amfAR, The Foundation for AIDS Research

When to Start?: Part 2–More Details Emerge on Question of When to Initiate ART


July 2009–The question of when it is best to start antiretroviral therapy (ART) has important consequences for the long-term health and survival of people with HIV/AIDS. In recent months, when to start has become the focus of much research, including a study described in the March 2009 TREAT Asia Report showing that those who waited until their CD4 counts were below 350 cells/mL3  had a 69 percent greater risk of dying than those who started with counts between 351 and 500 cells/mL3.1 Since then, several new studies have reinforced the idea that starting ART earlier at CD4 counts of at least 350 cells/mL3 leads to better treatment outcomes.

Masked patient
A patient at an HIV clinic in Cambodia (wearing a mask because of a cough) discusses treatment with a healthcare worker. (Photo: Karl Grobl) 


One of the new studies compared 45,000 patients in North America and Europe in whom HIV had not progressed to AIDS. Results showed that those who started ART at lower CD4 counts (251–350 cells/mL3) had a 28 percent greater risk of developing AIDS or dying than those who started treatment at higher CD4 counts (351–450 cells/mL3).2 This risk was not as high as that reported on in our March issue, but it emphasizes that waiting too long to start ART leads to higher rates of disease progression and death, even in resource-rich countries.

In many parts of the world, people are often not diagnosed with HIV until they experience an AIDS-related illness or opportunistic infection (OI) such as severe pneumonia. The appearance of these OIs often means that a person has a low CD4 count (for example, less than 200 cells/mL3). A study of patients in the U.S., Puerto Rico, and South Africa looked at the impact of starting ART as soon as an OI was diagnosed (not including tuberculosis) compared to waiting until finishing treatment for the infection.

When patients started this study, their CD4 counts were very low, with 70 percent having fewer than 50 cells/mL3. By the end, 14 percent who started ART right away had disease progression to AIDS or died, compared to 24 percent of those who started ART after finishing OI treatment. This translated to an almost 50 percent greater chance of disease progression or death in the group that was treated later.3 

The larger picture presented by these studies suggests that a greater emphasis on early HIV testing and CD4 monitoring, which could help bring patients to clinical care before their CD4 levels fall, would allow them to receive a greater benefit from ART. But most national programs in Asia still do not provide free ART before CD4 reaches 250 cells/mL3. Stronger advocacy could encourage international ART programs to review and accept these research results.

1 Kitahata MM, Gange SJ, Abraham AG, Merriman B, Saag M, et al. Effect of early versus deferred antiretroviral therapy for HIV on survival. New England Journal of Medicine. 30 April 2009; 360(18):1897–1899.

2 When To Start Consortium. Timing of initiation of antiretroviral therapy in AIDS-free HIV-1-infected patients: A collaborative analysis of 18 cohort studies. Lancet. 18 April 2009; 373(9672):1352–1363.

3 Zolopa AR, Anderson J, Komarow L, Sanne I, Sanchez A, et al. Early antiretroviral therapy reduces AIDS progression/death in individuals with acute opportunistic infections: a multicenter randomized strategy trial. Plos ONE. May 2009; Volume 4 (Issue 5): e5575.