Genotypic resistance tests for the management of the HIV-infected pregnant woman.

Abstract

Witness for the prosecution: Recommendations for genotypic resistance testing in HIV-infected pregnant women are the same as for non-pregnant women: acute HIV infection, virological failure or suboptimal viral suppression after initiation of antiretroviral therapy, or high likelihood of exposure to resistant virus based on community prevalence or source characteristics. All pregnant women with detectable HIV-RNA levels should perform resistance testing to maximize the response to antiretrovirals in pregnancy. Currently there are no data on the value of drug resistance testing to prevent vertical transmission. Most studies show that the most important factor in the risk of transmission is the amount of HIV-RNA at the moment of delivery. A strategy to overcome this problem would be to use of resistance testing to select a regimen, which has the greatest potential to reduce viral load at the moment of delivery. We would also like to use the same information to select the regimen that would be used to provide prophylaxis to the newborn. It is currently unknown whether zidovudine (ZDV) prevents transmission through another mechanism(s) in addition to reducing viral load, so one could argue that even if ZDV resistance has been found in the mother, it should still be included in the regimen. Witness for the defence: To reduce the risk of HIV vertical transmission, prospective controlled trials on the use of antiretroviral prophylactic treatment in different schedules during pregnancy were conducted. These studies assessed the efficacy of short- or medium-term antiretroviral therapy in reducing vertical transmission, but highlighted the concerns about the selection of resistant variants (monotherapy prophylaxis or suboptimal regimens). The availability of recent more complex multidrug regimens increased the prevalence of drug resistance among the HIV-1-infected population; so, women of childbearing age are at risk of becoming infected with resistant virus and those on treatment, living in developed countries, could harbour resistant virus before pregnancy. Therefore, there are growing concern about the role of these resistant variants in mother-to-child HIV-1 transmission. Several studies documenting HIV-resistant variants in vertical transmission form a compelling basis for recommending the use of HIV-1 genotypic drug resistance tests during pregnancy. Owing to the availability of different genotypic HIV-1 tests at variable costs, the choice of the most appropriate assay could take into account the prevalence and incidence of drug-resistant mutations, the availability of drugs and the antiretroviral experience setting, to choose the best long-term effective antiretroviral therapy for the mother and to avoid the risk of transmission to the offspring.