HIV drug resistance among patients experiencing antiretroviral therapy failure in Russia, 2019-2021.

Increasing HIV drug resistance is an important public health concern. The current study aimed to assess HIV drug resistance among people who live with HIV (PLWH) experiencing virological failure. Blood samples and epidemiological characteristics were collected in four Siberian regions from PLWH experiencing ART failure. Partial pol gene sequences were obtained for the study individuals. Drug resistance mutations (DRMs) were predicted using the Stanford HIVdb Program. The association of HIV DRM with epidemiological characteristics was estimated using logistic regression analysis. Further analysis was performed for children (0-14 y old) and adults (≥15 y old) separately. In total, 815 (89.4%) patients were included in the final dataset. Overall, 501 (61.5%) patients had DRM detected. NRTI DRM was more common in children, while NRTI+NNRTI DRM was more frequent in adults (P < 0.001). Krasnoyarsk region, male sex and high viral load were positively associated with the presence of DRM in adults, while higher CD4 cell count and PI/INSTI-based ART had a negative association. No association between epidemiological characteristics and DRM was identified in children. The remaining 38.5% of patients with virological failure had no DRM detected; those patients were likely to have insufficient ART adherence. Most (55.5%) patients had HIV CRF63_02A6, followed by sub-subtype A6 (39.2%). This study revealed poor ART adherence as a main factor driving ART failure among PLWH in the Siberian region. DRM was detected in over 60% of PLWH experiencing ART failure. The current results highlight an urgent need for the introduction of special programs focusing on ART adherence improvement.

Patterns of HIV-1 drug resistance among HIV-infected patients receiving first-line antiretroviral therapy in Novosibirsk Region, Russia.

OBJECTIVES: Antiretroviral (ARV) drugs have played a vital role in controlling the HIV-1 epidemic; however, some challenges remain. ARV drugs vary in their ability to control HIV infection, displaying differences in treatment-limiting factors and genetic barriers to resistance. The current report assesses the prevalence of HIV-1 drug resistance mutations (DRMs) among patients who failed first-line antiretroviral therapy (ART) and evaluates the genetic barrier of different regimens. METHODS: The study cohort (n = 271) included HIV-infected individuals who visited the Novosibirsk, Russia, HIV/AIDS clinic in 2018-2022. All patients received first-line ART prior to virological failure. Sociodemographic and HIV-related data were collected from medical records and self-reported questionnaires. HIV-1 pol gene sequences were generated, and the presence of HIV-1 DRM was assessed. The genetic barrier to resistance was assessed by combining treatment regimen and adherence data. RESULTS: Nonoptimal ART adherence was identified in 48.3% of patients and correlated with male sex, PWID, unemployment, and rural area residence. Most of the patients with high-level adherence were identified among those who were on TDF+3TC+DTG. HIV-1 DRMs were identified in 54.6% of the patients. The analysis of HIV-1 DRM, ART regimen, and adherence data classified TDF+3TC+DTG and TDF+3TC+LPV/r as treatment regimens with a high genetic barrier, whereas EFV-containing ART was classified as a regimen with a low genetic barrier. CONCLUSIONS: The current study delivers results on the efficacy of HIV-1 ART and treatment adherence in real-world practice settings. This report suggests that ART regimens with a high genetic barrier to resistance combined with improved treatment adherence may reduce the transmission of HIV-1 resistant variants.

Spatiotemporal dynamics of HIV-1 CRF63_02A6 sub-epidemic.

HIV-1 epidemic in Russia is one of the fastest growing in the world reaching 1.14 million people living with HIV-1 (PLWH) in 2021. Since mid-1990s, the HIV-1 epidemic in Russia has started to grow substantially due to the multiple HIV-1 outbreaks among persons who inject drugs (PWID) leading to expansion of the HIV-1 sub-subtype A6 (former Soviet Union (FSU) subtype A). In 2006, a local HIV-1 sub-epidemic caused by the distribution of novel genetic lineage CRF63_02A6 was identified in Siberia. In this study, we used a comprehensive dataset of CRF63_02A6 pol gene sequences to investigate the spatiotemporal dynamic of the HIV-1 CRF63_02A6 sub-epidemic. This study includes all the available CRF63_02A6 HIV-1 pol gene sequences from Los Alamos National Laboratory (LANL) HIV Sequence Database. The HIV-1 subtypes of those sequences were conferred using phylogenetic analysis, and two automated HIV-1 subtyping tools Stanford HIVdb Program and COMET. Ancestral state reconstruction and origin date were estimated using Nextstrain. Evolutionary rate and phylodynamic analysis were estimated using BEAST v 1.10.4. CRF63_02A6 was assigned for 872 pol gene sequences using phylogenetic analysis approach. Predominant number (n = 832; 95.4%) of those sequences were from Russia; the remaining 40 (4.6%) sequences were from countries of Central Asia. Out of 872 CRF63_02A6 sequences, the corresponding genetic variant was assigned for 75.7 and 79.8% of sequences by Stanford and COMET subtyping tools, respectively. Dated phylogenetic analysis of the CRF63_02A6 sequences showed that the virus most likely originated in Novosibirsk, Russia, in 2005. Over the last two decades CRF63_02A6 has been widely distributed across Russia and has been sporadically detected in countries of Central Asia. Introduction of new genetic variant into mature sub-subtype A6 and CRF02_AGFSU epidemics could promote the increase of viral genetic diversity and emergence of new recombinant forms. Further HIV-1 studies are needed due to a continuing rapid virus distribution. Also, the implementation of HIV-1 prevention programs is required to reduce HIV-1 transmission. This study also highlights the discrepancies in HIV-1 subtyping approaches. The reference lists of HIV-1 sequences implemented in widely used HIV-1 automated subtyping tools need to be updated to provide reliable results.

Characterization of HIV-1 Epidemic in Kyrgyzstan.

Kyrgyzstan has one of the highest rates of HIV-1 spread in Central Asia. In this study, we used molecular-epidemiological approaches to examine the HIV-1 epidemic in Kyrgyzstan. Samples were obtained from HIV-positive individuals who visited HIV/AIDS clinics. Partial pol gene sequences were used to identify HIV-1 subtypes and drug resistance mutations (DRMs) and to perform phylogenetic analysis. Genetic diversity and history reconstruction of the major HIV-1 subtypes were explored using BEAST. This study includes an analysis of 555 HIV-positive individuals. The study population was equally represented by men and women aged 1-72 years. Heterosexual transmission was the most frequent, followed by nosocomial infection. Men were more likely to acquire HIV-1 during injection drug use and while getting clinical services, while women were more likely to be infected through sexual contacts (p < 0.01). Heterosexual transmission was the more prevalent among individuals 25-49 years old; individuals over 49 years old were more likely to be persons who inject drugs (PWID). The major HIV-1 variants were CRF02_AG, CRF63_02A, and sub-subtype A6. Major DRMs were detected in 26.9% of the study individuals; 62.2% of those had DRMs to at least two antiretroviral (ARV) drug classes. Phylogenetic analysis revealed a well-defined structure of CRF02_AG, indicating locally evolving sub-epidemics. The lack of well-defined phylogenetic structure was observed for sub-subtype A6. The estimated origin date of CRF02_AG was January 1997; CRF63_02A, April 2004; and A6, June 1995. A rapid evolutionary dynamic of CRF02_AG and A6 among Kyrgyz population since the mid-1990s was observed. We observed the high levels of HIV-1 genetic diversity and drug resistance in the study population. Complex patterns of HIV-1 phylogenetics in Kyrgyzstan were found. This study highlights the importance of molecular-epidemiological analysis for HIV-1 surveillance and treatment implementation to reduce new HIV-1 infections.

Genetic Diversity of HIV-1 in Krasnoyarsk Krai: Area with High Levels of HIV-1 Recombination in Russia.

More than a quarter of HIV-infected individuals registered in Russia live in Siberia. Unlike Central Russia where HIV-1 subtype A6 is predominant, in most Siberian regions since 2012, a new HIV-1 CRF63_02A1 genetic variant has spread, with the share of this variant attaining 75-85% among newly identified HIV cases. Krasnoyarsk Krai is considered to be a high-risk territory according to morbidity rate and HIV infection incidence among the population. The current paper aims to study the molecular epidemiologic characteristics of HIV-1 spreading in Krasnoyarsk Krai. Phylogenetic and recombination analyses of pol (PR-RT, IN) and env regions of the virus were used for genotyping 159 HIV-1 isolated in Krasnoyarsk Krai. 57.2% of the isolates belonged to subtype A (A6) specific to Russia, 12.6% to CRF63_02A1, and 0.6% to CRF02_AGСА, and in 29.6% HIV-1 URFs were detected, including URF63/А (23.9%), URFА/В (4.4%), and URF02/А (1.3%). In 6 of 7, HIV-1 URFА/В identical recombination model was detected; the origin of 38 URF63/А was proven to be the result of individual recombination events. Since 2015, a share of the population with newly diagnosed HIV who were infected with HIV-1 URF reached an exceptionally high rate of 38.6%. As distinct from adjacent Siberian regions, the HIV-1 CRF63_02A1 prevalence rate in Krasnoyarsk Krai is within 16%; however, the increased contribution of new HIV-1 into the regional epidemic development was observed due to the recombination of viruses of subtypes А, В, and CRF63_02A1. The difference between the described molecular epidemiologic picture in Krasnoyarsk Krai and in adjacent areas is likely caused by differences in predominant routes of HIV transmission and by more recent HIV-1 CRF63_02A1 transmission in the PWID group, which had a high prevalence of HIV-1 subtype A by the time of the new virus transmission, resulting in increased possibility of coinfection with various HIV-1 genetic variants.

HIV-1 Epidemiology, Genetic Diversity, and Primary Drug Resistance in the Tyumen Oblast, Russia.

Introduction. Specific molecular epidemic features of HIV infection in Tyumen Oblast (TO), Russia, were studied. Methods. The genome sequences encoding HIV-1 protease-reverse transcriptase, integrase, and major envelope protein were examined for 72 HIV-1 specimens isolated from the TO resident infected in 2000-2015. Results. The recorded prevalence of HIV-1 subtype A (A1) is 93.1%; HIV-1 subtype B continues to circulate in MSM risk group (1.4%). Solitary instances of HIV-1 recombinant forms, CRF63_02A1 (1.4%) and CRF03_AB (1.4%), were detected as well as two cases of HIV-1 URF63_A1 (2.8%). Phylogenetic analysis showed no HIV-1 clustering according to the duration of infection and risk groups but revealed different epidemic networks confirming that HIV infection spread within local epidemic foci. A high incidence of CXCR4-tropic HIV-1 variants and a higher rate of secondary mutations influencing the virus fitness (K20R, L10V, and I) are observed among the virus specimens isolated from newly infected individuals. Conclusions. The current HIV-1 epidemic in TO develops within the local epidemic networks. Similar to the previous period, HIV-1 subtype A is predominant in TO with sporadic cases of importation of HIV-1 recombinant forms circulating in adjacent areas.