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Initiating Anti-HIV Therapy at High CD4 Count Increases AIDS-Free Survival

April 28, 2011

Starting combination antiretroviral therapy (ART) at the threshold of 500 CD4 cells/microliter, rather than at 350 or lower, significantly reduces HIV patients' risk of progressing to AIDS, a new study shows.

US recommendations indicate treatment at the 500-cell point for asymptomatic HIV patients, while European and World Health Organization guidelines call for treatment at the 350-cell level. The authors of the current study -- Dr. Lauren E. Cain, with the Harvard School of Public Health, and colleagues -- said information from randomized trials is inadequate to decide between the two approaches, and two large observational studies have yielded conflicting results.

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Cain and associates pooled observational data from a collaboration comprising 12 prospective cohort studies from five European nations and the United States. The researchers examined all-cause mortality and a combined endpoint of AIDS-defining illness or death in a cohort of 20,971 HIV-positive, treatment-naïve patients with no previous AIDS-defining illnesses, with follow-up starting the first time the CD4 cell count fell below 500.

Compared with starting ART at the threshold of 500 CD4 cells/microliter, the hazard ratios of AIDS-defining illness or death were 1.38 at the 350-cell level and 1.90 at 200 CD4 cells. Also compared to initiating therapy at the 500-cell threshold, the overall mortality hazard ratio was 1.01 at 350 cells and 1.20 at 200 cells.

The results demonstrate the advantages of early testing as well as early treatment, the authors wrote.

In an accompanying editorial, Drs. Jason V. Baker and Keith Henry, of the University of Minnesota School of Medicine, highlighted another benefit of early treatment. Because the lower viral load resulting from treatment is associated with less risk of transmission, "Expanded use of combined ART could substantially curtail the future HIV epidemic," they wrote.

The study, "When to Initiate Combined Antiretroviral Therapy to Reduce Mortality and AIDS-Defining Illness in HIV-Infected Persons in Developed Countries: An Observational Study," and the editorial, "If We Can't Get What We Want, Can We Get What We Need? Optimizing Use of Antiretroviral Therapy in the Current Era," were published in the Annals of Internal Medicine (2011;154(8):509-515 and 563-565, respectively).

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Reader Comments:

Comment by: Dr. Elizabeth Mwanukuzi (Harare Zimbabwe) Sat., Jun. 4, 2011 at 7:10 am EDT
Whereas there is no doubt about the effectiveness of starting HAART as early as possible, Africa south of the Sahara, is in a serious dilemma. The heavy burden of HIVAIDS is challenged by financial constraints,problems with staffing, infrastructure and political and social difficulties. Even with the current strategy of treatment at CD4 of 200 cells, not all patients can be reached, stock outs sometimes occur and there are numerous other problems. Paradoxically,over the last several years, funding has increased steeply in many countries in Africa and drugs have became more widely available but the epidemic has at best remained stable and at worst it has increased slightly. This leads me to believe that it is not just a matter of increasing funding, condom circumcision and providing drugs at an earlier time in the calendar of disease progression, the situation is much more complex. Even the much advocated test and treat all would prove difficult to implement for the same reasons. Africa, and perhaps the world at large needs to examine the priorities and strategies again because even in the developed world, with money and drugs galore the disease has persisted. My personal view is that we need to put more responsibility on the individual rather than just providing more money, condoms and drugs. This strategy is not working! We need to take up the advice by Hugh Henry of the Linacre Center that 'Promoting self esteem may be more effective than assuming that people must have sex and can only make it safer"
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