Risk of Non–AIDS–Defining Events Is Lower in Antiretroviral Therapy (ART)–Naive HIV Controllers Than in Normal Progressors on Suppressive ART

Background. We aimed to compare the non-AIDS event (nADE) risk between normal progressors using antiretroviral therapy (NP-ART) and people with human immunodeficiency virus (HIV, PWH) who naturally control HIV infection (HIV controllers), as well as the risk of nADE following ART in HIV controllers. Methods. The primary end point was the composite of cardiovascular disease, non-AIDS malignancy, or all-cause mortality, whichever came first. The role of ART in HIV controllers was assessed as a time-varying covariate. Results. We included 1007 ART-naive HIV controllers (60 of them were elite controllers), 1510 early-ART (<6 months after negative HIV test), and 15437 NP-ART (reference group), contributing 3813, 11 060, and 160 050 years of follow-up, respectively. HIV controllers had lower risk of the primary end point (hazard ratio [HR], 0.55; 95% confidence interval [CI]: .38–.81; P = .0023), all-cause mortality (adjusted HR [aHR], 0.45; 95% CI: .25–.79; P = .0054), and cardiovascular disease (aHR, 0.47; 95% CI: .22–.99; P = .046), but not non-AIDS malignancy (aHR, 0.74; 95% CI: .41–1.35; P = .33), compared with NP-ART. Among HIV controllers, each log₁₀ lower baseline viral load further decreased the risk of a nADE (aHR, 0.54; 95% CI: .29–.99; P = .045). ART in HIV controllers did not reduce the risk of any nADE (aHR, 1.22; 95% CI: .66–2.29; P = .53). Conclusions. HIV controllers had a lower n ADE risk than NP-ART, especially in those with low plasma viral loads. ART did not alter the nADE risk in HIV controllers. Our findings help clinicians to decide on prescribing ART in HIV controllers.