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

Abstract

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.

Molecular Epidemiology of HIV-1 in Eastern Europe and Russia

“…These patients did not have any other pDRMs. The L74I [ 11 , 12 , 13 ] was found in 164 of 176 (93.3%) A6 isolates ( Figure S3D ), which is in line with previous findings in the sub-subtype A6 [ 42 , 44 ], and in the two B/A6 URF ( Table S2 ) from Ukraine.…”

“…A high prevalence of the L74I mutation (93%) was found in the IN gene of Ukrainian A6 strains, consistent with earlier data [ 42 , 44 ]. A once monthly or bimonthly injectable combination of the INSTI CAB and the NNRTI RPV has resulted in confirmed virological failures.…”

“…The accessory NRTI A62V mutation, which partially restores the replication defect associated with the K65R mutation, was found exclusively in patients (210/700, 30%) infected with sub-subtype A6, a prevalence which is somewhat lower than previously obtained data for sub-subtype A6 (48–54%) [ 42 ]. This may be due to a strong clustering of this variant and therefore presumably a higher prevalence in some regions not included in our study.…”

“…Moreover, the number of PDRs was slightly higher than other recent studies in the region. 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 ].…”

Phylodynamics and migration data help describe HIV transmission dynamics in internally displaced people who inject drugs in Ukraine

“…Many IDPWID in our sample initiated IDU after the beginning of the conflict (30.2%), half of those (48%) started injecting after they reached Odesa. Substance use amongst forcibly displaced people as a coping mechanism following conflict, violence, and migration stress is well documented in current literature [30] and will require a special focus in Ukraine, particularly in regions that are currently occupied by Russia where drug use is criminalized (34). While these data are subject to reporting biases, we expect these to be low in our sample, as is often the case for those for whom the recall events were more emotional or marked a transition point in their life, like war or forced displacement events for IDPWID [32].…”