Risk factors for low-level viremia and virological failure in HIV patients in southwestern China who transitioned to second-line antiretroviral therapy after failure of first-line treatment: a retrospective cohort study

ObjectiveTo investigate factors associated with low-level viremia (LLV) and virological failure (VF) in HIV patients who transitioned to second-line antiretroviral therapy (ART) after first-line ART failure, aiming to inform management strategies for virological fluctuations among second-line ART patients in resource-limited settings.MethodsThis retrospective cohort study included HIV patients who switched to second-line ART regimens between January 1, 2000, and January 1, 2026, due to first-line ART failure. Baseline demographic data (e.g., age at diagnosis, sex) and clinical indicators (e.g., time from diagnosis to ART initiation, baseline viral load, baseline CD4+ T lymphocyte count) at enrollment were collected. LLV and VF were defined as outcomes. Cox proportional hazards regression models were used to evaluate the associations between baseline characteristics/clinical indicators and LLV and VF.ResultsA baseline CD4+ T lymphocyte count ≥350 was associated with a lower hazard of both LLV (aHR, 0.82; 95% CI: 0.60–0.88) and VF (aHR, 0.49; 95% CI: 0.29–0.76). HIV infection through homosexual transmission was associated with a higher hazard of LLV (aHR, 3.69; 95% CI: 1.48–9.23). Use of DTG + 3TC + TDF as a second-line regimen was associated with a higher hazard of both LLV (aHR, 2.25; 95% CI: 1.31–5.82) and VF (aHR, 2.23; 95% CI: 1.32–3.25). Co-infection with hepatitis B was associated with a higher hazard of LLV (aHR, 2.12; 95% CI: 1.13–6.23), whereas HCV seropositivity was associated with a higher hazard of both LLV (aHR, 3.01; 95% CI: 1.78–7.48) and VF (aHR, 2.79; 95% CI: 1.52–6.14). The M184V mutation was associated with a higher hazard of LLV (aHR, 6.35; 95% CI: 1.44–27.93). Both M184V (aHR, 4.76; 95% CI: 1.02–19.63) and K103N (aHR, 10.00; 95% CI: 4.12–24.30) mutations were associated with a higher hazard of VF.ConclusionLower baseline CD4+ T lymphocyte count, HIV infection through homosexual transmission, use of DTG + 3TC + TDF as a second-line regimen, hepatitis B co-infection or HCV seropositivity, and the presence of specific resistance-associated mutations were associated with a higher hazard of LLV and VF. Therefore, enhanced monitoring of resistance markers and immunological indicators is warranted among patients receiving second-line ART to facilitate timely clinical evaluation and treatment adjustment.