Dataset Information

Drug resistance mutations in HIV pol sequences from Argentinean patients under antiretroviral treatment: subtype, gender, and age issues.

ABSTRACT: We studied drug resistance mutations (DRMs) in 2623 pol sequences. Out of 94,828 amino acid substitutions that were detected, 8749 corresponded to nucleoside reverse transcriptase inhibitor (NRTI), 3765 to nonnucleoside reverse transcriptase inhibitor (NNRTI), and 7141 to protease inhibitor (PI) resistance-associated mutations. The most common DRMs were L10I, I54V, L90M, V82A, A71V, L10V, M46I, M184V, M41L, T215Y, D67N, L210W, K70R, N348I, V118I, K103N, Y181C, G190A, K101E, V108I, L100I, V90I, K101Q, and A98G. As expected, DRMs frequencies depended on viral genotype. The amounts of NRTI and PI resistance mutations among B and BF sequences from children were higher than among sequences from adults. The frequencies of PI and NRTI resistance mutations among B and BF sequences from adult men were higher than among sequences from women. Some of these observations can be explained in light of the available epidemiological information, but some cannot, indicating that further studies are needed to understand the antiretroviral resistance epidemics in Argentina.

SUBMITTER: Jones LR

PROVIDER: S-EPMC3399568 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature

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Drug resistance mutations in HIV pol sequences from Argentinean patients under antiretroviral treatment: subtype, gender, and age issues.

Jones Leandro R LR Moretti Franco F Calvo Andrea Y AY Dilernia Darío A DA Manrique Julieta M JM Gómez-Carrillo Manuel M Salomón Horacio H

AIDS research and human retroviruses 20111122 8

We studied drug resistance mutations (DRMs) in 2623 pol sequences. Out of 94,828 amino acid substitutions that were detected, 8749 corresponded to nucleoside reverse transcriptase inhibitor (NRTI), 3765 to nonnucleoside reverse transcriptase inhibitor (NNRTI), and 7141 to protease inhibitor (PI) resistance-associated mutations. The most common DRMs were L10I, I54V, L90M, V82A, A71V, L10V, M46I, M184V, M41L, T215Y, D67N, L210W, K70R, N348I, V118I, K103N, Y181C, G190A, K101E, V108I, L100I, V90I, K ...[more]

PMID: 21936717

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Project description:IntroductionAt low mutation-detection thresholds, next generation sequencing (NGS) for HIV-1 genotypic resistance testing is susceptible to artifactual detection of mutations arising from PCR error and APOBEC-mediated G-to-A hypermutation.MethodsWe analyzed published HIV-1 pol Illumina NGS data to characterize the distribution of mutations at eight NGS mutation detection thresholds: 20%, 10%, 5%, 2%, 1%, 0.5%, 0.2%, and 0.1%. At each threshold, we determined proportions of amino acid mutations that were unusual (defined as having a prevalence <0.01% in HIV-1 group M sequences) or signature APOBEC mutations.ResultsEight studies, containing 855 samples, in the NCBI Sequence Read Archive were analyzed. As detection thresholds were lowered, there was a progressive increase in the proportion of positions with usual and unusual mutations and in the proportion of all mutations that were unusual. The median proportion of positions with an unusual mutation increased gradually from 0% at the 20% threshold to 0.3% at the 1% threshold and then exponentially to 1.3% (0.5% threshold), 6.9% (0.2% threshold), and 23.2% (0.1% threshold). In two of three studies with available plasma HIV-1 RNA levels, the proportion of positions with unusual mutations was negatively associated with virus levels. Although the complete set of signature APOBEC mutations was much smaller than that of unusual mutations, the former outnumbered the latter in one-sixth of samples at the 0.5%, 1%, and 2% thresholds.ConclusionsThe marked increase in the proportion of positions with unusual mutations at thresholds below 1% and in samples with lower virus loads suggests that, at low thresholds, many unusual mutations are artifactual, reflecting PCR error or G-to-A hypermutation. Profiling the numbers of unusual and signature APOBEC pol mutations at different NGS mutation detection thresholds may be useful to avoid selecting a threshold that is too low and poses an unacceptable risk of identifying artifactual mutations.

Project description:Background Women represent an increasing percentage of interventional cardiologists in Italy compared with other countries. However, gaps exist in understanding and adapting to the impact of these changing demographics. Methods and Results We performed a national survey to analyze demographics, gender-based professional difference, needs in terms of catheterization laboratory (Cath-Lab) abstention, and radiation safety issues in Italian Cath-Lab settings. A survey supported by the Italian Society of Interventional Cardiology (Società Italiana di Cardiologia Interventistica-Gruppo Italiano di Studi Emodinamici SICI-GISE) was mailed to all SICI-GISE members. Categorical data were compared using the χ2 test. P<0.05 was considered significant. There were 326 respondents: 20.2% were <35 years old, and 64.4% had >10 years of Cath-Lab experience. Notably, 26.4% were women. Workload was not gender-influenced (women performed "on-call" duty 69.8% versus men 68.3%; P=0.97). Women were more frequently unmarried (22.1% women versus 8.7% men; P=0.002) and childless (43.9% versus 56.1%; P<0.001). Interestingly, 69.8% of women versus 44.6% of men (P<0.001) argued that pregnancy/breastfeeding negatively impacts professional skill development and career advancement. For Cath-Lab abstention, 38.9% and 69.6% of respondents considered it useful to perform percutaneous coronary intervention robotic simulations and "refresh-skill" sessions while they were absent or on return to work, respectively, without gender differences. Overall, 80% of respondents described current radioprotection counseling efforts as inadequate and not gender specific. Finally, 26.7% faced some type of job discrimination, a significantly higher proportion of whom were women. Conclusions Several gender-based differences exist or are perceived to exist among interventional cardiologists in Italian Cath-Labs. Joint strategies addressing Cath-Lab abstention and radiation exposure education should be developed to promote gender equity in interventional cardiologists.

Dataset Information

Drug resistance mutations in HIV pol sequences from Argentinean patients under antiretroviral treatment: subtype, gender, and age issues.

Publications

Drug resistance mutations in HIV pol sequences from Argentinean patients under antiretroviral treatment: subtype, gender, and age issues.

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