Evolution of estimated glomerular filtration rate in human immunodeficiency virus and hepatitis C virus‐coinfected patients receiving sofosbuvir‐based direct acting antivirals and antiretroviral therapy

Abstract Background Hepatitis C virus (HCV) coinfection among people with human immunodeficiency virus (HIV) might perturb immune function and HIV persistence. We aimed to evaluate the impact of HCV clearance with direct-acting antivirals (DAAs) on immune activation and HIV persistence in HIV/HCV-coinfected individuals on antiretroviral therapy (ART). Methods In a prospective observational study, ART-treated participants with HIV/HCV coinfection received sofosbuvir/daclatasvir ± ribavirin (n = 19). Blood samples were collected before DAA therapy, at the end of treatment, and 12 months after DAA termination (12MPT). T- and natural killer (NK)-cell phenotype, soluble plasma factors, cell-associated (CA)-HIV deoxyribonucleic acid (DNA) forms (total, integrated, 2LTR), CA-unspliced (US) and multiple-spliced ribonucleic acid (RNA), and plasma HIV RNA were evaluated. Results Hepatitis C virus clearance was associated with (1) a downmodulation of activation and exhaustion markers in CD4+, CD8+ T, and NK cells together with (2) decreased plasma levels of Interferon gamma-induced protein 10 (IP10), interleukin-8 (IL-8), soluble (s)CD163 and soluble intercellular adhesion molecule (sICAM). Cell-associated US HIV RNA was significantly higher at 12MPT compared to baseline, with no change in HIV DNA or plasma RNA. Conclusions Elimination of HCV in HIV/HCV-coinfected individuals alters immune function and the transcriptional activity of latently infected cells. This report provides insights into the effects of HCV coinfection in HIV persistence and regards coinfected subjects as a population in which HIV remission might prove to be more challenging.

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Improvement of Gut Diversity and Composition After Direct-Acting Antivirals in Hepatitis C Virus–Infected Patients With or Without Human Immunodeficiency Virus Coinfection

The Journal of Infectious Diseases ◽

10.1093/infdis/jiab094 ◽

2021 ◽

Author(s):

Natthaya Chuaypen ◽

Thananya Jinato ◽

Anchalee Avihingsanon ◽

Sakkarin Chirapongsathorn ◽

Supapon Cheevadhanarak ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Hepatitis C Virus ◽

Hepatitis C ◽

Gut Microbiota ◽

Alpha Diversity ◽

Healthy Controls ◽

Direct Acting Antivirals ◽

Microbial Dysbiosis ◽

Immunodeficiency Virus ◽

Direct Acting

Abstract Background The influence of direct-acting antivirals (DAAs) on the composition of gut microbiota in hepatitis C virus (HCV)–infected patients with or without human immunodeficiency virus (HIV) is unclear. Methods We enrolled 62 patients with HCV monoinfection and 24 patients with HCV/HIV coinfection receiving elbasvir-grazoprevir from a clinical trial. Fecal specimens collected before treatment and 12 weeks after treatment were analyzed using amplicon-based 16S ribosomal RNA sequencing. Results Sustained virological response rates in the monoinfection and coinfection groups were similar (98.4% vs 95.8%). Pretreatment bacterial communities in the patient groups were less diverse and distinct from those of healthy controls. Compared with HCV-monoinfected patients, HCV/HIV-coinfected individuals showed comparable microbial alpha diversity but decreased Firmicutes-Bacteroidetes ratios. The improvement of microbial dysbiosis was observed in responders achieving sustained virological response across fibrosis stages but was not found in nonresponders. Responders with a low degree of fibrosis exhibited a recovery in alpha diversity to levels comparable to those in healthy controls. Reciprocal alterations of increased beneficial bacteria and reduced pathogenic bacteria were also observed in responders. Conclusions This study indicates a short-term effect of direct-acting antivirals in restoration of microbial dysbiosis. The favorable changes in gut microbiota profiles after viral eradication might contribute toward the reduction of HCV-related complications among infected individuals.

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Evaluation of Kidney Function Tests in HIV-Positive Patients Receiving Combined Antiretroviral Therapy

10.22541/au.161806151.16736028/v1 ◽

2021 ◽

Author(s):

emre aydın ◽

Fatma Yılmaz Aydın ◽

Yakup Demir ◽

Yaşar Yıldırım ◽

Mustafa Kemal Çelen

Keyword(s):

Human Immunodeficiency Virus ◽

Glomerular Filtration Rate ◽

Antiretroviral Therapy ◽

Filtration Rate ◽

Estimated Glomerular Filtration Rate ◽

Hiv Positive ◽

Group 4 ◽

Immunodeficiency Virus ◽

Combined Antiretroviral Therapy ◽

Group 5

Introduction: Human Immunodeficiency virus is a chronic infection that attacks the immune system of the human body, particularly CD4 T lymphocytes. Combined antiretroviral therapies are highly effective in virological suppression of human immunodeficiency virus infection. It has been shown that some retroviral therapies have a higher nephrotoxicity potential. As a result of renal injury, serum creatinine increases, and the estimated glomerular filtration rate is reduced. The aim of our study was to assess changes in kidney function during a 24-month period in HIV-positive patients who were begun on combined antiretroviral therapy. Material-method: A total of 127 HIV positive patients were enrolled. The patients were divided into five groups; patients who received no therapy were designated as Group 1; those that received Dolutegravir/Abacavir/Lamivudine combination as Group 2; those that received Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Fumarate combination as Group 3; those that received Emtricitabine/Tenofovir Disoproxil Fumarate/Dolutegravir combination as Group 4; and those that received Emtricitabine/Tenofovir Disoproxil Fumarate/Raltegravir combination as Group 5. We compared the effects of these drugs on estimated glomerular filtration rate during a 24-month follow-up period. Results: At the 24th month of therapy, a significant difference was observed between the eGFR levels of the study groups (p:<0.001). eGFR level was significantly higher in Group 4 compared to Groups 1, 2, and 3 (p:0.009, p:<0.001, p:<0.001, respectively) while it was significantly lower in Group 5 than groups 1, 2, and 3 (p:0.005, p:<0.001, p:<0.001, respectively). No significant eGFR difference was found between Group 4 and Group 5 (p>0.05). Serum creatinine level was significantly higher in Groups 4 and 5 compared to the other groups (p<0.001). Conclusion: The use of TDF-containing regimens causes renal dysfunction. Therefore, we recommend close monitoring of renal function, especially in patients treated with TDF.

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