Long-term exposure to combination antiretroviral therapy and risk of death from specific causes: no evidence for any previously unidentified increased risk due to antiretroviral therapy

Published: December 1, 2011

Background: Despite the known substantial benefits of combination antiretroviral
therapy (cART), cumulative adverse effects could still limit the overall long-term
treatment benefit. Therefore we investigated changes in the rate of death with increasing
exposure to cART.

Methods: 12069 patients were followed from baseline, which was defined as the time
of starting cART or enrolment into EuroSIDA whichever occurred later, until death or six
months after last follow-up visit. Incidence rates (IR) of death were calculated per 1000
person-years of follow-up (PYFU) and stratified by time of exposure to cART (?3
antiretrovirals): <2, 2–3.99, 4–5.99, 6–7.99 and >8 years. Duration of cART exposure
was the cumulative time actually receiving cART. Poisson regression models were fitted
for each cause of death separately.

Results: 1297 patients died during 70613 PYFU (IR 18.3 per 1000 PYFU, 95%CI: 17.4–
19.4), 413 due to AIDS (5.85, 95%CI: 5.28–6.41) and 884 due to non-AIDS-related
cause (12.5, 95%CI: 11.7–13.3). After adjustment for confounding variables, including
baseline CD4 cell count and HIV RNA, there was a significant decrease in the rate of allcause
and AIDS-related death between 2–3.99 years and longer exposure time. In the
first two years on cART the risk of non-AIDS death was significantly lower, but no
significant difference in the rate of non-AIDS-related deaths between 2–3.99 years and
longer exposure to cART was observed.

Conclusions: In conclusion, we found no evidence of an increased risk of both allcause
and non-AIDS related deaths with long-term cumulative cART exposure.

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