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. 2008 Oct 1;198(7):1075-82.
doi: 10.1086/591503.

Analysis of nevirapine (NVP) resistance in Ugandan infants who were HIV infected despite receiving single-Dose (SD) NVP versus SD NVP plus daily NVP up to 6 weeks of age to prevent HIV vertical transmission

Jessica D Church  1 , Saad B Omer, Laura A Guay, Wei Huang, Jessica Lidstrom, Philippa Musoke, Francis Mmiro, J Brooks Jackson, Susan H Eshleman
Affiliations

Analysis of nevirapine (NVP) resistance in Ugandan infants who were HIV infected despite receiving single-Dose (SD) NVP versus SD NVP plus daily NVP up to 6 weeks of age to prevent HIV vertical transmission

Jessica D Church et al. J Infect Dis. .

Abstract

Background: Single-dose nevirapine (SD NVP) at birth plus NVP prophylaxis for the infant up to 6 weeks of age is superior to SD NVP alone for prevention of vertical transmission of human immunodeficiency virus (HIV) through breastfeeding. We analyzed NVP resistance in HIV-infected Ugandan infants who received either SD NVP or extended NVP prophylaxis.

Methods: We tested plasma HIV by using a genotyping assay (ViroSeq; Celera Diagnostics), a phenotypic resistance assay (PhenoSense; Monogram Biosciences), and sensitive point mutation assay (LigAmp, for K103N, Y181C, and G190A).

Results: When infants were 6 weeks old, ViroSeq detected NVP resistance in a higher proportion of infants in the extended NVP arm than in the SD NVP arm (21 of 25 [84%] vs. 12 of 24 [50%]; P = .01). Similar results were obtained with LigAmp and PhenoSense. In both study arms, infants who were HIV infected at birth frequently had NVP resistance detected. In contrast, infants in the extended NVP arm who were HIV infected after birth were more likely to have resistance detected at 6 weeks, compared with infants in the SD NVP arm. The use of extended NVP prophylaxis was also associated with detection of NVP resistance by ViroSeq at 6 months (7 of 7 [100%] infants in the extended NVP arm had resistance detected, compared with 1 of 6 [16.7%] infants in the SD NVP arm; P = .005).

Conclusions: The use of extended NVP prophylaxis was associated with increased selection for and persistence of NVP resistance in HIV-infected Ugandan infants.

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Conflict of interest statement

Conflict of Interest Statement None of the authors have a commercial or other association that might pose a conflict of interest with the following exception: (1) Dr. Susan Eshleman is a co-inventor of the LigAmp assay and Johns Hopkins University has filed a patent application with the US-Patent and Trademark Office. The inventors may receive royalty payments if the patent is awarded and licensed. (2) Wei Huang is an employee and stockholder of Monogram Biosciences, Inc. (3) Susan Eshleman is a member of the Clinical Advisory Board of Monogram Biosciences.

Figures

Figure 1
Figure 1. Resistance results for infants in the SD NVP and Extended NVP arms
Resistance results from infants in the SD NVP arm (white bars) and in the extended NVP arm (shaded bars) are shown. The p-values for comparisons of proportions (Fisher's exact test) are shown above the bars. The number of infants with resistance / the number of infants tested in each subgroup is shown in each bar. For each subgroup, the age of infant at diagnosis of HIV infection (Age at diagnosis), the age of the infant at the time of collection of the sample used for resistance testing (Age at testing), and the test method used for testing (Test method) are shown below the bar graph. Panels A and B: Portion of infants with NVP resistance detected by ViroSeq at 6 weeks of age. Panel A: Results for all infants tested. Panel B: Results for infants who were diagnosed with HIV infection at birth (left) and results for infants who were HIV-uninfected at birth and were diagnosed with HIV infection at 2 or 6 weeks of age (right). Panel C: Portion of infants with NVP resistance detected by ViroSeq at 6 month of age. Panel D: Portion of late-infected infants with NVP resistance mutations (K103N, Y181C, or G190A) detected by the LigAmp assay at the time of HIV diagnosis.
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References

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