Drug Resistance in HIV Following First-line ART Failure: Insights from a Cross-sectional Study in India

Our study assesses human immunodeficiency virus (HIV) drug resistance (HIVDR) in patients failing first-line (1L) antiretroviral therapy (ART) with dual nucleoside analog reverse transcriptase inhibitor (NRTI) and non-nucleoside reverse transcriptase inhibitor (NNRTI) regimens in India.

In this cross-sectional study, consecutive HIV-1-infected patients aged 13 years or older, failing 1L ART after at least 12 months exposure, underwent HIV genotyping and drug resistance testing (DRT) using the ViroSeq™ HIV-1 Genotyping System and the Stanford HIV-1 Database, with HIVDR classification based on a penalty score of ≥30.

Among 115 eligible participants, 110 underwent DRT, revealing efavirenz (EFV) or nevirapine (NVP) resistance rates of 85.3% (n = 93/109) and 87.2% (n = 95/109), respectively, and substantial cross-resistance to rilpivirine (RPV) (37.6%, n = 41/109), etravirine (ETV) (30.3%, n = 33/109), and doravirine (DOR) (60.5%, n = 66/109). The cohort was categorized into 3 groups based on their previous ARV drug exposure: group A (36.4%, n = 40) with prior TA exposure (AZT or d4T) but no TFV exposure; group B (19.1%, n = 21) with prior nonconcomitant exposure to both TAs and TFV; and group C (44.5%, n = 49), exposed to TFV only. Despite group B's 1L ART regimen failure with TFV, the prevalence of AZT resistance was similar (difference in proportions, ∇P: 14.6%, p = 0.277) between group A [57.5% (n = 23/40)] and group B [42.9% (n = 9/21)]. TFV resistance was comparable (∇P: 0.8%, p = 0.947) between group A (32.5%, n = 13/40) and group B (33.3%, n = 7/21), despite group A's lack of TFV exposure, and was also similar to the TFV-only-exposed group (group C: 38.8%, n = 19/49). Regarding distinct DRM patterns, the prevalence of K65R DRM was higher (∇P: 22.4%, p = 0.060) among TFV-only-exposed patients (group C: 36.7%, n = 18/49) compared with PLH exposed to both TAs and TFV (group B: 14.3%, n = 3/21), whereas multiple TAMs occurred at similar rates (∇P: 12.1%, p = 0.367) among TA-exposed patients [group A: 55.0% (n = 22/40) vs group B: 42.9% (n = 9/21)].

The research provides insights into the complexities of HIVDR, emphasizing the interplay of resistance patterns and the role of drug exposure history, especially in the context of resistance to TFV and second-generation NNRTIs.

Ensuring adequate drug exposure history in patients can prevent poor outcomes in PLH being treated with ART due to resistance. Resistance profiling is especially relevant following first-line ART failure.