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; Saad B. Omer; Laura A. Guay; Wei Huang; Jessica Lidstrom; Philippa Musoke; Francis Mmiro; J. Brooks Jackson; Susan H. Eshleman

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

School of Medicine

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47 Scopus citations

Abstract

Background. Single-dose nevirapine (SD NVP) at birth plus NVP prophylaxis for the infant up to 6 weeks of age is superior to SDNVP 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.

Original language	English (US)
Pages (from-to)	1075-1082
Number of pages	8
Journal	Journal of Infectious Diseases
Volume	198
Issue number	7
DOIs	https://doi.org/10.1086/591503
State	Published - Oct 1 2008

ASJC Scopus subject areas

Immunology and Allergy
Infectious Diseases

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Church, J. D., Omer, S. B., Guay, L. A., Huang, W., Lidstrom, J., Musoke, P., Mmiro, F., Jackson, J. B., & Eshleman, S. H. (2008). 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. Journal of Infectious Diseases, 198(7), 1075-1082. https://doi.org/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. / Church, Jessica D.; Omer, Saad B.; Guay, Laura A. et al.

In: Journal of Infectious Diseases, Vol. 198, No. 7, 01.10.2008, p. 1075-1082.

Research output: Contribution to journal › Article › peer-review

Church, JD, Omer, SB, Guay, LA, Huang, W, Lidstrom, J, Musoke, P, Mmiro, F, Jackson, JB & Eshleman, SH 2008, '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', Journal of Infectious Diseases, vol. 198, no. 7, pp. 1075-1082. https://doi.org/10.1086/591503

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title = "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",

abstract = "Background. Single-dose nevirapine (SD NVP) at birth plus NVP prophylaxis for the infant up to 6 weeks of age is superior to SDNVP 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.",

author = "Church, {Jessica D.} and Omer, {Saad B.} and Guay, {Laura A.} and Wei Huang and Jessica Lidstrom and Philippa Musoke and Francis Mmiro and Jackson, {J. Brooks} and Eshleman, {Susan H.}",

note = "Funding Information: Financial support: HIV Prevention Trials Network, sponsored by the National Institutes of Allergy and Infectious Diseases (NIAID), National Institute of Child Health and Human Development (NICHD), National Institute on Drug Abuse, National Institute of Mental Health, and Office of AIDS Research, of the National Institutes of Health, Department of Health and Human Services (grant 5U01AI46745 to J.B.J., 5U01AI48054 to L.A.G., and 1U01AI068613 to S.H.E.); International Maternal Pediatric and Adolescent AIDS Clinical Trials Group (grant 1U01AI068632 to J.B.J., NIAID, NICHD; 3R01AI34235 to J.B.J., NIAID; and 5U01AI038576-07 to A.J.R., NIAID). a Deceased Reprints and correspondence: Susan Eshleman, MD, PhD, Dept. of Pathology, The Johns Hopkins Medical Institutions, Ross Bldg. 646, 720 Rutland Ave., Baltimore, MD 21205 (seshlem@jhmi.edu).",

year = "2008",

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doi = "10.1086/591503",

language = "English (US)",

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TY - JOUR

T1 - 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

AU - Church, Jessica D.

AU - Omer, Saad B.

AU - Guay, Laura A.

AU - Huang, Wei

AU - Lidstrom, Jessica

AU - Musoke, Philippa

AU - Mmiro, Francis

AU - Jackson, J. Brooks

AU - Eshleman, Susan H.

N1 - Funding Information: Financial support: HIV Prevention Trials Network, sponsored by the National Institutes of Allergy and Infectious Diseases (NIAID), National Institute of Child Health and Human Development (NICHD), National Institute on Drug Abuse, National Institute of Mental Health, and Office of AIDS Research, of the National Institutes of Health, Department of Health and Human Services (grant 5U01AI46745 to J.B.J., 5U01AI48054 to L.A.G., and 1U01AI068613 to S.H.E.); International Maternal Pediatric and Adolescent AIDS Clinical Trials Group (grant 1U01AI068632 to J.B.J., NIAID, NICHD; 3R01AI34235 to J.B.J., NIAID; and 5U01AI038576-07 to A.J.R., NIAID). a Deceased Reprints and correspondence: Susan Eshleman, MD, PhD, Dept. of Pathology, The Johns Hopkins Medical Institutions, Ross Bldg. 646, 720 Rutland Ave., Baltimore, MD 21205 (seshlem@jhmi.edu).

PY - 2008/10/1

Y1 - 2008/10/1

N2 - Background. Single-dose nevirapine (SD NVP) at birth plus NVP prophylaxis for the infant up to 6 weeks of age is superior to SDNVP 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.

AB - Background. Single-dose nevirapine (SD NVP) at birth plus NVP prophylaxis for the infant up to 6 weeks of age is superior to SDNVP 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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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

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