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Emergence and Fading of Nevirapine Resistance after First versus Repeated Use of Single-dose Nevirapine for Prevention of Mother-to-Child HIV Transmission: Women and Infants in the Repeat Pregnancy Study in Uganda
Susan Eshleman*1, T Flys1, M McConnell2, F Matovu3, J Church1, D Bagenda3, P Bakaki4, M Thigpen2, C Eure2, and M Fowler1
1Johns Hopkins Univ Sch of Med, Baltimore, MD, US; 2CDC, Atlanta, GA, US; 3Makerere Univ Johns Hopkins Univ Res Collaboration, Kampala, Uganda; and 4Case Western Reserve Univ, Cleveland, OH, US
Background: Single-dose
nevirapine (NVP) significantly reduces HIV mother-to-child transmission (MTCT).
However, NVP resistance often emerges in women and HIV-infected infants after single-dose
NVP exposure. We compared emergence and persistence of NVP resistance after
first-time versus repeated maternal use of single-dose NVP in a Ugandan study.
Methods: NVP resistance
was analyzed in 91 women (57 previously single-dose NVP-naïve and 34 previously
single-dose NVP-experienced), and in 17 of their HIV-infected infants who
received single-dose NVP in the Repeat Pregnancy study in Uganda (HIVNET 012 regimen). HIV genotyping was performed using the ViroSeq HIV Genotyping
System. K103N-containing HIV-1 variants were detected and quantified using the
LigAmp assay (assay cutoff: 0.5% K103N).
Results: Prior to
administration of single-dose NVP in the Repeat Pregnancy study, 0 of the 91
women had NVP-resistance mutations detected with ViroSeq, and only 3 (3.4%) had
K103N detected with LigAmp (see the table). At 6 weeks, the proportion of women
with NVP-resistance mutations detected using ViroSeq, or with K103N detected
using LigAmp, was similar in the 2 groups. The types of NVP-resistance
mutations and the level of K103N-containing HIV variants were also similar in
these 2 groups. Persistence of K103N was analyzed in the subset of women who
had detectable K103N at 6 weeks. At 6 and 12 months, K103N was detected using
LigAmp in a higher proportion of single-dose NVP-experienced women. However,
these differences were not statistically significant. Using ViroSeq, the
proportion of infants with NVP-resistance mutations at 6 weeks of age was
similar among those born to single-dose NVP-naïve women vs single-dose
NVP-experienced women (4 of 11 = 36.4% vs 3 of 6 = 50%, respectively; p =
0.64). LigAmp did not detect additional infants with resistance.
|
Time of testing
|
Test
|
Single-dose NVP-naïve
|
Single-dose NVP-experienced
|
p value
(Fisher’s exact test)
|
|
Baseline
|
ViroSeq
|
0/57
|
0/34
|
|
|
|
LigAmp
|
2/56
|
1/33
|
|
|
6 weeks
|
ViroSeq
|
13/57 (22.8%)
|
8/34 (23.5%)
|
1.00
|
|
|
LigAmp
|
26/57 (45.6%)
|
15/33 (45.5%)
|
1.00
|
|
6 months
|
LigAmp
|
10/26 (38.5%)
|
7/14 (50%)
|
0.52
|
|
12 months
|
LigAmp
|
2/9 (22.2%)
|
4/6 (66.7%)
|
0.14
|
Conclusions: The
proportion of women with NVP resistance, the types of mutations detected, and
the frequency and level of K103N were similar among previously single-dose NVP-naïve
and single-dose NVP-experienced women after single-dose NVP exposure. Prior MATERNAL
SINGLE-DOSE NVP exposure did not appear to influence emergence of resistance in
infants who were HIV-infected despite single-dose NVP prophylaxis.
|
