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Professor of Medicine
Consultant in Infectious Diseases
Department of Infectious, Tropical Diseases and Acquired Immunodeficiency
Pomeranian Medical University
Milosz Parczewski, MD, PhD, has disclosed that he has received consulting fees from Gilead Sciences, Janssen, MSD, and ViiV/GlaxoSmithKline and fees for non-CME services from Gilead Sciences, Janssen, and MSD.
Between 2010 and 2018, the Eastern European and Central Asian regions experienced the greatest rise of the HIV epidemic, with a 29% increase in annual new HIV infections. The Central and Eastern European (CEE) region continues to face epidemiologic challenges related to the intersecting infections of HIV, hepatitis C virus (HCV), and tuberculosis (TB). In this commentary, I highlight new data presented at Conference on Retroviruses and Opportunistic Infection (CROI) 2022 that have particular relevance for infectious diseases in CEE.
Long-Acting HIV Pre-Exposure Prophylaxis
The CEE region faces a significant delay in the implementation of the pre-exposure prophylaxis (PrEP) programs, which is linked to the poor political awareness and lack of infrastructure and human resources. Existing PrEP programs in the region are largely funded privately or by nongovernmental organizations operating outside of the auspices of national prevention programs. Nevertheless, to eliminate HIV, we must keep thinking about PrEP implementation and novel PrEP strategies.
At CROI 2022, Landowitz and colleagues shared updated results from the unblinded phase of the HPTN-083 trial of long-acting (LA) injectable cabotegravir (CAB) vs daily oral tenofovir disoproxil (TDF)/emtricitabine (FTC) for PrEP. The data showed that the relative efficacy of LA CAB and daily oral TDF/FTC as PrEP remained consistent with the results from the blinded phase, with a relative risk reduction of 67% in the LA CAB group (HR: 0.33; 95% CI: 0.17-0.66). The stable safety signal in the unblinded phase was also encouraging.
However, unexpectedly, both groups experienced a higher incidence of HIV infections in the unblinded phase compared with the blinded phase. The study authors attribute this to decreased adherence over time and increased person-years of HIV exposure in the high-prevalence regions.
Although the road to implementing LA injectable PrEP in CEE seems long, particularly if one considers the reasons to use HIV-1 RNA testing to monitor efficacy, the expanding availability of oral PrEP and the exciting new data on LA injectable PrEP give us hope for the future. A note of caution, however: The A6/A1 subtype remains the most prevalent HIV-1 subtype in parts of CEE—and the second most prevalent subtype in my country, Poland—and the impact of the A6/A1 subtype on PrEP efficacy is not fully elucidated.
HCV Treatment Among People With HIV
Sexualized drug use is an understudied issue in CEE because of stigma, but it contributes to the high rate of acute HCV infections among men who have sex with men. Van Santen and colleagues presented an analysis of International Collaboration on Hepatitis C Elimination in HIV Coinfection data from Western Europe showing that access to direct-acting antivirals (DAAs) is effective in preventing HCV transmission among people with HIV (PWH). Broad access to DAAs decreased the predicted incidence of new HCV infections in PWH from 0.97-0.98/100 person-years (pre-DAA and restricted DAA access) to 0.48/100 person-years.
Both HCV incidence in PWH and access to DAAs vary greatly across CEE countries, with some countries (eg, Georgia) successfully implementing DAAs and HCV elimination programs and other countries lacking the political will to make HCV elimination a priority. These data lend further support for the implementation of DAAs in treatment as prevention programs.
Treatment of Multidrug-Resistant Tuberculosis
CEE has a high prevalence of tuberculosis (TB), and TB is the most common opportunistic infection among patients with AIDS in Russia, Ukraine, Latvia, Lithuania, and Romania. In particular, treatment of multidrug-resistant (MDR) TB remains a challenge, so I noted with great interest the data from the TB-PRACTECAL study of novel treatments for rifampin-resistant TB.
The study enrolled patients from CEE countries, Uzbekistan and Belarus, as well as from South Africa. Fluoroquinolone resistance was present in 25% to 34% of patients, and 22% to 23% were coinfected with HIV. Outcomes were compared in 3 arms receiving investigational treatment regimens vs a control arm receiving the World Health Organization standard of care. The investigational regimens were bedaquiline, pretomanid, linezolid (BPaL), BPaL plus clofazimine (BPaLC), or BPaL plus moxifloxacin (BPaLM).
Nyang’wa and colleagues reported striking differences among the groups in rates of unfavorable outcomes (including treatment failure, death, treatment discontinuation, recurrence, or loss to follow-up): 48.5% for the control group vs 23.3% for BPaL, 18.8% for BPaLC, and 11.3% for BPaLM, in the modified intention-to-treat population. The safety profile in the 3 BPaL arms was favorable compared with the control group, and the positive results in the BPaL arms prompted the Data and Safety Monitoring Board to terminate randomization in March 2021. These results are encouraging news for patients with MDR TB.
In your practice, how often do you encounter patients who would benefit from implementation of PrEP, improved access to DAAs for HCV treatment, or new treatment regimens for MDR-TB? Join the discussion by posting a comment. For more details on this and other key HIV issues from CROI 2022, review more CCO Conference Coverage, including Capsule Summary slidesets and other ClinicalThought commentaries highlighting US and global perspectives.