The HIV-CAUSAL Collaboration
Most clinical guidelines recommend that AIDS-free, HIV-infected persons with CD4 cell counts below 0.350 × 109 cells/L initiate combined antiretroviral therapy (cART), but the optimal CD4 cell count at which cART should be initiated remains a matter of debate.
To identify the optimal CD4 cell count at which cART should be initiated.
Prospective observational data from the HIV-CAUSAL Collaboration and dynamic marginal structural models were used to compare cART initiation strategies for CD4 thresholds between 0.200 and 0.500 × 109 cells/L.
HIV clinics in Europe and the Veterans Health Administration system in the United States.
20 971 HIV-infected, therapy-naive persons with baseline CD4 cell counts at or above 0.500 × 109 cells/L and no previous AIDS-defining illnesses, of whom 8392 had a CD4 cell count that decreased into the range of 0.200 to 0.499 × 109 cells/L and were included in the analysis.
Hazard ratios and survival proportions for all-cause mortality and a combined end point of AIDS-defining illness or death.
Compared with initiating cART at the CD4 cell count threshold of 0.500 × 109 cells/L, the mortality hazard ratio was 1.01 (95% CI, 0.84 to 1.22) for the 0.350 threshold and 1.20 (CI, 0.97 to 1.48) for the 0.200 threshold. The corresponding hazard ratios were 1.38 (CI, 1.23 to 1.56) and 1.90 (CI, 1.67 to 2.15), respectively, for the combined end point of AIDS-defining illness or death.
CD4 cell count at cART initiation was not randomized. Residual confounding may exist.
Initiation of cART at a threshold CD4 count of 0.500 × 109 cells/L increases AIDS-free survival. However, mortality did not vary substantially with the use of CD4 thresholds between 0.300 and 0.500 × 109 cells/L.
National Institutes of Health.
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. ;154:509–515. doi: 10.7326/0003-4819-154-8-201104190-00001
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Published: Ann Intern Med. 2011;154(8):509-515.
HIV, Hospital Medicine, Infectious Disease.
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Print ISSN: 0003-4819 | Online ISSN: 1539-3704
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