Tropism prediction in HIV-1 variants circulating in Cuba, 2017-2019: Implications for the pathogenesis of infection and response to Maraviroc

Abstract

Background: Tropism is determined by the ability of HIV-1 to bind to the receptors CCR5 or CXCR4 to enter the target cell, which has implications for the pathogenesis of the disease and affects treatment options. This study determined the relationship between the tropism of HIV-1 variants circulating in Cuba, with different variables, and the implications for the use of co-receptor inhibitors. Methods: Plasma samples from 69 of HIV-1 seropositive patients, period 2017-2019, were analyzed. Fragments of the env and pol regions of the virus were sequenced. The subtype and prediction of the viral phenotype, viral mutations, as well as the relationship of the phenotype and subtype with clinical, epidemiological, and virological variables were determined. Results: The recombinant CRF19_cpx (p=0.0234) showed a significant association with viruses that use the X4 and R5X4/X4 Co-receptor, even in untreated patients. Of the viruses studied, 78.26% presented at least one mutation associated with resistance to Maraviroc, although the patients had not received prior therapy with this drug. Conclusion: The preferential tropism for the CXCR4 co-receptor, detected in the CRF19_cpx variant, accompanied by greater viral replication and unrelated to the time of diagnosis of the patients, reinforces the hypothesis that viral variant is more pathogenic. The high frequency of polymorphisms and mutations that confer resistance to Maraviroc in the V2 and V3 regions of HIV-1 of the Cuban recombinant forms indicate that there could be a natural resistance to this antiretroviral.