Randomized Trial in Haiti Shows Benefits of Early Antiretroviral Therapy

SUMMARY: An analysis of HIV positive people starting antiretroviral therapy (ART) in Haiti has produced some of the first evidence from a randomized clinical trial showing that early treatment is beneficial. As reported in the July 15, 2010 issue of New England Journal of Medicine, ART initiation when CD4 cell count fell below 350 cels/mm3 reduced the risk of death and incident tuberculosis (TB). These findings support updated World Health Organization (WHO) guidelines recommending ART initiation at a CD4 count threshold of 350 cells/mm3 for people in resource-limited settings.


Patrice Severe from GHESKIO (Groupe Haitien d'Etude du Sarcome de Kaposi et des Infections Opportunistes) and colleagues conducted a randomized, open-label trial of early initiation of ART in Haiti.

As background, they noted that the optimal timing of treatment for people with CD4 counts in the 200-350 cells/mm3 range in low-resource areas had not been determined. WHO previously recommended ART initiation at 200 cells/mm3 for people in resource-limited areas, but in late 2009 the organization raised this threshold to 350 cells/mm3 -- more in keeping with recommendations for wealthier areas.

This randomized, open-label trial included 816 adult HIV positive participants in Port au Prince enrolled between 2005 and 2008. At baseline, they had a confirmed CD4 T-cell count greater than 200 but less than 350 cells/mm3 and no history of AIDS-defining illnesses.

Baseline characteristics were similar between the 2 groups. A majority (58%) were women and the median age was 40 years. The average CD4 count at the time of enrollment was 281 cells/mm3. Patients who had previously used antiretroviral drugs were excluded.

The researchers compared outcomes in patients with early ART initiation versus standard timing of treatment according to the WHO guidelines in effect at the time. The 408 participants randomly assigned to the early-treatmet group started therapy within 2 weeks after enrollment, while the remainder in the standard-treatment group started when their CD4 count first fell below 200 cells/mm3 or they developed clinical AIDS. All participants received a regimen of zidovudine (AZT, Retrovir), lamivudine (3TC, Epivir), and efavirenz (Sustiva), with limited substitutions permitted if drug toxicities emerged.

Participants in both groups underwent monthly monitoring. All patients received opportunistic infection prophylaxis using trimethoprim-sulfamethoxazole (Bactrim, Septra), and those with a positive TB test also took isoniazid prophylaxis. In addition, everyone received nutritional support. Follow-up continued for a median of 20 months. The primary study end-point was survival.