Palombi L, Marazzi MC, Voetberg A, Magid NA. Treatment acceleration program and the experience of the DREAM program in prevention of mother-to-child transmission of HIV. AIDS 2007 Jul;21 Suppl 4:S65-71.
To compare the safety and efficacy of formula feeding of infants in the first six months of age in preventing late postnatal transmission of HIV against the safety and efficacy of exclusive breastfeeding by HIV-infected mothers continuing highly active antiretroviral therapy (HAART) for six months postnatally.
A comparative analysis of two prospective observational cohorts in the Drug Resource Enhancement against AIDS and Malnutrition (DREAM) program. A description of the DREAM program structure and laboratory diagnostic methods has been reported previously.(1,2) Briefly, it is a nationwide health program that encourages cooperation between faith-based and local non-governmental organizations and provides a free package of care, consisting of education and social support; voluntary counseling and testing; HAART (since February 2002); treatment of opportunistic infections, sexually transmitted infections, and malaria; nutrition evaluation and supplementation; laboratory diagnostics, including viral load and CD4 count; mother and child HIV prevention and care; home care; information technology and data management; and operational research. DREAM is financed by the Regional HIV/AIDS Treatment Acceleration Program of the World Bank. It monitors and provides assistance to more than 15,000 HIV-infected people in Mozambique, of whom more than 50% are receiving HAART. The first cohort enrolled HIV-1-positive pregnant women between January 2004 and December 2006 in Mozambique, Tanzania, and Malawi, while the second cohort enrolled HIV-1-positive pregnant women and their infants between August 2005 and July 2006 in Mozambique.
Mozambique, Tanzania and Malawi.
HIV-1-positive pregnant women and their infants. The first cohort consisted of 914 women who delivered 879 live-born infants. Women who were approached and refused participation in the program comprised about 14% of the original cohort, and an additional 4% withdrew during pregnancy. Of the 879 infants, 40 were excluded because maternal HAART was delivered for less than one month during pregnancy. An additional 30 infants (3.4%) died during the observation period and were excluded from analysis because a definitive diagnosis was not available. Thus, 809 infants were evaluated at one and six months. In the second cohort, 341 infants were delivered and evaluated at one month. Patient refusal to participate was 11.1% of the approached patients, and an additional 2.5% withdrew from the program during pregnancy. Follow-up is still underway in this cohort; 251 of the 341 infants with data available at one month have completed six months of follow-up. Additionally, 7/341 infants (2.1%) died between the two periods and 21 (6.2%) have been lost to follow-up, including two who tested HIV-positive in the first month of life.
All of the women received HAART free of charge from the 25th week of gestation, irrespective of clinical stage, CD4 count, and viral load, and their infants received post-exposure prophylaxis. The women received water filters and formula for the first six months of lactation. Women in the first cohort were not given HAART after delivery. Women in the second cohort were given HAART for up to six months after delivery and were given the option to exclusively breastfeed. The authors conducted a comparative analysis of the two cohorts of HIV-positive pregnant women followed prospectively and evaluated HIV-1 mother-to-child transmission rates, infant morbidity, and mortality in both cohorts.
Mother-to-child HIV transmission (MTCT) rates at one and six months were compared in the two cohorts. In addition, mortality and measures of infant morbidity, such as anemia and malnutrition, were assessed.
At age one month, HIV-1 MTCT rates were 4/341 (1.2%) among breastfed infants and 7/809 (0.8%) among formula-fed infants. At age six months, HIV-1 MTCT rates were 2/251 (0.8%) among breastfed infants of women receiving HAART and 15/809 (1.8%) among formula-fed infants (χ2=0.77, p=0.38). The cumulative incidence rate at six months of age was 2.7% for the formula-fed infants and 2.2% for breastfed infants (χ2=0.27, p=0.60). There was a trend towards HIV-1 infection rates being slightly higher among formula-fed infants, though overall MTCT rates in both cohorts were extremely low. Assuming a 25% overall rate of MTCT, the reduction in risk of HIV acquisition in formula-fed infants was 96.4% at one month of age. Assuming a late postnatal transmission of 15%, the reduction in risk of acquiring HIV was 88% at six months of age. In the breastfed cohort, using the same assumptions, the reduction in risk of acquiring HIV was 95.2% at one month and 94.7% at six months of age. Z scores ≤2.0 for weight by age occurred in 92/809 formula-fed infants (11.4%) and in 28/251 breastfed infants (11.1%). Observed Z scores were greater than among the general infant population in the community (rates not given). Rates of anemia in the study infant populations were lower than that of the general population. A hemoglobin value <8g/dl was found in 40/809 formula-fed infants (4.9%) and 17/251 breastfed infants (6.8%) (X2=0.92, p=0.33). The mortality rate at six months of age was 27 per 1,000 person-years among formula-fed infants and 28.5 per 1,000 person-years among breastfed infants. The observed infant mortality rate in Mozambique is 101 per 1,000 person-years.
The authors concluded that the DREAM HIV-1 PMTCT protocol was safe and efficacious in reducing HIV transmission in infants at one and six months of age, with results comparable to those from developed countries. The authors further concluded that breastfeeding among HIV-1 infected mothers receiving HAART posed no additional risk of late postnatal HIV-1 transmission to the infant by six months of age.
This study was of adequate quality. Rates of refusal and withdrawal were similar between the two cohorts. Adherence to HAART, viral suppression rates, and duration of therapy were not reported, although the low transmission rates suggest they were good. Because the cohorts were recruited from different areas and enrolled at different time periods, differences in transmission rates could be unrelated to the interventions. Additionally, not all data have been recorded for the second cohort, and the final results may differ. Finally, although subject to inaccuracy, reports of exclusive breastfeeding in the second cohort would have been useful for data interpretation.
Overall reduction of HIV-1 transmission observed in this study are comparable to those observed in developed countries.(3)
The findings of this study indicate that the provision off HAART to mothers during the first six months of breastfeeding is feasible and highly successful in reducing late postnatal mother-to-child transmission of HIV. Generalizability of the results of this study may be limited given the extensive support provided through the DREAM program. Each PMTCT program must consider the availability and sustainability of resources in deciding which infant-feeding options can be supported.
- Marazzi MC, Guidotti G, Liotta G, Palombi L. DREAM: an integrated faith-based initiative to treat HIV/AIDS in Mozambique, case study. Perspectives and practice in antiretroviral treatment. Community of Sant' Egido and Geneva: World Health Organization; 2005.
- Marazzi MC, Germano P, Liotta G, Guidotti G, Loureiro S, da Cruz Gomes A, et al. Safety of nevirapine-containing antiretroviral triple therapy regimens to prevent vertical transmission in an African cohort of HIV-1-infected pregnant women. HIV Med 2006 Jul;7(5):338-44.
- The PETRA Study Team. Efficacy of three short-course regimens of zidovudine and lamivudine in preventing early and late transmission of HIV-1 from mother to child in Tanzania, South Africa, and Uganda (PETRA Study): a randomized double-blind, placebo-controlled trial. Lancet 2002 Apr 6;359(9313):1178-86.