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Clin Infect Dis. 2018 Oct 15. doi: 10.1093/cid/ciy881. [Epub ahead of print]

Impact of next generation sequencing defined HIV pre-treatment drug resistance on virological outcomes in the ANRS 12249 treatment as prevention trial.

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Africa Health Research Institute (AHRI), Mtubatuba, South Africa.
Sorbonne University, UPMC Univ. Paris 06, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique (IPLESP UMRS 1136), Paris, France.
Department of Global Health and Infection, Brighton and Sussex Medical School, Brighton, United Kingdom.
Institute for Global Health, University College London, London, United Kingdom.
KwaZulu-Natal Research Innovation and Sequencing Platform (KRISP), School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa.
Université de Bordeaux, ISPED, Centre INSERM 1219, Bordeaux, France.
Division of Infection and Immunity, University College London, London, United Kingdom.



Previous studies in HIV-positive individuals on thymidine analogue backbone antiretroviral therapy (ART) with either nevirapine or efavirenz have suggested poorer virological outcomes in the presence of pretreatment drug resistance (PDR). We assessed the impact of PDR on virological suppression (VS) [<50copies/mL] in individuals prescribed primarily tenofovir/emtricitabine/efavirenz in rural KwaZulu-Natal within a Treatment as Prevention trial.


Among 1,557 HIV-positive individuals reporting no prior ART at study entry and provided plasma samples, 1,328 individuals with entry viral load (VL) >1,000 copies/mL had next generation sequencing (NGS) of the HIV pol gene with MiSeq technology. Results were obtained for 1,148 individuals and the presence of PDR assessed at 5% and 20% detection thresholds. Virological outcome was assessed using Cox regression in 837 of 920 ART initiators with at least one follow-up VL after ART initiation.


PDR prevalence was 9.5% (109/1,148) and 12.8% (147/1,148) at 20% and 5% thresholds respectively. After a median of 1.36years (IQR 0.91-2.13), mostly on fixed-dose combination (FDC) tenofovir/emtricitabine/efavirenz, presence of both NRTI/NNRTI PDR vs. no PDR was associated with longer time to VS [aHR 0.32, 95%CI=0.12-0.86] while there was no difference between those with only NNRTI PDR vs. no PDR [aHR 1.05, 95%CI=0.82-1.34] at the 5% threshold. Similar differences were observed for mutations detected at the 20% threshold, although without statistical significance.


NGS uncovered a high prevalence of PDR amongst participants enrolled in trial clinics in rural KwaZulu-Natal. Dual class PDR to a mainly tenofovir/emtricitabine/efavirenz was associated with poorer VS. However, there was no impact of NNRTI PDR alone.


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