The presence of resistance-associated mutations in reverse transcriptase gene is associated with cerebrospinal fluid HIV-1 escape: a multicentric retrospective analysis

Higher risk of cerebrospinal fluid escape (CVE) has been associated with the use of specific antiretroviral (ARV) classes, such as protease inhibitors. We assessed whether archived resistance-associated mutations (RAMs) can mediate this relationship by identifying patients treated with incompletely active antiretroviral regimens. A retrospective multicentric study on 282 adult people with HIV on antiretroviral therapy (ART) and available historical plasma genotype resistance testing (HGRT) for reverse transcriptase (RT) and protease genes between 2001 and 2021. The odds ratio for demographic, clinic-, and ART-related variables and CVE was estimated by multivariable modeling. HGRT-adjusted central nervous system effectiveness penetration (CPE) score was computed in modeling the risk. Median age, plasma VL, and CD4 count were 49 years, <50?copies/mL, and 310?cells/µL. CVE was detected in 51 participants (17.0%). No difference in CVE prevalence was observed according to ART type, number of ARVs or ARV classes. Participants with CVE had more frequently plasma (52.9% vs. 32.1%, p?=?0.005) and CSF RAMs in RT (n?=?63, 57.1% vs. 28.6%, p?=?0.029), but not in protease gene. The presence of plasma RAMs in RT associated with increased odds of CVE in adjusted analyses (aOR 3.9, p?