Cuban history of CRF19 recombinant subtype of HIV-1
Authors: Zhukova Anna , Voznica Jakub , Dávila Felipe Miraine , To Thu-Hien , Pérez Lissette , Martínez Yenisleidys , Pintos Yanet , Méndez Melissa , Gascuel Olivier , Kouri Vivian 
Published: February 2021

AbstractCRF19 is a recombinant form of HIV-1 subtypes D, A1 and G, which was first sampled in Cuba in 1999, but was already present there in 1980s. CRF19 was reported almost uniquely in Cuba, where it accounts for ~25% of new HIV-positive patients and causes rapid progression to AIDS (~ 3 years).We analyzed a large data set comprising ~ 350polandenvsequences sampled in Cuba over the last 15 years and ~ 350 from Los Alamos database. This data set contained both CRF19 (~ 315), and A1, D and G sequences. We performed and combined analyses for the three A1, G and D regions, using fast maximum likelihood approaches, including: (1) phylogeny reconstruction, (2) spatio-temporal analysis of the virus spread, and ancestral character reconstruction for (3) transmission mode and (4) drug resistance mutations (DRMs). This allowed us to acquire new insights on the CRF19 origin and transmission patterns. We showed that CRF19 recombined between 1966 and 1977, most likely in Cuban community stationed in Congo region. We further investigated CRF19 spread on the Cuban province level, and discovered that the epidemic started in 1970s, most probably in Villa Clara, that it was at first carried by heterosexual transmissions, and then quickly spread in the 1980swithin the “men having sex with men” (MSM) community, with multiple transmissions back to heterosexuals. The analysis of the transmission patterns of common DRMs showed mostly acquired drug resistance rather than transmitted one.Our results show a very early introduction of CRF19 in Cuba, which could explain its local epidemiological success. Ignited by a major founder event, the epidemic then followed a similar pattern as other subtypes and CRFs in Cuba. The reason for the short time to AIDS remains to be understood and requires specific surveillance, in Cuba and elsewhere.Author summaryCRF19 is a recombinant form of HIV-1, which causes rapid progression to AIDS (~ 3 years versus 5 – 10 years for other subtypes and CRFs). CRF19 is reported almost uniquely in Cuba, where it is highly prevalent (~ 25%) among newly detected HIV-1 patients. In this study, we found that CRF19 most likely recombined around the 1970sin the Cuban community that was stationed in Democratic Republic of the Congo and Angola at that time. It was introduced very early into the Cuban province of Villa Clara, from where it had several introductions to La Habana in the 1980sand then further spread to other Cuban provinces. The CRF19 epidemic most probably started with heterosexual transmissions, followed in the 1980sby multiple introductions into “men having sex with men” (MSM) community, followed by multiple transmissions back to heterosexuals (often females). The early introduction of CRF19 into Cuba most likely explains its success, not observed in other parts of the world. However, importantly, its rapid progression to AIDS makes it crucial to survey CRF19 sub-epidemics not only in Cuba, but also in other parts of the world having regular exchanges with Cuba.