RESUMO
As the immune system develops with age, children combat infections better. HIV-1, however, targets an activated immune system, potentially rendering children increasingly permissive to HIV-1 infection as they grow. How HIV-1 fitness changes with age in children is unknown. Here, we estimated the within-host basic reproductive ratio, R0, a marker of viral fitness, in HIV-1 subtype C-infected children in India, aged between 84 days and 17 years. We measured serial viral load and CD4 T cell counts in 171 children who initiated first-line ART. For 25 children, regular and frequent measurements provided adequate data points for analysis using a mathematical model of viral dynamics to estimate R0. For the rest, we used CD4 counts for approximate estimation of R0. The viral load decline during therapy was biphasic. The mean lifespans of productively and long-lived infected cells were 1.4 and 27.8 days, respectively. The mean R0 was 1.5 in children aged < 5 years, increased with age, and approached 6.0 at 18 years, close to 5.8 estimated previously for adults. The tolerogenic immune environment thus compromises HIV-1 fitness in young children. Early treatment initiation, when the R0 is small, will likely improve viral control, in addition to suppressing the latent reservoir.
Assuntos
Aptidão Genética/genética , Infecções por HIV/genética , HIV-1/genética , Carga Viral/genética , Adolescente , Antirretrovirais/administração & dosagem , Terapia Antirretroviral de Alta Atividade/normas , Contagem de Linfócito CD4 , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/virologia , Criança , Pré-Escolar , Feminino , Aptidão Genética/imunologia , Infecções por HIV/sangue , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Soropositividade para HIV/genética , Soropositividade para HIV/imunologia , HIV-1/imunologia , HIV-1/patogenicidade , Humanos , Lactente , Recém-Nascido , Masculino , Carga Viral/imunologiaRESUMO
AIM: To compare the markers of inflammation and immune activation in virally suppressed HIV-infected children on antiretroviral therapy, who practiced regular structured exercise comprising running and yoga to those who did not over a 2-year period. METHODS: This retrospective cohort study included 72 children aged 8 to 16 years divided into 2 groups, exercisers (n = 36) and the nonexercisers (n = 36) based on their intentional physical activity. The analyses were carried out at baseline and after 2 years (Y2) for the soluble biomarkers of inflammation and immune activation (tumor necrosis factor alpha, interleukin-6, interleukin-10, interferon gamma, sCD14, and sCD163). In addition, cell-associated biomarker (CD38), lipopolysaccharides, and the gene expression of interleukin-2 and brain-derived neurotrophic factor were also measured at Y2. RESULTS: Reduction in levels of sCD14 (effect size [ES], -0.6; 95% confidence interval [CI], -1.08 to -0.14), tumor necrosis factor alpha (ES, -0.7; 95% CI, -1.18 to -0.23), interferon gamma (ES, -0.7; 95% CI, -1.17 to -0.22), and interleukin-10 (ES, -0.6; 95% CI, -1.08 to -0.14) was observed among exercisers as compared with nonexercisers at Y2. In addition, CD38+ expressing CD4+ T cells were found to be lower among exercisers (P = .01) at Y2. However, the differences in levels of interleukin-6, sCD163, lipopolysaccharides, interleukin-2, and brain-derived neurotrophic factor were not significantly different among the 2 groups. CONCLUSION: The study result suggests that regular structured physical activity improves the inflammatory profile of antiretroviral therapy-treated HIV-infected children.
