Immunological Discordance in People with HIV Receiving Contemporary Integrase Inhibitor-Based Antiretroviral Therapy: A Multicenter Retrospective Cohort Study from Türkiye.

Abstract

Immunological discordance, the persistence of CD4+ T-cell depletion despite sustained virological suppression on antiretroviral therapy (ART) in people with HIV, remains incompletely characterized in the contemporary integrase strand transfer inhibitor (INSTI) era. A multicenter, retrospective cohort study was conducted through chart review at four Turkish tertiary infectious diseases units across three regions. Adults with HIV-1 who had received ART for at least 12 consecutive months were eligible. The primary outcome was immunological discordance, defined as a current CD4+ count <350 cells/µL despite plasma HIV-1 RNA <50 copies/mL. Associations were examined using Firth-penalized logistic regression with bootstrap internal validation and E-value sensitivity analysis. Among 207 participants (median age 38 years, 85.5% male, 99.0% on INSTI-based regimens), 23 (11.1%; 95% CI: 7.5-16.2) had immunological discordance, 180 (87.0%) had concordant responses, three (1.4%) had virological discordance (HIV-1 RNA ≥50 copies/mL despite CD4+ ≥350 cells/µL), and one (0.5%) had dual nonresponse. In the multivariable Firth-penalized analysis, advanced disease at diagnosis (adjusted odds ratio: 5.74; 95% CI: 2.08-16.34), age greater than 50 years (3.71; 1.25-11.07), and previous AIDS-defining opportunistic infection (3.42; 1.09-10.85) were independent predictors of immunological discordance (area under the curve: 0.81; optimism-corrected: 0.78). In this contemporary INSTI-treated cohort, approximately one in nine virologically suppressed patients failed to achieve adequate CD4+ recovery. Late HIV diagnosis emerged as the principal modifiable upstream driver of incomplete immune recovery, reinforcing the need for earlier diagnosis and rapid linkage to care in Türkiye.