Subtype analysis and mutations to antiviral drugs in HIV-1-infected patients from Mozambique before initiation of antiretroviral therapy: results from the DREAM programme.
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.
Bellocchi
Maria Concetta
MC
INMI L, Spallanzani, Rome, Italy.
Forbici
Federica
F
Palombi
Leonardo
L
Gori
Caterina
C
Coelho
Elisabeth
E
Svicher
Valentina
V
D'Arrigo
Roberta
R
Emberti-Gialloreti
Leonardo
L
Ceffa
Susanna
S
Erba
Fulvio
F
Marazzi
Maria Cristina
MC
Silberstein
Francesca Ceccherini
FC
Perno
Carlo-Federico
CF
D019943:Amino Acid Substitution / Q000235:genetics; D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use; D024882:Drug Resistance, Viral / Q000235:genetics*; D015751:Genes, pol; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D016333:HIV Protease / Q000235:genetics; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000145:classification / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D009073:Mozambique; D009154:Mutation; D010802:Phylogeny
D019380:Anti-HIV Agents; D054303:HIV Reverse Transcriptase; D016333:HIV Protease