Prevalence and Structure of Hiv-1 Drug Resistance Among Treatment Naïve Patients Since the Introduction of Antiretroviral Therapy in the Russian Federation

Kirichenko, Alina; Kireev, Dmitry; Lopatukhin, Alexey; Murzakova, Anastasia; Lapovok, Ilya; Ладная, Н. Н.; Покровский, В В

doi:10.22328/2077-9828-2019-11-2-75-83

Cited by 13 publications

(17 citation statements)

References 7 publications

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“…The highest prevalence of TDR was found in patients from the central district (10.3%), which is most likely explained by the longer and wider use of ART compared to other districts. Earlier studies revealed that the prevalence of TDR has significantly increased in past few years due to ART becoming more available and has already reached 6,1% in 2016 [30]. Comparatively, higher prevalence of TDR was found in Eastern European countries.…”

Section: Discussionmentioning

confidence: 99%

Primary HIV drug resistance among newly HIV type-1 diagnosed patients in St. Petersburg

Ингабире¹,

Семенов²,

Эсауленко³

et al. 2021

VIČ-infekc. immunosupr.

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There is concern that the widespread use of antiretroviral drugs (ARV) to treat human immunodeficiency virus 1 (HIV-1) infection may result in the emergence of transmission of drug-resistant virus among persons newly infected with HIV-1. Russia is one of a growing number of countries in the world where drug-resistant HIV is becoming a serious health problem because it has the potential to compromise the efficacy of antiretroviral therapy (ART) at the population level.Materials and methods. We performed a genetic analysis of the HIV-1 plasma derived pol gene among the newly diagnosed ART-naïve HIV-1 infected patients during the period from November 2018 to October 2019 in the St. Petersburg Clinical Infectious Diseases Hospital named after S.P. Botkin. We used reverse transcriptase polymerase chain reaction (RT-PCR) followed by direct sequencing of PCR products to determine the prevalence of primary drug resistance (PDR) conferring mutations. HIV-1 genotypes were determined by phylogenetic analysis.Results. The predominant HIV-1 subtype was A1 (87.2%), followed by B (11.8%) and CRF06_cpx (1%). The overall prevalence of PDR was 11%. Virus with known resistance-conferring mutations to any nucleoside reverse transcriptase inhibitors (NRTIs) was found in 8 individuals, to any non NRTIs in 5 subjects, and to any protease inhibitors in 1 case. Multidrug-resistant virus was identified in 2 individuals (2%).Conclusion. The distribution of HIV-1 genotypes in St. Petersburg, Russia is diverse. The emerging prevalence of PDR in ART-naïve patients demonstrates the significance of constant monitoring due to the challenges it presents towards treatment.

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Section: Discussionmentioning

confidence: 99%

Primary HIV drug resistance among newly HIV type-1 diagnosed patients in St. Petersburg

Ингабире¹,

Семенов²,

Эсауленко³

et al. 2021

VIČ-infekc. immunosupr.

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“…In this region, nationwide estimates of DR are not available, and data about the prevalence, pattern, and trend of HIV DR are very sparse and scattered. A number of studies conducted in Russia showed an increase in the prevalence of HIV DR among naïve patients from 0-1.5% in 1998-2014 [18,19] to 5.3% in a recent study [20]. In other EECA countries, there were limited or nonexistent data.…”

Section: Introductionmentioning

confidence: 99%

Prevalence of HIV-1 drug resistance in Eastern European and Central Asian countries

et al. 2022

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Background Eastern Europe and Central Asia (EECA) is one of the regions where the HIV epidemic continues to grow at a concerning rate. Antiretroviral therapy (ART) coverage in EECA countries has significantly increased during the last decade, which can lead to an increase in the risk of emergence, transmission, and spread of HIV variants with drug resistance (DR) that cannot be controlled. Because HIV genotyping cannot be performed in these countries, data about HIV DR are limited or unavailable. Objectives To monitor circulating HIV-1 genetic variants, assess the prevalence of HIV DR among patients starting antiretroviral therapy, and reveal potential transmission clusters among patients in six EECA countries: Armenia, Azerbaijan, Belarus, Russia, Tajikistan, and Uzbekistan. Materials and methods We analyzed 1071 HIV-1 pol-gene fragment sequences (2253–3369 bp) from patients who were initiating or reinitiating first-line ART in six EECA counties, i.e., Armenia (n = 120), Azerbaijan (n = 96), Belarus (n = 158), Russia (n = 465), Tajikistan (n = 54), and Uzbekistan (n = 178), between 2017 and 2019. HIV Pretreatment DR (PDR) and drug resistance mutation (DRM) prevalence was estimated using the Stanford HIV Resistance Database. The PDR level was interpreted according to the WHO standard PDR survey protocols. HIV-1 subtypes were determined using the Stanford HIV Resistance Database and subsequently confirmed by phylogenetic analysis. Transmission clusters were determined using Cluster Picker. Results Analyses of HIV subtypes showed that EECA, in general, has the same HIV genetic variants of sub-subtype A6, CRF63_02A1, and subtype B, with different frequencies and representation for each country. The prevalence of PDR to any drug class was 2.8% in Uzbekistan, 4.2% in Azerbaijan, 4.5% in Russia, 9.2% in Armenia, 13.9% in Belarus, and 16.7% in Tajikistan. PDR to protease inhibitors (PIs) was not detected in any country. PDR to nucleoside reverse-transcriptase inhibitors (NRTIs) was not detected among patients in Azerbaijan, and was relatively low in other countries, with the highest prevalence in Tajikistan (5.6%). The prevalence of PDR to nonnucleoside reverse-transcriptase inhibitors (NNRTIs) was the lowest in Uzbekistan (2.8%) and reached 11.1% and 11.4% in Tajikistan and Belarus, respectively. Genetic transmission network analyses identified 226/1071 (21.1%) linked individuals, forming 93 transmission clusters mainly containing two or three sequences. We found that the time since HIV diagnosis in clustered patients was significantly shorter than that in unclustered patients (1.26 years vs 2.74 years). Additionally, the K103N/S mutation was mainly observed in clustered sequences (6.2% vs 2.8%). Conclusions Our study demonstrated different PDR prevalence rates and DR dynamics in six EECA countries, with worrying levels of PDR in Tajikistan and Belarus, where prevalence exceeded the 10% threshold recommended by the WHO for immediate public health action. Because DR testing for clinical purposes is not common in EECA, it is currently extremely important to conduct surveillance of HIV DR in EECA due to the increased ART coverage in this region.

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“…We observed similar issue in Russia, where the frequency of the E138A polymorphic mutation in patients infected with the dominant HIV A6 virus ranges from 4 to 8%. This mutation is not associated with the transmission of resistant viruses, since the frequency of its occurrence before the use of RPV and ETR in Russia (until 2011) differed marginally from that in the subsequent time period [30].…”

Section: Discussionmentioning

confidence: 90%

The efficacy of first-line ART regimens based on RPV in HIV-infected patients with pre-existing E138A mutation in reverse transcriptase

Кузнецова

Lebedev

Gromov

et al. 2021

Preprint

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Introduction It was previously shown that the presence of the E138A mutation is associated with resistance to rilpivirine (RPV). Detection of this mutation is considered as contraindication for RPV use within the first-line ART. It is a lack of knowledge regarding efficacy of first-line RPV-based ART in patients bearing HIV with E138A mutation. In absence of HIV genotyping in naïve patients it may influence the clinical decisions.Methods We have collected all available patients unconventionally treated with RPV and carefully analyzed the ART efficacy in E138A carriers from the EuResist database. The viral load data in patients with E138A mutation at baseline was extracted from the database. Due to uniqueness of these cases only 11 HIV infected patients were found. The virologic outcome was analyzed according to the national and international ART guidelines.Results The full virologic efficacy of the first-line RPV-based ART regimen was demonstrated in 11 out of 11 patients according to all guidelines.Conclusions Our data suggest that the influence of the pre-existing E138A mutation on the sensitivity to RPV is very low or insignificant. The results support importance of investigation of polymorphic pre-existing HIV drug mutations for ART efficacy.

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Prevalence and Structure of Hiv-1 Drug Resistance Among Treatment Naïve Patients Since the Introduction of Antiretroviral Therapy in the Russian Federation

Cited by 13 publications

References 7 publications

Primary HIV drug resistance among newly HIV type-1 diagnosed patients in St. Petersburg

Primary HIV drug resistance among newly HIV type-1 diagnosed patients in St. Petersburg

Prevalence of HIV-1 drug resistance in Eastern European and Central Asian countries

The efficacy of first-line ART regimens based on RPV in HIV-infected patients with pre-existing E138A mutation in reverse transcriptase

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