Global increase in recombinant HIV-1 strains stifles vaccine development

Circulating recombinant forms (CRFs) and unique recombinant forms (URFs) constitute the highest proportion of circulating HIV-1 subtypes among key populations, according to results of a study published in The Journal of Infectious Diseases.

Researchers performed a systematic literature review and meta-analysis to characterize HIV-1 and HIV-2 subtypes across geographic regions and key populations. The review included data on HIV-1 and HIV-2 subtype prevalence that were captured between January 2010 and June 2021. A total of 454 studies were evaluated, representing a sample size of 610,000 patients and 91 countries.

Among patients with HIV infection included in the analysis, 23.0% had subtype C, 16.7% had subtype A, and 9.5% had subtype CRF01_AE. Overall, CRFs and URFs comprised 29% of all circulating subtypes. Of note, CRFs were most prevalent in West and Central Africa (CRF02_AG), the Middle East and North Africa (other CRFs), and Asia and the Pacific (CRF01_AE). Subtype B was most prevalent in Western and Central Europe, North America, and Latin America; subtype C was most prevalent in Eastern and Southern Africa; and subtype A was most prevalent in Eastern Europe and Central Asia.

Of 35,000 high-risk patients across 104 studies with available data on HIV subtype prevalence, 41% were men who have sex with men (MSM), 29% were injection drug users, and 22% identified as heterosexual. Among MSM, subtype B was the most prevalent (21%; 95% CI, 19.2-23.4), with CRFs comprising 57% of all HIV infections in this population. In addition, subtype A accounted for 28% (95% CI, 11.4-40.4) of all HIV infections in injection drug users, and CRFs accounted for approximately 40% of all circulating subtypes in those who identified as heterosexual.

Further analysis was performed to assess trends in the global pooled prevalence of major subtypes across time. Overall, subtype trends did not significantly change between 2010 and 2021, with the exception of an increase of approximately 8% in CRFs and URFs. In Latin America and the Caribbean, the prevalence of other CRFs (excluding CRF01_AE and CRF02_AG) increased by 25% between 2010 and 2015 and 2016 and 2021.

Limitations of this review include the potential underestimation or overestimation of subtype prevalence as data from most studies were collected via convenience sampling. Other limitations were high study heterogeneity, small sample sizes across a plurality of studies, and unequal representation of the geographic regions and countries evaluated. The researchers also noted that the results may have included subtypes that were circulating prior to the cutoff date of 2010.

“Among the hurdles facing HIV vaccine development is the global HIV-1 genetic diversity, where recombinants (CRFs and URFs) now constitute the highest proportion of circulating HIV while continuing to increase in prevalence,” the researchers noted.

Disclosure: This research was supported by Janssen Pharmaceuticals, and multiple study authors declared affiliations with industry. Please see the original reference for a full list of disclosures.

By Lisa Kuhns, PhD

References:

Williams A, Menon S, Crowe M, et al. Geographic and population distributions of HIV-1 and HIV-2 circulating subtypes: a systematic literature review and meta-analysis (2010-2021). J Infect Dis. Published online August 18, 2023. doi:10.1093/infdis/jiad327