RESUMO
A cross-sectional study was undertaken among drug-naïve HIV patients at the University Hospital in Ouagadougou shortly before and after the introduction of large-scale antiretroviral therapy (ART) in Burkina Faso. Baseline clinical and virological data as well as protease (PR) and 5' reverse transcriptase (RT) sequences from 104 HIV infected patients were analyzed. Genotypic classification revealed the following subtypes and recombinant forms: CRF06_cpx, n = 46 (44.2%); CRF02_AG, n = 39 (37.5%); subtype A, n = 4 (3.8%); CRF09_cpx, n = 2 (1.9%); and unclassified, n = 13 (12.5%). Bootstrap analysis of CRF02_AG and CRF06_cpx viruses showed that >80% had a similar structure to their respective prototypes. The prevalence of primary drug resistance mutations was 12.5%, all mutations arising in the RT sequences in accordance with the dominance of this drug class in Burkina Faso. The mutations were distributed as follows: NRTI (10.6%): M41L (n = 2), D67N (n = 2), K70K/E (n = 2), L210W (n = 1), T215S/Y (n = 2), and K219K/Q (n = 2); NNRTI (6.1%): K103K/N (n = 2), Y181C (n = 2), G190G/A (n = 1), and P236P/L (n = 1). Subtype specific secondary polymorphisms such as K20I and M36I in the PR were observed in almost all patients. Drug resistance mutations occurred at similar frequencies (12.8% and 10.8%, respectively) among patients infected with CRF02_AG and CRF06_cpx. Some subtype specific polymorphisms were observed within important HLA epitopes, including B35, B7, and A2 in the RT, and A*6802 in the PR sequences. The observed resistance mutations are most likely to have been transmitted based on the timing of the study but prior undocumented use of ART cannot be excluded.
Assuntos
Farmacorresistência Viral , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , HIV-1/genética , Mutação de Sentido Incorreto , Produtos do Gene pol do Vírus da Imunodeficiência Humana/genética , Adolescente , Adulto , Burkina Faso , Criança , Análise por Conglomerados , Estudos Transversais , Feminino , Genótipo , Protease de HIV/genética , Transcriptase Reversa do HIV/genética , HIV-1/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Filogenia , Recombinação Genética , Análise de Sequência de DNA , Homologia de Sequência , Adulto JovemRESUMO
OBJECTIVE: Determine the pattern of drug resistance among HIV infected drug exposed patients failing therapy in Ouagadougou, Burkina Faso. METHODS: The protease (PR) and reverse transcriptase (RT) of 87 samples from 75 treatment exposed HIV infected patients failing therapy were PCR amplified, sequenced, subtyped and analyzed for the presence of drug resistance mutations. RESULTS: The most common drugs used were 3TC, AZT (or d4T) and EFV. The dominant subtypes were CRF06_cpx (48%) and CRF02_AG (40%). The prevalence of resistance mutations among patients failing therapy was: PR inhibitors (PI), 40%; non-nucleoside RT-inhibitors (NNRTI), 76% and nucleoside RT-inhibitors (NRTI), 85%. Dominant mutations included M46I (37%), 154V (26%), V82A/T/F (30%) in PR; K103N (44%), G190A/S (16%) and T215F/Y (48%) (NRTIs) in RT. Some resistance mutations, notably D67N/G, K70R and L210W (thymidine analogue mutations-TAMs); K101E, V179E in RT, 154V, V82A/T/F and L90M in PR were significantly higher among CRF06_cpx than CRF02_AG strains (P < 0.05). Although not significant, other TAMs (M41L, T215F/Y, K219Q/E) also occurred more frequently among CRF06_cpx strains as well. CONCLUSION: There is a high prevalence of drug resistance mutations among ARV exposed patients in Burkina Faso with an unexpected subtype-specific difference. Validation of this result will require larger sample sizes and in vitro drug susceptibility studies with CRF06_cpx strains.
