Mortality Same With Low HIV Load, High CD4s as in General Population
HIV-positive people who did not inject drugs, had a recent undetectable viral load, and had a CD4 count above 500 cells/μL had the same death risk as a general-population comparison group, according to an analysis of SMART and ESPRIT trial participants.
As people with HIV live longer thanks to antiretroviral therapy, recent studies have calculated life spans with HIV approaching those of the general population groups. This analysis of HIV-positive people taking continuous antiretroviral therapy in the SMART and ESPRIT trials found that some of them had a death risk identical to that of the general population—if they met certain treatment-response criteria set by the researchers.
The investigators selected people between 20 and 70 years old in the continuous-therapy control arms of these two trials, meaning they were taking standard antiretroviral combinations with no planned treatment breaks. Study participants could not be injection drug users and had to have a CD4 count at or above 350 cells/μL and a viral load at or below 500 copies/mL at any time in the past 6 months.
The SMART/ESPRIT team counted how many HIV-positive people died during follow-up. Then they calculated standardized mortality ratios (SMR) by comparing death rates in HIV groups with death rates in the Human Mortality Database.
The analysis included 3280 HIV-positive people, 665 of them (20%) women. Study participants had a median age of 43 years, and follow-up reached 12,375 person-years. During that time 62 HIV-positive people died, usually because of cardiovascular disease or sudden death (31%) or a non-AIDS malignancy (19%). An AIDS disease caused only 3% of deaths.
HIV-positive people with a CD4 count between 350 and 499 cells/μL had a 77% higher death risk than the general population (SMR 1.77, 95% confidence interval [CI] 1.17 to 2.55). But HIV-positive people with a CD4 count above 500 cells/μL had a death risk identical to the general population (SMR 1.0, 95% CI 0.69 to 1.40).
The researchers conclude that “in non-IDU individuals in the continuous ART control arms of the ESPRIT and SMART trials, we identified no evidence for a raised risk of death compared with the general population in HIV-infected individuals on ART, with an undetectable viral load, who maintained or had recovery of CD4+ T-cell counts to at least 500 cells/μl.”
Although previous cohort studies yielded similar findings, the authors observe, deaths may be missed in HIV cohorts, and such omissions could result in underestimation of mortality in people with HIV. Mortality data were missing for only about 5% of ESPRIT and SMART participants.
The investigators urged caution in interpreting their findings because measured and unmeasured confounders could skew the results. For example, the study group may have included a lower proportion of smokers than is generally seen in HIV populations.
Source: Alison J. Rodger, Rebecca Lodwick, Mauro Schechter, Steven Deeks, Janaki Amin, Richard Gilson, Roger Paredes, Elzbieta Bakowska, Frederik N. Engsig, Andrew Phillips, for the INSIGHT SMART, ESPRIT Study Groups. Mortality in well controlled HIV in the continuous antiretroviral therapy arms of the SMART and ESPRIT trials compared with the general population. AIDS. 2013; 27: 973-979.
Written by Mark Mascolini on behalf of the International AIDS Society