Highly active antiretroviral therapy (HAART) has been shown to delay progression of AIDS and reduce mortality, yet the optimal time to start it is unknown.
Current federal and other guidelines suggest initiating therapy when counts are between 200/ìL (200 per microliter) and 350/ìL. Those levels may be too low, however, and therapy begun too late for optimal results, according to a study of injection drug users in the September 15 issue of The Journal of Infectious Diseases, now available online.
The authors, Cun-lin Wang and coworkers at Johns Hopkins University and The New York Academy of Medicine, studied both HIV-positive and HIV-negative injection drug users in order to compare data in persons with the same mortality risk category. The expectation was that such a comparison would provide a more accurate picture than heretofore reported of the degree to which the survival rate associated with HAART may be improved to approximate that of an uninfected population.
A total of 1,503 subjects were followed from 1997 to 2000; 920 were HIV-negative throughout the study period, 556 were HIV-infected at the outset, and 27 became HIV-infected during the study. The investigators stratified subjects according to HIV status, HAART use, and CD4 cell level at HAART initiation. Analysis of survival accounted for all-cause mortality, AIDS-related mortality, and non-AIDS-related mortality and was adjusted for factors associated with HAART access, such as active drug use or enrollment in a drug treatment program.
The results: Mortality among HIV-infected injection drug users with CD4 cell counts greater than 350/ìL who received HAART (24.1/1,000 person-years) was similar to that of HIV-seronegative injection drug users (19.9/1,000). Furthermore, both groups had lower mortality than HIV-infected subjects with CD4 cell counts greater than 350/ìL who did not receive HAART (43/1,000) and those with CD4 counts between 200/ìL and 350/ìL who did receive such therapy (50.5/1,000). “Assuming that the goal of HIV treatment is to produce outcomes similar to those seen in HIV-negative persons,” said the investigators, “our results suggest initiating or switching to HAART at higher CD4 counts than in current recommendations.”
In an accompanying editorial, Mauro Schechter of the Federal University of Rio de Janeiro, Brazil, characterized the study as “an important contribution to the debate on when to start therapy.” He noted, however, that the findings had several limitations, including the study’s observational design and lack of randomization, incomplete information on socio-behavioral differences in the study groups, and no data on adherence to treatment. Cautioning that evidence is mixed regarding the CD4 cell level at which to begin HAART, he concluded that it remains reasonable to start therapy for most asymptomatic patients with HIV infection whose CD4 cell counts are less than 350/ìL but that guidelines on when to initiate therapy may change as more data emerge.