[pronut-hiv] Persistence of Nevirapine Resistance After Single Dose Underestimated

["ProNut-HIV" <pronut-hiv@healthnet.org>]

Persistence of Nevirapine Resistance After Single Dose Underestimated
By Megan Rauscher

NEW YORK (Reuters Health) Apr 28 - The results of a study using a
sensitive allele-specific PCR assay confirm high rates of nevirapine
(NVP)-resistant HIV in women given a single-dose of the drug for
prevention of mother-to-child HIV transmission. Using this assay, the
researchers also found that NVP-resistant variants often persist longer
than suggested by the results of standard genotype assays.

Single-dose NVP, which is recommended by the World Health Organization
as one way to reduce vertical HIV transmission in resource-limited
countries, is known to foster NVP-resistant HIV. However, the frequency
and duration of these resistant strains is not well defined.

Dr. Sarah Palmer from the HIV Drug Resistance Program at the National
Cancer Institute in Frederick, Maryland and colleagues used an
allele-specific PCR assay to assess the emergence and persistence of
NVP-resistant variants in 22 HIV-infected pregnant women who received
single-dose NVP as part of the Soweto, South Africa MTCT
(mother-to-child transmission) trial.

Standard genotyping identified six women with NVP resistance at 2 and 6
months, but not at 12 months, after single-dose NVP; nine had NVP
resistance at 2 months but not at 6 months; and seven had no NVP
resistance detected at any time.

In contrast, allele-specific PCR for the two most common NVP-resistance
mutations (K103N and Y181C) detected these variants in most (16 of 21)
samples that were negative for NVP resistance by standard genotype, at
levels ranging from 01.% to 20% by 12 months after single-does NVP, the
research team reports in the April 24th issue of PNAS Early Edition.

The frequency of NVP-resistant HIV, Dr. Palmer told Reuters Health,
"declined with time but persisted above pre-dose levels for at least 12
months in 60% of the women who had resistance detected by conventional
genotyping methods 2 months after receiving single-dose NVP."

"Therefore, based on our extrapolations, at least 23% of women enrolled
in the Soweto study who received single-dose NVP during labor still
harbor drug resistant variants more than one year later," she said.

The long-term persistence of NVP-resistant HIV is potentially important
for women who may receive single-dose NVP in later pregnancies or
antiretroviral therapy.

Yet, "for the 90% of women in developing countries who do not have
access to highly active antiretroviral treatment, there still may be a
role for treatment with single-dose NVP, due to the fact that (it)
reduces the transmission of HIV from mother to child," Dr. Palmer said.

PNAS Early Edition 2006.