Sensitive drug-resistance assays reveal long-term persistence of HIV-1 variants with the K103N nevirapine (NVP) resistance mutation in some women and infants after the administration of single-dose NVP: HIVNET 012.
The HIV Network for Prevention Trials (HIVNET) 012 trial showed that NVP resistance (NVPR) emerged in some women and children after the administration of single-dose nevirapine (SD-NVP). We tested whether K103N-containing human immunodeficiency virus (HIV)-1 variants persisted in women and infants 1 year or more after the administration of SD-NVP.



We analyzed samples from 9 women and 5 infants in HIVNET 012 who had NVPR 6-8 weeks after the administration of SD-NVP. Samples were analyzed with the ViroSeq system and with 2 sensitive resistance assays, LigAmp and TyHRT.



ViroSeq detected the K103N mutation in 8 of 9 women and in 2 of 5 infants. LigAmp detected the K103N mutation at low levels in 8 of 9 women and in 4 of 5 infants. K103N was not detected by ViroSeq 12-24 months after the administration of SD-NVP but was detected by LigAmp in 3 of 9 women and in 1 of 5 infants. K103N was also detected in those samples by use of the TyHRT assay.



K103N-containing variants persist in some women and infants for 1 year or more after the administration of SD-NVP. Sensitive resistance assays may provide new insight into the impact of antiretroviral drug exposure on HIV-1 evolution.
Flys
Tamara
T
Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland 21205, USA.
Nissley
Dwight V
DV
Claassen
Cassidy W
CW
Jones
Dana
D
Shi
Chanjuan
C
Guay
Laura A
LA
Musoke
Philippa
P
Mmiro
Francis
F
Strathern
Jeffrey N
JN
Jackson
J Brooks
JB
Eshleman
James R
JR
Eshleman
Susan H
SH
D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000517:prevention & control*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics*; D006801:Humans; D007223:Infant; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control; D009154:Mutation; D019829:Nevirapine / Q000008:administration & dosage / Q000494:pharmacology*; D011247:Pregnancy; D013997:Time Factors; D014764:Viral Proteins / Q000235:genetics
D019380:Anti-HIV Agents; D014764:Viral Proteins; D019829:Nevirapine