CRF19_cpx is an Evolutionary fit HIV-1 Variant Strongly Associated With Rapid Progression to AIDS in Cuba

Vivian Kouri, Ricardo Khouri, Yoan Alemán, Yeissel Abrahantes, Jurgen Vercauteren, Andrea Clemencia Pineda-Peña, Kristof Theys, Sarah Megens, Michel Moutschen, Nico Pfeifer, Johan Van Weyenbergh, Ana B. Pérez, Jorge Pérez, Lissette Pérez, Kristel Van Laethem, Anne Mieke Vandamme

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

Background: Clinicians reported an increasing trend of rapid progression (RP) (AIDS within 3. years of infection) in Cuba. Methods: Recently infected patients were prospectively sampled, 52 RP at AIDS diagnosis (AIDS-RP) and 21 without AIDS in the same time frame (non-AIDS). 22 patients were sampled at AIDS diagnosis (chronic-AIDS) retrospectively assessed as >. 3. years infected. Clinical, demographic, virological, epidemiological and immunological data were collected. Pol and env sequences were used for subtyping, transmission cluster analysis, and prediction of resistance, co-receptor use and evolutionary fitness. Host, immunological and viral predictors of RP were explored through data mining. Findings: Subtyping revealed 26 subtype B strains, 6 C, 6 CRF18_cpx, 9 CRF19_cpx, 29 BG-recombinants and other subtypes/URFs. All patients infected with CRF19 belonged to the AIDS-RP group. Data mining identified CRF19, oral candidiasis and RANTES levels as the strongest predictors of AIDS-RP. CRF19 was more frequently predicted to use the CXCR4 co-receptor, had higher fitness scores in the protease region, and patients had higher viral load at diagnosis. Interpretation: CRF19 is a recombinant of subtype D (C-part of Gag, PR, RT and nef), subtype A (N-part of Gag, Integrase, Env) and subtype G (Vif, Vpr, Vpu and C-part of Env). Since subtypes D and A have been associated with respectively faster and slower disease progression, our findings might indicate a fit PR driving high viral load, which in combination with co-infections may boost RANTES levels and thus CXCR4 use, potentially explaining the fast progression. We propose that CRF19 is evolutionary very fit and causing rapid progression to AIDS in many newly infected patients in Cuba.

Original languageEnglish (US)
Pages (from-to)244-254
Number of pages11
JournalEBioMedicine
Volume2
Issue number3
DOIs
StatePublished - Mar 1 2015

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this