Abstract Body

Background:

HIV/HCV co-infection is associated with impaired immune recovery and cognitive impairment. This study compared the clinical and neuropsychiatric parameters before and after direct-acting antiviral (DAA) therapy with sustained virologic response (SVR) in people with HIV (PWH) on stable antiretroviral therapy (ART).

Methods:

RV254 cohort participants were enrolled during acute HIV (AHI/baseline, Fiebig I-V) and initiated ART within days. They underwent assessments at pre-ART baseline, weeks 24 and 96, and every 48 weeks afterwards, including blood tests (complete blood count, liver enzymes, CD4+ & CD8+ T-cell counts, HIV RNA, lipid profile and HCV screening), neurological examination, depressive and stress symptoms assessment by Patient Health Questionnaire-9 (PHQ-9, score 0-27) and Distress Thermometer (DT, score 0-10), and a 4-test neuropsychiatric (NP) battery. The battery included Color Trails 1 (CT1) & 2 (CT2), non-dominant hand Grooved Pegboard (GPB), and Trails Making A (TMA). An NPZ-4 score was generated by averaging the z-scores of the 4 tests. To control ART effects, only participants on ≥24 weeks of ART with plasma HIV suppression (HIV RNA < 50 cps/ml) were included. Parameters before and after SVR were compared by Wilcoxon signed-rank test or McNemar’s test.

Results:

Between May 2009 and July 2022, 79 of 688 participants with at least week 24 visit became HCV seropositive; 50 had sustained HCV viremia and received DAA with SVR. All were male with a median age of 30 years [IQR 26-35]; 33 (66%) were diagnosed with other sexually transmitted infections within 6 months of HCV seroconversion; 31 (62%) denied any past intravenous methamphetamine use. The durations between AHI and HCV seroconversion and between HCV seroconversion and DAA initiation were 192 [IQR 96-312] and 58 [IQR 27-70] weeks. AST and ALT declined (p< 0.001), and total cholesterol, LDL-C, and triglycerides increased (all p< 0.01) after SVR (Table 1). CD4+ and CD8+ T-cell counts did not change significantly, but CD4/CD8 ratio increased after achieving SVR (p=0.012). The frequency of peripheral neuropathy and PHQ-9 scores remained unchanged, but stress scores by DT increased after DAA (p=0.045). NPZ-4 (p=0.004) and z-TMA (p=0.028) improved significantly post-DAA. Of note, no improvements in CD4/CD8 ratio and NP battery were observed between HCV seroconversion and DAA initiation.

Conclusions:

In PWH on stable ART with HCV co-infection, CD4/CD8 ratio and cognitive test performance improved after DAA therapy with SVR.

Laboratory and clinical outcomes of participants who achieved sustained virologic response (SVR) after DAA therapy (N&#3f50)