Subtype analysis and mutations to antiviral drugs in HIV-1-infected patients from Mozambique before initiation of antiretroviral therapy: Results from the DREAM programme

Maria Concetta Bellocchi, Federica Forbici, Leonardo Palombi, Caterina Gori, Elisabeth Coelho, Valentina Svicher, Roberta D'Arrigo, Leonardo Emberti-Gialloreti, Susanna Ceffa, Fulvio Erba, Maria Cristina Marazzi, Francesca Ceccherini Silberstein, Carlo Federico Perno

Research output: Contribution to journalArticlepeer-review

Abstract

Phylogenetic analysis and evaluation of drug-resistance were carried out upon 59 plasma samples from 58 treatment-naïve HIV-1 infected patients from Mozambique, enrolled in a free antiviral-therapy protocol in the frame of Drug-Resource-Enhancement against AIDS and Malnutrition (DREAM) programme. Sequencing of the first 1,300 bases of the pol-gene shows that all virus strains cluster within clade C, with the exception of a single patient carrying a G-subtype virus. Relevant mutations in the reverse transcriptase (RT) are rare: 118A/I/L/G (four patients), 179E/D/I (three patients), 333E/D (two patients), 101R, and 210F (one patient each). In Protease (PR), V82I (10.3%) is the only relevant mutation, while natural polymorphisms/secondary mutations are found, some at very high frequency: 20R (25.9%), 36I (91.4%), 36L (8.6%), 60E (31.0%), 63P (29.3%), and 93L (96.6%). Among them, mutations with a frequency >25% were further investigated to assess their covariation pattern with PI resistance associated mutations. The pattern of covariation observed for K20R and D60E (but not L63P and M36I) was different between C and B subtype isolates from PR-inhibitor-treated patients. The sequences were also analyzed to calculate the ratio of non-synonymous to synonymous substitution. The ratio for PR and RT was 0.116 and 0.093, respectively, suggesting a greater conservation in RT than PR in both subtypes B and C HIV strains. Taken together, the results demonstrate a consistent clade-homogeneity of viral strains circulating in Mozambique, and the very limited presence, in drug-naïve patients, of mutations associated with resistance to RT-inhibitors. The high frequency of secondary mutations/polymorphisms in HIV-PR deserves further studies to evaluate its relevance in clinical settings.

Original languageEnglish
Pages (from-to)452-458
Number of pages7
JournalJournal of Medical Virology
Volume76
Issue number4
DOIs
Publication statusPublished - Aug 2005

Keywords

  • Africa
  • Drug resistance
  • Drug-naïve patients
  • Mozambique
  • Phylogenetic analysis
  • pol gene

ASJC Scopus subject areas

  • Virology

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