Early antiretroviral therapy: the role of cohorts.
ABSTRACT To review the data that contribute to the debate on the optimal time to initiate highly active antiretroviral therapy in HIV-infected individuals, with a focus on the information that is available from cohort studies.
The findings from cohort studies generally support initiation of highly active antiretroviral therapy at CD4 cell counts more than 350 cells/microl. In particular, the findings that death rates among treated HIV-infected individuals are higher than those in the general population, and that the risks of AIDS and serious non-AIDS events are higher in those with lower CD4 cell counts (even when the count remains >350 cells/microl), suggest that earlier initiation of highly active antiretroviral therapy may prevent some excess morbidity and mortality. However, given the lack of adjustment for lead-time bias in many analyses, the potential for residual confounding and the possible incomplete ascertainment of relevant outcomes in cohorts, it cannot be concluded that the benefits of highly active antiretroviral therapy when started at higher CD4 cell counts will outweigh the possible detrimental effects.
Whereas the data from cohort studies currently support initiation of highly active antiretroviral therapy at CD4 cell counts more than 350 cells/microl, there is an urgent need for data from randomized trials to inform this decision.
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ABSTRACT: To compare the proportion, timing and hazards of non-AIDS death and AIDS death among men and women who initiated HAART at different CD4 cell counts to mortality risks of HIV-uninfected persons with similar risk factors. Prospective cohort studies. We used parametric mixture models to compare proportions of AIDS and non-AIDS mortality and ages at death, and multivariable Cox models to compare cause-specific hazards of mortality, across levels of CD4 cell count at HAART initiation (≤200 cells/μl: 'late', 201-350 cells/μl: 'intermediate', >350 cells/μl: 'early') and with HIV-uninfected individuals from the Multicenter AIDS Cohort Study and the Women's Interagency HIV Study. We used multiple imputation methods to address lead-time bias in sensitivity analysis. Earlier initiators were more likely to die of non-AIDS causes (early: 78%, intermediate: 74%, late: 49%), and at older ages (median years 72, 69, 66), relative to later initiators. Estimated median ages at non-AIDS death for each CD4 cell count category were younger than that estimated for the HIV-uninfected group (75 years). In multivariable analysis, non-AIDS death hazard ratios relative to early initiators were 2.15 for late initiators (P < 0.01) and 1.66 for intermediate initiators (P = 0.01); AIDS death hazard ratios were 3.26 for late initiators (P < 0.01) and 1.20 for intermediate initiators (P = 0.28). Strikingly, the adjusted hazards for non-AIDS death among HIV-uninfected individuals and early initiators were nearly identical (hazard ratio1.01). Inferences were unchanged after adjustment for lead-time bias. Results suggest the possibility of reducing the risk of non-AIDS mortality among HIV-infected individuals to approximate that faced by comparable HIV-uninfected individuals.AIDS (London, England) 10/2013; · 6.56 Impact Factor
- AIDS (London, England) 06/2010; 24(10):1583-4. · 6.56 Impact Factor
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ABSTRACT: Recommendations for the initiation of combination antiretroviral therapy in HIV-positive individuals are largely based on data from observational studies. Whilst all guidelines recommend immediate treatment in individuals with a CD4 count of less than 350 cells/mm(3), guidelines vary in their recommendations for treatment at higher CD4 counts. Several large cohort studies have published findings that contribute to the debate, although conclusions vary and results from these studies may be subject to bias.F1000 Medicine Reports 11/2010; 2:81.