Ruth M. Bland

Mother-to-child transmission of HIV-1 infection during exclusive breastfeeding in the first 6 months of life: an intervention cohort study.

BACKGROUND Exclusive breastfeeding, though better than other forms of infant feeding and associated with improved child survival, is uncommon. We assessed the HIV-1 transmission risks and survival associated with exclusive breastfeeding and other types of infant feeding. METHODS 2722 HIV-infected and uninfected pregnant women attending antenatal clinics in KwaZulu Natal, South Africa (seven rural, one semiurban, and one urban), were enrolled into a non-randomised intervention cohort study. Infant feeding data were obtained every week from mothers, and blood samples from infants were taken monthly at clinics to establish HIV infection status. Kaplan-Meier analyses conditional on exclusive breastfeeding were used to estimate transmission risks at 6 weeks and 22 weeks of age, and Coxs proportional hazard was used to quantify associations with maternal and infant factors. FINDINGS 1132 of 1372 (83%) infants born to HIV-infected mothers initiated exclusive breastfeeding from birth. Of 1276 infants with complete feeding data, median duration of cumulative exclusive breastfeeding was 159 days (first quartile [Q1] to third quartile [Q3], 122-174 days). 14.1% (95% CI 12.0-16.4) of exclusively breastfed infants were infected with HIV-1 by age 6 weeks and 19.5% (17.0-22.4) by 6 months; risk was significantly associated with maternal CD4-cell counts below 200 cells per muL (adjusted hazard ratio [HR] 3.79; 2.35-6.12) and birthweight less than 2500 g (1.81, 1.07-3.06). Kaplan-Meier estimated risk of acquisition of infection at 6 months of age was 4.04% (2.29-5.76). Breastfed infants who also received solids were significantly more likely to acquire infection than were exclusively breastfed children (HR 10.87, 1.51-78.00, p=0.018), as were infants who at 12 weeks received both breastmilk and formula milk (1.82, 0.98-3.36, p=0.057). Cumulative 3-month mortality in exclusively breastfed infants was 6.1% (4.74-7.92) versus 15.1% (7.63-28.73) in infants given replacement feeds (HR 2.06, 1.00-4.27, p=0.051). INTERPRETATION The association between mixed breastfeeding and increased HIV transmission risk, together with evidence that exclusive breastfeeding can be successfully supported in HIV-infected women, warrant revision of the present UNICEF, WHO, and UNAIDS infant feeding guidelines.

Cohort Profile: Hlabisa HIV Treatment and Care Programme

This article evaluates the Hlabisa HIV treatment and Care Programme in South Africa. The goal of this program is to promote prevention practices as part of HIV services with the ultimate goal of curbing the HIV epidemic. A cohort study monitored the success of this integrated system and the impact on the communities. It includes a tracking system treatment checkpoints and children evaluations. The study concluded that this program is properly placed in a location where the population needs a variety of services and a complex approach to treatment. However more research is needed to determine whether maternal health ART treatment and TB are impacted by this program.

Maternal recall of exclusive breast feeding duration

Background: Both the pattern and duration of breast feeding are important determinants of health outcomes. In vertical HIV transmission research, reliable documentation of early breast feeding practices is important in order to correctly attribute postnatal transmission to feeding pattern. Aims: To validate methods of collecting data on the duration of exclusive breast feeding (EBF) in an area of South Africa with a high HIV prevalence rate. Methods: A total of 130 mothers were interviewed weekly, postnatally. At every interview a 48 hour and a seven day recall breast feeding history were taken. A subset of 70 mothers also received two intermediate visits per week during which additional 48 hour, non-overlapping, recall interviews were conducted. Ninety three infants were revisited at 6–9 months of age when mothers’ recall of EBF duration from birth was documented. The different methods of recalling EBF status were compared against an a priori “best comparison” in each case. Results: Reported breast feeding practices over the previous 48 hours did not reflect EBF practices since birth (specificity 65–89%; positive predictive value 31–48%). Six month EBF duration recall was equally poor (sensitivity at 2 weeks 79%; specificity 40%). Seven day recall accurately reflected EBF practices compared with thrice weekly recall over the same time period (sensitivity 96%, specificity 94%). Conclusions: 48 hour EBF status does not accurately reflect feeding practices since birth. Long term recall data on EBF are even more inaccurate. We recommend that data on duration of EBF be collected prospectively at intervals of no longer than one week.

Pregnancy Outcomes in HIV-Infected and Uninfected Women in Rural and Urban South Africa

Objective:To describe pregnancy outcomes among clade C HIV-infected and uninfected women in South Africa. Design:A longitudinal cohort study. Methods:Pregnant women attending 9 rural/urban antenatal clinics were prospectively recruited and followed up. Women were seen at the clinic or at home after delivery on 4 occasions after enrollment: 2 times within the first 2 weeks of the newborns life at home, and every 2 weeks thereafter until their first health clinic visit when the infant was 6 weeks old. Results:A total of 3465 women were enrolled; 615 withdrew after delivery, moved away, or had a missing or indeterminate HIV status, leaving 2850 women (1449 HIV-infected women). Six women died after delivery and there were 17 spontaneous abortions and 104 stillbirths. An adverse pregnancy outcome was independently associated with HIV infection (adjusted odds ratio [AOR] = 1.63; P = 0.015), urban enrollment (AOR = 0.39; P = 0.020), and nonhospital delivery (AOR = 13.63; P < 0.001) as well as with a CD4 count <200 cells/mL among HIV-infected women (AOR = 1.86; P = 0.127). Among 2529 singleton liveborn babies, birth weight was inversely associated with maternal HIV (AOR = 1.45; P = 0.02) and maternal middle upper arm circumference (AOR = 0.93; P < 0.001). Early infant mortality was not significantly associated with maternal HIV (hazard ratio [HR] = 1.18; P = 0.52) but was with urban sites (HR = 0.34; P = 0.045). Low birth weight substantially increased mortality (AOR = 8.3; P < 0.001). HIV status of infants by 8 weeks of age (14.6%, 95% confidence interval: 12.5% to 17.0%) was inversely associated with maternal CD4 cell count and birth weight. Conclusions:HIV-infected women are at a significantly increased risk of adverse pregnancy outcomes. Low-birth-weight infants of HIV-infected and uninfected women are at substantially increased risk of dying.

Neurodevelopment in Children Born to HIV-Infected Mothers by Infection and Treatment Status

BACKGROUND: We reviewed the impact of HIV, HIV exposure, and antiretroviral therapy/prophylaxis on neurodevelopmental outcomes of HIV-infected and HIV-exposed-uninfected infants and children. METHODS: A literature search of Medline, Embase, PsychINFO, Web of Science, PubMed, and conference Web sites (1990–March 2011) using the search terms, infant, child, HIV, neurodevelopment, cognition, language, and antiretroviral therapy, identified 31 studies of HIV/antiretroviral exposure using standardized tools to evaluate infant/child development as the main outcome. Articles were included if results were reported in children <16 years of age who were exposed to HIV and antiretrovirals in fetal/early life, and excluded if children did not acquire HIV from their mothers or were not exposed to antiretrovirals in fetal/early life. RESULTS: Infants who acquired HIV during fetal and early life tended to display poorer mean developmental scores than HIV-unexposed children. Mean motor and cognitive scores were consistently 1 to 2 SDs below the population mean. Mean scores improved if the infant received treatment before 12 weeks and/or a more complex antiretroviral regimen. Older HIV-infected children treated with highly active antiretroviral therapy demonstrated near normal global mean neurocognitive scores; subtle differences in language, memory, and behavior remained. HIV-exposed-uninfected children treated with antiretrovirals demonstrated subtle speech and language delay, although not universally. CONCLUSIONS: In comparison with resource-rich settings, HIV-infected and HIV-exposed-uninfected infants/children in resource-poor settings demonstrated greater neurodevelopmental delay compared with HIV-unexposed infants. The effects on neurodevelopment in older HIV-infected children commenced on antiretroviral therapy from an early age and HIV-exposed-uninfected children particularly in resource-poor settings remain unclear.

Intervention to promote exclusive breast-feeding for the first 6 months of life in a high HIV prevalence area

Objectives:We report on a nonrandomized intervention cohort study to increase exclusive breast-feeding rates for 6 months after delivery in HIV-positive and HIV-negative women in KwaZulu-Natal, South Africa. Methods:Lay counselors visited women to support exclusive breast-feeding: four times antenatally, four times in the first 2 weeks postpartum and then fortnightly to 6 months. Daily feeding practices were collected at weekly intervals by separate field workers. Cumulative exclusive breast-feeding rates from birth were assessed by Kaplan–Meier analysis and association with maternal and infant variables was quantified in a Cox regression analysis. Findings:One thousand, two hundred and nineteen infants of HIV-negative and 1217 infants of HIV-positive women were followed postnatally. Median duration of exclusive breast-feeding was 177 (R = 1–180; interquartile range: 150–180) and 175 days (R = 1–180; interquartile range: 137–180) in HIV-negative and HIV-positive women, respectively. Using 24-h recall, exclusive breast-feeding rates at 3 and 5 months were 83.1 and 76.5%, respectively, in HIV-negative women and 72.5 and 66.7%, respectively, in HIV-positive women. Using the most stringent cumulative data, 45% of HIV-negative and 40% of HIV-positive women adhered to exclusive breast-feeding for 6 months. Counseling visits were strongly associated with adherence to cumulative exclusive breast-feeding at 4 months, those who had received the scheduled number of visits were more than twice as likely to still be exclusively breast-feeding than those who had not (HIV-negative women: adjusted odds ratio: 2.07, 95% confidence interval: 1.56–2.74, P < 0.0001; HIV-positive women: adjusted odds ratio: 2.86, 95% CI 2.13–3.83, P < 0.0001). Conclusion:It is feasible to promote and sustain exclusive breast-feeding for 6 months in both HIV-positive and HIV-negative women, with home support from well trained lay counselors.

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.

Infant feeding counselling for HIV-infected and uninfected women: appropriateness of choice and practice

OBJECTIVE To examine infant feeding intentions of HIV-infected and uninfected women and the appropriateness of their choices according to their home resources; and to determine their adherence to their intentions in the first postnatal week. METHODS Feeding intentions of pregnant women were compared against four resources that facilitate replacement feeding: clean water, adequate fuel, access to a refrigerator and regular maternal income. First-week feeding practices were documented. FINDINGS The antenatal feeding intentions of 1253 HIV-infected women were: exclusive breastfeeding 73%; replacement feeding 9%; undecided 18%. Three percent had access to all four resources, of whom 23% chose replacement feeding. Of those choosing replacement feeding, 8% had access to all four resources. A clean water supply and regular maternal income were independently associated with intention to replacement feed (adjusted odds ratio (AOR) 1.94, 95% confidence interval (CI) 1.2-3.2; AOR 2.1, 95% CI: 1.2-3.5, respectively). Significantly more HIV-infected women intending to exclusively breastfeed, rather than replacement feed, adhered to their intention in week one (exclusive breastfeeding 78%; replacement feeding 42%; P<0.001). Of 1238 HIV-uninfected women, 82% intended to exclusively breastfeed; 2% to replacement feed; and 16% were undecided. Seventy-five percent who intended to exclusively breastfeed adhered to this intention postnatally, and only 11 infants (<1%) received no breast milk. The number of antenatal home visits significantly influenced adherence to feeding intention. CONCLUSION Most HIV-infected women did not have the resources for safe replacement feeding, instead choosing appropriately to exclusively breastfeed. Adherence to feeding intention among HIV-infected women was higher in those who chose to exclusively breastfeed than to replacement feed. With appropriate counselling and support, spillover of suboptimal feeding practices to HIV-negative women is minimal.

Infant feeding, HIV transmission and mortality at 18 months: the need for appropriate choices by mothers and prioritization within programmes

Objectives: To determine the late HIV transmission and survival risks associated with early infant feeding practices. Design: A nonrandomized intervention cohort. Methods: HIV-infected pregnant women were supported in their infant feeding choices. Infant feeding data were obtained weekly; blood samples from infants were taken monthly to diagnose HIV infection. Eighteen-month mortality and HIV transmission risk were assessed according to infant feeding practices at 6 months. Results: One thousand one hundred and ninety-three live-born infants were included. Overall 18-month probabilities of death (95% confidence interval) were 0.04 (0.03–0.06) and 0.53 (0.46–0.60) for HIV-uninfected and HIV-infected children, respectively. The eighteen-month probability of survival was not statistically significantly different for HIV-uninfected infants breastfed or replacement fed from birth. In univariate analysis of infant feeding practices, the probability of HIV-free survival beyond the first 6 months of life in children alive at 6 months was 0.98 (0.89–1.00) amongst infants replacement fed from birth, 0.96 (0.90–0.98; P = 0.25) and 0.91 (0.87–0.94; P = 0.03) in those breastfed for less or more than 6 months, respectively. In multivariable analyses, maternal unemployment and low antenatal CD4 cell count were independently associated with more than three-fold increased risk of infant HIV infection or death. Conclusion: Breastfeeding and replacement feeding of HIV-uninfected infants were associated with similar mortality rates at 18 months. However, these findings were amongst mothers and infants who received excellent support to first make, and then practice, appropriate infant feeding choices. For programmes to achieve similar results, the quality of counselling and identification of mothers with low CD4 cell count need to be the targets of improvement strategies.

The contribution of maternal HIV seroconversion during late pregnancy and breastfeeding to mother-to-child transmission of HIV

Background:The prevention of mother-to-child transmission (PMTCT) of HIV has been focused mainly on women who are HIV positive at their first antenatal visit, but there is uncertainty regarding the contribution to overall transmission from mothers who seroconvert after their first antenatal visit and before weaning. Method:A mathematical model was developed to simulate changes in mother-to-child transmission of HIV over time, in South Africa. The model allows for changes in infant feeding practices as infants age, temporal changes in the provision of antiretroviral prophylaxis and counseling on infant feeding, as well as temporal changes in maternal HIV prevalence and incidence. Results:The proportion of mother-to-child transmission (MTCT) from mothers who seroconverted after their first antenatal visit was 26% [95% confidence interval (CI): 22% to 30%] in 2008, or 15,000 of 57,000 infections. It is estimated that by 2014, total MTCT will reduce to 39,000 per annum, and transmission from mothers seroconverting after their first antenatal visit will reduce to 13,000 per annum, accounting for 34% (95% CI: 29% to 39%) of MTCT. If maternal HIV incidence during late pregnancy and breastfeeding were reduced by 50% after 2010, and HIV screening were repeated in late pregnancy and at 6-week immunization visits after 2010, the average annual number of MTCT cases over the 2010–2015 period would reduce by 28% (95% CI: 25% to 31%), from 39,000 to 28,000 per annum. Conclusion:Maternal seroconversion during late pregnancy and breastfeeding contributes significantly to the pediatric HIV burden and needs greater attention in the planning of prevention of MTCT programs.