Late HIV diagnosis (i.e CD4≤350 cells/µL) is associated with poorer outcomes. However, determinants of long-term mortality and factors influencing immune recovery within the first years after antiretroviral treatment (ART) initiation are poorly defined. From PISCIS cohort, we included all HIV-positive adults, two-year survivors after initiating ART between 2005–2019. The primary outcome was all-cause mortality according to the two-year CD4 count. We used Poisson regression. The secondary outcome was incomplete immune recovery (i.e., two-year CD4500 cells/µL, reference population). Overall, 113 patients (4·2%) died. Mortality was higher among LP with two-year CD4 count 200–500 cells/µL (aMRR 1·95[95%CI:1·06-3·61]) or 500 cells/µL, regardless of being initially LP or non-LP (aMRR 1·05[0·50-2·21]). Mortality rates within each two-year CD4 strata were not affected by the initial CD4 count at ART initiation (test-interaction, p = 0·48). The stronger factor influencing immune recovery was the CD4 count at ART initiation. First-line integrase-inhibitor-(INSTI)-based regimens were associated with reduced mortality compared to other regimens (aMRR 0·54[0·31-0·93]) and reduced risk of incomplete immune recovery in LP (aOR 0·70[0·52-0·95]). Two-year immune recovery is a good early predictor of long-term mortality in LP after surviving the first high-risk 2 years. Nearly half experienced a favorable immune recovery with a life expectancy similar to non-LP. INSTI-based regimens were associated with higher rates of successful immune recovery and better survival compared to non-INSTI regimens. Southern-Denmark University, Danish AIDS-foundation, and Region of Southern Denmark.

With widespread and effective antiretroviral therapy, the life expectancy in the HIV population has dramatically improved over the last two decades. Consequently, as patients are aging with HIV, other age-related comorbidities, such as metabolic disturbances and cardiovascular disease (CVD), have emerged as important causes of morbidity and mortality. An overrepresentation of traditional cardiovascular risk factors (RF), toxicities associated with long exposure to antiretroviral therapy, together with residual chronic inflammation and immune activation associated with HIV infection are thought to predispose to these metabolic complications and to the excess risk of CVD observed in the HIV population. The metabolic syndrome (MS) represents a clustering of RF for CVD that includes abdominal obesity, hypertension, dyslipidemia and insulin resistance. Hypertension is a prevalent feature of the MS in HIV, in particular in the aging population, and constitutes an important RF for CVD. Physicians should screen their patients for metabolic and cardiovascular risk at the regular visits to reduce MS and the associated CVD risk among people aging with HIV, since many of RF are under-diagnosed and under-treated conditions. Interventions to reduce these RF can include lifestyle changes and pharmacological interventions such as antihypertensive and lipid-lowering therapy, and treatment of glucose metabolism disturbances. Changes in antiretroviral therapy to more metabolic neutral antiretroviral drugs may also be considered.