Integrase Inhibitors Use and Cytomegalovirus Infection Predict Immune Recovery in People Living With HIV Starting First-Line Therapy

BACKGROUND: We explored predictors of CD4/CD8 ratio improvement and optimal immunological recovery (OIR) after initiation of antiretroviral therapy (ART) in naive people living with HIV (PLWH). METHODS: Retrospective multicenter study including naive PLWH starting ART with 2 nucleos(t)ide reverse transcriptase inhibitors + 1 integrase strand transfer inhibitor (InSTI) or non-NRTI or protease inhibitor (PI). PLWH were followed from the time of ART initiation (baseline) to the discontinuation of first-line regimen, virological failure, death, or loss to follow-up. Estimated incidence and predictors of time to CD4/CD8 ratio normalization (defined as ≥1) and OIR (defined as CD4/CD8 ratio ≥ 1 plus CD4 ≥ 500 cells/µL plus CD4% ≥ 30%) were explored by Kaplan-Meier curves and Cox regression analysis. RESULTS: Overall, 1428 PLWH (77.8% males, median age 39 years, 55.1% with positive cytomegalovirus (CMV) antibodies, median HIV-RNA 4.80 log copies/mL, median CD4 323 cells/µL, median CD4/CD8 ratio 0.32) were included, of which 21.5% (n = 307), 44.5% (n = 636), and 34% (n = 485) treated with InSTI-, PI-, and NNRTI-based regimens, respectively. The estimated proportion of CD4/CD8 normalization and OIR at 36 months was 38.6% and 32.9%, respectively. Multivariate analysis showed that InSTI-based regimens had a higher probability of CD4/CD8 ratio normalization and OIR both in the total population (P < 0.001 versus PI) and in advanced naive PLWH (P ≤ 0.001 versus PI and NNRTI). Moreover, subjects with positive CMV serology showed a lower probability of CD4/CD8 ratio normalization and OIR (P < 0.001). CONCLUSIONS: InSTI-based regimens showed a better immune recovery, suggesting that the type of first-line ART can influence immune reconstitution. PLWH with positive CMV serology showed an increased risk of suboptimal immune recovery.