclusively breastfed to 3 months than in those who received mixed feeding before 3 months (14·6% [7·7–21·4] vs 24·1% [19·0–29·2], p=0·03). After adjustment for potential confounders (maternal CD4-cell/CD8-cell ratio, syphilis screening test results, and preterm delivery), exclusive breastfeeding carried a significantly lower risk of HIV-1 transmission than mixed feeding (hazard ratio 0·52 [0·28–0·98]) and a similar risk to no breastfeeding (0·85 [0·51–1·42]). Interpretations Our findings have important implications for prevention of HIV-1 infection and infant-feeding policies in developing countries and further research is essential. In the meantime, breastfeeding policies for HIV-1-infected women require urgent review. If our findings are confirmed, exclusive breastfeeding may offer HIV-1-infected women in developing countries an affordable, culturally acceptable, and effective means of reducing mother-to-child transmission of HIV-1 while maintaining the overwhelming benefits of breastfeeding.

Secretory Leukocyte Protease Inhibitor in Vaginal Fluids and Perinatal Human Immunodeficiency Virus Type 1 Transmission

The presence of both viral particles and antiviral mucosal proteins may represent critical determinants of perinatal human immunodeficiency virus type 1 (HIV-1) transmission. In 60 HIV-1-infected women, concentrations of the innate mucosal protein, secretory leukocyte protease inhibitor (SLPI), were lower in vaginal fluid samples from 17 women whose babies became infected than in samples from nontransmitting women (mean+/-SE, 57+/-11 vs. 557+/-177 ng/mL, respectively; P=.01). Rates of transmission among women with higher SLPI concentrations (>100 ng/mL) were lower than those among women with lower concentrations (<100 ng/mL; 8.7% vs. 40.5%, respectively; P=.01). Concentrations of other putative HIV-1-inhibitory innate immune factors were similar in both groups. Concentrations of vaginal HIV-1 tended to be higher in transmitting than in nontransmitting women (407 vs. 174 virions/mL; P=.09). Increased concentrations of selected innate mucosal immune factors, such as SLPI, seem to be associated with reduced rates of perinatal HIV-1 transmission and may contribute to natural antiretroviral defense.

Breastfeeding practices in an area of high HIV prevalence in rural South Africa

Exclusive breastfeeding (EBF) from 0 to 6 mo of age is recommended by the World Health Organization as the optimal feeding method for infants, including infants of human immunodeficiency virus (HIV)‐infected women from developing countries who choose to breastfeed. EBF may be associated with less risk of postnatal HIV transmission than mixed feeding, but is still uncommonly practised for reasons that are poorly understood. This study aimed to assess EBF rates and the impediments to EBF in a South African rural area of high HIV prevalence where most mothers are unaware of their status. In a longitudinal study, 130 women attending 3 clinics, chosen for their disparate socioeconomic characteristics, were interviewed at weekly postnatal intervals. Follow‐up to 16wk was completed on 119 infants. In an additional cross‐sectional survey mothers of 445 infants, aged 0–12 mo, attending immunization clinics were interviewed. In the longitudinal study 46% of infants received non‐breast‐milk fluids or feeds within 48 h of birth; only 10% were exclusively breastfed for 6 wk and 6% for 16wk. Supplements, most commonly formula milk, were introduced for perceived milk insufficiency. Feeding choices were mainly self‐determined (43% of women), but health staff (22%) and grandmothers (16%) were cited as sources of advice. In the cross‐sectional survey caregivers reported that 47% of infants aged 2 wk, 40% aged 6 wk and 33% aged 12 wk had been exclusively breastfed since birth.

Influence of Infant Feeding Patterns on Early Mother‐to‐Child Transmission of HIV‐1 in Durban, South Africa

Abstract: Previous studies on the effect of breastfeeding on mother‐to‐child transmission (MTCT) of HIV have not attempted to examine the influence of different types of breastfeeding practice. To attempt to address some of these inadequacies, infant feeding practices of 549 HIV‐infected women involved in a trial in Durban, South Africa were documented prospectively. Women were counseled on infant feeding choices according to UNAIDS guidelines, and those who chose to breastfeed were encouraged to practice exclusive breastfeeding. The MTCT rates of HIV‐1 at 3 months were compared in the three different feeding groups (never breastfed, exclusive breastfeeding, and mixed breast‐feeding). At 3 months, 18.8% of 156 never‐breastfed children were infected compared to 21.3% of 393 breastfed children (p= 0.50). Children exclusively breastfed to at least 3 months (n= 103) were less likely to be infected (14.3%) than those receiving mixed feeding before 3 months (24.1%) (p= 0.03). After adjustment for potential confounders (maternal CD4:CD8 ratio, syphilis screening test results, and preterm delivery), exclusive breastfeeding carried a significantly lower risk of HIV‐1 transmission than mixed feeding (hazard ratio [HR] 0.52, 95% CI: 0.28‐0.98) and an equivalent risk to no breastfeeding (HR 0.85, 95% CI: 0.51‐1.42). Our findings have important implications for HIV and infant feeding policies in developing countries, and it is critical that further research be undertaken. In the meantime, breastfeeding policies for HIV‐infected women require urgent review. If confirmed, exclusive breastfeeding may offer HIV‐infected women in developing countries an affordable, culturally acceptable, and effective means of reducing MTCT of HIV‐1 while maintaining the overwhelming benefits of breastfeeding.

Subclinical mastitis as a risk factor for mother-infant HIV transmission.

Subclinical mastitis, as diagnosed by an elevated sodium/potassium ratio in milk accompanied by an increased milk concentration of the inflammatory cytokine, interleukin-8 (IL8), was found to be common among breast feeding women in Bangladesh and Tanzania. Subclinical mastitis results in leakage of plasma constituents into milk, active recruitment of leukocytes into milk, and possible infant gut damage from inflammatory cytokines. Therefore, we wished to investigate whether subclinical mastitis was related to known risk factors for postnatal mother-to-child HIV transmission, that is, high milk viral load or increased infant gut permeability. HIV-infected South African women were recruited at the antenatal clinic of McCords Hospital, Durban. Risks and benefits of different feeding strategies were explained to them and, if they chose to breast feed, they were encouraged to do so exclusively. Women and infants returned to the clinic at 1, 6 and 14 weeks postpartum for an interview about infant health and current feeding pattern, a lactulose/mannitol test of infant gut permeability, and milk sample collection from each breast separately for analysis of Na/K ratio, IL8 concentration and viral load in the cell-free aqueous phase. Only preliminary cross-sectional analyses from an incomplete database are available at this point. Moderately (0.6-1.0) or greatly (>1.0) raised Na/K ratio was common and was often unilateral, although as a group right and left breasts did not differ. Considering both breasts together, normal, moderately raised or greatly raised Na/K was found, respectively, in 51%, 28%, 21% of milk samples at 1 week (n=190); 69%, 20%, 11% at 6 weeks (n=167); and 72%, 16%, 12% at 14 weeks (n=122). IL8 concentration significantly correlated with both Na/K and viral load at all times. Na/K correlated with viral load at 1 and 14, but not 6 weeks. At 1 and 14 weeks, geometric mean viral loads in samples with Na/K > 1.0 were approximately 4 times those in samples with Na/K < 0.6. At 1 week but not later times, exclusive breast feeding was associated with lower milk viral load than was mixed feeding. Gut permeability was unrelated to milk Na/K ratio or IL8 concentration and was not significantly increased by inclusion of other foods than breast milk in the infants diet. The results suggest that subclinical mastitis among HIV-infected women may increase the risk of vertical transmission through breast feeding by increasing milk viral load. The importance of various causes of subclinical mastitis, which likely differ at 1 week from at later times and may include local infection or sterile inflammation, systemic infection, micronutrient deficiencies, or poor lactation practices, needs to be further clarified so that appropriate interventions can be implemented.

Morbidity in Children Born to Women Infected With Human Immunodeficiency Virus in South Africa: Does Mode of Feeding Matter?

Aim: To examine infant morbidity risks associated with refraining from breastfeeding where it is used in an attempt to prevent mother‐to‐child transmission (MTCT) of human immunodeficiency virus (HIV). Methods: The population consisted of infants born to HIV‐infected women in South Africa who were participating in a vitamin A intervention trial to prevent MTCT of HIV. Women chose to breastfeed or formula feed their infants according to UNAIDS guidelines. Actual feeding practices and morbidity were recorded at clinic follow‐up visits at 1 wk, 6 wk, 3 mo and every 3 mo thereafter until 15 mo of age or cessation of breastfeeding. The infants HIV status was assessed according to a predetermined algorithm. Results: HIV‐infected infants who were never breastfed had a poorer outcome than those who were breastfed; 9 (60%) of those who were never breastfed had 3 or more morbidity episodes compared with 15 (32%) of breastfed children [odds ratio (OR) 4.05, 95% confidence interval (95% CI) 0.91–20.63, p = 0.05]. During the first 2 mo of life, never‐breastfed infants (regardless of HIV status) were nearly twice as likely to have had an illness episode than breastfed infants (OR 1.91, 95% CI 1.17‐3.13, p = 0.006).

The early natural history of vertically transmitted HIV-1 infection in African children from Durban South Africa.

Forty-eight children with vertically transmitted HIV-1 infection and 93 uninfected infants were followed up at regular intervals from birth for a mean of 26 months. They were examined physically, growth and development were assessed and illnesses recorded. Seventy per cent of infected infants were symptomatic by 6 months. Relative risks in the infected infants were highest for lymphadenopathy (4.56; CI 2.7-7.7), failure to thrive (4.48; 2.57-7.81), and neurological abnormalities (3.32; 1.9-5.58). The most frequent findings were diarrhoea (78%), pneumonia (76%) and lymphadenopathy (70%). Thrush and pneumonia occurred early but declined over time, whereas diarrhoea and neurological abnormalities occurred later and increased in frequency. A diagnosis of AIDS was made in 44% of infected infants by 12 months of age. Mortality in infected infants was 35.4%, and 76% of deaths occurred within the 1st year. About two-thirds of HIV-infected infants survived into early childhood. In South African children with vertically acquired HIV-1 infection the onset of disease is early and deterioration to AIDS and death are rapid. Infected infants can be easily recognized clinically, the majority by 6 months of age.

A randomized controlled trial of the effect of antihelminthic treatment and micronutrient fortification on health status and school performance of rural primary school children

Summary Single interventions for helminthic infections and micronutrient deficiencies are effective, but it is not clear whether combined interventions will provide equal, additive or synergistic effects to improve childrens health. The study objective was to determine the impact of single and combined interventions on nutritional status and scholastic and cognitive performance of school children. A double-blind, randomized, placebo-controlled trial in 11 rural South African primary schools randomly allocated 579 children aged between 8 and 10 years into six study groups, half of whom received antihelminthic treatment at baseline. The de-wormed and non-de-wormed arms were further divided into three groups and given biscuits, either unfortified or fortified with vitamin A and iron or with vitamin A only, given daily for 16 weeks. The outcome measures were anthropometric, micronutrient and parasite status, and scholastic and cognitive test scores. There was a significant treatment effect of vitamin A on serum retinol (p < 0.01), and the suggestion of an additive effect between vitamin A fortification and de-worming. Fortified biscuits improved micronutrient status in rural primary school children; vitamin A with de-worming had a greater impact on micronutrient status than vitamin A fortification alone and antihelminthic treatment significantly reduced the overall prevalence of parasite infection. The burden of micronutrient deficiency (anaemia, iron and vitamin A) and stunting in this study population was low and, coupled with the restricted duration of the intervention (16 weeks), might have limited the impact of the interventions.

A health and nutritional profile of rural school children in KwaZulu-Natal, South Africa.

Summary A community-based cross-sectional study was undertaken to measure anthropometric indices, micronutrient status and prevalence of parasite infections in 579 rural South African primary school children. Eleven schools were selected randomly from a Magisterial District in southern KwaZulu-Natal (KZN). In each school, all pupils aged between 8 and 10 years were selected. The following outcome measures were obtained: anthropometric—height for age, weight for age and body mass index; micronutrient status—anaemia, serum ferritin and vitamin A; and prevalence of parasite infections—Ascaris lumbricoides, Trichuris trichiura and Schistosoma haematobium. The observed prevalences were: stunting 7.3%, underweight for age 0.7%, and obesity 3.1%; anaemia 16.5% (Hb < 12 g/dl), vitamin A deficiency 34.7% (serum retinol < 20 μg/dl) and 28.1% with reduced serum ferritin (< 12 ng/ml); Trichuris trichiura 53.9%, Ascaris lumbricoides 27.3% and Schistosoma haematobium 24.5%. We conclude that micronutrient deficiency, parasitic infestations and stunting remain significant problems among school-aged children in South Africa. Micronutrient supplementation and de-worming provide opportunities for school-based health promotion and primary health care interventions, and might produce significant health and educational benefits.

GB Virus Type C Coinfection in HIV-Infected African Mothers and Their Infants, KwaZulu Natal, South Africa

GB virus type C (GBV-C) infection was studied in a convenience sample of 75 antiretroviral (ART)-naive African mothers with human immunodeficiency virus infection and their infants. GBV-C RNA was extracted from serum and amplified by reverse-transcriptase polymerase chain reaction. Twenty-seven (36%) of these 75 HIV-infected women tested positive for GBV-C RNA. To study transmission dynamics, we chose a random subsample of 20 of these women and their infants. In this cohort, there was evidence of postnatal transmission of GBV-C; however, it was not possible to demonstrate evidence of in utero or intrapartum transmission. In this pilot observational study, transmission of HIV from mother-to-infant occurs independently of the GBV-C infection status of the mother. The immunological indices measured tend to suggest an association with protection and or delayed progression of HIV disease in GBV-C-infected mothers.