The Impact of War in Ukraine: Studies From HIV Glasgow 2022

Key Takeaways

• Despite the hardships and disruptions of war, Ukraine has successfully maintained PrEP access across most of the country with continued substantial increases in uptake through 2022.
• War-associated migration has placed significant pressure on the medical system in Poland, with 94% of migrants receiving HIV treatment requiring a change in regimen because of differing drug access in Ukraine and Poland.

Since the war in Ukraine began in February 2022, internal displacement, international migration, and restricted access to medical care have affected more than 10 million people in Europe. The HIV disease burden in Ukraine remains a vital issue of concern, with an estimated 210,000-260,000 people with HIV, approximately 130,000 of whom are receiving antiretroviral therapy (ART), including approximately 2700 children and adolescents. The war has affected continuity of ART and access to healthcare and disease prevention modalities, including HIV pre-exposure prophylaxis (PrEP) and opioid agonist treatment. Furthermore, the war may markedly alter the HIV epidemic in Europe, with a shift in the predominant transmission route to heterosexual sex, differences in viral subtype variations across regions, increases in new HIV diagnoses, and unmet needs for ART modifications and expanded PrEP access.

In line with these urgent challenges affecting HIV care across the European region, particularly in Central and Eastern Europe, several important studies evaluating the effects of the war in Ukraine on HIV care were presented at the 2022 HIV Drug Therapy conference held in Glasgow, Scotland, including analyses of the effects on PrEP implementation in Ukraine and on HIV care for refugees in Poland.

In this commentary, I discuss those studies as well as the potential impact of alterations in HIV-1 subtype patterns across Europe because of war-related migration and displacement, with specific consideration of the role viral subtype plays in predicting efficacy of long-acting cabotegravir (CAB) plus rilpivirine (RPV).

PrEP Implementation in Ukraine: New Challenges Brought on by the Russian Invasion
Implementation of PrEP in real-world clinical practice in Ukraine began in 2018, with only 130 clients in that year. Uptake increased considerably from 2019 to 2022 and continued to increase throughout 2022 to reach a total of 8734 clients. Remarkably, of this total, 52.2% reflect initiations that occurred in 2022. Although there was a notable decline in the number of new PrEP initiations at the beginning of the Russian invasion (with only 185 new clients in March 2022), uptake quickly returned to normal levels and even exceeded pre-war numbers, with 731 new initiations reported in June 2022. 

A considerable proportion of PrEP recipients in Ukraine are women (26.0%), and the majority of PrEP clients are aged 30-45 years (65.6%). PrEP medications have been successfully delivered to all Ukrainian provinces during the war except for occupied areas and with expected war-related fluctuations (eg, declines in delivery where military actions were most active and increases in delivery in the West due to internal displacement).

Despite the setting of ongoing war, PrEP programs in Ukraine continue to be supported by social assistance systems, online education for medical professionals, and even a pilot PrEP initiation project in prisons! These data demonstrating maintenance of a critical HIV prevention program within the country despite the hardships of war reflect the resilience of the nation of Ukraine.

Impacts of War in Ukraine on Clinical HIV Care of Refugees in Poland
War-associated cross-border migrations have also had effects on HIV care in countries neighboring Ukraine, with Poland receiving the largest number of refugees (>1.4 million Ukrainian citizens registered for migrant protection). Since the beginning of the war, 2647 migrants have entered HIV care in Poland, resulting in an approximately 15% increase in the number of treated cases in only 8 months, placing significant pressure on the Polish medical system. 

Of importance from the perspective of HIV care in Europe, Ukrainian migrants entering HIV care in Poland were predominantly female (71%), with a majority having acquired HIV by heterosexual transmission (71%) and a notable percentage with serologic features of hepatitis C virus (HCV) coinfection (29.5% positive for anti-HCV antibody).

The majority of antiretroviral-treated patients who entered care had been receiving a dolutegravir (DTG)-based regimen, most commonly DTG/tenofovir disoproxil fumarate (TDF)/lamivudine (3TC) (70.3%). Despite the difficulties of war, migration, and refugee status, 89.5% of the assessed population maintained HIV-1 RNA <50 copies/mL, and no integrase resistance mutations were observed, reflecting the high treatment efficacy and high genetic barrier to resistance of DTG-based regimens.

Unfortunately, as DTG/TDF/3TC is not available in the European Union, 93.5% of patients required a change in their HIV treatment (86.9% switched within the same antiretroviral medication classes). The need for a change in ART among war migrants from Ukraine who are receiving DTG/TDF/3TC also may be common in other European countries where DTG remains less accessible.

Effect of War-Related Migration on HIV-1 Subtype Distribution in Europe
War-associated migrations may change the distribution pattern of HIV-1 subtypes in Europe, as the A6 variant is predominant in Ukraine. Indeed, 88% of people with HIV migrating from Ukraine who had sequencing available for subtype determination (n = 50) had the A6 variant. Prevalence of this subtype is important in the context of the roll-out of long-acting CAB plus RPV as an HIV switch regimen (and possibly of long-acting CAB for PrEP) because the A6 variant has been identified as a risk factor for virologic failure with this regimen in a pooled analysis of the ATLAS, FLAIR, and ATLAS-2M trials.

This finding was confirmed with longer-term follow-up data from these 3 trials presented at HIV Glasgow 2022. In a baseline factor analysis of pooled data from 1431 individuals switched to long-acting CAB plus RPV, HIV-1 subtype A6/A1 alongside with RPV resistance and BMI ≥30 kg/m² were key factors predicting virologic failure, but only when more than 1 of these factors were present. 

It is not yet clear how the HIV-1 A6 subtype may affect efficacy of long-acting injectable CAB as HIV PrEP. Certainly, long-acting CAB given every 2 months could be an attractive prophylactic option for migrating populations; however, the risk of loss to follow-up and the potential impact of the A6 variant require careful study when assessing the utility of this long-acting PrEP option in regions of Europe with high A6 prevalence. 

Closing Thoughts
The war in Ukraine is already changing the nature of the HIV epidemic in Europe, with an increase in the number of women entering care in some countries, which will warrant more focus on contraception, pregnancy planning, and gynecologic follow-up.

Furthermore, HCV elimination goals, particularly among populations with HIV/HCV coinfection, may need to be revisited in light of war-related challenges.

Finally, a change in the distribution of HIV subtypes across Europe owing to migration and displacement may affect treatment outcomes with long-acting CAB plus RPV therapy and possibly with long-acting CAB as PrEP; molecular surveillance will be needed to follow these changing patterns.

Your Thoughts?
Do you provide HIV care or prevention services in Eastern Europe? If so, what has your experience been in working to overcome the challenges presented by the war, either directly or indirectly? Join the discussion and share your experiences by posting a comment.