Greater suppression of nevirapine resistance with 21- vs 7-day antiretroviral regimens after intrapartum single-dose nevirapine for prevention of mother-to-child transmission of HIV.

TitleGreater suppression of nevirapine resistance with 21- vs 7-day antiretroviral regimens after intrapartum single-dose nevirapine for prevention of mother-to-child transmission of HIV.
Publication TypeJournal Article
Year of Publication2013
AuthorsMcMahon DK, Zheng L, Hitti J, Chan ES, Halvas EK, Hong F, Kabanda J, Taulo F, Kumarasamy N, Bonhomme J, Wallis CL, Klingman KL, Hughes MD, Mellors JW
JournalClin Infect Dis
Volume56
Issue7
Pagination1044-51
Date Published2013 Apr
ISSN1537-6591
KeywordsAdult, Anti-HIV Agents, Antiretroviral Therapy, Highly Active, Drug Resistance, Viral, Female, HIV, HIV Infections, Humans, Infant, Newborn, Infectious Disease Transmission, Vertical, Nevirapine, Pregnancy, Pregnancy Complications, Infectious, Prospective Studies, Time Factors, Young Adult
Abstract

BACKGROUND: Nevirapine (NVP) resistance emerges in up to 70% of women exposed to single-dose (sd) NVP for prevention of mother-to-child transmission of human immunodeficiency virus (HIV).

METHODS: HIV-infected pregnant women were randomized to receive sdNVP and either zidovudine/lamivudine (3TC), tenofovir/emtricitabine (FTC), or lopinavir/ritonavir for either 7 or 21 days. The primary endpoint was the emergence of new NVP resistance mutations as detected by standard population genotype at 2 and 6 weeks after treatment. Low-frequency NVP- or 3TC/FTC-resistant mutants at codons 103, 181, and 184 were sought using allele-specific polymerase chain reaction (ASP).

RESULTS: Among 484 women randomized, 422 (87%) received study treatment. Four hundred twelve (98%) women had primary endpoint results available; of these, 5 (1.2%) had new NVP resistance detected by population genotype: 4 of 215 in the 7-day arms (1.9%; K103N in 4 women with Y181C, Y188C, or G190A in 3 of 4) and 1 of 197 (0.5%; V108I) in the 21-day arms (P = .37). Among women with ASP results, new NVP resistance mutations emerged significantly more often in the 7-day arms (13/74 [18%]) than in the 21-day arms (3/66 [5%], P = .019). 3TC/FTC-resistant mutants (M184V/I) emerged infrequently (7/134 [5%]), and their occurrence did not differ by arm.

CONCLUSIONS: Three short-term antiretroviral strategies, begun simultaneously with the administration of sdNVP, resulted in a low rate (1.2%) of new NVP-resistance mutations when assessed at 2 and 6 weeks following completion of study treatment by standard genotype. ASP revealed that 21-day regimens were significantly better than 7-day regimens at preventing the emergence of minor NVP resistance variants. Clinical Trials Registration.NCT00099632.

DOI10.1093/cid/cis1219
Alternate JournalClin. Infect. Dis.
PubMed ID23300238
PubMed Central IDPMC3588119
Grant List1 U01A10 68636-01 / / PHS HHS / United States
1U01 AI069494-01 / AI / NIAID NIH HHS / United States
1U01AI068634-01 / AI / NIAID NIH HHS / United States
1U01AI068636-01 / AI / NIAID NIH HHS / United States
U01 AI068634 / AI / NIAID NIH HHS / United States
U01 AI068636 / AI / NIAID NIH HHS / United States