Development of phenotypic HIV-1 drug resistance after exposure to single-dose nevirapine.
OBJECTIVE
Single-dose nevirapine (sdNVP) used to prevent mother-to-child transmission of HIV-1 results in the selection of genotypic drug resistance mutations. To assess the levels of phenotypic resistance conferred by these mutations, we examined the ability of sample-derived HIV-1 reverse transcriptase to function in the presence of nevirapine (NVP).


METHODS
Plasma samples from HIV-1 pregnant women before and after exposure to sdNVP were used to extract viral reverse transcriptase for the Cavidi ExaVir Drug susceptibility assay. The fold increases in phenotypic resistance for each sample were compared with the genotypic profiles determined by population-based sequencing.


RESULTS
None of the women sampled before sdNVP exposure had phenotypic resistance (median fold increase 0.7). Seven weeks after sdNVP, there was a 16-fold increase in phenotypic resistance among women who had NVP resistance mutations compared with only a 1.9-fold increase among NVP-exposed women with wild-type virus. Phenotypic resistance decayed with time coincident with the fading of genotypic mutations, and by 18 months, all samples were phenotypically susceptible.


CONCLUSIONS
Exposure of pregnant women to sdNVP was associated with the transient appearance of viral populations that displayed phenotypic resistance to NVP. Overall, there was good concordance between phenotypic resistance to NVP, as measured with this enzymatic assay, and the presence of NVP genotypic mutations.
Basson
Adriaan E
AE
AIDS Virus Research Unit, National Institute for Communicable Diseases, Johannesburg, South Africa.
Ntsala
Matshediso
M
Martinson
Neil
N
Tlale
Emily
E
Corrigan
Gary E
GE
Shao
Xingwu
X
Gray
Glenda
G
McIntyre
James
J
Puren
Adrian
A
Morris
Lynn
L
D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000635:transmission / Q000821:virology; D054303:HIV Reverse Transcriptase / Q000378:metabolism; D015497:HIV-1 / Q000145:classification / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D007223:Infant; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control*; D019829:Nevirapine / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D010641:Phenotype; D011247:Pregnancy
D019380:Anti-HIV Agents; D019829:Nevirapine; D054303:HIV Reverse Transcriptase