Our analysis shows that ART was found to be a greater risk factor among PLHIV compared with treatment-naïve patients and the increased risk was

particularly found for abacavir in the NRTI group among the ART classes. In contrast, a recent meta-analysis of RCT studies (published after our literature search) found that abacavir was not associated with a greater risk of MI or major CVD events, despite the significant impact of abacavir on the risk of CVD in some cohort studies [41]. This meta-analysis included HIV clinical trial data from studies that had a follow-up period of at least 24 weeks, with the check details majority of included studies having approximately 1 year of average follow-up. In contrast, a 96-week RCT follow-up study found that abacavir, compared with tenofovir, was associated with a greater risk for CVD, as discussed above. Of note, it may be that short-term use of abacavir has a low risk for CVD events among PLHIV. More specifically, we found that the annual RR associated with abacavir use was very low (RR 1.09; 95% CI 1.02, 1.16), SCH772984 but that the risk increased with duration of ART. It is important to note that the majority of the cardiovascular events associated with the use of antiretroviral drugs were confined to patients who were already at increased absolute risk of CVD. Study type/design was not found to be a significant predictor of heterogeneity in our

estimates. A longer follow-up RCT measuring the use of abacavir and other antiretrovirals associated with CVD events would assist in ascertaining the role of abacavir among all patients as they continue to use ART long-term. We found that HIV, ART type and duration and CD4 cell count are associated with increased risk of CVD. The risk of CVD is greater in PLHIV than in people PFKL not living with HIV, and higher again for people exposed to ART, and particularly PI-based regimens, and increases with the duration of treatment. Despite being a risk factor for CVD, ART use has increased the quality and

length of life of PLHIV by restoring immune function, reversing AIDS-defining events and reducing AIDS-related mortality rates. It is possible that the use of ART increases life expectancy and hence increases the average age of those taking ART in comparison to the reference group, which may lead to confounding of results. Although the health and survival of PLHIV have improved with effective ARTs, PLHIV are at substantially greater risk of developing other comorbidities, such as CVD, compared with uninfected people. Given that CVD is responsible for a large number of deaths world-wide, this is a significant issue for the population of PLHIV, particularly as they get older and become more treatment-experienced with second-line, third-line or more complex antiretroviral regimens. Increasingly, HIV-positive populations will require long-term clinical management of numerous conditions along with their HIV infection.