A Single Dose of Nevirapine May Establish Antiretroviral Resistance Within the Latent Reservoir

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Dear all

one more recent evidence to prove that NVP single dose can create resistance.

Please read:

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A Single Dose of Nevirapine May Establish Antiretroviral Resistance Within the

Latent Reservoir. Medscape Medical News, April 27, 2009

News Author: Laurie Barclay, MD

CME Author: Laurie Barclay, MD

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April 27, 2009 A single dose of nevirapine can establish antiretroviral

resistance within the latent reservoir, suggesting a potentially lifelong risk

for reemergence of nevirapine-resistant HIV, according to the results of a study

reported in the May 1 issue of the Journal of Infectious Diseases.

" Intrapartum single-dose nevirapine decreases mother-to-child transmission of

human immunodeficiency virus type 1 (HIV-1) but promotes nevirapine resistance, "

write Wind-Rotolo, from the School of Medicine, s Hopkins University

in Baltimore, land, and colleagues. " 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. "

Six months or more after receiving single-dose nevirapine, 60 women from South

Africa and Uganda gave blood samples for selective analysis of nevirapine

resistance in the stable latent form of HIV-1.

For specific isolation of viruses produced by cells with stably integrated

proviral DNA, resting CD4+ T cells were isolated and activated in the presence

of reverse-transcriptase inhibitors and integrase inhibitors.

Each blood sample only had a small number of latently infected cells (mean, 162

cells), but nevirapine resistance mutations (K103N and G190A) were detected in

the latent reservoir of 4 (8%) of 50 evaluable women.

" A single dose of nevirapine can establish antiretroviral resistance within the

latent reservoir, " the study authors write. " 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. "

Limitations of this study include inability of the study method to detect

resistant virus present at levels of 0.1% or less, suggesting that archived

nevirapine resistance may be more prevalent than identified in this study; and

limited duration of follow-up.

" This study proves the principle that archiving of resistant virus can occur

after receipt of a single dose of nevirapine, " the study authors conclude..

" Nevirapine-resistant virus was identified in the latent reservoir of 4 women

15-37 months after exposure to nevirapine. This archiving could potentially

create lifelong resistance to a key agent in the first-line HAART [highly active

antiretroviral therapy] regimen recommended by the World Health Organization and

could have important consequences for the choice of HAART regimens in women

exposed to NNRTIs [nonnucleoside reverse-transcriptase inhibitors] to prevent

mother-to-child transmission of HIV-1. "

In an accompanying editorial, Viktor Dahl and Palmer, from the Swedish

Institute for Infectious Disease Control and Karolinska Institute in Stockholm,

Sweden, emphasize that nevirapine is a potent nonnucleoside

reverse-transcriptase inhibitor of HIV-1, but when administered as monotherapy,

it rapidly selects for resistant variants.

" The simplicity and low cost of single-dose nevirapine made it a common regimen

for preventing mother-to-child transmission in developing countries, and its

widespread use has resulted in the exposure of large numbers of women to this

regimen, " Drs. Dahl and Palmer write. " The findings by Wind-Rotolo and

colleagues, which demonstrate the latent and, therefore, long-term persistence

of nevirapine-resistant HIV strains, indicate that future studies should focus

on the long-term risk for virological failure during ART [antiretroviral

therapy] initiated after treatment with single-dose nevirapine. "

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The HIV Prevention Trials Network, sponsored by the National Institute of

Allergy and Infectious Diseases, National Institute of Child Health and Human

Development, National Institute on Drug Abuse, National Institute of Mental

Health, and Office of AIDS Research, National Institutes of Health, Department

of Health and Human Services; International Maternal Pediatric Adolescent AIDS

Clinical Trials Network; and Medical Institute supported this

study. One of the study authors manages a grant from US President’s Emergency

Plan for AIDS Relief that provides antiretroviral treatment, and another is a

coinventor of the LigAmp assay, for which s Hopkins University has filed a

patent application with the US Patent and Trademark Office; the inventors may

receive royalty payments if the patent is awarded and licensed.

Drs. Dahl and Palmer have disclosed no relevant financial relationships.

J Infect Dis. 2009;199:1258-1260, 1292-1300.

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MSFOCB Mumbai Aidscare Field Coordinator

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