Background:  The clinical implications of HIV-1 diversity remain unclear. The genetic variability of viral strains might affect the development of resistance to antiretroviral drugs. In Argentina, about the half of the circulating strains are B/F recombinant viruses (RecBF). The aim of this work was to study the impact of such genetic background on the occurrence of resistance-associated mutations.

Methods:  Plasma samples were collected from 316 HIV-1 Argentinean patients from Buenos Aires city and Buenos Aires province (87%), and the rest of the country (13%). Subjects were treated with antiretroviral drugs and attended the FUNDAI Laboratory between June 1999 and February 2002 due to treatment failure. Viral RNA from plasma samples was analyzed with the HIV Genotyping System (Applied Biosystems), using an ABI 310 DNA Sequencer (pol gene sequences comprised the protease and the first 320 codons of the reverse transcriptase [RT]). Phylogenetic analysis was implemented with ClustalX and recombinant sequences were confirmed with the Simplot software. Fisher’s exact test, c², Kruskal-Wallis, and Student’s t-test were used for statistical analysis.

Results:  The subtype distribution resulted in 164 (51.9%) sequences from subtype B; 151 (47.8%) RecBF, and a single (0.3%) subtype F sequence. Intersubtype breakpoint mapping of RecBF revealed a prevalent structure (5’F/B/F/B3’) showing 3 breakpoints also found in CRF12_BF previously reported in Argentina; other 2 common structures showing minor differences with the former, and a high diversity of mosaics (48%, 22%, and 30% of RecBF, respectively). Although there was a variety of administered antiretroviral regimens, there were non-significant differences in treatment history between patients carrying either RecBF or subtype B viruses. However, significant differences between RecBF and subtype B were found in the frequencies of several RAMs, both in protease (K20R/M, I54V/L, V82A/F/T were prevalent in RecBF, while M46L/I, A71V/T, G73S/C, I84V, L90M, in subtype B), and in reverse transcriptase (M41L, K43E/Q/N, E44D/A, V118I, and L210W were prevalent in subtype B). Interestingly, V82A/F/T was highly associated with K20R/M and I54V/L, in RecBF (74% vs 19% in subtype B, p <0.001), but with A71V/T, M46L/I, or I54V/L, in subtype B (64% vs 11% in RecBF, p <0.001).

Conclusions:  The genetic background of RecBF may affect the genetic routes to resistance by influencing the emergence of resistance-associated genotypic profiles.

Keywords: recombinant; resistance; genotyping