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J Infect Dis. 2009 May 1;199(9):1301-9. doi: 10.1086/597759.

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

Author information

  • 1Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, USA. mwrotolo@gmail.com

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.

Comment in

PMID:
19338474
[PubMed - indexed for MEDLINE]
PMCID:
PMC2703715
Free PMC Article

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