People who begin antiretroviral (ARV) therapy before their CD4 counts fall to 200 or less have a 75 percent reduction in the risk of death compared with people who wait to start treatment until their CD4 count is below 200. These data, from a Haitian study, were published July 15 in The New England Journal of Medicine.

HIV treatment guidelines for resource-poor countries have usually taken quite a while to catch up to those adopted in the United States and other developed countries. This is because resources are so scarce in the developing world and significant survival benefits must be demonstrated to justify the additional expense of expanded treatment programs.

In 2009, the World Health Organization (WHO) changed its HIV treatment guidelines for resource-poor nations. Whereas older guidelines recommended initiating ARV therapy when CD4 counts fell to 200 or less, the new guidelines now recommend starting ARV therapy earlier, when a person's CD4 count falls to 350. This change was largely based on the results of the Strategies for Management of Anti-Retroviral Therapy (SMART) study, which found that delaying or discontinuing ARVs until CD4 counts fell to 200 resulted in increased AIDS- and non-AIDS-related deaths.

There have been no randomized controlled studies until now, however, to document the degree of benefit from starting treatment earlier. As a result of this, some resource-poor countries have been slow to adopt the new WHO guidelines.

To determine the survival benefit from earlier treatment, Patrice Severe, MD, from Groupe Haitien d'Etude du Sarcome de Kaposi et des Infections Opportunistes (GHESKIO), in Port au Prince, Haiti, and his colleagues enrolled 816 HIV-positive Haitians between 2005 and 2008. In 408 of the participants, ARV therapy was deferred until their CD4 count dropped to 200 or below, or until they developed an AIDS-defining condition. In the second group of 408, ARVs were initiated within two weeks of study recruitment.

Both groups were nearly identical in terms of CD4 count (the average in both groups was about 280) and other characteristics. The study was originally planned to run for a number of years, and statisticians estimated that a difference in the treatment strategies would only become detectable after about 65 people had died.

The study was stopped early, after only 29 deaths had been recorded, because survival rates were so much better in people who started treatment earlier. After the study was terminated, and all the data were compiled, Severe and his colleagues found 23 deaths among those who waited to start ARVs until their CD4s dropped to 200 or below, compared with only six deaths in those who started treatment immediately. This amounted to a four-fold increase in the risk of death in those who waited to start treatment. Moreover, new cases of tuberculosis—which is a significant cause of death among people with HIV in Haiti—were twice as high among those who deferred treatment, compared with those who started early.

“Early antiretroviral therapy decreased the rate of death by 75 percent in HIV-infected adults who had a CD4 T-cell count that was greater than 200 and less than 350,” the authors conclude. “Access to antiretroviral therapy should be expanded to all HIV-infected adults who have a CD4 T-cell count of less than 350 per cubic millimeter, including those who live in locations with limited resources.”