Identification of the K103N resistance mutation in Ugandan women receiving nevirapine to prevent HIV-1 vertical transmission.
OBJECTIVE
A recent trial in Uganda demonstrated that a simple, inexpensive regimen of nevirapine (NVP) prophylaxis can dramatically reduce HIV-1 vertical transmission risk. In this regimen, women receive a single dose of NVP at the onset of labor and infants receive a single dose of NVP within 72 h of birth. The objective of this study was to determine whether HIV-1 variants with NVP resistance mutations were selected in Ugandan women who received this regimen in the Phase I/II trial HIVNET 006.


METHODS
Reverse transcriptase (RT) sequences from plasma HIV-1 were analyzed from 15 women 6 weeks after NVP dosing. RT sequences from plasma collected prior to NVP dosing were also analyzed.


RESULTS
The K103N NVP resistance mutation was detected 6 weeks after NVP administration in three (20%) out of 15 women (95% confidence interval, 0-40%). Pre-dose samples were available from two of the three women; both pre-dose samples lacked the mutation. Other NVP resistance mutations were absent from all 15 women. Women with the K103N mutation had a longer median NVP elimination half-life, decreased median oral clearance, and increased median area under the concentration time curve than those without the mutation. An evaluable sample was obtained from one of these three women 33 months after delivery; the K103N mutation was not detected in that sample.


CONCLUSIONS
This preliminary study demonstrates that HIV-1 with the RT K103N mutation can be detected in some Ugandan women following a single dose of NVP. This suggests that non-nucleoside RT inhibitor resistance may be selected in some people by single dose NVP prophylaxis. Pharmacokinetic data suggested that a more prolonged exposure to NVP after dosing may favor selection of NVP-resistant HIV-1.
Jackson
J B
JB
Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21205, USA.
Becker-Pergola
G
G
Guay
L A
LA
Musoke
P
P
Mracna
M
M
Fowler
M G
MG
Mofenson
L M
LM
Mirochnick
M
M
Mmiro
F
F
Eshleman
S H
SH
D019380:Anti-HIV Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D004352:Drug Resistance, Microbial / Q000235:genetics; D005260:Female; D015658:HIV Infections / Q000517:prevention & control / Q000635:transmission / Q000821:virology*; D054303:HIV Reverse Transcriptase / Q000235:genetics*; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control*; D009154:Mutation; D019829:Nevirapine / Q000493:pharmacokinetics / Q000494:pharmacology*; D018894:Reverse Transcriptase Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D014454:Uganda
D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D019829:Nevirapine; D054303:HIV Reverse Transcriptase