Analysis of NVP Resistance in Ugandan Infants Who Were HIV-infected despite Receiving Single-dose Nevirapine vs Single-dose NVP Plus up to 6 Weeks of Daily NVP to Prevent HIV Vertical Transmission
Jessica Church*1, S Omer2, L Guay1, W Huang3, P Musoke4, F Mmiro5, J Jackson1, and S Eshleman1
1Johns Hopkins Univ Sch of Med, Baltimore, MD, US; 2Johns Hopkins Univ Bloomberg Sch of Publ Hlth, Baltimore, MD, US; 3Monogram Biosci, South San Francisco, CA, US; 4Makerere Univ, Kampala, Uganda; and 5Makerere Univ Johns Hopkins Univ Res Collaboration, Kampala, Uganda
Background: The SWEN Study in Uganda, Ethiopia, and India compared a regimen of single-dose NVP (the HIVNET 012 regimen) to a
regimen of single-dose NVP plus up to 6 weeks of daily NVP to the infant for
prevention of HIV transmission in breastfeeding infants. We analyzed HIV
genotypic resistance, phenotypic resistance, and replication capacity in
Ugandan infants in this study.
Methods: Plasma samples were available from 49 (71%)
of 69 infants diagnosed with HIV infection by 6 weeks of age (24 in the single-dose
NVP arm; 25 in the extended NVP arm). In the extended NVP arm, the median
number of NVP doses received was 14 (range 3 to 33) in infants diagnosed with
HIV infection at birth (n = 17), 14 (range 7 to 26) in infants diagnosed
at 2 weeks of age (n = 5), and 34 (range 21 to 35) in infants diagnosed
with HIV infection by 6 weeks of age (n = 3). Samples were analyzed
using the ViroSeq system, the PhenoSense GT assay (Monogram Biosciences), and a
quantitative point mutation assay (LigAmp, for K103N, Y181C, and G190A). If NVP
resistance was detected at 6 weeks, a 6-month sample was tested.
Results: Maternal CD4 cell count, infant viral load,
and HIV subtypes were similar in the 2 study arms. Using ViroSeq, NVP
resistance was detected at 6 weeks in a higher portion of infants in the
extended NVP arm compared to the SD NVP arm (21/25=84% vs. 12/24=50%, p=0.01).
A higher portion of infants in the extended NVP arm also had at least one NVP
resistance mutation detected using the LigAmp assay (19 of 25 = 79% vs 7 of 24 =
35%, p = 0.004). In the extended NVP arm, detection of NVP resistance
was not associated with the number of NVP doses received or the HIV status at
birth. Among infants with resistance at 6 weeks, only 1 of 6 infants in the single-dose
NVP arm had NVP resistance detected by ViroSeq at 6 months. In contrast, all 7
infants in the extended NVP arm still had NVP resistance detected at 6 months.
Phenotypic resistance results were available for 42 (85.7%) of 49 infants
analyzed at 6 weeks. The portion of infants with phenotypic resistance was
higher in the extended NVP arm than in the single-dose NVP arm (19 of 22 =
86.3% vs 9 of 20 = 45%, p = 0.005). Phenotypic results were consistent
with genotypic resistance results. The median HIV RC was similar among infants
in the 2 study arms, and among infants with and without NVP resistance.
Conclusions: HIV-infected Ugandan infants who
received extended NVP prophylaxis were more likely to have genotypic and
phenotypic NVP resistance than those who received only single-dose NVP.