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1.
Int J Mol Sci ; 25(5)2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38474018

RESUMO

Early gene therapy studies held great promise for the cure of heritable diseases, but the occurrence of various genotoxic events led to a pause in clinical trials and a more guarded approach to progress. Recent advances in genetic engineering technologies have reignited interest, leading to the approval of the first gene therapy product targeting genetic mutations in 2017. Gene therapy (GT) can be delivered either in vivo or ex vivo. An ex vivo approach to gene therapy is advantageous, as it allows for the characterization of the gene-modified cells and the selection of desired properties before patient administration. Autologous cells can also be used during this process which eliminates the possibility of immune rejection. This review highlights the various stages of ex vivo gene therapy, current research developments that have increased the efficiency and safety of this process, and a comprehensive summary of Human Immunodeficiency Virus (HIV) gene therapy studies, the majority of which have employed the ex vivo approach.


Assuntos
Infecções por HIV , HIV , Humanos , HIV/genética , Vetores Genéticos , Terapia Genética , Engenharia Genética , RNA
2.
PLoS One ; 10(7): e0132287, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26208212

RESUMO

BACKGROUND: Injection drug use is steadily rising in Kenya. We assessed the prevalence of both human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) infections among injecting heroin users (IHUs) at the Kenyan Coast. METHODS: A total of 186 IHUs (mean age, 33 years) from the Omari rehabilitation center program in Malindi were consented and screened for HIV-1 and HCV by serology and PCR and their CD4 T-cells enumerated by FACS. RESULTS: Prevalence of HIV-1 was 87.5%, that of HCV was 16.4%, co-infection was 17.9% and 18/152 (11.8%) were uninfected. Only 5.26% of the HIV-1 negative injectors were HCV positive. Co-infection was higher among injectors aged 30 to 40 years (20.7%) and among males (22.1%) than comparable groups. About 35% of the injectors were receiving antiretroviral treatment (ART). Co-infection was highest among injectors receiving D4T (75%) compared to those receiving AZT (21.6%) or TDF (10.5%) or those not on ART (10.5%). Mean CD4 T-cells were 404 (95% CI, 365 - 443) cells/mm3 overall, significantly lower for co-infected (mean, 146; 95% CI 114 - 179 cells/mm3) than HIV mono infected (mean, 437, 95% CI 386 - 487 cells/mm3, p<0.001) or uninfected (mean, 618, 95% CI 549 - 687 cells/mm3, p<0.001) injectors and lower for HIV mono-infected than uninfected injectors (p=0.002). By treatment arm, CD4 T-cells were lower for injectors receiving D4T (mean, 78; 95% CI, 0.4 - 156 cells/mm3) than TDF (mean 607, 95% CI, 196 - 1018 cells/mm3, p=0.005) or AZT (mean 474, 95% CI -377 - 571 cells/mm3, p=0.004). CONCLUSION: Mono and dual infections with HIV-1 and HCV is high among IHUs in Malindi, but ART coverage is low. The co-infected IHUs have elevated risk of immunodeficiency due to significantly depressed CD4 T-cell numbers. Coinfection screening, treatment-as-prevention for both HIV and HCV and harm reduction should be scaled up to alleviate infection burden.


Assuntos
Coinfecção/virologia , Infecções por HIV/virologia , HIV-1/fisiologia , Hepacivirus/fisiologia , Hepatite C/virologia , Dependência de Heroína/virologia , Adulto , Análise de Variância , Antirretrovirais/uso terapêutico , Contagem de Linfócito CD4 , Coinfecção/tratamento farmacológico , Coinfecção/epidemiologia , Comorbidade , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , HIV-1/efeitos dos fármacos , Hepacivirus/efeitos dos fármacos , Hepatite C/tratamento farmacológico , Hepatite C/epidemiologia , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Humanos , Quênia/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência
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