Pre‐existing singleton E138A mutations in the reverse transcriptase gene do not affect the efficacy of first‐line antiretroviral therapy regimens using rilpivirine in human immunodeficiency virus‐infected patients

Кузнецова, А. И.; Lebedev, Aleksey; Gromov, Konstantin; Kazennova, Elena; Zazzi, Maurizio; Incardona, Francesca; Sönnerborg, Anders; Bobkova, Marina

doi:10.1002/ccr3.5373

Cited by 10 publications

(8 citation statements)

References 26 publications

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“…For example, Theys et al [ 29 ] observed that the emergence of K65R in the reverse transcriptase coding region was significantly favored in HIV-1 subtype C in PLWH being treated with tenofovir, suggesting subtype-specific pathways that facilitate the emergence of an otherwise-rare RAM. More recently, Kuznetsova et al [ 30 ] identified 11 individuals in the EuResist database harboring the reverse transcriptase natural polymorphism E138A who started a first-line ART including rilpivirine. Even though the variant E138A moderately decreases susceptibility to RPV in vitro and is included in the list of rilpivirine RAMs in several algorithms, treatment with RPV-based ART was fully effective in all 11 patients, supporting the effectiveness of RPV in first-line therapy in countries such as those belonging to the Russian Federation, where the natural polymorphism E138A is present in 4–8% of circulating strains.…”

Section: Findings To Datementioning

confidence: 99%

Cohort Profile: A European Multidisciplinary Network for the Fight against HIV Drug Resistance (EuResist Network)

et al. 2023

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The EuResist cohort was established in 2006 with the purpose of developing a clinical decision-support tool predicting the most effective antiretroviral therapy (ART) for persons living with HIV (PLWH), based on their clinical and virological data. Further to continuous extensive data collection from several European countries, the EuResist cohort later widened its activity to the more general area of antiretroviral treatment resistance with a focus on virus evolution. The EuResist cohort has retrospectively enrolled PLWH, both treatment-naïve and treatment-experienced, under clinical follow-up from 1998, in nine national cohorts across Europe and beyond, and this article is an overview of its achievement. A clinically oriented treatment-response prediction system was released and made available online in 2008. Clinical and virological data have been collected from more than one hundred thousand PLWH, allowing for a number of studies on the response to treatment, selection and spread of resistance-associated mutations and the circulation of viral subtypes. Drawing from its interdisciplinary vocation, EuResist will continue to investigate clinical response to antiretroviral treatment against HIV and monitor the development and circulation of HIV drug resistance in clinical settings, along with the development of novel drugs and the introduction of new treatment strategies. The support of artificial intelligence in these activities is essential.

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Section: Findings To Datementioning

confidence: 99%

Cohort Profile: A European Multidisciplinary Network for the Fight against HIV Drug Resistance (EuResist Network)

et al. 2023

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“…We found it in 5.8% of the patients with an association with sub-subtype A6, which is in line with earlier report in sub-subtype A6, where the frequency was 4–8% depending on the region [ 38 ]. It has recently been reported that this singleton mutation, before starting treatment with RPV, may not affect the efficacy of the ART [ 43 ]. In the protease ORF, the L33F (0.7%) polymorphism was found, which is similar to the frequency observed in other subtypes.…”

Section: Resultsmentioning

confidence: 99%

Molecular Epidemiology of HIV-1 in Eastern Europe and Russia

Klundert

Антонова²,

Teodoro

et al. 2022

Viruses

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The HIV epidemic in Eastern Europe and Russia is large and not well-controlled. To describe the more recent molecular epidemiology of HIV-1, transmitted drug resistance, and the relationship between the epidemics in this region, we sequenced the protease and reverse transcriptase genes of HIV-1 from 812 people living with HIV from Ukraine (n = 191), Georgia (n = 201), and Russia (n = 420) before the initiation of antiretroviral therapy. In 190 Ukrainian patients, the integrase gene sequence was also determined. The most reported route of transmission was heterosexual contact, followed by intravenous drug use, and men having sex with men (MSM). Several pre-existing drug resistance mutations were found against non-nucleoside reverse transcriptase inhibitors (RTIs) (n = 103), protease inhibitors (n = 11), and nucleoside analogue RTIs (n = 12), mostly polymorphic mutations or revertants. In the integrase gene, four strains with accessory integrase strand transfer inhibitor mutations were identified. Sub-subtype A6 caused most of the infections (713/812; 87.8%) in all three countries, including in MSM. In contrast to earlier studies, no clear clusters related to the route of transmission were identified, indicating that, within the region, the exchange of viruses among the different risk groups may occur more often than earlier reported.

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“…Another polymorphic mutation in sub-subtype A6 E138A (5.3%) was the most common NNRTI mutation detected in treatment-naïve Russian patients. In vitro data from site-directed mutagenesis showed that E138A causes a two-fold reduction in susceptibility to RPV [43,44]; however, this does not appear to affect the effectiveness of RPV-containing treatment in real practice [45,46].…”

Section: Discussionmentioning

confidence: 97%

“…In 2021, the percentage of PLWH who achieved an undetectable HIV viral load (VL) was 46.4%, and it was 79.9% among those receiving ART [10]. It has been shown that achieving the third target of "95-95-95" for viral suppression is key to reducing the rate of new HIV infections [12].…”

Section: Introductionmentioning

confidence: 99%

HIV-1 Drug Resistance among Treatment-Naïve Patients in Russia: Analysis of the National Database, 2006–2022

Kirichenko

Kireev

Lapovok

et al. 2023

Viruses

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In Russia, antiretroviral therapy (ART) coverage has significantly increased, which, in the absence of routine genotyping testing, could lead to an increase in HIV drug resistance (DR). The aim of this study was to investigate the patterns and temporal trends in HIV DR as well as the prevalence of genetic variants in treatment-naïve patients from 2006 to 2022, using data from the Russian database (4481 protease and reverse transcriptase and 844 integrase gene sequences). HIV genetic variants, and DR and DR mutations (DRMs) were determined using the Stanford Database. The analysis showed high viral diversity, with the predominance of A6 (78.4%), which was the most common in all transmission risk groups. The overall prevalence of surveillance DRMs (SDRMs) was 5.4%, and it reached 10.0% in 2022. Most patients harbored NNRTI SDRMs (3.3%). The prevalence of SDRMs was highest in the Ural (7.9%). Male gender and the CRF63_02A6 variant were association factors with SDRMs. The overall prevalence of DR was 12.7% and increased over time, primarily due to NNRTIs. Because baseline HIV genotyping is unavailable in Russia, it is necessary to conduct surveillance of HIV DR due to the increased ART coverage and DR prevalence. Centralized collection and unified analysis of all received genotypes in the national database can help in understanding the patterns and trends in DR to improve treatment protocols and increase the effectiveness of ART. Moreover, using the national database can help identify regions or transmission risk groups with a high prevalence of HIV DR for epidemiological measures to prevent the spread of HIV DR in the country.

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Pre‐existing singleton E138A mutations in the reverse transcriptase gene do not affect the efficacy of first‐line antiretroviral therapy regimens using rilpivirine in human immunodeficiency virus‐infected patients

Cited by 10 publications

References 26 publications

Cohort Profile: A European Multidisciplinary Network for the Fight against HIV Drug Resistance (EuResist Network)

Cohort Profile: A European Multidisciplinary Network for the Fight against HIV Drug Resistance (EuResist Network)

Molecular Epidemiology of HIV-1 in Eastern Europe and Russia

HIV-1 Drug Resistance among Treatment-Naïve Patients in Russia: Analysis of the National Database, 2006–2022

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