Prevalence of Antiretroviral Drug Resistance Mutations Among Pretreatment and Antiretroviral Therapy-Failure HIV Patients in Uzbekistan

Mamatkulov, Adkhamjon; Kazakova, Evgeniya; Ibadullaeva, Nargiz; Joldasova, Elizaveta; Bayjanov, A. K.; Musabaev, Erkin; Kan, Nataliya; Mustafaeva, Dildora; Lebedev, Aleksey; Bobkova, Marina; Kazennova, Elena; Zohrabyan, Lev

doi:10.1089/aid.2020.0096

Cited by 4 publications

(12 citation statements)

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“…The trends of HIV DR over time differed from country to country. The overall prevalence of PDR in Uzbekistan in this study was 2.8% for samples collected from 2017-2019, which were in accordance with a previous study that found a prevalence of 2.96% for samples collected from 2015-2016 [21]. It is important to note that the prevalence of PDR in Armenia has markedly increased during the last decade (2009-2010) from 1.5% [22] to 9.2%.…”

Section: Plos Onesupporting

confidence: 91%

“…DR level was classified according to the Stanford Penalty Score as high (60), intermediate , or low (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29).…”

Section: Hiv-1 Drug Resistance Interpretationmentioning

confidence: 99%

“…In other EECA countries, there were limited or nonexistent data. Uzbekistan reported a DR prevalence of 2.96% for samples collected in 2015-2016 [21]. In Armenia, the prevalence of HIV DR for samples collected in 2009-2010 was 1.5% [22].…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Plos Onesupporting

confidence: 91%

“…DR level was classified according to the Stanford Penalty Score as high (60), intermediate , or low (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29).…”

Section: Hiv-1 Drug Resistance Interpretationmentioning

confidence: 99%

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

et al. 2022

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“…NRTI and NNRTI resistance mutations have occurred at similar rates, in many cases together, causing resistance to most reverse transcriptase inhibitors. A similar pattern of HIV DR mutations is found both in patients with primary drug resistance in Russia and in patients with newly diagnosed HIV and ART failure in some neighboring countries [ 13 , 25 , 26 ].…”

Section: Discussionsupporting

confidence: 58%

Detection of Patient HIV-1 Drug Resistance Mutations in Russia’s Northwestern Federal District in Patients with Treatment Failure

et al. 2022

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Highly active antiretroviral therapy (HAART) is currently a combination of three (less frequently four) antiretroviral drugs; these target pathways involved in various stages of HIV replication in the body. Treatment failure is a problem facing doctors and patients using HAART. The most common cause of therapeutic failure is the development of HIV drug resistance. The emergence of resistance is associated with processes involving mutation occurring in the viral genome under the influence of evolutionary factors. Sequencing reactions were performed using the AmpliSens HIV Resist-Seq. Assembly of consensus sequences from fragments obtained during sequencing was carried out using Unipro UGENE softwar. Isolate genotyping was performed using the MEGA-X software with the Neighbor-joining algorithm. According to the analysis, 72.05% of patients had at least one significant mutation associated with drug resistance for the corresponding viral subtype. HIV-1 A6 remains the predominant HIV-1 genetic variant in Russia’s Northwestern Federal District. Among samples with drug resistance mutations, in all cases, mutations associated with pharmacological resistance to two or three drug groups were found. Given the high incidence of resistance mutations in patients on ineffective ART, surveillance of HIV-1 drug resistance, in both ART-receiving and ART-naive individuals, appears necessary. A lack of vigilance and control measures may lead to the spread of primary ART-resistant HIV strains.

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“…A study from 2022 estimated that the prevalence of PDR to any drug class was 2.8% in Uzbekistan, 4.2% in Azerbaijan, 4.5% in Russia (7% in Krasnodar), 9.2% in Armenia, 13.9% in Belarus, and 16.7% in Tajikistan [ 42 ], although it should be noted that, due to the limited availability of data, these studies were not statistically significant according to WHO recommendations. The only statistically reliable study in the region was carried out in Uzbekistan in 2016, when the PDR was found to be 2.96% [ 46 ].…”

Section: Discussionmentioning

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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Prevalence of Antiretroviral Drug Resistance Mutations Among Pretreatment and Antiretroviral Therapy-Failure HIV Patients in Uzbekistan

Cited by 4 publications

References 11 publications

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

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

Detection of Patient HIV-1 Drug Resistance Mutations in Russia’s Northwestern Federal District in Patients with Treatment Failure

Molecular Epidemiology of HIV-1 in Eastern Europe and Russia

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