HIV This Week

Kagaayi J, Gray RH, Brahmbhatt H, Kigozi G, Nalugoda F, Wabwire-Mangen F, Serwadda D, Sewankambo N, Ddungu V, Ssebagala D, Sekasanvu J, Kigozi G, Makumbi F, Kiwanuka N, Lutalo T, Reynolds SJ, Wawer MJ. Survival of Infants Born to HIV-Positive Mothers, by Feeding Modality, in Rakai, Uganda. PLoS ONE. 2008;3(12):e3877.

Data comparing survival of formula-fed to breast-fed infants in programmatic settings are limited. Kagaayi and colleagues compared mortality and HIV-free of breast and formula-fed infants born to HIV-positive mothers in a program in rural, Rakai District Uganda. 182 infants born to HIV-positive mothers were followed at one, six and twelve months postpartum. Mothers were given infant-feeding counselling and allowed to make informed choices as to whether to formula-feed or breast-feed. Eligible mothers and infants received antiretroviral therapy if indicated. Mothers and their newborns received prophylaxis for prevention of mother-to-child HIV transmission (pMTCT) if they were not receiving antiretroviral therapy. Infant HIV infection was detected by polymerase chain reaction (Roche Amplicor 1.5) during the follow-up visits. Kaplan-Meier time-to-event methods were used to compare mortality and HIV-free survival. The adjusted hazard ratio (Adjusted HR) of infant HIV-free survival was estimated by Cox regression. Seventy-five infants (41%) were formula-fed while 107 (59%) were breast-fed. Exclusive breast feeding was practiced by only 25% of breast-feeding women at one month postpartum. The cumulative 12-month probability of infant mortality was 18% (95% CI = 11%-29%) among the formula-fed compared to 3% (95% CI = 1%-9%) among the breast-fed infants (unadjusted hazard ratio (HR) = 6.1(95% CI = 1.7-21.4, P-value<0.01). There were no statistically significant differentials in HIV-free survival by feeding choice (86% in the formula-fed compared to 96% in breast-fed group (Adjusted HR = 2.8[95%CI = 0.67-11.7, P-value = 0.16]. Formula feeding was associated with a higher risk of infant mortality than breastfeeding in this rural population. The authors conclude that these findings suggest that formula feeding should be discouraged in similar African settings.

Editors’ note: This small study in which women self-selected to breastfeed found a striking six-fold increased infant mortality among infants that were fed breast milk substitutes. The excess mortality remained even when infants found to have HIV infection at one month of age were excluded from the analysis. Less than 4% of the households had access to tap water and most mothers did not follow guidelines for sterile preparation and storage of formula, cleansing of utensils, and avoidance of bottle feeds. Strategies for HIV-positive mothers such as prolonged infant prophylaxis or material antiretroviral treatment during lactation need closer consideration.

The KIDS-ART-LINC Collaboration. Low Risk of Death, but Substantial Program Attrition, in Pediatric HIV Treatment Cohorts in Sub-Saharan Africa. J Acquir Immune Defic Syndr. 2008 – see if published 2008;49(5) 521-31.

To date, an estimated 10% of children eligible for antiretroviral treatment receive it, and the frequency of retention in programmes is unknown. The authors evaluated the 2-year risks of death and loss to follow-up of children after antiretroviral treatment initiation in a multicenter study in sub-Saharan Africa. Pooled analysis of routine individual data from 16 participating clinics produced overall Kaplan-Meier estimates of the probabilities of death or loss to follow-up after antiretroviral treatment initiation. Risk factors analysis used Weibull regression, accounting for between-cohort heterogeneity. The median age of 2405 children at antiretroviral treatment initiation was 4.9 years (12%, younger than 12 months), 52% were male, 70% had severe immunodeficiency, and 59% started antiretroviral treatment with a nonnucleoside reverse transcriptase inhibitor. The 2-year risk of death after antiretroviral treatment initiation was 6.9% (95% confidence interval [CI]: 5.9 to 8.1), independently associated with baseline severe anaemia (adjusted hazard ratio [aHR]: 4.10 [CI: 2.36 to 7.13]), immunodeficiency (adjusted aHR: 2.95 [CI: 1.49 to 5.82]), and severe clinical status (adjusted aHR: 3.64 [CI: 1.95 to 6.81]); the 2-year risk of loss to follow-up was 10.3% (CI: 8.9 to 11.9), higher in children with severe clinical status. The authors conclude that, once on treatment, the 2-year risk of death is low but the loss to follow-up risk is substantial. Antiretroviral treatment is still mainly initiated at advanced disease stage in African children, reinforcing the need for early HIV diagnosis, early initiation of antiretroviral treatment, and procedures to increase programme retention.

Editors’ note: Although the 2-year risk of mortality after initiation of antiretroviral treatment was low, 75% of these deaths occurred in the first 6 months of treatment, with baseline HIV stage, nutritional status, and anaemia playing a role. The 10% programme attrition due to loss to follow-up constitutes a serious programme weakness that may reflect unreported death or moving; caregiver illness or death; inability to pay for transport, drugs, or laboratory tests; lack of follow-up procedures for no shows, or other causes. All programmes, whether adult or paediatric, should strive to minimize losses to follow-up by determining the causes and addressing them.