Genotipagem para resistência primária e secundária em pacientes infectadospelo HIV-1 do estado de Goiás
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2009-08-04
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Universidade Federal de Goiás
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HIV-1 resistance to antiretroviral (ARV): nucleoside reverse transcriptase inhibitors
(NRTI), non-nucleoside reverse transcriptase inhibitors (NNRTI), protease inhibitors (PI)
and new ARV classes, like enfurvitide (T-20), represents a challenge for sustainable
virological and immunologic responses. This study describes the prevalence of primary
and secondary HIV-1 drug resistance and subtypes circulating in Central West Brazil.
HIV-1 phylogenetic diversity and ARV resistance mutations were assessed among 97
ARV naïve patients, 48 ARV experienced patients and 77 HIV-1 pregnant women from
Goiânia/GO. Protease (PR), partial reverse transcriptase (RT) and gp41 genes were
amplified and sequenced from plasma RNA. HIV-1 pol subtypes were assigned by
phylogenetic analysis and env/gag subtypes were identified by heteroduplex mobility
analysis (HMA). ARV resistance mutations were analyzed by Stanford University
Database, Internacional AIDS Society, Los Alamos Database and other sources. Among
ARV naïve patients, primary drug resistance ranged from 8-10%. IP (n=2), NRTI (n=3),
NRTI (n=1), IP+NRTI (n=1) e NRTI+NNRTI (n=3). Subtype B represented 82.5%,
subtype F1 6.2%, subtype C 3.1%, BPR/F1RT 7.2% and one sample was F1PR/CBRT
mosaic. Among ARV experienced patients, secondary drug resistance was 79%: NRTI
(n=1), NNRTI (n=1), PI+NRTI or NRTI+NNRTI (n=20), PI+NRTI+NNRTI (n=16,
considered multidrug resistant-MDR). In the HIV-1 pol gene, subtype B represented
79.2%, subtype F1 4.2%, subtype C 2.1%, F1PR/BRT 8.3% and BPR/F1RT 6.3%. Among
MDR patients, the mosaic F1PR/BRT/F1ENV (n=1) and subtype BPR/BRT/BENV (n=13) were
identified. G36E, N42T and N43S T-20 resistance mutations were observed in 3 MDR
patients. In the group of pregnant women, none had primary drug resistance mutations.
Among 42 ARV experienced pregnant women, 16.7% presented HIV-1 isolates with
drug resistance mutations: NRTI (n=2), NRTI + NNRTI (n=2), PI + NTRI (n=2) and
PI+NRTI+NNRTI (n=1). Regarding HIV-1 subtypes in env gag/PR RT genes, 66.2%
were subtype B, 3.9% subtype C and 6.5% subtype F1. Our data from Central West
Brazil show extensive genetic diversity with a significant proportion of distinct BF1
recombinants and the co-circulation of subtypes B, F1 and C. Moreover our data show
that ARV naïve and ARV experienced patients, including pregnant women, can benefit from genotyping for ARV drug resistance, to improve clinical management and salvage
therapy, which are also important to control HIV-1 transmission.
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CARDOSO, L. P. V. Genotipagem para resistência primária e secundária em pacientes infectadospelo HIV-1 do estado de Goiás. 2009. 157 f. Tese (Doutorado em Medicina Tropical e Saúde Publica) - Universidade Federal de Goiás, Goiânia, 2009.