Detection of K103N in Ugandan women after repeated exposure to single dose nevirapine.
OBJECTIVE
Use of single dose nevirapine (SD NVP) for prevention of HIV-1 mother-to-child transmission (pMTCT) is associated with selection of K103N-containing HIV variants. Repeat use of SD NVP for pMTCT may influence emergence and persistence of NVP-resistant variants.


METHODS
K103N-containing variants were studied in 48 Ugandan women who received SD NVP in the HIVNET 012 trial, and were re-exposed to SD NVP in one (n = 44) or two (n = 4) subsequent pregnancies during a 5-year follow-up study.


METHODS
Samples were analyzed using the LigAmp assay (assay cutoff: 0.5% K103N).


RESULTS
Among 44 women who were re-exposed to SD NVP in one subsequent pregnancy, 37.8% had K103N detected within 1 year of SD-NVP re-exposure. Detection of K103N was independently associated with detection of K103N 6-8 weeks after the first SD NVP exposure and with pre-NVP viral load. The portion of women with undetectable K103N by 2 years after SD NVP administration was similar after first versus second use of SD NVP for pMTCT. K103N was undetectable in 93.2% of evaluable women by 3 years of re-exposure. Only two of four women who received SD NVP in two pregnancies during the follow-up study had K103N detected after the last SD NVP exposure.


CONCLUSIONS
K103N was detected in some women within 1 year of SD NVP re-exposure, but faded from detection in most women by 3 years after re-exposure. Detection of K103N by 1 year after SD NVP re-exposure was associated with prior selection of K103N-containing variants and with pre-NVP viral load.
Flys
Tamara S
TS
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Mwatha
Anthony
A
Guay
Laura A
LA
Nakabiito
Clemensia
C
Donnell
Deborah
D
Musoke
Philippa
P
Mmiro
Francis
F
Jackson
J Brooks
JB
Eshleman
Susan H
SH
D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000235:genetics* / Q000517:prevention & control / Q000635:transmission; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics; D006801:Humans; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control; D019829:Nevirapine / Q000008:administration & dosage / Q000494:pharmacology*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000235:genetics* / Q000517:prevention & control; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D014454:Uganda; D019562:Viral Load
D018894:Reverse Transcriptase Inhibitors; D019829:Nevirapine