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.
Assuntos
Terapia Antirretroviral de Alta Atividade , Farmacorresistência Viral , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Adolescente , Adulto , Burkina Faso/epidemiologia , Criança , Feminino , HIV-1/genética , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Carga ViralRESUMO
SUMMARY: : On introduction of a program for prevention of mother-to-child transmission (PMTCT) of HIV in Nouna, rural Burkina Faso, we determined HIV prevalence in this region to be 3.6%, which is significantly lower than the 7% reported for 2 major cities of Burkina Faso. Forty-three samples from drug-naive pregnant women and patients before introduction of antiretroviral therapy (ART) were genotypically characterized in gag, pol, and env regions. One individual each was infected with HIV-2 or dually infected with HIV-1 and HIV-2. The most dominant HIV-1 subtypes were CRF02_AG and CRF06_cpx, similar to what has been observed in other West African countries. A discordant genotype was observed in almost half of the analyzed samples, with most putative recombinants deriving from CRF02_AG and CRF06_cpx. Recently reported strains like the CRF09_cpx and the sub-subtype A3 as well as some unique recombinant forms of HIV like D/D/CRF02_AG and CRF02_AG/CRF02.AG/CRF_09cpx were also detected. Analysis of drug resistance-associated polymorphisms detected the nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance mutations K103N/E and V118I in 1 individual each, suggesting transmission of drug-resistant viruses or prior use of antiretroviral drugs. Resistance-associated polymorphisms (K20I and M36I) were prevalent in the complete protease (PR) region, but no primary drug resistance mutations were detected. Analysis of the HR1 and HR2 regions of gp41, important for T-20 sensitivity, revealed no known resistance mutations but several polymorphisms of unknown importance. Monitoring for drug resistance mutations among naive subjects is important in this area on introduction of antiretroviral drugs.