Intrapartum tenofovir and emtricitabine reduces low-concentration drug resistance selected by single-dose nevirapine for perinatal HIV prevention.
A single dose of tenofovir/emtricitabine (TDF/FTC) during labor significantly reduces peripartum nevirapine-associated viral drug resistance when measured by consensus HIV sequencing. It is unknown whether this effect extends to HIV subpopulations of <25-50%. We conducted a randomized trial of single-dose TDF/FTC added to peripartum nevirapine to reduce drug resistance associated with nonnucleoside reverse transcriptase inhibitors (NNRTIs). To detect mutations for NNRTIs comprising > or = 2% of the viral population, we used an oligonucleotide ligation assay (OLA) at codons 103, 106, 181, and 190 of HIV reverse transcriptase. To assess development of drug resistance mutations to our study intervention, OLA was also performed at codons 65 and 184. Among the 328 women included in the 2-week analysis, those receiving TDF/FTC were less likely to have NNRTI resistance by OLA (RR = 0.40, 95% CI = 0.21-0.77). A similar trend was observed among the 315 women included in the 6-week analysis (RR = 0.45, 95% CI = 0.31-0.66). Only two (1%) specimens had detectable K65R by OLA. Both were at 6 weeks postpartum; one was detected in the intervention arm and one in the control arm (p = 0.96). M184V was not detected. The ability of single-dose TDF/FTC to protect against peripartum NVP-induced NNRTI resistance extends to minority populations. This efficacy is achieved without significant selection of TDF- or FTC-resistant viruses.
Chi
Benjamin H
BH
Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. bchi@uab.edu
Ellis
Giovanina M
GM
Chintu
Namwinga
N
Cantrell
Ronald A
RA
Sinkala
Moses
M
Aldrovandi
Grace M
GM
Warrier
Ranjit
R
Mbewe
Felistas
F
Nakamura
Kyle
K
Stringer
Elizabeth M
EM
Frenkel
Lisa M
LM
Stringer
Jeffrey S A
JS
D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral / Q000187:drug effects*; D004359:Drug Therapy, Combination; D000068679:Emtricitabine; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000635:transmission / Q000821:virology; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control*; D009154:Mutation; D019829:Nevirapine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D063065:Organophosphonates / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D000068698:Tenofovir; D016896:Treatment Outcome
D019380:Anti-HIV Agents; D063065:Organophosphonates; D018894:Reverse Transcriptase Inhibitors; D003841:Deoxycytidine; D019829:Nevirapine; D000068698:Tenofovir; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase; D000068679:Emtricitabine; D000225:Adenine