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

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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. J. Med. Virol. 76:452–458, 2005.

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