P-E5 Whole genome deep sequencing of HIV reveals extensive multi-class drug resistance in Nigerian patients failing first-line antiretroviral therapy

Abstract

Background: Whole genome deep sequencing (WGS) could improve understanding of treatment failure and the emergence of resistance by revealing the distribution of mutations throughout the viral population over time. Methods: Adult patients receiving 1L ART (2 NRTI and 1 NNRTI) at the University of Abuja Teaching Hospital, Nigeria, were included if they had experienced virological failure (HIV-1 RNA >1000 copies/mL, at least 6 months after ART initiation, confirmed by clinician-driven testing), and had a stored plasma sample available for WGS. Results: Sixty participants were sampled during 1L failure (73% female; median age 30 (interquartile ratio [IQR] 28–35); median CD4+ cell count 110 cells/mm3 (IQR 63–191); median 28 months after ART initiation (IQR 18–41)). At 1L failure, 57% of participants had thymidine analogue mutations (TAMs), with 30% harbouring 3 or more TAMs, 95% had other (non-TAM) NRTI mutations and 100% had NNRTI mutations. The most common mutations were M184V, Y181C, G190A, K65R and K103N. Overall, 17% (61/367) of the mutations identified were low-level minority variants (present at 2%–20% of the intra-host viral population), which would not have been detected by standard resistance testing methods, 24% (88/367) were present at 20%–90% frequency, and 59% (218/367) were dominant majority variants representing >90% of the participant's viral population. Conclusions: Diverse Nigerian HIV clades exhibit multi-class drug resistance at 1LART failure. The predominance of high-frequency mutations suggests that emergent resistance had become fixed in the viral population by the time of sampling.