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.
- AIDS (London, England) 06/2010; 24(10):1583-4. DOI:10.1097/QAD.0b013e32833ac7d4 · 5.55 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. DOI:10.3410/M2-81
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ABSTRACT: Background To estimate the clinical benefit of highly active antiretroviral therapy (HAART) initiation vs deferral in a given month in patients with CD4 cell counts less than 800/μL.Methods In this observational cohort study of human immunodeficiency virus type 1 seroconverters from CASCADE (Concerted Action on SeroConversion to AIDS and Death in Europe), we constructed monthly sequential nested subcohorts between January 1996 and May 2009, including all eligible HAART-naive, AIDS-free individuals with a CD4 cell count less than 800/μL. The primary outcome was time to AIDS or death in those who initiated HAART in the baseline month compared with those who did not, pooled across subcohorts and stratified by CD4 cell count. Using inverse probability-of-treatment weighted survival curves and Cox proportional hazards regression models, we estimated the absolute and relative effects of treatment with robust 95% confidence intervals (CIs).Results Of 9455 patients with 52 268 person-years of follow-up, 812 (8.6%) developed AIDS and 544 (5.8%) died. In CD4 cell count strata of 200 to 349, 350 to 499, and 500 to 799/μL, HAART initiation was associated with adjusted hazard ratios (95% CIs) for AIDS/death of 0.59 (0.43-0.81), 0.75 (0.49-1.14), and 1.10 (0.67-1.79), respectively. In the analysis of all-cause mortality, HAART initiation was associated with adjusted hazard ratios (95% CIs) of 0.71 (0.44-1.15), 0.51 (0.33-0.80), and 1.02 (0.49-2.12), respectively. Numbers needed to treat (95% CIs) to prevent 1 AIDS event or death within 3 years were 21 (14-38) and 34 (20-115) in CD4 cell count strata of 200 to 349 and 350 to 499/μL, respectively.Conclusion Compared with deferring in a given month, HAART initiation at CD4 cell counts less than 500/μL (but not 500-799/μL) was associated with slower disease progression.Archives of Internal Medicine 09/2011; 171(17):1560. DOI:10.1001/archinternmed.2011.401 · 17.33 Impact Factor