Early initiation of antiretroviral therapy improves HIV survival rates, study says

The New York Times on Thursday examined a study that found asymptomatic HIV-positive people who delayed antiretroviral treatment until their disease reached an advanced stage faced higher mortality rates than those who initiated treatment earlier.

According to the Times, current national guidelines recommend starting HIV-positive people on antiretroviral treatment when CD4+ T cell counts fall below 350; however, the recent study suggests that initiating treatment earlier could reduce the risk of death. The study, as well as a related editorial, appeared online in the New England Journal of Medicine earlier this month and both will appear in the April 30 edition of the journal. In addition, a separate study published online earlier this month in the journal Lancet developed similar conclusions about the benefits of earlier antiretroviral therapy initiation, the Times reports.

For the NEJM study, researchers led by Mari Kitahata, director of clinical epidemiology at the Center for AIDS and Sexually Transmitted Infections at the University of Washington, tracked survival rates for 17,517 asymptomatic HIV-positive people in the U.S. and Canada who received care from 1996 to 2005 and who had never previously taken antiretroviral therapy. For their first analysis, the researchers examined a group of 8,362 patients, 2,084 of whom started therapy when CD4+ counts were between 351 and 500. They also examined 6,278 participants with similar CD4+ counts who delayed therapy until their counts declined below 350. According to the study, the patients who delayed treatment had a 69% higher risk of death compared with those who initiated treatment earlier. For the researchers' second analysis, they examined 9,155 HIV-positive people with CD4+ counts of more than 500. Of those, 2,220 started therapy within six months, while 6,935 delayed therapy. Among those who postponed treatment, 3,881 experienced a decline in CD4+ levels and 539 started antiretroviral treatment within six months of having a CD4+ count of 500 or less. In addition, the researchers found that those who deferred therapy had a 94% greater mortality risk than those who initiated treatment earlier.

According to Kitahata, the study examined "one of the most important questions in the last decade: what the optimal timing is for starting therapy." She added that the recent research "provides evidence that patients would live longer if antiretroviral treatment was begun when their CD4+ count was above 500." According to the Times, the study is "not the final word on the matter" (Rabin, New York Times, 4/30).

The study is available online.

Related Editorials

Two related editorials also appeared in the April 30 edition of NEJM. Summaries appear below.

• "When To Start Antiretroviral Therapy: Ready When You Are?:" Although the results of Kitahata's study are "striking," they "cannot be considered definitive evidence that everyone with HIV should start receiving antiretroviral therapy," Paul Sax and Lindsey Baden of the Division of Infectious Diseases at Brigham and Women's Hospital write. They continue that despite the researchers' "relatively large" sample size and use of "advanced statistical methods," their study was not a "randomized trial, and the patients who chose to begin therapy early might have differed in other important ways from those who chose to defer therapy -- ways that improved survival but were not measured." Sax and Baden add that "a conclusion would require data from a randomized, prospective clinical trial, and at least three such studies are either ongoing or planned." They conclude that despite the study's "limitations," evidence supporting the benefits of earlier antiretroviral therapy "continues to increase, making strategies to identify patients with HIV infection before the onset of substantial immunodeficiency all the more compelling" (Sax/Baden, New England Journal of Medicine, 4/30).
• "Rationing Antiretroviral Therapy in Africa: Treating Too Few, Too Late:" Although the international health community has achieved "striking advances" in increasing access to antiretroviral treatment in Africa, "too few people are receiving treatment" and health workers "are waiting until people are symptomatic" before administering antiretroviral therapy, Nathan Ford -- head of the medical unit of Medicines Sans Frontieres in Cape Town, South Africa, and research associate at the School of Public Health and Family Medicine at the University of Cape Town -- and colleagues write. They continue that although "delaying therapy may mean saving money on drugs," the "long-term cost of such delays is increased substantially by the need for more intensive clinical care, decreased income and likely regimen switches." In addition, later antiretroviral initiation "encourages the spread of tuberculosis" and could increase the risk of HIV transmission "by allowing patients to remain viremic longer," the authors write. They conclude, "The battle to start providing antiretroviral therapy in the developing world has been won. The battle to provide the best care we can is just beginning" (Ford et al., New England Journal of Medicine, 4/30).