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Abstract & Commentary
By Stan Deresinski, MD, FACP, FIDSA, Clinical Professor of Medicine, Stanford, Associate Chief of Infectious Diseases, Santa Clara Valley Medical Center, is Editor for Infectious Disease Alert.
Synopsis: Early initiation of antiretroviral therapy is associated with increased AIDS-free survival.
Source: The HIV-CAUSAL Collaboration. When to initiate combined antiretroviral therapy to reduce mortality and AIDS-defining illness in HIV-infected persons in developed countries: An observational study. Ann Intern Med 2011;154:509-515.
In a prospective observational study, investigators of the HIV-CAUSAL Collaboration evaluated data from participating HIV clinics in Europe and the U.S. Veterans Administration system to determine the optimal CD4+ T cell count at which combination antiretroviral therapy (cART) should be initiated. The analyzed population consisted of 8,392 patients among 20,971 with baseline CD4+ T cell counts ≥ 500/mm3 whose counts decreased into the range of 200-499/mm3. cART was initiated based on the judgment of treating physicians.
A complex analysis led to an estimate that, compared to initiating cART when the CD4+ T cell count first decreased below 500/mm3, delaying initiation until the CD4+ T cell count decreased below 350/mm3 would result in a 38% increase in the incidence of AIDS-defining illness or death. The prevention of one new instance of reaching these endpoint would require the treatment of 48 patients at the higher CD4 count. No reduction in death itself was identified.
Previous non-randomized cohort analyses have yielded conflicting results in examining similar data sets, leading to a degree of confusion. At the same time, the efficacy, simplicity, and toxicity of antiretroviral therapy have continually evolved over time. As described in an accompanying editorial,1 HIV clinicians attempting to follow national guidelines have experienced a roller coaster ride in their decisions regarding the time at which to initiate cART. The U.S. Department of Health and Human Services recommended its initiation at any CD4+ T cell count < 500/mm3 in 1998, subsequently changed the threshold to 200-350/ mm3, and in 2011 changed course once again. At that time, they recommended that cART be routinely initiated at CD4+ T cell count < 500/mm3 and that its initiation be considered at higher counts.
The investigators and others recommend that the issue be settled via randomized clinical trials. I disagree. I personally believe the issue is settled, and the results could be anticipated from a priori considerations. The ease of use, efficacy, and lack of toxicity of current cART regimens, together with considerations of the public health benefit of reducing the "community HIV load," as well as a vague notion that it cannot be good for an individual to be exposed to unrestricted viral replication, suggest to me that therapy should be offered to all infected individuals. While resource considerations are necessary, they should have little or no role in an economically advanced society. Forget huge expensive clinical trials to deal further with this issue move on and spend the money and effort more wisely.