Rollins NC, Becquet R, Bland RM, Coutsoudis A, Coovadia HM, Newell ML. Infant feeding, HIV transmission and mortality at 18 months: the need for appropriate choices by mothers and prioritization within programmes. AIDS 2008;22:2349-2357.
To determine the impact of infant feeding practice on 18 months HIV transmission and HIV-free survival among HIV-exposed infants.
Semi-urban antenatal clinics in KwaZulu Natal, South Africa
Live-born infants born between late October 2001 and mid-April 2005 to mothers receiving antenatal care at study clinics.
HIV-free survival between 7 and 18 months of age according to feeding practices from birth until 6 months of age who were HIV uninfected at 6 weeks of age.
HIV-infected women were enrolled into the cohort if they delivered live born infants. All women received counseling regarding infant feeding options. Mothers of formula-fed infants were visited at home antenatally and instructed on safe preparation of formula. All mothers were visited at home by counselors 3-4 times the first two weeks post-partum and every two weeks until the infant was 6 months old. Formula-feeding mothers received additional support from the supervisors or nurses if the counselor indicated that the mother was having difficulty with feeding. Follow-up clinic visits were at 6 weeks, then monthly until 9 months and then every three months until aged 18 months. HIV RNA testing was done at every clinic visit. HIV status was measured at 5 months and used to guide feeding practices after 6 months of age. Records of feeding were obtained by independent field monitors and reflected daily feeds for the preceding week.
At 5 months, breastfeeding mothers were counseled to discontinue this if the infants were confirmed as uninfected while HIV-infected infants could continue to receive breast milk. Counselors instructed all mothers on supplemental feeding at 6 months. Single-dose nevirapine was given to women during labor and to infants at delivery and cotrimoxazole was given to infants. Free formula was provided for 6 months. CD4 counts were collected from mothers antenatally but these results were not used in the counseling of women on infant feeding choices. Women were weighed at each clinic visit, checked for symptoms and referred for additional care if needed. HAART was not available during the study period.
Cumulative HIV-free survival was assessed using the Kaplan-Meier product limit method and the Cox proportional hazards model was used to identify associations between maternal and infant characteristics and survival. Variables included in the proportional hazards model included multiple birth outcome, the child's sex, maternal education, water access, low birth weight (<2.5kg), maternal unemployment, and maternal ante-natal CD4 count. Variables with p values under 0.20 were retained in the model.
Feeding categories were determined using an algorithm that first classified infant's feeding practices on each day of life and then determined the cumulative pattern from birth. The WHO definitions of exclusive breastfeeding, mixed breastfeeding and replacement feeding were used.
The 18-month HIV-free survival was measured first according to the infant feeding practice implemented at birth and second, on cumulative feeding recall histories. Any provision of fluid or food other than breast milk resulted in the infant being reclassified as receiving mixed feedings. Infants without feeding or test information were excluded from analysis and for those with missing data , information was censored at the last infant visit.
A total of 1,193 live-births were included. By 18 months, 147 children had died and 237 were HIV-infected. Of the deaths, 133 (77%) were among the HIV-infected children. The overall 18-month probability of death was 0.04 (95% confidence interval [CI] 0.03-0.06) for HIV-uninfected children and 0.53 (95% CI, 0.46-0.60) for HIV-infected children. Risk for death was 17 times greater among the HIV-infected children (unadjusted hazards ratio 16.9, 95% CI 11.5-24.8). By 18 months, 21% of infants acquired HIV-infection (range 19-23%). The overall probability of HIV-free survival at 18 months was 0.76, (95% CI 0.73-0.78). The overall risk estimate for HIV transmission at 18 months for breastfeeding was 9.1 cases per 100 child-years of breastfeeding (95% CI, 5.8, 12.5). The adjusted hazards ratio of HIV infection /death was 1.5 (95% CI 1.1-2.2) for low birth weight children, 1.9 (95% CI 1.3-2.9) for children whose mothers were unemployed, and 2.4 (95% CI 1.7-3.2) for children born to mothers with antenatal CD4 counts <200 cells/mm3.
Feeding practices at birth for the infants included 937 (78%) who were exclusively breastfed, 75 (71.4%) received breast milk and other liquids or solids, and 30 (28.6) received both breast milk and formula, and 118 (10%) only received formula. The other children were excluded. The probability of remaining HIV-uninfected at 18 months according to infant feeding practices implemented at birth was 0.75, (95% CI 0.72-0.78) among exclusively breastfed children, was 0.79 (95% CI 0.70-0.86) among mixed feeding infants, and among those given formula only was 0.80 (95% CI 0.72-0.87). The probability of survival at 18 months according to feeding practices at birth was 0.86 ((95% CI 0.830-88) for exclusively breastfed infants, was 0.87 (95% CI 0.78-0.93) for the mixed fed infants, and 0.87 (95% CI 0.78-0.92) for those on replacement feedings.
Among the 893 children alive at 6 months and not HIV-infected peripartum, 69 (8%) were never breastfed, 136 (15%) were breastfed for less than 6 months, and 688 (76%) were breastfed over 6 months. Of those breastfed beyond 6 months, 278 (31%) were exclusively breastfed for the first 6 months of life, 42 (5%) received other liquids, and 368 (40%) received other foods and liquids including non human milk. The probability of breastfeeding declined from 0.74 (95% CI 0.71-0.78) at 7 months to 0.22 (95% CI) 0.19-0.25) at 18 months. Independent predictors of an increased risk of HIV infection or death among infants between 7 and 18 months were breastfeeding beyond 6 months (adjusted relative hazards [ARH] 2.7, 95% CI 1.2-6.0), having an unemployed mother (ARH 3.4, 95% CI 1.1-11.0), and a mother with CD4 count , 200 cells/mm3 (ARH 3.6, 95% CI2.0-6.4).
The probability of HIV-free survival at 18 months (for infants alive at 6 months) was 0.98 (95% CI 0.89-1.00 in those receiving replacement feeds, 0.96 (95% CI 0.90-0.98) in infants who received any breast milk up to 6 months of age, and 0.91 (95% CI 0.87-0.94) among infants breastfed for more than 6 months. Compared to children who received replacement feeds or breastfed for less than 6 month, children who were breastfed for more than 6 months had a lower probability of HIV-free survival (0.91, 95% CI 0.88-0.93) compared to 0.96 (95% CI 0.93-0.98; p=0.001). Breastfeeding beyond 6 months increased the risk of HIV-infection (ARH 3.3, 95% CI 1.0-10.5) when compared to breastfeeding for less than 6 months. If the infants HIV status is included in the model, the probability of survival beyond 6 months did not differ by breastfeeding duration, when compared to replacement feeding (p=0.86).
Breastfeeding and replacement feeding resulted in similar survival at 18 months. This finding may reflect the additional support mothers in this study were provided with.
This study was of fair quality. It is an intervention (support for feeding practice) but was not randomized. If evaluated as an observational study the quality is somewhat better. The outcome was not present (or detectable) at the start of the study and ascertainment was accurate although HIV testing was not performed on all infants and many infants were lost to follow-up. Although information on ascertainment of exposure was provided, it did not appear that there was any validation or quality assurance conducted. Despite these weaknesses, the topic is extremely important and additional studies, particularly randomized trials to examine survival and HIV transmission beyond 6 months, will be very important.
Decisions regarding feeding practices for HIV-exposed infants poses a dilemma for women in developing countries. Although exclusive breastfeeding has been shown to have a lower risk of HIV transmission in the first 6 months of life(1) it is infrequently practiced or supported.(2, 3) HIV transmission does not occur in infants fed with formula but increases the risk of death because of improper preparation(4, 5) Information on feeding patterns beyond the first 6 months of life and their impact on HIV transmission and death have not been adequately studied and therefore, well researched recommendations are not available.
Although replacement and breastfeeding resulted in similar survival, HIV transmission occurred more frequently in the breastfed infants. This study was conducted prior to ongoing treatment with antiretroviral of HIV-infected mothers during pregnancy. With increasing availability of HAART for women throughout their pregnancy risk of HIV transmission with breastfeeding may decline. Providing support to women, regardless of their infant feeding practice is an important service. This is evident from a prior study in which infants who were provided with replacement feeds under circumstances that were not ideal had the highest HIV transmission or death rate.(3)
- Coovadia HM, Rollins NC, Bland RM, Little K, Coutsoudis A, Bennish ML, et al. Mother-to-child transmission of HIV-1 infection during exclusive breastfeeding in the first 6 months of life: an intervention cohort study. Lancet 2007; 369:1107-1116.
- Chopra M, Rollins N. Infant feeding in the time of HIV: Assessment of infant feeding policy and programmes in four African countries scaling up prevention of mother to child transmission programmes. Arch Dis Child 2008; 93:288-291.
- Doherty T, Chopra M, Jackson D, Goga A, Colvin M, Persson LA. Effectiveness of the WHO/UNICEF guidelines on infant feeding for HIV-positive women: results from a prospective cohort study in South Africa. AIDS 2007; 21:1791-1797.
- Mbori-Ngacha D, Nduati R, John G, Reilly M, Richardson B, Mwatha A, et al. Morbidity and mortality in breastfed and formula-fed infants of HIV-1-infected women: A randomized clinical trial. JAMA 2001; 286:2413-2420.
- Thior I, Lockman S, Smeaton LM, Shapiro RL, Wester C, Heymann SJ, et al. Breastfeeding plus infant zidovudine prophylaxis for 6 months vs formula feeding plus infant zidovudine for 1 month to reduce mother-to-child HIV transmission in Botswana: a randomized trial - the Mashi Study. JAMA 2006;296:794-805.