Special Report on Drug Resistance

Drug-resistance patterns in women discovered

Resistance testing necessary, expert says

If HIV-1 drug resistance is found in a woman’s plasma, it’s likely the same resistance is present in her genital tract, suggesting that drug resistance among pregnant, HIV-infected women, requires further investigation, a new study shows.

"We wanted to look at the question of drug resistance to HIV-1 in different compartments in infected women, particularly in the genital tract in contrast to the blood," says Harold Burger, MD, PhD, co-director of HIV research at the Wadsworth Center of the New York State Department of Health in Albany. Burger also is professor of medicine at the Albany Medical College.

Burger and co-investigators looked at the blood plasma and cervicovaginal lavage (CVL) of 20 U.S. women, who were infected with HIV-1 and who were not pregnant.1

"The genital mucosa are the site for initial contact for HIV for a majority of exposed individuals, including many infants infected by mother-to-child transmission (MTCT)," he notes.

"Although prophylaxis may reduce mother-to-child transmission, drug resistance may emerge."

Investigators found that 11 of the 20 patients studied displayed high-level genotypic, HIV-1 drug resistance, Burger says.

"When detected, drug-resistance mutations were found in both blood and genital-tract compartments," he explains.

"Although mutations at each site were similar in almost all women, two patients displayed a different pattern of resistance in the two compartments," Burger points out.

The data suggest that when genotypic HIV-1 drug resistance is found in a woman’s plasma, it also may serve as a good predictor of resistance in the genital tract, and this is relevant to projects involving nevirapine therapy to prevent MTCT in resource-poor areas, he says.

"Serial studies of viral resistance, replicative capacity, and compartmentalization of sequences suggest that under the selective pressure of antiretroviral therapy, HIV-1 strains with the greatest in-vivo fitness will evolve in both sites leading to concordant patterns of resistance," Burger continues.

"Drug-resistant HIV-1 variants can spread through heterosexual or mother-to-child transmission," he notes.

So studying the development of genotypic, HIV-1 drug resistance in blood and in the female genital tract is highly relevant to the prevention of heterosexual and MTCT and to the development of new therapies, he adds.

One of the problems with using nevirapine to prevent MTCT in regions of the world where antiretroviral drugs and resources are lacking is that a woman may develop nevirapine-resistant virus after taking the drug during one pregnancy and then transmit nevirapine-resistant virus to infants born in subsequent pregnancies, Burger explains.

"If she’s only treated with nevirapine for the later pregnancy, in principle, she might transmit nevirapine-resistant virus to the second or later child," he adds.

While Burger’s group has not studied this potential, other investigators have, he notes.

"Our study was not a clinical trial; it was a small, focused pathogenesis study to look at the details of HIV-1 drug resistance in infected women," he adds.

Reference

1. Burger H, Kemal K, Weiser B, et al. HIV-1 drug resistance in women: Resistance patterns in the genital tract and plasma. Presented at the 44th Interscience Conference on Antimicrobial Agents and Chemotherapy. Washington, DC; November 2004. Abstract: H-197.