Genotypic resistance and immunologic outcomes among HIV-1-infected women with viral failure

Stephen J. Gange, Michael F. Schneider, Robert M. Grant, Teri Liegler, Audrey French, Mary Young, Kathryn Anastos, Tracey E. Wilson, Claudia Ponath, Ruth Greenblatt

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Objectives: To describe the prevalence of specific protease inhibitor (PI) and nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance mutations and the relationship between the presence of these mutations and immunologic outcomes following PI/NNRTI initiation among a cohort of HTV-1-infected women. Methods: Viral genotypic resistance testing was done for 366 women enrolled in the Women's Interagency HIV Study at the visit immediately prior to 1st reported use of PI or NNRTI (baseline) and at the visit approximately 1 year after PI/NNRTI initiation. We modeled the changes in CD4+ T-cell counts and HIV RNA levels approximately 1 year after therapy initiation as a function of baseline and follow-up markers, type of antiretroviral therapy used, and resistance mutations. Results: At baseline, 52% of women showed only nucleoside reverse transcriptase inhibitor (NRTI) mutations, 38% showed no mutations, and 10% showed PI or NNRTI mutations. Only 40% of women showed viral response (HIV-1 RNA ≤ 80 copies/mL) 1 year after initiating a PI or NNRTI. Among those without a viral response, 54% developed PI or NNRTI mutations. NNRTI (among those with baseline NRTI mutations) and PI resistance mutations were associated with better CD4+ cell count changes (mean increase of 118 cells/mm3 and 64 cells/mm3, respectively, as compared with viral nonresponders with no PI or NNRTI mutations). Conclusions: In this population-based cohort, virologic failure with PI or NNRTI resistance was common. Viremia with these resistance mutations was associated with preserved CD4+ T-cell count responses, providing evidence of reduced virulence or viral fitness.

Original languageEnglish (US)
Pages (from-to)68-74
Number of pages7
JournalJournal of Acquired Immune Deficiency Syndromes
Volume41
Issue number1
DOIs
StatePublished - Jan 2006

Fingerprint

Reverse Transcriptase Inhibitors
HIV-1
Protease Inhibitors
Mutation
CD4 Lymphocyte Count
Nucleosides
HIV
RNA
T-Lymphocytes
Viremia
Virulence

Keywords

  • Antiviral resistance
  • Cohort study
  • HIV/AIDS epidemiology

ASJC Scopus subject areas

  • Virology
  • Immunology

Cite this

Gange, S. J., Schneider, M. F., Grant, R. M., Liegler, T., French, A., Young, M., ... Greenblatt, R. (2006). Genotypic resistance and immunologic outcomes among HIV-1-infected women with viral failure. Journal of Acquired Immune Deficiency Syndromes, 41(1), 68-74. https://doi.org/10.1097/01.qai.0000174652.40782.4e

Genotypic resistance and immunologic outcomes among HIV-1-infected women with viral failure. / Gange, Stephen J.; Schneider, Michael F.; Grant, Robert M.; Liegler, Teri; French, Audrey; Young, Mary; Anastos, Kathryn; Wilson, Tracey E.; Ponath, Claudia; Greenblatt, Ruth.

In: Journal of Acquired Immune Deficiency Syndromes, Vol. 41, No. 1, 01.2006, p. 68-74.

Research output: Contribution to journalArticle

Gange, SJ, Schneider, MF, Grant, RM, Liegler, T, French, A, Young, M, Anastos, K, Wilson, TE, Ponath, C & Greenblatt, R 2006, 'Genotypic resistance and immunologic outcomes among HIV-1-infected women with viral failure', Journal of Acquired Immune Deficiency Syndromes, vol. 41, no. 1, pp. 68-74. https://doi.org/10.1097/01.qai.0000174652.40782.4e
Gange, Stephen J. ; Schneider, Michael F. ; Grant, Robert M. ; Liegler, Teri ; French, Audrey ; Young, Mary ; Anastos, Kathryn ; Wilson, Tracey E. ; Ponath, Claudia ; Greenblatt, Ruth. / Genotypic resistance and immunologic outcomes among HIV-1-infected women with viral failure. In: Journal of Acquired Immune Deficiency Syndromes. 2006 ; Vol. 41, No. 1. pp. 68-74.
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AU - Schneider, Michael F.

AU - Grant, Robert M.

AU - Liegler, Teri

AU - French, Audrey

AU - Young, Mary

AU - Anastos, Kathryn

AU - Wilson, Tracey E.

AU - Ponath, Claudia

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N2 - Objectives: To describe the prevalence of specific protease inhibitor (PI) and nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance mutations and the relationship between the presence of these mutations and immunologic outcomes following PI/NNRTI initiation among a cohort of HTV-1-infected women. Methods: Viral genotypic resistance testing was done for 366 women enrolled in the Women's Interagency HIV Study at the visit immediately prior to 1st reported use of PI or NNRTI (baseline) and at the visit approximately 1 year after PI/NNRTI initiation. We modeled the changes in CD4+ T-cell counts and HIV RNA levels approximately 1 year after therapy initiation as a function of baseline and follow-up markers, type of antiretroviral therapy used, and resistance mutations. Results: At baseline, 52% of women showed only nucleoside reverse transcriptase inhibitor (NRTI) mutations, 38% showed no mutations, and 10% showed PI or NNRTI mutations. Only 40% of women showed viral response (HIV-1 RNA ≤ 80 copies/mL) 1 year after initiating a PI or NNRTI. Among those without a viral response, 54% developed PI or NNRTI mutations. NNRTI (among those with baseline NRTI mutations) and PI resistance mutations were associated with better CD4+ cell count changes (mean increase of 118 cells/mm3 and 64 cells/mm3, respectively, as compared with viral nonresponders with no PI or NNRTI mutations). Conclusions: In this population-based cohort, virologic failure with PI or NNRTI resistance was common. Viremia with these resistance mutations was associated with preserved CD4+ T-cell count responses, providing evidence of reduced virulence or viral fitness.

AB - Objectives: To describe the prevalence of specific protease inhibitor (PI) and nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance mutations and the relationship between the presence of these mutations and immunologic outcomes following PI/NNRTI initiation among a cohort of HTV-1-infected women. Methods: Viral genotypic resistance testing was done for 366 women enrolled in the Women's Interagency HIV Study at the visit immediately prior to 1st reported use of PI or NNRTI (baseline) and at the visit approximately 1 year after PI/NNRTI initiation. We modeled the changes in CD4+ T-cell counts and HIV RNA levels approximately 1 year after therapy initiation as a function of baseline and follow-up markers, type of antiretroviral therapy used, and resistance mutations. Results: At baseline, 52% of women showed only nucleoside reverse transcriptase inhibitor (NRTI) mutations, 38% showed no mutations, and 10% showed PI or NNRTI mutations. Only 40% of women showed viral response (HIV-1 RNA ≤ 80 copies/mL) 1 year after initiating a PI or NNRTI. Among those without a viral response, 54% developed PI or NNRTI mutations. NNRTI (among those with baseline NRTI mutations) and PI resistance mutations were associated with better CD4+ cell count changes (mean increase of 118 cells/mm3 and 64 cells/mm3, respectively, as compared with viral nonresponders with no PI or NNRTI mutations). Conclusions: In this population-based cohort, virologic failure with PI or NNRTI resistance was common. Viremia with these resistance mutations was associated with preserved CD4+ T-cell count responses, providing evidence of reduced virulence or viral fitness.

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KW - HIV/AIDS epidemiology

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