Differential In Vitro Kinetics of Drug Resistance Mutation Acquisition in HIV-1 RT of Subtypes B and C

Abstract

BackgroundHIV-1 subtype B is the most prevalent in developed countries and, consequently, it has been extensively studied. On the other hand, subtype C is the most prevalent worldwide and therefore is a reasonable target for future studies. Here we evaluate the acquisition of resistance and the viability of HIV-1 subtype B and C RT clones from different isolates that were subjected to in vitro selection pressure with zidovudine (ZDV) and lamivudine (3TC).Methods/Principal FindingsMT4 cells were infected with chimeric virus pseudotyped with RT from subtype B and C clones, which were previously subjected to serial passage with increasing concentrations of ZDV and 3TC. The samples collected after each passage were analyzed for the presence of resistance mutations and VL. No differences were found between subtypes B and C in viral load and resistance mutations when these viruses were selected with 3TC. However, the route of mutations and the time to rebound of subtype B and C virus were different when subjected to ZDV treatment. In order to confirm the role of the mutations detected, other clones were generated and subjected to in vitro selection. RT subtype B virus isolates tended to acquire different ZDV resistance mutations (Q151M and D67N or T215Y, D67D/N and F214L) compared to subtype C (D67N, K70R, T215I or T215F).Conclusions/SignificanceThis study suggests that different subtypes have a tendency to react differently to antiretroviral drug selection in vitro. Consequently, the acquisition of resistance in patients undergoing antiretroviral therapy can be dependent on the subtypes composing the viral population.

Use of Proviral DNA to Investigate Virus Resistance Mutations in HIV-infected Zimbabweans

“…T215Y) mutations [ 27 , 28 ]. However, it remains that the two pathways are not mutually exclusive [ 29 ]. One of the sequences had all TAM-1 mutations, and another had all TAM-2 mutations Table 4 Two of these TAMS: D67N and T215K were also observed in a study recently carried out in Zimbabwe [ 17 ].…”

Prevalence of Transmitted HIV-1 Drug Resistance among Young Adults Attending HIV Counselling and Testing Clinics in Kigali, Rwanda

“…The predominant HIV-1 subtype in Rwanda is A1, while Uganda has a mixture of subtypes A and D [22]. Differential rates of HIV DR development between various HIV-1 subtypes has been reported for some DR mutations [23][24][25], which could account for some differences in HIV DR prevalence. Possible programmatic reasons for these different rates could include a longer duration of ART exposure in the community in Uganda or the relative success of the Rwanda national programme in reducing loss to follow-up and maintaining strong ART adherence levels [26].…”

Global Comparison of Drug Resistance Mutations After First-Line Antiretroviral Therapy Across Human Immunodeficiency Virus-1 Subtypes

“…Although high viral genetic diversity and variable ART adherence are known to contribute to drug resistance and ART failure, subtype contributions to treatment outcomes remains actively researched through in vitro [ 7 – 9 ] and surveillance [ 10 – 13 ] methods. Subtype-specific codon use results in more frequent mutations at codons 65 and 106 in the HIV-1 subtype C RT gene under treatment selection [ 14 , 15 ].…”