Starting cART earlier may increase AIDS-free survival time

Starting combined antiretroviral therapy (cART) in HIV patients earlier may stave off symptoms, prevent HIV transmission and prolong AIDS-free survival without affecting mortality, according to an observational study that used pooled data from 12 large cohorts.

Clinical guidelines differ on when to start cART. European guidelines and the World Health Organization recommend starting cART in asymptomatic people whose CD4 cell count is less than 0.350 × 10⁹ cells/L, while U.S. guidelines from the International AIDS Society-USA panel and from the Department of Health and Human Services recommend a level of 0.500 × 10⁹ cells/L.

Researchers reviewed prospective observational data from the HIV-CAUSAL Collaboration and dynamic marginal structural models to compare cART initiation strategies for 20,971 HIV-infected, therapy-naive people who had not yet undergone treatment. Patients had a baseline CD4 cell count above 0.500 × 10⁹ cells/L and no previous AIDS-defining illnesses. In the study, 8,392 patients' CD4 cell counts subsequently decreased to 0.200 to 0.499 × 10⁹ cells/L.

The study population was from HIV clinics in Europe and the U.S. Veterans Health Administration system. CART initiation was defined as the date on which a person started three or more antiretroviral drugs, two ritonavir-boosted protease inhibitors, or a nonnucleoside reverse-transcriptase inhibitor and a boosted protease inhibitor. The study was funded by the National Institutes of Health, and results appear in the April 19 Annals of Internal Medicine.

Outcomes were 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 (95% CI, 0.97 to 1.48) for the 0.200 threshold. Estimates showed little mortality change as the CD4 threshold increased from 0.300 to 0.500. The corresponding hazard ratios were 1.38 (95% CI, 1.23 to 1.56) and 1.90 (95% CI, 1.67 to 2.15), respectively, for the combined end point of AIDS-defining illness or death.

Delaying cART initiation until the CD4 cell count decreased below 0.350 would result in a 38% increase in the incidence of AIDS-defining illness or death, compared with a threshold of 0.500. The authors wrote that 48 patients would need to start cART when their CD4 cell count decreased below 0.500 rather than 0.350 to prevent one new case of an AIDS-defining illness or death during the first five years. However, randomized, controlled trials are needed to validate this observational series, the authors concluded.

The authors of an accompanying editorial suggested that expanded use of cART could substantially curtail future HIV infections, as decreasing viral load decreases transmission risk. “Encouraging results from clinical studies, modeling studies, real-world observations, and public health reporting have led to a sense that the HIV epidemic can be controlled by expanding the indications for cART,” the editorialists wrote. “Unfortunately, in the current fiscal reality, the ‘test and treat everyone’ strategy seems to require more resources than are available.”