• HIV-CAUSAL Collaboration, Lauren E Cain, Roger Logan, James M Robins, Jonathan A C Sterne, Caroline Sabin, Loveleen Bansi, Amy Justice, Joseph Goulet, Ard van Sighem, Frank de Wolf, Heiner C Bucher, Viktor von Wyl, Anna Esteve, Jordi Casabona, Julia del Amo, Santiago Moreno, Remonie Seng, Laurence Meyer, Santiago Perez-Hoyos, Roberto Muga, Sara Lodi, Emilie Lanoy, Dominique Costagliola, and Miguel A Hernan.
• Harvard School of Public Health, Boston, MA, USA.
• Ann. Intern. Med. 2011 Apr 19; 154 (8): 509-15.

BackgroundMost clinical guidelines recommend that AIDS-free, HIV-infected persons with CD4 cell counts below 0.350 × 10(9) cells/L initiate combined antiretroviral therapy (cART), but the optimal CD4 cell count at which cART should be initiated remains a matter of debate.ObjectiveTo identify the optimal CD4 cell count at which cART should be initiated.DesignProspective 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 × 10(9) cells/L.SettingHIV clinics in Europe and the Veterans Health Administration system in the United States.Patients20, 971 HIV-infected, therapy-naive persons with baseline CD4 cell counts at or above 0.500 × 10(9) 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 × 10(9) cells/L and were included in the analysis.MeasurementsHazard ratios and survival proportions for all-cause mortality and a combined end point of AIDS-defining illness or death.ResultsCompared with initiating cART at the CD4 cell count threshold of 0.500 × 10(9) 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.LimitationsCD4 cell count at cART initiation was not randomized. Residual confounding may exist.ConclusionInitiation of cART at a threshold CD4 count of 0.500 × 10(9) cells/L increases AIDS-free survival. However, mortality did not vary substantially with the use of CD4 thresholds between 0.300 and 0.500 × 10(9) cells/L.

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