AEGiS-14IAC: Assessing HIV-1 diversity and resistance to protease inhibitors in a sample of injection drug users (IDUs) of Rio de Janeiro, Brazil.

14th International AIDS Conference

Barcelona, Spain - July 7-12, 2002

Assessing HIV-1 diversity and resistance to protease inhibitors in a sample of injection drug users (IDUs) of Rio de Janeiro, Brazil.

Int Conf AIDS 2002 Jul 7-12; 14:(abstract no. A10031)

Teixeira SL, Bastos FI, Hacker M, Morgado MG, Telles PR
Lab. of AIDS &Molec. Immunol., Dept. of Immunol., Oswaldo Cruz Inst., Fiocruz, Rio de Janeiro, Brazil

BACKGROUND: IDUs are a key source for the dissemination of HIV-1 subtypes and drug resistant variant viruses, due to their double-exposure to parenteral and sexually-transmitted infections and difficulties to comply with clinical follow-up. In a context of universal access to HAART and evolving therapies including protease inhibitors is pivotal to monitor virus diversity and resistance in this population

METHODS: As part of WHO-II study, 684 IDUs were interviewed, answered a questionnaire and had 30 ml of their blood collected. Samples were tested for HIV-status using two Elisa and confirmed by WB. CD4+ and CD8+ T cell counts were assessed by flow cytometry. Positive samples were tested for viral load (NASBA). DNA samples were PCR amplified and gag/env HIV-1 subtypings were carried out using heteroduplex mobility assays (HMA). DNA sequencing of the protease (pro) region has been performed to assess HIV-1 subtyping and resistance mutations to protease inhibitors

RESULTS: Fifty-eight (8.5%) samples were seropositive for HIV-1 infection. HIV-1 HMA subtyping showed 36 (72%) subtype B infections, 7 (14%) F and 7 (14%) B/F or F/B discordant gag/env genomes. A subset of 20 samples from antiretroviral drug-naïve IDUs has already been sequenced, showing that most viruses have accessory mutations, such as L63P, V77I, L10I, M36I, I93L. Of special concern was the finding that one of them (5%) showed the V82A mutation, which confers resistance to IDV, RTV and LPV.

CONCLUSIONS: A sizeable proportion of prevalent infections of this population seem to be involving recombinant Bgag/Bpro/Fenv, Fgag/Fpro/Benv and Fgag/Bpro/Fenv viruses. Samples so far analyzed from antiretroviral drug-naïve IDUs presented basically accessory mutations. However, a primary resistance mutation for protease inhibitors has already been documented for one of them, which is of a major concern in terms of the dissemination of drug resistant viruses.

Keywords: AEGIS, HIV-1, HIV Infections, Protease Inhibitors, HIV Protease Inhibitors, HIV-1 Reverse Transcriptase, Variation (Genetics), Mutation, Idoxuridine, Brazil, genetics

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A10031