Quantitative analysis of HIV-1 variants with the K103N resistance mutation after single-dose nevirapine in women with HIV-1 subtypes A, C, and D

Tamara S. Flys, Shu Chen, Dana C. Jones, Donald R. Hoover, Jessica D. Church, Susan A. Fiscus, Anthony Mwatha, Laura A. Guay, Francis Mmiro, Philippa Musoke, Newton Kumwenda, Taha E Taha, J. Brooks Jackson, Susan Eshleman

Research output: Contribution to journalArticle

Abstract

INTRODUCTION: We used a sensitive point mutation assay, LigAmp, to detect and quantify K103N-containing variants in African women who received single-dose nevirapine (NVP) to prevent mother-to-child HIV-1 transmission. METHODS: Plasma for testing was collected 6 to 8 weeks postpartum from 301 women (144 subtype A, 63 subtype C, and 94 subtype D). RESULTS: The portion of women with 0.5% or more K103N-containing variants was lowest for subtype A (60/144, 41.7%) and highest for subtype C (44/63, 69.8%; P <0.0001). K103N was rarely detected in pre-NVP samples. In a multivariate model, K103N detection was associated with HIV-1 subtype (C > A), after adjusting for log10 delivery viral load, the number of days between NVP dosing and sample collection, age, and parity. Among women with K103N detected: (1) the median %K103N was lower for subtype A (2.2%) than C (11.7%, P = 0.0001) or D (5.5%, P = 0.04), and (2) in a multivariate linear model, higher log10 (%K103N) was associated with HIV subtype (C > A, P = 0.0001; D > A, P = 0.01; and C vs D, no difference), but not other factors. CONCLUSIONS: After administration of single-dose NVP, K103N was detected more frequently and at higher levels in women with subtypes C and D than A. Further studies are needed to evaluate the clinical significance of NVP-resistant variants in this setting.

Original languageEnglish (US)
Pages (from-to)610-613
Number of pages4
JournalJournal of Acquired Immune Deficiency Syndromes
Volume42
Issue number5
DOIs
StatePublished - Aug 2006

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Nevirapine
HIV-1
Mutation
Parity
Viral Load
Point Mutation
Postpartum Period
Linear Models
Mothers
HIV

Keywords

  • Africa
  • HIV-1
  • Mother-to-child transmission
  • Nevirapine
  • Resistance

ASJC Scopus subject areas

  • Virology
  • Immunology

Cite this

Quantitative analysis of HIV-1 variants with the K103N resistance mutation after single-dose nevirapine in women with HIV-1 subtypes A, C, and D. / Flys, Tamara S.; Chen, Shu; Jones, Dana C.; Hoover, Donald R.; Church, Jessica D.; Fiscus, Susan A.; Mwatha, Anthony; Guay, Laura A.; Mmiro, Francis; Musoke, Philippa; Kumwenda, Newton; Taha, Taha E; Jackson, J. Brooks; Eshleman, Susan.

In: Journal of Acquired Immune Deficiency Syndromes, Vol. 42, No. 5, 08.2006, p. 610-613.

Research output: Contribution to journalArticle

Flys, Tamara S. ; Chen, Shu ; Jones, Dana C. ; Hoover, Donald R. ; Church, Jessica D. ; Fiscus, Susan A. ; Mwatha, Anthony ; Guay, Laura A. ; Mmiro, Francis ; Musoke, Philippa ; Kumwenda, Newton ; Taha, Taha E ; Jackson, J. Brooks ; Eshleman, Susan. / Quantitative analysis of HIV-1 variants with the K103N resistance mutation after single-dose nevirapine in women with HIV-1 subtypes A, C, and D. In: Journal of Acquired Immune Deficiency Syndromes. 2006 ; Vol. 42, No. 5. pp. 610-613.
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abstract = "INTRODUCTION: We used a sensitive point mutation assay, LigAmp, to detect and quantify K103N-containing variants in African women who received single-dose nevirapine (NVP) to prevent mother-to-child HIV-1 transmission. METHODS: Plasma for testing was collected 6 to 8 weeks postpartum from 301 women (144 subtype A, 63 subtype C, and 94 subtype D). RESULTS: The portion of women with 0.5{\%} or more K103N-containing variants was lowest for subtype A (60/144, 41.7{\%}) and highest for subtype C (44/63, 69.8{\%}; P <0.0001). K103N was rarely detected in pre-NVP samples. In a multivariate model, K103N detection was associated with HIV-1 subtype (C > A), after adjusting for log10 delivery viral load, the number of days between NVP dosing and sample collection, age, and parity. Among women with K103N detected: (1) the median {\%}K103N was lower for subtype A (2.2{\%}) than C (11.7{\%}, P = 0.0001) or D (5.5{\%}, P = 0.04), and (2) in a multivariate linear model, higher log10 ({\%}K103N) was associated with HIV subtype (C > A, P = 0.0001; D > A, P = 0.01; and C vs D, no difference), but not other factors. CONCLUSIONS: After administration of single-dose NVP, K103N was detected more frequently and at higher levels in women with subtypes C and D than A. Further studies are needed to evaluate the clinical significance of NVP-resistant variants in this setting.",
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T1 - Quantitative analysis of HIV-1 variants with the K103N resistance mutation after single-dose nevirapine in women with HIV-1 subtypes A, C, and D

AU - Flys, Tamara S.

AU - Chen, Shu

AU - Jones, Dana C.

AU - Hoover, Donald R.

AU - Church, Jessica D.

AU - Fiscus, Susan A.

AU - Mwatha, Anthony

AU - Guay, Laura A.

AU - Mmiro, Francis

AU - Musoke, Philippa

AU - Kumwenda, Newton

AU - Taha, Taha E

AU - Jackson, J. Brooks

AU - Eshleman, Susan

PY - 2006/8

Y1 - 2006/8

N2 - INTRODUCTION: We used a sensitive point mutation assay, LigAmp, to detect and quantify K103N-containing variants in African women who received single-dose nevirapine (NVP) to prevent mother-to-child HIV-1 transmission. METHODS: Plasma for testing was collected 6 to 8 weeks postpartum from 301 women (144 subtype A, 63 subtype C, and 94 subtype D). RESULTS: The portion of women with 0.5% or more K103N-containing variants was lowest for subtype A (60/144, 41.7%) and highest for subtype C (44/63, 69.8%; P <0.0001). K103N was rarely detected in pre-NVP samples. In a multivariate model, K103N detection was associated with HIV-1 subtype (C > A), after adjusting for log10 delivery viral load, the number of days between NVP dosing and sample collection, age, and parity. Among women with K103N detected: (1) the median %K103N was lower for subtype A (2.2%) than C (11.7%, P = 0.0001) or D (5.5%, P = 0.04), and (2) in a multivariate linear model, higher log10 (%K103N) was associated with HIV subtype (C > A, P = 0.0001; D > A, P = 0.01; and C vs D, no difference), but not other factors. CONCLUSIONS: After administration of single-dose NVP, K103N was detected more frequently and at higher levels in women with subtypes C and D than A. Further studies are needed to evaluate the clinical significance of NVP-resistant variants in this setting.

AB - INTRODUCTION: We used a sensitive point mutation assay, LigAmp, to detect and quantify K103N-containing variants in African women who received single-dose nevirapine (NVP) to prevent mother-to-child HIV-1 transmission. METHODS: Plasma for testing was collected 6 to 8 weeks postpartum from 301 women (144 subtype A, 63 subtype C, and 94 subtype D). RESULTS: The portion of women with 0.5% or more K103N-containing variants was lowest for subtype A (60/144, 41.7%) and highest for subtype C (44/63, 69.8%; P <0.0001). K103N was rarely detected in pre-NVP samples. In a multivariate model, K103N detection was associated with HIV-1 subtype (C > A), after adjusting for log10 delivery viral load, the number of days between NVP dosing and sample collection, age, and parity. Among women with K103N detected: (1) the median %K103N was lower for subtype A (2.2%) than C (11.7%, P = 0.0001) or D (5.5%, P = 0.04), and (2) in a multivariate linear model, higher log10 (%K103N) was associated with HIV subtype (C > A, P = 0.0001; D > A, P = 0.01; and C vs D, no difference), but not other factors. CONCLUSIONS: After administration of single-dose NVP, K103N was detected more frequently and at higher levels in women with subtypes C and D than A. Further studies are needed to evaluate the clinical significance of NVP-resistant variants in this setting.

KW - Africa

KW - HIV-1

KW - Mother-to-child transmission

KW - Nevirapine

KW - Resistance

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