ArticlesEarly time-limited antiretroviral therapy versus deferred therapy in South African infants infected with HIV: results from the children with HIV early antiretroviral (CHER) randomised trial
Introduction
HIV infection causes high mortality and rapid disease progression in infants.1, 2 If untreated, more than a third of infected infants die during infancy and about half by 2 years of age.3, 4 Although early antiretroviral therapy (ART) is life-saving, treatment duration is lifelong. ART options are scarce in resource-poor settings, and even fewer are available for infants because of formulation and pharmacokinetic limitations and the risk of resistance after exposure to drugs used to prevent mother-to-child transmission.5 The cumulative effects of treatment in the growing child are worrying, with long-term pharmacovigilance data unavailable. Therefore, we postulated that compared with deferred ART, a strategy of early time-limited ART initiated close to primary infection would prevent disease progression and safely allow a subsequent period off ART, thus preserving future treatment options.
In 2007, when the median follow-up time of the CHER trial was 40 weeks (IQR 24–58), interim data showed that early ART reduced the risk of death by 75% compared with deferred ART,2 and subsequently became the standard of care.6, 7, 8 Here, we report the 5-year results of the completed CHER trial.
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Study design and participants
Infants aged 6–12 weeks with confirmed HIV infection test results and a percentage of CD4-positive T lymphocytes (CD4%) of 25% or higher were eligible for inclusion in the study. No previous ART was allowed, apart from treatment for prevention of mother-to-child transmission. Exclusion criteria included birthweight less than 2 kg, grade 3 or 4 laboratory abnormalities (transaminases, neutrophil count, haemoglobin, electrolytes, and creatinine), clinically significant medical events, and
Results
Of 591 HIV-infected infants screened, 411 had CD4% of 25% or higher; of these infants, 377 were enrolled in the study and randomly allocated to ART-Def (n=125), ART-40W (126), or ART-96W (126) between July, 2005, and February, 2007. An additional 34 infants were randomly allocated to ART-40W (17) or ART-96W (17) between September, 2007, and March, 2008, after the Data Safety Monitoring Board recommended that recruitment to ART-Def should be stopped in June, 2007 (figure 1 and appendix).
The
Discussion
The results of the completed CHER trial show that early time-limited ART in young infants is better than deferred ART over an extended period. During planned interruption after primary therapy, the rapid disease course noted with deferred ART2 was not recorded, perhaps because the children given early time-limited ART were older when ART was discontinued than were those who had not started ART in the ART-Def group. Another explanation is that initiation of ART shortly after infection limits
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