Clinical Newswire, July 22, 2010 (Vienna, Austria) - A new study of HAART timing and outcomes in a large cohort of people newly infected with HIV reveals that early treatment, when the CD4 cell count remains as high as 500 cells/mm3, has a beneficial effect on survival. The analysis of data from the CASCADE (Concerted Action on SeroConversion to AIDS and Death in Europe) cohort was presented by Dr Joseph Eron, of the University of North Carolina at Chapel Hill, USA, on 22nd July at AIDS 2010, Vienna.
Data from 9,455 patients who had recently seroconverted to HIV-1 positive were obtained from the CASCADE cohort from January 1996 to May 2009. The data represented a total of 52,268 person-years of follow-up. To minimize lead-time bias, monthly sequential nested subcohorts were constructed in which HAART-naive, AIDS-free individuals were classified as initiating HAART or not during the baseline month. Inverse-probability-of-treatment weighted survival curves and Cox proportional hazards models were used to estimate adjusted effects. Outcomes were time to AIDS or death, and all-cause mortality. These were compared between those who initiated HAART and those who did not in each subcohort, pooled across subcohorts and stratified by CD4.
Of the patients included in the analysis, 812 (8.6%) developed AIDS and 544 (5.8%) died. The adjusted hazard ratio for AIDS or death was 0.59 (0.43, 0.81) for patients with baseline CD4 counts 200-349, and 0.75 (0.49, 1.14) for those with 350-499 CD4 cells/mm3 at baseline. Both favour treatment, but this effect was not seen for CD4 counts greater than 500. Overall, at CD4 counts of 350-499, the number-needed-to-treat (NNT) to avoid one case of AIDS or death was 34; for death alone the NNT was 74.
‘Initiation at CD4 below 500 appears to reduce risk compared to deferring at baseline, ’ concluded Dr Eron, adding that ‘there was no apparent benefit to initiation for the larger population of patients with CD4 counts of 500 to 799.’
Last year, the WHO updated its treatment guidelines, recommending HAART initiation for people with CD4 counts ≦350 cells/mm3. The CASCADE study data strongly supports this decision, and suggests that an early treatment benefit would still be obtained for those with CD4 counts of up to 599 cells/mm3. However, the risks inherent in HAART itself must be weighed against the benefits of starting ART early, and limitations of the study included a lack of accounting for confounders such as comorbid conditions, treatment interruptions, and lack of viral suppression.
Abstract: THLBB201
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