Impact of V179D/E mutations on antiretroviral therapy outcomes in people living with HIV-1: a 3-year retrospective study.

BACKGROUND

HIV-1 mutation V179D/E can confer potential low-level resistance to multiple non-nucleoside reverse transcriptase inhibitors (NNRTIs), and its detection rate has increased in recent years. However, its effect on antiretroviral therapy (ART) outcomes remains unclear.

METHODS

This study included people living with HIV-1 (PLWH) with only V179D/E mutation detected by pre-treatment drug resistance (PDR) testing at Guangzhou Eight People's Hospital between January 2018 and December 2022. Two control groups were matched 1:1:1 using propensity score matching (PSM): a PDR-negative group and an NNRTI-DR group with low-level or higher NNRTI resistance. Virological and immunological outcomes were compared over 3 years. Logistic regression analyzed virological failure (VF) risk factors in the V179D/E group and assessed acquired drug resistance (ADR).

RESULTS

Among 6021 patients tested, the detection rate of V179D/E was 14.8%. After exclusions, 626 patients were included in this study. Additionally, 195 patients met the criteria for the NNRTI-DR group. After 1:1:1 PSM, the baseline characteristics were balanced across the three groups. In 1 year, the V179D/E group showed lower virological suppression and higher VF than the PDR-negative group, with no significant difference from the NNRTI-DR group. Differences disappeared by years 2 and 3. In the V179D/E group, NNRTI-based regimens increased VF risk, while baseline CD4+ T cell counts >200 cells/μL were protective. Among 37 patients with VF tested for ADR in the V179D/E group, 54.1% developed new mutations, 85.0% of whom were on efavirenz (EFV)-based regimens.

CONCLUSIONS

V179D/E is highly prevalent among ART-naïve PLWH in Guangzhou and may impair early virological response to NNRTI-based regimens, particularly EFV-based regimens while increasing ADR risk.