Molecular epidemiology reveals the role of war in the spread of HIV in Ukraine.

Ukraine has one of the largest HIV epidemics in Europe, historically driven by people who inject drugs (PWID). The epidemic showed signs of stabilization in 2012, but the recent war in eastern Ukraine may be reigniting virus spread. We investigated the movement of HIV-infected people within Ukraine before and during the conflict. We analyzed HIV-1 subtype-A pol nucleotide sequences sampled during 2012-2015 from 427 patients of 24 regional AIDS centers and used phylogeographic analysis to reconstruct virus movement among different locations in Ukraine. We then tested for correlations between reported PWID behaviors and reconstructed patterns of virus spread. Our analyses suggest that Donetsk and Lugansk, two cities not controlled by the Ukrainian government in eastern Ukraine, were significant exporters of the virus to the rest of the country. Additional analyses showed that viral dissemination within the country changed after 2013. Spearman correlation analysis showed that incoming virus flow was correlated with the number of HIV-infected internally displaced people. Additionally, there was a correlation between more intensive virus movement and locations with a higher proportion of PWID practicing risky sexual behaviors. Our findings suggest that effective prevention responses should involve internally displaced people and people who frequently travel to war-affected regions. Scale-up of harm reduction services for PWID will be an important factor in preventing new local HIV outbreaks in Ukraine.

Low daily oral PrEP adherence and low validity of self-report in a randomized trial among PWID in Ukraine.

BACKGROUND: The efficacy of daily oral pre-exposure prophylaxis (PrEP) in preventing HIV transmission among people who inject drugs (PWID) was demonstrated over a decade ago. However, only a few studies among PWID have since measured PrEP adherence using laboratory markers. METHODS: In this trial, we randomized recently injecting PWID in Kyiv, Ukraine, to receive daily oral TDF/FTC with or without SMS reminders. Enrollment and PrEP initiation took place at an HIV clinic. Subsequent visits at months 1, 3, and 6 were conducted at a community harm reduction center and included a structured interview, adherence counseling, PrEP dispensing, and dried blood spot collection. PrEP adherence was assessed using standard self-reported measures and TDF/FTC biomarkers. RESULTS: A total of 199 PWID (99 SMS, 100 No-SMS) were enrolled, of whom 24 % were women, with a median age of 37. At month 6, 79.4 % (158/199) of participants were retained, with 84 % (133/158) reporting opioid injection and 20 % (31/158) reporting stimulant injection in the past 30 days. 77 % (122/158) reported taking >95 % of PrEP doses in the past month, and 87 % reported taking the last dose within 2 days. Tenofovir diphosphate was detected in 17 % (28/158) of participants, and emtricitabine triphosphate was detected in 25 % (40/158). Only 3 % (5/158) had metabolite levels indicative of consistent PrEP uptake at 4+ doses per week. There was no association between the SMS intervention and TDF/FTC metabolite detection. CONCLUSION: Adherence to daily oral PrEP among actively injecting PWID, without daily supervision or incentives, was extremely low, despite supportive counseling and SMS reminders. We also observed a high rate of discordance between self-report and classification by a validated biomarker of adherence. Given the scarcity of evidence and emerging data suggesting low oral PrEP adherence among PWID, additional implementation studies with TDF/FTC biomarkers are needed to study whether a sufficient level of adherence to daily PrEP is attainable among PWID, especially as long-acting injectable PrEP offers a promising alternative.

Population-level prevalence of detectable HIV viremia in people who inject drugs (PWID) in Ukraine: Implications for HIV treatment and case finding interventions.

Achievement of viral load suppression among people living with HIV is one of the most important goals for effective HIV epidemic response. In Ukraine, people who inject drugs (PWID) experience the largest HIV burden. At the same time, this group disproportionally missed out in HIV treatment services. We performed a secondary data analysis of the national-wide cross-sectional bio-behavioral surveillance survey among PWID to assess the population-level prevalence of detectable HIV viremia and identify key characteristics that explain the outcome. Overall, 11.4% of PWID or 52.6% of HIV-positive PWID had a viral load level that exceeded the 1,000 copies/mL threshold. In the group of HIV-positive PWID, the detectable viremia was attributed to younger age, monthly income greater than minimum wage, lower education level, and non-usage of antiretroviral therapy (ART) and opioid agonistic therapy. Compared with HIV-negative PWID, the HIV-positive group with detectable viremia was more likely to be female, represented the middle age group (35-49 years old), had low education and monthly income levels, used opioid drugs, practiced risky injection behavior, and had previous incarceration history. Implementing the HIV case identification and ART linkage interventions focused on the most vulnerable PWID sub-groups might help closing the gaps in ART service coverage and increasing the proportion of HIV-positive PWID with viral load suppression.

Tracking SARS-COV-2 variants using Nanopore sequencing in Ukraine in 2021.

The use of real-time genomic epidemiology has enabled the tracking of the global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), informing evidence-based public health decision making. Ukraine has experienced four waves of the Coronavirus Disease 2019 (COVID-19) between spring 2020 and spring 2022. However, insufficient capacity for local genetic sequencing limited the potential application of SARS-CoV-2 genomic surveillance for public health response in the country. Herein, we report local sequencing of 103 SARS-CoV-2 genomes from patient samples collected in Kyiv in July-December 2021 using Oxford Nanopore technology. Together with other published Ukrainian SARS-CoV-2 genomes, our data suggest that the third wave of the epidemic in Ukraine (June-December 2021) was dominated by the Delta Variant of Concern (VOC). Our phylogeographic analysis revealed that in summer 2021 Delta VOC was introduced into Ukraine from multiple locations worldwide, with most introductions coming from Central and Eastern European countries. The wide geographic range of Delta introductions coincides with increased volume of travel to Ukraine particularly from locations outside of Europe in summer 2021. This study highlights the need to urgently integrate affordable and easily scaled pathogen sequencing technologies in locations with less developed genomic infrastructure, in order to support local public health decision making.

Tracking SARS-COV-2 Variants Using Nanopore Sequencing in Ukraine in Summer 2021.

Since spring 2020, Ukraine has experienced at least two COVID-19 waves and has just entered a third wave in autumn 2021. The use of real-time genomic epidemiology has enabled the tracking of SARS-CoV-2 circulation patterns worldwide, thus informing evidence-based public health decision making, including implementation of travel restrictions and vaccine rollout strategies. However, insufficient capacity for local genetic sequencing in Ukraine and other Lower and Middle-Income countries limit opportunities for similar analyses. Herein, we report local sequencing of 24 SARS-CoV-2 genomes from patient samples collected in Kyiv in July 2021 using Oxford Nanopore MinION technology. Together with other published Ukrainian SARS-COV-2 genomes sequenced mostly abroad, our data suggest that the second wave of the epidemic in Ukraine (February-April 2021) was dominated by the Alpha variant of concern (VOC), while the beginning of the third wave has been dominated by the Delta VOC. Furthermore, our phylogeographic analysis revealed that the Delta variant was introduced into Ukraine in summer 2021 from multiple locations worldwide, with most introductions coming from Central and Eastern European countries. This study highlights the need to urgently integrate affordable and easily-scaled pathogen sequencing technologies in locations with less developed genomic infrastructure, in order to support local public health decision making.

HIV treatment cascade among people who inject drugs in Ukraine.

The HIV treatment cascade is an effective tool to track progress and gaps in the HIV response among key populations. People who inject drugs (PWID) remain the most affected key population in Ukraine with HIV prevalence of 22% in 2015. We performed secondary analysis of the 2017 Integrated Bio-Behavioral Surveillance (IBBS) survey data to construct the HIV treatment cascade for PWID and identify correlates of each indicator achievement. The biggest gap in the cascade was found in the first "90", HIV status awareness: only 58% [95% CI: 56%-61%] of HIV-positive PWID reported being aware of their HIV-positive status. Almost 70% [67%-72%] of all HIV-infected PWID who were aware of their status reported that they currently received antiretroviral therapy (ART). Almost three quarters (74% [71%-77%]) of all HIV-infected PWID on ART were virally suppressed. Access to harm reduction services in the past 12 months and lifetime receipt of opioid agonist treatment (OAT) had the strongest association with HIV status awareness. Additionally, OAT patients who were aware of HIV-positive status had 1.7 [1.2-2.3] times the odds of receiving ART. Being on ART for the last 6 months or longer increased odds to be virally suppressed; in contrast, missed recent doses of ART significantly decreased the odds of suppression. The HIV treatment cascade analysis for PWID in Ukraine revealed substantial gaps at each step and identified factors contributing to achievement of the outcomes. More intensive harm reduction outreach along with targeted case finding could help to fill the HIV awareness gap among PWID in Ukraine. Scale up of OAT and community-level linkage to care and ART adherence interventions are viable strategies to improve ART coverage and viral suppression among PWID.

Phylodynamics Helps to Evaluate the Impact of an HIV Prevention Intervention.

Assessment of the long-term population-level effects of HIV interventions is an ongoing public health challenge. Following the implementation of a Transmission Reduction Intervention Project (TRIP) in Odessa, Ukraine, in 2013-2016, we obtained HIV pol gene sequences and used phylogenetics to identify HIV transmission clusters. We further applied the birth-death skyline model to the sequences from Odessa (n = 275) and Kyiv (n = 92) in order to estimate changes in the epidemic's effective reproductive number (Re) and rate of becoming uninfectious (δ). We identified 12 transmission clusters in Odessa; phylogenetic clustering was correlated with younger age and higher average viral load at the time of sampling. Estimated Re were similar in Odessa and Kyiv before the initiation of TRIP; Re started to decline in 2013 and is now below Re = 1 in Odessa (Re = 0.4, 95%HPD 0.06-0.75), but not in Kyiv (Re = 2.3, 95%HPD 0.2-5.4). Similarly, estimates of δ increased in Odessa after the initiation of TRIP. Given that both cities shared the same HIV prevention programs in 2013-2019, apart from TRIP, the observed changes in transmission parameters are likely attributable to the TRIP intervention. We propose that molecular epidemiology analysis can be used as a post-intervention effectiveness assessment tool.

The Changing Epidemiological Profile of HIV-1 Subtype B Epidemic in Ukraine.

While HIV-1 subtype B has caused a large epidemic in the Western world, its transmission in Ukraine remains poorly understood. We assessed the genetic diversity of HIV-1 subtype B viruses circulating in Ukraine, characterized the transmission group structure, and estimated key evolutionary and epidemiological parameters. We analyzed 120 HIV-1 subtype B pol sequences (including 46 newly generated) sampled from patients residing in 11 regions of Ukraine between 2002 and 2017. Phylogenies were estimated using maximum likelihood and Bayesian phylogenetic methods. A Bayesian molecular clock coalescent analysis was used to estimate effective population size dynamics and date the most recent common ancestors of identified clades. A phylodynamic birth-death model was used to estimate the effective reproductive number (Re) of these clades. We identified two phylogenetically distinct predominantly Ukrainian (≥75%) clades of HIV-1 subtype B. We found no significant transmission group structure for either clade, suggesting frequent mixing among transmission groups. The estimated dates of origin of both subtype B clades were around early 1970s, similar to the introduction of HIV-1 subtype A into Ukraine. Re was estimated to be 1.42 [95% highest posterior density (HPD) 1.26-1.56] for Clade 1 and 1.69 (95% HPD 1.49-1.84) for Clade 2. Evidently, the subtype B epidemic in the country is no longer concentrated in specific geographical regions or transmission groups. The study results highlight the necessity for strengthening preventive and monitoring efforts to reduce the further spread of HIV-1 subtype B.