Time trends in the prevalence of drug resistance to antiretroviral therapy (ART) in pregnant women have not been studied. Treatment and prophylactic efficacy could be compromised by drug-resistant HIV strains. We conducted a repeated cross-sectional study of antiretroviral resistance mutations to nucleoside reverse transcriptase inhibitors (NRTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs) and of major mutations to protease inhibitors (PIs) in virus isolates from 300 HIV-infected pregnant women in New York City from 1991 to early 2001. The overall prevalence of mutations for NRTIs from 1991 to early 2001 was higher for ART-experienced (25.6% [95% confidence interval (CI): 19.1% to 32.1%]) than ART-naive (8.6% [95% CI: 3.7% to 13.4%]) mothers (P < 0.002). For NNRTIs, the overall prevalence of mutations was somewhat higher among ART-experienced (5.8% [95% CI: 2.3% to 9.3%]) versus ART-naive (1.6% [95% CI: 0% to 3.7%]) women (P = 0.06), and increased over time for ART-naive women (0%-7.4%; P = 0.03) and ART-experienced women (0%-19.4%; P = 0.0002). The prevalence of PI-associated mutations was also higher overall among ART-experienced mothers (5.8% [95% CI: 2.3% to 9.3%] vs. 1.6% [95% CI: 0% to 3.7%]; P = 0.06), with increases over time seen for ART-naive women (0%-7.4%; P = 0.03) and ART-experienced women (0%-16.1%; P = 0.0008). The increasing prevalence of drug resistance in pregnant women, including those who are drug-naive, underscores the necessity for resistance testing to guide treatment to achieve suppression of the mother's virus.
[Show abstract][Hide abstract] ABSTRACT: A substantial number of studies have been performed across the world to determine transmitted drug resistance. Large variations between different parts of the world can be expected because of differences in availability over time of treatment. Time trend analyses are often not possible because of small numbers of included patients. In this review, we present the available data on the transmission of drug-resistant HIV, with a major emphasis on the time trends of drug resistance prevalences. We identified relevant literature by searching in PubMed through September 2009. Studies were grouped, according to the year of data collection, into the following time periods: < 2001, 2001-2003, > 2003. We selected a total of 215 studies, which included 43,170 patients. The following prevalences of transmission of drug-resistant HIV were found, in rank order: North America (12.9%), Europe (10.9%), Latin America (6.3%), Africa (4.7%), and Asia (4.2%). Changes over time in particular drugs classes were found in all parts of the world. Nucleoside reverse transcriptase inhibitor resistance declined over time in North America (p = 0.03), Europe (p < 0.001), and Latin America (p < 0.001). The decline in nucleoside reverse transcriptase inhibitor resistance reflects the improvement of treatment regimens in resource-rich settings. In contrast the resistance prevalence increased in Asia (p = 0.047) and Africa (p < 0.001). This can be explained by the antiretrovirals becoming more available during recent years in these continents. Nonnucleoside reverse transcriptase inhibitor resistance rose over time in North America (p < 0.001), Europe (p < 0.001), Latin America (p < 0.001), and Asia (p = 0.01). This paper gives a complete overview of the epidemiology of resistance of antiretroviral drugs in drug-naive patients worldwide. The time trends that were observed seem to reflect changes in describing prescriptions over time. Changes include the more wide-spread use of antiretroviral drugs in developing countries and the development of therapies from low-active mono-therapies to highly active antiretroviral regimens in the industrialized countries.
AIDS reviews 11/2011; 14(1):17-27. · 3.79 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Using a highly sensitive allele-specific polymerase chain reaction assay we detected the M184V mutation for lamivudine resistance in plasma from 9.4% of HIV-1-infected pregnant women enrolled in the Women and Infant Transmission Study between 1998 and 2004. The prevalence of nelfinavir resistance (D30N) was 6.3%. These results suggest a high prevalence of primary lamivudine and nelfinavir resistance among HIV-1-infected pregnant women in the United States, and support routine genotypic resistance testing before initiating mother-to-child-transmission prophylaxis.
AIDS 11/2007; 21(15):2103-6. DOI:10.1097/QAD.0b013e3282ef3822 · 5.55 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Allele-specific PCR (ASPCR) is a highly sensitive, and reproducible method for the study of minor HIV-1 variants harboring resistance mutations and is significantly less labor-intensive and time-consuming than other techniques used for similar purposes. Furthermore, ASPCR has multiple applications in HIV research: it provides earlier and more sensitive detection of evolving resistance mutations, a more accurate assessment of transmitted drug-resistant mutants and a better evaluation of resistance selection after post-exposure or mother-to-child-transmission prophylaxis programs. This article outlines the principles of ASPCR and illustrates technical challenges in the design and application of ASPCR protocols by describing ASPCR assays developed for detecting resistance mutations in the protease (PR)- and reverse transcriptase (RT)-coding regions of pol and env. The assays achieved sensitivities of <1% for the D30N mutation in HIV-1 PR, M184V and I mutations in RT, and V38A in gp41. This method can be easily adapted to the quantitative detection of other mutations in HIV-1 or other viruses by introducing minor modifications to the methods described. In addition, ASPCR can be used to assess the dynamics of mutant populations in the viral quasispecies in response to changing selection pressures, allowing inferences on viral fitness in vivo through mathematical modeling.
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