Identification of nevirapine-resistant HIV-1 in the latent reservoir after single-dose nevirapine to prevent mother-to-child transmission of HIV-1

Megan Wind-Rotolo, Christine Durand, Lisa Cranmer, Alison Reid, Neil Martinson, Meg Caroline Doherty, Benjamin L. Jilek, Joseph Kagaayi, Allan Kizza, Visva Pillay, Oliver B. Laeyendecker, Steven James Reynolds, Susan Eshleman, Bryan M Lau, Stuart Campbell Ray, Janet M Siliciano, Thomas C Quinn, Robert F Siliciano

Research output: Contribution to journalArticle

Abstract

Background. Intrapartum single-dose nevirapine decreases mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) but promotes nevirapine resistance. Although resistant viruses fade to undetectable levels in plasma, they may persist as stably integrated proviruses within the latent reservoir in resting CD4-T cells, potentially complicating future treatment. Methods. Blood samples were collected from 60 women from South Africa and Uganda-6 months after they had received single-dose nevirapine. To selectively analyze the stable latent form of HIV-1, resting CD4-T cells were isolated and activated in the presence of reverse-transcriptase inhibitors and integrase inhibitors, which allows for the specific isolation of viruses produced by cells with stably integrated proviral DNA. These viruses were then analyzed for nevirapine resistance. Results. Although only a small number of latently infected cells were present in each blood sample (mean, 162 cells), nevirapine resistance mutations (K103N and G190A) were detected in the latent reservoir of 4 (8%) of 50 evaluable women. Conclusions. A single dose of nevirapine can establish antiretroviral resistance within the latent reservoir. This results in a potentially lifelong risk of reemergence of nevirapine-resistant virus and highlights the need for strategies to prevent transmission that do not compromise successful future treatment.

Original languageEnglish (US)
Pages (from-to)1301-1309
Number of pages9
JournalJournal of Infectious Diseases
Volume199
Issue number9
DOIs
StatePublished - May 1 2009

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Nevirapine
HIV-1
Mothers
Viruses
Integrase Inhibitors
T-Lymphocytes
Proviruses
Reverse Transcriptase Inhibitors
Uganda
South Africa
Mutation
DNA
Therapeutics

ASJC Scopus subject areas

  • Infectious Diseases
  • Immunology and Allergy

Cite this

@article{c87027bf25a84051a42719432198e252,
title = "Identification of nevirapine-resistant HIV-1 in the latent reservoir after single-dose nevirapine to prevent mother-to-child transmission of HIV-1",
abstract = "Background. Intrapartum single-dose nevirapine decreases mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) but promotes nevirapine resistance. Although resistant viruses fade to undetectable levels in plasma, they may persist as stably integrated proviruses within the latent reservoir in resting CD4-T cells, potentially complicating future treatment. Methods. Blood samples were collected from 60 women from South Africa and Uganda-6 months after they had received single-dose nevirapine. To selectively analyze the stable latent form of HIV-1, resting CD4-T cells were isolated and activated in the presence of reverse-transcriptase inhibitors and integrase inhibitors, which allows for the specific isolation of viruses produced by cells with stably integrated proviral DNA. These viruses were then analyzed for nevirapine resistance. Results. Although only a small number of latently infected cells were present in each blood sample (mean, 162 cells), nevirapine resistance mutations (K103N and G190A) were detected in the latent reservoir of 4 (8{\%}) of 50 evaluable women. Conclusions. A single dose of nevirapine can establish antiretroviral resistance within the latent reservoir. This results in a potentially lifelong risk of reemergence of nevirapine-resistant virus and highlights the need for strategies to prevent transmission that do not compromise successful future treatment.",
author = "Megan Wind-Rotolo and Christine Durand and Lisa Cranmer and Alison Reid and Neil Martinson and Doherty, {Meg Caroline} and Jilek, {Benjamin L.} and Joseph Kagaayi and Allan Kizza and Visva Pillay and Laeyendecker, {Oliver B.} and Reynolds, {Steven James} and Susan Eshleman and Lau, {Bryan M} and Ray, {Stuart Campbell} and Siliciano, {Janet M} and Quinn, {Thomas C} and Siliciano, {Robert F}",
year = "2009",
month = "5",
day = "1",
doi = "10.1086/597759",
language = "English (US)",
volume = "199",
pages = "1301--1309",
journal = "Journal of Infectious Diseases",
issn = "0022-1899",
publisher = "Oxford University Press",
number = "9",

}

TY - JOUR

T1 - Identification of nevirapine-resistant HIV-1 in the latent reservoir after single-dose nevirapine to prevent mother-to-child transmission of HIV-1

AU - Wind-Rotolo, Megan

AU - Durand, Christine

AU - Cranmer, Lisa

AU - Reid, Alison

AU - Martinson, Neil

AU - Doherty, Meg Caroline

AU - Jilek, Benjamin L.

AU - Kagaayi, Joseph

AU - Kizza, Allan

AU - Pillay, Visva

AU - Laeyendecker, Oliver B.

AU - Reynolds, Steven James

AU - Eshleman, Susan

AU - Lau, Bryan M

AU - Ray, Stuart Campbell

AU - Siliciano, Janet M

AU - Quinn, Thomas C

AU - Siliciano, Robert F

PY - 2009/5/1

Y1 - 2009/5/1

N2 - Background. Intrapartum single-dose nevirapine decreases mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) but promotes nevirapine resistance. Although resistant viruses fade to undetectable levels in plasma, they may persist as stably integrated proviruses within the latent reservoir in resting CD4-T cells, potentially complicating future treatment. Methods. Blood samples were collected from 60 women from South Africa and Uganda-6 months after they had received single-dose nevirapine. To selectively analyze the stable latent form of HIV-1, resting CD4-T cells were isolated and activated in the presence of reverse-transcriptase inhibitors and integrase inhibitors, which allows for the specific isolation of viruses produced by cells with stably integrated proviral DNA. These viruses were then analyzed for nevirapine resistance. Results. Although only a small number of latently infected cells were present in each blood sample (mean, 162 cells), nevirapine resistance mutations (K103N and G190A) were detected in the latent reservoir of 4 (8%) of 50 evaluable women. Conclusions. A single dose of nevirapine can establish antiretroviral resistance within the latent reservoir. This results in a potentially lifelong risk of reemergence of nevirapine-resistant virus and highlights the need for strategies to prevent transmission that do not compromise successful future treatment.

AB - Background. Intrapartum single-dose nevirapine decreases mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) but promotes nevirapine resistance. Although resistant viruses fade to undetectable levels in plasma, they may persist as stably integrated proviruses within the latent reservoir in resting CD4-T cells, potentially complicating future treatment. Methods. Blood samples were collected from 60 women from South Africa and Uganda-6 months after they had received single-dose nevirapine. To selectively analyze the stable latent form of HIV-1, resting CD4-T cells were isolated and activated in the presence of reverse-transcriptase inhibitors and integrase inhibitors, which allows for the specific isolation of viruses produced by cells with stably integrated proviral DNA. These viruses were then analyzed for nevirapine resistance. Results. Although only a small number of latently infected cells were present in each blood sample (mean, 162 cells), nevirapine resistance mutations (K103N and G190A) were detected in the latent reservoir of 4 (8%) of 50 evaluable women. Conclusions. A single dose of nevirapine can establish antiretroviral resistance within the latent reservoir. This results in a potentially lifelong risk of reemergence of nevirapine-resistant virus and highlights the need for strategies to prevent transmission that do not compromise successful future treatment.

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DO - 10.1086/597759

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SP - 1301

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