Integrase Inhibitors Use and Cytomegalovirus Infection Predict Immune Recovery in People Living With HIV Starting First-Line Therapy. (1st January 2021)

• Record Type: Journal Article
• Authors: Fabbiani, Massimiliano; Borghetti, Alberto; Squillace, Nicola; Colafigli, Manuela; Taramasso, Lucia; Lombardi, Andrea; Rossetti, Barbara; Ciccullo, Arturo; Colella, Elisa; Picarelli, Chiara; Berruti, Marco; Latini, Alessandra; Montagnani, Francesca; Sambo, Margherita; Di Biagio, Antonio; Gori, Andrea; Di Giambenedetto, Simona; Bandera, Alessandra
• Is Part Of: Journal of acquired immune deficiency syndromes. Volume 86:Number 1(2021)
• Publication Date: 2021-01-01
• Subjects: HIV-1 -- CMV -- integrase strand transfer inhibitors -- protease inhibitors -- nonnucleoside reverse transcriptase inhibitors -- immune reconstitution; AIDS (Disease) -- Periodicals; Acquired Immunodeficiency Syndrome -- Periodicals; AIDS (Disease); Periodicals; 616.9792005
• DOI: 10.1097/QAI.0000000000002525
• Languages: English
• ISSNs: 1525-4135

Abstract

Abstract : 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.