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People with Well-Controlled HIV Can Match Lifespan of HIV Negatives

People with HIV who are able to achieve good viral suppression and CD4 cell recovery on antiretroviral therapy (ART) have a mortality rate similar to that of uninfected people in the general population, according to results from the large SMART and ESPRIT studies, published in the March 27, 2013 issue of AIDS.

AIDS often brought rapid death in the early years of the epidemic, but the advent of effective combination ART in the mid-1990s dramatically reduced mortality. As treatment has continued to improve, some studies have suggested that death rates of people with HIV are now approaching those of HIV negative individuals -- that is, if they can access treatment, stay on therapy, and achieve good response.

Alison Rodger from University College London and colleagues compared mortality rates among adults with well-controlled HIV in the SMART and ESPRIT trials, comparing them to those of the general population. The SMART treatment interruption trial (n=5472) revealed unexpected risks of stopping ART, while the ESPRIT trial (n=4112) found that adding interleukin-2 to ART did not significantly improve CD4 T-cell recovery.

The present analysis included a total of 3280 participants who were randomly assigned to the control groups in the 2 trials (uninterrupted ART in SMART and no IL-2 in ESPRIT). About 80% were men, the median age was 43 years, about half were from North America, and 40% were from Europe; about 12% were coinfected with hepatitis B or C. They had low viral load (<400 or <500 copies/mL) and high CD4 counts (>350 cells/mm³) during the past 6 months. Injection drug users were excluded, as this group has a higher risk of death due to causes unrelated to HIV.

Altogether, participants contributed 12,357 person-years of follow-up data. The researchers calculated standardized mortality ratios (SMRs), comparing death rates among study participants versus a general population of the same age and sex from the same countries. Results were previously presented in part at the 2012 Conference on Retroviruses and Opportunistic Infections (CROI 2012).

Results

• A total of 62 study participants died from any cause during follow-up, for an overall mortality rate of 5.02 per 1000 person­-years.  
• The most common causes of death were cardiovascular disease or sudden death (19 people, 31%) and non-AIDS cancers (12 people, 19%), followed by "unnatural deaths" such as accidents or suicides (11 people, 18%).
• Infections other than HIV or hepatitis (6 people, 10%) and liver disease (5 people, 8%) were also prominent causes.
• Only 2 deaths (3%) were due to AIDS­-related causes.
• Overall, participants had a 24% higher risk of death compared with the general population (SMR 1.24).
• Among individuals with CD4 counts in the 300-499 cells/mm³ range (accounting for 28 deaths), the SMR was 1.77, indicating a 77% higher mortality rate.
• Among people with >500 cells/mm³ (accounting for 34 deaths), however, the SMR was 1.00, indicating the same mortality risk as the general population.   

Based on these findings, the study authors concluded, "In HIV-infected individuals on ART, with a recent undetectable viral load, who maintained or had recovery of CD4+ cell counts to at least 500 cells/[mm³], we identified no evidence for a raised risk of death compared with the general population."

These results add to the growing body of evidence that early ART is beneficial. In their discussion, however, the researchers noted that even people who start treatment later with a low CD4 count <200 cells/mm³ can still reduce their risk of death to near that of the general population (SMR 1.18) if they experience good immunological response and attain a CD4 level >500 cells/mm³.

6/19/13

Reference

AJ Rodger, R Lodwick, M Schechter, et al. Mortality in well controlled HIV in the continuous antiretroviral therapy arms of the SMART and ESPRIT trials compared with the general population. AIDS 27(6):973-979. March 27, 2013.