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Despite the success of antiretroviral prophylaxis in preventing mother-to-child HIV transmission, many infants still die from HIV-related causes in countries where seroprevalence of the virus is high. Now, with partial support from industry, investigators have conducted a phase III, randomized, open-label trial at two centers in South Africa to determine whether initiating antiretroviral therapy (ART) soon after birth might slow disease progression and reduce early mortality in infants with in utero or intrapartum HIV infection.
A total of 377 HIV-infected 6- to 12-week-old infants were enrolled; all had CD4-cell percentages ≥25%. They were randomly assigned to one of three treatment strategies: early ART (generally lopinavir/ritonavir, zidovudine, and lamivudine; initiated immediately) for either 40 weeks or 96 weeks, or deferred therapy (initiation determined by CD4-cell percentage or clinical criteria). After randomization, the infants were seen every 4 weeks until week 24, then every 8 weeks until week 48, and then every 12 weeks.
Disease progression to CDC stage C or severe stage B occurred in only 6.3% of infants in the early-therapy groups (combined), compared with 25.6% of those in the delayed-therapy group (hazard ratio, 0.25; 95% confidence interval, 0.15–0.41). Mortality was also markedly lower in the early-therapy groups than in the delayed-therapy group (4.0% vs. 16.0%; HR, 0.24; 95% CI, 0.11–0.51).
Violari A et al. Early antiretroviral therapy and mortality among HIV-infected infants. N Engl J Med 2008 Nov 20; 359:2233.
Comment
Differences in disease progression and in mortality between the combined early-therapy groups and the delayed-therapy group were striking and prompted intervention by the data and safety monitoring board, even though accrual had been completed by the time these differences were demonstrated. Consequently, the deferred-therapy group was modified; infants in this group were all evaluated for possible initiation of ART.
Early diagnosis in HIV-exposed infants and prompt ART initiation (regardless of CD4-cell percentage or count), as recommended in the latest U.S. Department of Health and Human Services guidelines, should be adopted.