BACKGROUND: Hepatitis C virus (HCV) coinfection may further compromise immunological and cognitive function in people with HIV (PWH). This study compared laboratory and neuropsychiatric measures across the periods of HCV seroconversion and direct-acting antiviral (DAA) therapy with sustained virologic response (SVR) among PWH who initiated antiretroviral therapy (ART) during acute HIV infection (AHI) and acquired HCV after 24 weeks of ART. METHODS: Participants from the RV254 AHI cohort underwent paired laboratory and neuropsychiatric assessments during follow-up visits. The former included measurements of CD4 + and CD8 + T-cell counts, HIV RNA, liver enzymes, and lipid profiles. The latter included the Patient Health Questionnaire-9 (PHQ-9), Distress Thermometer (DT), and a 4-test cognitive battery that evaluated psychomotor speed, executive function, fine motor speed, and dexterity. The raw scores in the battery were standardized and averaged to create an aggregate performance (NPZ-4) score. Parameters of HCV-coinfected participants were compared across the periods of HCV seroconversion and DAA treatment. RESULTS: Between 2009 and 2022, 79 of 703 RV254 participants acquired HCV after ≥ 24 weeks of ART
53 received DAA, and 50 (94%) achieved SVR. All participants were Thai males (median age: 30 years)
34 (68%) denied past intravenous drug use, and 41 (82%) had a history of other sexually transmitted infections during follow-up. Following SVR, aspartate transferase (AST) and alanine transaminase (ALT) decreased (p <
0.001), while total cholesterol, low-density lipoprotein, and triglycerides increased (p <
0.01). The median CD4 + /CD8 + ratio increased from 0.91 to 0.97 (p = 0.012). NPZ-4 improved from 0.75 to 0.91 (p = 0.004). The median DT score increased from 1.7 to 2.7 (p = 0.045), but the PHQ-9 score remained unchanged. CONCLUSION: HCV coinfection is common in this group of high-risk PWH, highlighting the need for regular screening, early diagnosis, and treatment. The study participants exhibited a modest improvement in the CD4 + /CD8 + T-cell ratio and cognitive performance following DAA therapy and SVR. Future studies should examine potential neuropsychiatric impacts during early HCV infection as well as the longer-term neuropsychiatric outcomes after DAA treatment with SVR.