Genotypic Resistance to Antiretroviral Drugs in Patients Infected with Several HIV Type 1 Genetic Forms in Cuba

Abstract

The main objective of this study is to evaluate the prevalence of resistance-associated mutations to reverse transcriptase (RT) and protease (PR) inhibitors (I) 2 years after the introduction of antiretroviral treatment in Cuba, analyzing the mutations corresponding to different HIV-1 genetic forms circulating in Cuba. A total of 425 plasma samples were collected in 2003, corresponding to 175 (41.2%) subtype B and 250 (58.8%) non-B genetic forms, including 56 (22.4 %) non-B subtypes, 112 (44.8%) circulating recombinant forms (CRFs), and 82 (32.8%) unique RFs (URFs). Of these, 175 (41.2%) patients were under highly active antiretroviral therapy (HAART) and 250 (58.8%) were treatment-naive. The presence of RT and PR resistance-associated mutations was established by sequencing. Levels of resistance were evaluated according to the Stanford Database program (http://hivdb.stanford.edu). The prevalence of resistance to RTI was 52.2% among RTI-treated patients, 51.5% for subtype B, and 53.2% for non-B genetic forms, including CRF18_cpx, CRF19_cpx, subtype C, and BG URF. In treatment-naive patients it was 6.4% in subtype B and 4.2% in non-B subtypes and RFs. The prevalence of resistance to PRI was 30% among PRI-treated patients, 28% in subtype B and 31% in non-B genetic forms, and 3.2% among treatment-naive subjects, mostly BG recombinants. In conclusion, significant differences in the prevalence of resistance to RTI and PRI were not detected among the most frequent genetic forms from treated patients, suggesting that the genetic diversity of HIV-1 in Cuba does not play a main role in the development of resistance to antiretroviral drugs. The presence of transmitted resistance mutations supports the study of resistance at baseline of treatment.