Avaliação das contagens de linfócitos T CD8+ em pacientes infectados pelo HIV e sua evolução clínica
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Data
2019-02-26
Autores
Martins, Thalita Cortez
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Universidade Estadual Paulista (Unesp)
Resumo
Segundo dados do Programa Conjunto das Nações Unidas sobre HIV/Aids (UNAIDS), existem atualmente 36,9 milhões de pessoas vivendo com HIV no mundo. A disponibilização e eficácia da terapia antirretroviral (TARV) permitiu uma mudança no cenário desta pandemia, reduzindo consideravelmente a mortalidade associada à aids. Devido à redução da carga viral plasmática do HIV (CV) para níveis indetectáveis, a TARV permite que ocorra a recuperação de células T CD4+, principal alvo do vírus, e melhora no prognóstico das pessoas que vivem com o HIV/aids (PVHA). Entretanto, as mudanças no compartimento de linfócitos T CD8+, responsáveis pelo controle da replicação viral, são relativamente pouco entendidas durante os vários estágios da infecção. Desta forma, o presente estudo, de caráter retrospectivo, teve o objetivo de avaliar, a partir do levantamento das contagens de células T CD8+, as possíveis correlações entre esta variável e a evolução clínica da infecção, considerando as contagens de células T CD4+, quantificações da CV, tempo de TARV, classe terapêutica utilizada, aparecimento de infecções oportunistas e desfecho clínico (paciente assintomático, progressão para aids ou morte). Para isso, foram analisados 200 prontuários eletrônicos de PVHA acompanhadas no Serviço de Ambulatórios Especializados de Infectologia “Domingos Alves Meira” (SAEI-DAM) e diagnosticadas a partir de 2012. Para a análise dos dados, foram realizados os testes, binomial negativa, correlação de Pearson e analisados modelos multivariados de regressão linear. Os resultados mostraram que as menores contagens de linfócitos T CD8+ no momento inicial, foram encontradas tanto em pacientes que apresentavam menores médias nas contagens iniciais de T CD4+ categorizadas (<200 cél/mm³, p=0,0008) quanto menor nadir de linfócitos T CD4+ categorizado (<200 cél/mm³, p=0,004). Quando estas variáveis foram analisadas de forma contínua, o T CD8+ inicial também mostrou correlação negativa com estágio de aids inicial (p<0,0001) e correlações positivas com T CD4+ inicial (p=0,0007), seu nadir (p=0,0003) e com a CV inicial (p=0,0353). Além disso, as contagens de células T CD8+ iniciais se correlacionaram positivamente com as finais (p=<0,0001). Já em relação às contagens de T CD8+ no momento final estudado, foi possível observar correlação positiva com as contagens de T CD4+ finais (p=0,025) e, negativa com o estágio de aids neste último momento (p<0,0001). O esquema terapêutico utilizado pareceu interferir nas últimas contagens de linfócitos T CD8+, pois os indivíduos que utilizavam a classe de inibidores de transcriptase reversa não análogos a nucleosídeos apresentavam, também, as menores médias destas células quando comparados aos que utilizavam inibidores de protease (p=0,037) ou de integrase (p=0,046). A quantidade de trocas terapêuticas e fatores epidemiológicos, tais como, álcool, fumo e uso de drogas, não influenciaram nas contagens de T CD8+. Já na análise pelo modelo de regressão linear, as médias finais de linfócitos T CD8+ foram correlacionadas positivamente tanto com o nadir destas células (p<0,0001) quanto com a condição de aids no momento inicial (p=0,021). Além disso, houve correlação negativa entre T CD8+ final e o nadir de T CD4+(p<0,0001). Devido a grande divergência entre os dados encontrados aqui, mais estudos são necessários para elucidar de maneira mais eficaz a atuação dos linfócitos T CD8+ frente à progressão da doença, bem como a sua influência com os esquemas terapêuticos, visando a melhoria na qualidade de vida das PVHA.
According to data from the Joint United Nations Program on HIV/aids (UNAIDS), there are currently 36.9 million people living with HIV worldwide. The availability and effectiveness of antiretroviral therapy (ART) allowed a change in the scenario of this pandemic, reducing considerably the mortality associated with AIDS. Due to the reduction in plasma HIV viral load (VL) to undetectable levels, ART allows the recovery of CD4+ T cells, the main target of the virus, and improves the prognosis of people living with HIV/aids (PLHA). However, changes in the CD8+ T lymphocyte compartment are relatively poorly understood during the various stages of infection. In this way, the present retrospective study aimed to evaluate the possible correlations between this variable and the clinical evolution of the infection, considering the CD4+ T cell counts, quantifications of the VL, time of ART, therapeutic schemes used, appearance of opportunistic infections and clinical outcome (asymptomatic patient, progression to aids or death). We analyzed 200 electronic records of PLHA attended at "Domingos Alves Meira" Specialized Ambulatory Service (SAEI-DAM) and diagnosed from 2012 to 2018. For the data analysis, we used negative binomial, correlation of Pearson and multivariate linear regression models. The results showed that the lowest CD8+ T lymphocyte counts at baseline were found in both patients with lower CD4+ T mean counts (<200 cells/mm³, p= 0.0008) and lower T CD4+ nadir (<200 cells/mm³, p=0,004). When these variables were analyzed continuously, initial CD8+ T also showed negative correlation with initial aids stage (p<0,0001) and positive correlations with initial CD4+ T (p=0,0007), nadir (p = 0,0003) and the initial VL (p=0,0353). In addition, baseline initial CD8+ T cell counts are correlated positively with the last counts of these cells (p=<0,0001). Regarding the CD8+ T counts at the final moment studied, it was possible to observe a positive correlation with the final CD4+ T counts (p=0,025) and a negative correlation with the aids stage at this last moment (p<0,0001). The therapeutic regimen used appeared to interfere with the latest CD8+ T lymphocyte counts, since the individuals using the class of non-nucleoside reverse transcriptase inhibitors also had the lowest mean values of these cells when compared to those using protease inhibitors (p=0,037) or integrase (p=0,046). The therapeutic schemes changes and epidemiological factors, such as alcohol, smoking and drug use, did not influence CD8+ T counts. In the analysis by the linear regression model, the final means of CD8+ T lymphocytes were positively correlated both with the nadir of these cells (p<0,0001) and with the aids condition at the initial moment (p=0,021). In addition, there was a negative correlation between final CD8+ T and nadir CD4+ T (p<0.0001). Due to the great divergence between the data found here, more studies are needed to more effectively elucidate the performance of CD8+ T lymphocytes against disease progression, as well as their influence with the therapeutic regimens, aiming to improve the quality of life of the patients. PLHA.
According to data from the Joint United Nations Program on HIV/aids (UNAIDS), there are currently 36.9 million people living with HIV worldwide. The availability and effectiveness of antiretroviral therapy (ART) allowed a change in the scenario of this pandemic, reducing considerably the mortality associated with AIDS. Due to the reduction in plasma HIV viral load (VL) to undetectable levels, ART allows the recovery of CD4+ T cells, the main target of the virus, and improves the prognosis of people living with HIV/aids (PLHA). However, changes in the CD8+ T lymphocyte compartment are relatively poorly understood during the various stages of infection. In this way, the present retrospective study aimed to evaluate the possible correlations between this variable and the clinical evolution of the infection, considering the CD4+ T cell counts, quantifications of the VL, time of ART, therapeutic schemes used, appearance of opportunistic infections and clinical outcome (asymptomatic patient, progression to aids or death). We analyzed 200 electronic records of PLHA attended at "Domingos Alves Meira" Specialized Ambulatory Service (SAEI-DAM) and diagnosed from 2012 to 2018. For the data analysis, we used negative binomial, correlation of Pearson and multivariate linear regression models. The results showed that the lowest CD8+ T lymphocyte counts at baseline were found in both patients with lower CD4+ T mean counts (<200 cells/mm³, p= 0.0008) and lower T CD4+ nadir (<200 cells/mm³, p=0,004). When these variables were analyzed continuously, initial CD8+ T also showed negative correlation with initial aids stage (p<0,0001) and positive correlations with initial CD4+ T (p=0,0007), nadir (p = 0,0003) and the initial VL (p=0,0353). In addition, baseline initial CD8+ T cell counts are correlated positively with the last counts of these cells (p=<0,0001). Regarding the CD8+ T counts at the final moment studied, it was possible to observe a positive correlation with the final CD4+ T counts (p=0,025) and a negative correlation with the aids stage at this last moment (p<0,0001). The therapeutic regimen used appeared to interfere with the latest CD8+ T lymphocyte counts, since the individuals using the class of non-nucleoside reverse transcriptase inhibitors also had the lowest mean values of these cells when compared to those using protease inhibitors (p=0,037) or integrase (p=0,046). The therapeutic schemes changes and epidemiological factors, such as alcohol, smoking and drug use, did not influence CD8+ T counts. In the analysis by the linear regression model, the final means of CD8+ T lymphocytes were positively correlated both with the nadir of these cells (p<0,0001) and with the aids condition at the initial moment (p=0,021). In addition, there was a negative correlation between final CD8+ T and nadir CD4+ T (p<0.0001). Due to the great divergence between the data found here, more studies are needed to more effectively elucidate the performance of CD8+ T lymphocytes against disease progression, as well as their influence with the therapeutic regimens, aiming to improve the quality of life of the patients. PLHA.
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Palavras-chave
HIV/aids, HIV/aids, CD8+ T lymphocytes, Linfócitos T CD8+, Progressão da doença, Disease progression