HIV-1 Drug Resistance by Ultra-Deep Sequencing Following Short Course Zidovudine, Single-Dose Nevirapine, and Single-Dose Tenofovir with Emtricitabine for Prevention of Mother-to-Child Transmission.
Antiretroviral drug resistance following pMTCT strategies remains a significant problem. With rapid advancements in next generation sequencing technologies, there is more focus on HIV drug-resistant variants of low frequency, or the so-called minority variants. In South Africa, AZT monotherapy for pMTCT, similar to World Health Organization option A, has been used since 2008. In 2010, a single dose of co-formulated TDF/FTC was included in the strategy for prevention of resistance conferred by single-dose nevirapine (sd NVP). The study was conducted in KwaZulu-Natal, South Africa, among pMTCT participants who received AZT monotherapy from 14 weeks of gestation, intrapartum AZT and sd NVP, and postpartum sd TDF/FTC. Twenty-six specimens collected at 6 weeks post-delivery were successfully sequenced using 454 ultra-deep sequencing. Non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance was detected in 17 of 26 (65%) patients, 2 (7%) had Thymidine analogue mutations, and 3 (11%) had K65R. Of the 17 patients with NNRTI resistance, 11 (65%) had high-level NNRTI resistance, whereas 6 (35%) had intermediate NNRTI resistance. The levels of NNRTI resistance are much higher than would be expected, given the inclusion of antepartum AZT and postpartum TDF/FTC. This high level of NNRTI resistance could impact future NNRTI-containing treatment for a large proportion of pMTCT-exposed women. The detection of Thymidine analogue mutations highlights the need to understand the clinical impact of these on AZT-containing antiretroviral treatment in women exposed to AZT monotherapy.
*Department of Virology, National Health Laboratory Service, University of KwaZulu-Natal, Durban, South Africa; †IrsiCaixa AIDS Research Institute, Badalona, Catalonia, Spain; ‡Universitat de Vic, Vic, Catalonia, Spain; §HIV Unit, Hospital Universitari Germans Trias i Pujol, Badalona, Catalonia, Spain; ∥Universitat Autonoma de Barcelona, Barcelona, Catalonia, Spain; and ¶Department of Virology, HIV Pathogenesis Laboratory, Nelson R Mandela Medical School, University of KwaZulu-Natal, Durban, South Africa.
Reshmi
R
Samuel
Marc Noguera
MN
Julian
Roger
R
Paredes
Raveen
R
Parboosing
Pravi
P
Moodley
Lavanya
L
Singh
Anneta
A
Naidoo
Michelle
M
Gordon
D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D000068679:Emtricitabine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D015658:HIV Infections / Q000517:prevention & control* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control*; D009154:Mutation; D019829:Nevirapine / Q000494:pharmacology / Q000627:therapeutic use; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000821:virology; D000068698:Tenofovir / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D019562:Viral Load; D015215:Zidovudine / Q000494:pharmacology / Q000627:therapeutic use
D019380:Anti-HIV Agents; D015215:Zidovudine; D019829:Nevirapine; D000068698:Tenofovir; D000068679:Emtricitabine