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

Ndembi, Nicaise, MPhiL, PhD*; Elbouzidi, Kate, MD†,‡; Kwaghe, Vivian, MD§; Ogbanufe, Obinna, MD; Murtala-Ibrahim, Fati, MPH*; Charurat, Man, PhD; Dakum, Patrick, MD*; Sabin, Caroline, MD, PhD

JAIDS Journal of Acquired Immune Deficiency Syndromes: April 2018 - Volume 77 - Issue - p 61
doi: 10.1097/01.qai.0000532498.24783.d7
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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.

*Institute of Human Virology Nigeria;

Division of Infection and Immunity, University College London, London, United Kingdom;

Department of Infection and Population Health, University College London, London, United Kingdom;

§University of Abuja Teaching Hospital, Abuja, Nigeria;

US Centers for Disease Control and Prevention, US Embassy, Abuja, Nigeria; and

Institute of Human Virology, University of Maryland School of Medicine

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