Effect of Early Versus Deferred Antiretroviral Therapy for HIV on Survival

"The optimal time for the initiation of antiretroviral therapy for asymptomatic patients with [HIV] is uncertain," the authors wrote in introducing the current study.

The researchers conducted two parallel analyses involving a total of 17,517 asymptomatic HIV patients receiving medical care in the United States or Canada from 1996 to 2005. None had previously received antiretroviral therapy. Patients in each group were stratified according to the CD4+ count at the initiation of antiretroviral therapy (351-500 cells per cubic millimeter or more than 500 cells per cubic millimeter). In each group, the researchers compared the relative risk of death for patients who started therapy when the CD4+ count was above each of the two thresholds of interest ("early therapy group") with that of patients who deferred therapy until the CD4+ count fell below these thresholds ("deferred therapy group").

The first analysis involved 8,362 patients: 2,084 (25 percent) initiated therapy at a CD4+ count of 351-500, and 6,278 (75 percent) deferred therapy. Following adjustments for calendar year, cohort of patients, and demographic and clinical characteristics, patients in the deferred therapy group had an increase in the risk of death of 69 percent compared with the early therapy group (relative risk in the deferred therapy group, 1.69; 95 percent CI, 1.26 to 2.26; P<0.001).

The second analysis involved 9,155 patients: 2,220 (24 percent) initiated therapy at a CD4+ count of more than 500, and 6,935 (76 percent) deferred therapy. Among patients in the deferred therapy group, there was a 94 percent increase in the risk of death (relative risk, 1.94; 95 percent CI, 1.37 to 2.79; P<0.001).

"The early initiation of antiretroviral therapy before the CD4+ count fell below two prespecified thresholds significantly improved survival, as compared with deferred therapy," the authors concluded.