Effect of M184v mutation selection and maintenance on the antiretroviral treatment response

• Autor(a) principal: Carvalho, Alexandre
• Data de Publicação: 2008
• Tipo de documento: Artigo
• Idioma: por
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: https://doi.org/10.34632/cadernosdesaude.2008.2778

The mutation M184V in the reverse transcriptase gene is associated with high level of resistance to lamiduvine and emtricitabine. It emerges shortly after therapy with these antiretrovirals has begun. It does not provoke cross-resistance within the class of reverse transcriptase nucleoside inhibitors and reduces viral fitness in a way it could be an interesting option for patients with incomplete viral suppression and few therapeutic options, making it an interesting model for the study of a potential clinical benefit obtained by the continuation of antiretroviral therapy to which HIV has a reduced susceptibility. Methodology: It’s an open label, prospective study, in which antiretroviral treatment of 22 patients infected with HIV 1 bearing the M184V mutation was altered, based in a genotypic resistance test while the prescription of lamiduvine or emtricitabine was continued. Through comparison with a historical control group, the existence or lack thereof of viral or immunological benefits was established. Results: Couldn’t be found any difference between immunologic or virologic responses on both groups. In laboratorial adverse events, the 3TC group experienced ALT negative variation (-14.3 U/ml±31.3) and control group has an increase of 12.1 U/ml±50.4 (p<0.05). In subgroup analysis, for subtype non-b HIV infected patients, in 3TC group 50% ended with more than 350 CD4 per mm3 against 21.4% in control group (p=0.127); in 3TC group 83.3% ended with viral load <1000 copies/ml against 57.1% in control group (p=0.149). With a number of TAM ≤3, 93.3% of the patients in 3TC group ended with viral load <1000 copies/ml against 74.1% in control group (p=0.128); for reverse transcriptase mutations ≤4, 100% of the patients in 3TC group ended with viral load <1000 copies/ml against 68.2% in control group (p=0.05). Conclusions: It was concluded the strategy of adding lamiduvine or emtricitabine to the antiretroviral regimen designed for patients for whom treatment is failing, infected with a strain of the virus carrying the M184V mutation is not inferior to the usual practice of suspension of treatment. This strategy does not imply increased toxicity. From the analysis of subgroups it also can be concluded that patients infected with HIV of subtypes other than b have a tendency to benefit in viral and immunological terms. A tendency to benefit in viral terms has also been identified in the 3TC group if mutations were inferior to three thymidine analogue mutations or four nucleoside analogue mutations in addition to M184V.