gs-5816 and HIV-Infections

Direct-acting antivirals (DAAs) have tremendously improved the treatment of hepatitis C virus (HCV) infections also in human immunodeficiency virus (HIV)-positive individuals. Curing HCV infection is of particular importance in HIV-positive individuals as liver disease progression is accelerated in the course of concomitant HIV infection. Former challenges, such as safety and tolerability as well as reduced treatment uptake of pegylated interferon and ribavirin-based treatments, have been overcome with the approval of DAAs. Indeed, rates of discontinuation under modern all-oral DAA therapy in HIV/HCV coinfection have been reported to be <1%. Rates of sustained virological response (SVR) following treatment have aligned with those seen in HCV monoinfected patients, resulting in an equalisation of treatment recommendations for HCV monoinfected and HIV/HCV coinfected patients. Nevertheless, coinfection with HIV has been associated with slightly higher relapse rates in some real-world cohorts, arousing discussion regarding more individualised treatment once again. Moreover, an ongoing epidemic of acute HCV infections in HIV-positive men who have sex with men with high re-infection rates challenges physicians and researchers. The present review gives a concise summary of the remaining challenges in HCV treatment of HIV-positive individuals.

Topics: Antiretroviral Therapy, Highly Active; Antiviral Agents; Benzimidazoles; Carbamates; Coinfection; Drug Interactions; Drug Therapy, Combination; Fluorenes; Hepacivirus; Hepatitis C, Chronic; Heterocyclic Compounds, 4 or More Rings; HIV Infections; Humans; Interferon alpha-2; Interferon-alpha; Liver Cirrhosis; Polyethylene Glycols; Recombinant Proteins; Ribavirin; Sexual and Gender Minorities; Sofosbuvir; Sustained Virologic Response; Treatment Outcome

Topics: Adult; Antiviral Agents; Carbamates; Drug Administration Schedule; Drug Resistance, Viral; Drug Therapy, Combination; Hepatitis C, Chronic; Heterocyclic Compounds, 4 or More Rings; HIV Infections; Humans; Liver Cirrhosis; Ribavirin; Sofosbuvir; Treatment Outcome

Cure rates in response to retreatment with sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) are high, but this regimen has not been studied in patients with a history of poor adherence or treatment interruption, nor in patients with HIV/HCV coinfection. Herein, we aimed to assess the safety and efficacy of this combination in patients with genotype 1 HCV infection who had relapsed following combination direct-acting antiviral (DAA) therapy, regardless of HIV infection or previous treatment course.. The RESOLVE study was a multicenter, open-label, phase IIb study investigating the safety, tolerability and efficacy of SOF/VEL/VOX in 77 patients with virologic rebound following combination DAA therapy. Efficacy was defined as HCV RNA below the lower limit of detection 12 weeks after the end of treatment (SVR12), while safety endpoints included the incidence of grade 3 and 4 adverse events (AEs) following treatment, and the proportion of patients who stopped treatment prematurely due to AEs.. In an intent-to-treat analysis, 70/77 (90.9%, 95% CI 82.1-95.8%) patients achieved SVR12, including 14/17 (82.4%) HIV coinfected participants and 18/22 (81.8%) of those with previous non-completion of DAA therapy. In an analysis of all patients who completed 12 weeks of study medication, 70/71 patients (99%) achieved SVR12. One patient experienced a grade 3 AE, and 4 experienced a grade 4 AE, all unrelated to study participation. Reported AEs were similar in HIV-coinfected patients, and patients receiving dolutegravir-based antiretroviral treatment experienced no clinically significant increases in aminotransferases.. Retreatment with 12 weeks of SOF/VEL/VOX was safe and effective in patients with relapsed HCV following initial combination DAA-based treatment. Treatment response was not affected by HIV coinfection or previous treatment course.. Twelve weeks of the combination of direct-acting antivirals (SOF/VEL/VOX) was safe and effective in patients with relapsed hepatitis C virus infection who had previously received combination therapy with direct-acting antivirals. Treatment response was not diminished by HIV coinfection, or non-completion of previous direct-acting antiviral-based therapy.

Topics: Aged; Aminoisobutyric Acids; Antiviral Agents; Carbamates; Cyclopropanes; Drug Therapy, Combination; Female; Follow-Up Studies; Genotype; Hepacivirus; Hepatitis C, Chronic; Heterocyclic Compounds, 4 or More Rings; HIV Infections; HIV-1; Humans; Lactams, Macrocyclic; Leucine; Macrocyclic Compounds; Male; Middle Aged; Pilot Projects; Proline; Quinoxalines; Recurrence; RNA, Viral; Sofosbuvir; Sulfonamides; Sustained Virologic Response

A safe, simple, effective, and pan-genotypic regimen to treat hepatitis C virus (HCV) infection in patients coinfected with human immunodeficiency virus type 1 (HIV-1) remains a medical need. We assessed the efficacy and safety of the NS5B polymerase inhibitor sofosbuvir and the NS5A inhibitor velpatasvir for HCV in patients coinfected with HIV-1.. This phase 3, open-label, single-arm study at 17 sites in the United States enrolled patients with HCV of any genotype and HIV-1 coinfection, including those with compensated cirrhosis. All patients received sofosbuvir-velpatasvir once daily for 12 weeks. The primary endpoint was sustained virologic response 12 weeks after treatment (SVR12). Efficacy and safety were assessed in all patients receiving at least 1 dose of treatment.. Of 106 patients, 91 (86%) were men, 48 (45%) were black, and 19 (18%) had cirrhosis. SVR12 was achieved by 101 of 106 (95% [95% confidence interval {CI}, 89%-99%]) patients: 74 of 78 (95% [95% CI, 87%-99%]) with genotype 1; all 11 (100% [95% CI, 72%-100%]) with genotype 2; 11 of 12 (92% [95% CI, 62%-100%]) with genotype 3; and all 5 (100% [95% CI, 48%-100%]) with genotype 4. All 19 patients with cirrhosis had SVR12. Two patients relapsed, 2 were lost to follow-up, and 1 withdrew consent. Two discontinued treatment due to adverse events and 2 had serious adverse events. The most common adverse events were fatigue (25%), headache (13%), upper respiratory tract infection (8%), and arthralgia (8%).. Sofosbuvir-velpatasvir for 12 weeks was safe and provided high rates of SVR12 in patients coinfected with HCV and HIV-1.. NCT02480712.

Topics: Adult; Aged; Antiviral Agents; Carbamates; Coinfection; Female; Hepatitis C; Heterocyclic Compounds, 4 or More Rings; HIV Infections; Humans; Male; Middle Aged; Sofosbuvir; United States

Hepatitis C virus (HCV) infection is more prevalent in people living with HIV-AIDS (PLHA) and portends a poorer prognosis. Pharmacokinetic studies suggest the absence of significant interaction between velpatasvir and dolutegravir which has been recently recommended as part of preferred first-line antiretroviral therapy (ART) regimens by WHO. However, clinical data on the use of velpatasvir-based regimen in PLHA taking dolutegavir is lacking. Hence, we aimed to assess the efficacy and safety of sofosbuvir and velpatasvir (SOF + VEL) in HCV and HIV coinfected patients on dolutegravir-based ART. Forty-five consecutive PLHA with HCV coinfection on dolutegravir-based ART were prospectively enrolled. All patients were treated SOF + VEL for 12 weeks. Complete haemogram, liver and renal function tests were assessed at baseline, 4 weeks and at end of treatment. Sustained virological response (SVR) was assessed at 12 weeks after end of treatment. The majority were males (95.5%) with a mean age of 32.8 ± 12.3 years. Cirrhosis was present in 6 (13.3%) patients. All patients completed 12 weeks of therapy with SOF + VEL, but SVR could not be assessed in two patients. Forty-two (97.7%) of the remaining 43 patients attained SVR-12. SVR-12 rate was 97.7% and 93.3% by per protocol and intention to treat analysis, respectively. No grade III/IV adverse events were reported, and there was no worsening of blood counts, liver or renal function test parameters. The pan-genotypic regimen of SOF + VEL is safe and effective in PLHA with HCV coinfection who are on dolutegravir-based ART.

Topics: Adult; Antiviral Agents; Coinfection; Female; Genotype; Hepacivirus; Hepatitis C; Hepatitis C, Chronic; HIV Infections; Humans; Male; Middle Aged; Sofosbuvir; Treatment Outcome; Young Adult

Report the real-world experience of the efficacy and safety of sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) in chronic hepatitis C virus (HCV) infected patients who have previously experienced a direct-acting antiviral (DAA) containing regimen.. Consecutive patients who have previously failed or did not tolerate a DAA containing regimen for chronic HCV who was treated with SOF/VEL/VOX were studied. Baseline clinical and laboratory data including NS5A RAS mutation testing were collected.. SOF/VEL/VOX resulted in an end of treatment undetectable HCV viral load in all patients and a sustained virologic response 12 rate of 100% despite the presence of NS5A RAS mutation, HIV infection, and cirrhosis. Treatment with SOF/VEL/VOX was well tolerated and there were no adverse events.. SOF/VEL/VOX is well tolerated and effective in treating patients who have been exposed to prior DAA therapy outside of clinical trials. SOF/VEL/VOX should be considered as the first-line regimen in HCV infected patients who have experienced prior DAA failure.

Topics: Aminoisobutyric Acids; Antiviral Agents; Carbamates; Cyclopropanes; Genotype; Hepacivirus; Hepatitis C; Hepatitis C, Chronic; Heterocyclic Compounds, 4 or More Rings; HIV Infections; Humans; Lactams, Macrocyclic; Leucine; Proline; Quinoxalines; Sofosbuvir; Sulfonamides; Sustained Virologic Response

Real-world data on sofosbuvir/velpatasvir with and without ribavirin (SOF/VEL ± RBV), particularly among patients with genotype 3 (GT3) decompensated cirrhosis, prior treatment, coinfection, and hepatocellular carcinoma (HCC), are scarce. We aimed to assess the efficacy and safety of SOF/VEL ± RBV in a real-world setting that included both community and incarcerated GT3 hepatitis C virus (HCV) patients.. We included all GT3 HCV patients treated with SOF/VEL ± RBV in our institution. The primary outcome measure was the overall sustained virological response 12 weeks after treatment (SVR12), reported in both intention-to-treat (ITT) and per-protocol analyses. The secondary outcome measures were SVR12 stratified by the presence of decompensated cirrhosis, prior treatment, HCC, and HIV/hepatitis C virus coinfection and the occurrence rate of serious adverse events requiring treatment cessation or hospitalization.. A total of 779 HCV patients were treated with 12 weeks of SOF/VEL ± RBV, of which 85% were treated during incarceration. Among the 530 GT3 HCV patients, 31% had liver cirrhosis, and 6% were treatment-experienced. The overall SVR12 for GT3 was 98.7% (95% confidence interval: 97.3%, 99.5%) and 99.2% (95% confidence interval: 98.1%, 99.8%) in ITT and per-protocol analyses, respectively. High SVR12 was also seen in ITT analysis among GT3 HCV patients with decompensated cirrhosis (88%), prior treatment (100%), HCC (100%), and HIV/hepatitis B virus coinfection (100%). Apart from one patient who developed myositis, no other serious adverse events were observed.. The SOF/VEL ± RBV is a safe and efficacious treatment option for GT3 HCV patients in a real-world setting. SOF/VEL with RBV may be considered for decompensated GT3 HCV patients.

Topics: Adult; Carbamates; Coinfection; Drug Therapy, Combination; Female; Genotype; Hepacivirus; Hepatitis C, Chronic; Heterocyclic Compounds, 4 or More Rings; HIV Infections; Humans; Male; Middle Aged; Retrospective Studies; Ribavirin; Sofosbuvir; Sustained Virologic Response; Treatment Outcome

The advent of direct-acting antiviral (DAA) therapies has dramatically transformed HCV treatment, with most recent trials demonstrating high efficacy rates (>90%) across all genotypes and special populations, including patients with HIV/HCV coinfection. The efficacy rates of HCV treatment are nearly identical between patients with HCV monofection and patients with HIV/HCV coinfection; however, there are limited studies to compare real-world efficacy with efficacy observed in clinical trials. Using a database from HIV clinics across the United States (US), we identified 432 patients with HIV/HCV coinfection who completed DAA therapy from January 1, 2014 to March 31, 2017 and were assessed for efficacy. Efficacy was evaluated as sustained virologic response (SVR) 12 weeks after DAA completion; furthermore, factors associated with achieving SVR12 were identified. In this analysis, we found DAA therapies to be effective, with 94% of the patients achieving SVR12 and 6% experiencing virologic failure. Baseline variables, including older age, HCV viral load <800K IU/ML, FIB-4 score <1.45, absence of depression, diabetes, substance abuse, and use of DAA regimens without ribavirin were significant predictors of achieving SVR12. Patients with fewer comorbidities, better liver health, and lower HCV viral loads at baseline were more likely to achieve treatment success. Our results were consistent with other real-world studies, supporting the use of HCV therapy in HIV/HCV coinfected patients.

Topics: Adult; Aged; Antiviral Agents; Benzimidazoles; Carbamates; Coinfection; Drug Therapy, Combination; Female; Fluorenes; Hepacivirus; Hepatitis C; Hepatitis C, Chronic; Heterocyclic Compounds, 4 or More Rings; HIV Infections; Humans; Male; Middle Aged; Retrospective Studies; Ribavirin; Simeprevir; Sofosbuvir; Sustained Virologic Response; Treatment Outcome; United States; Uridine Monophosphate; Viral Load

A 30-year-old woman living with HIV was diagnosed with genotype 2b hepatitis C virus (HCV) infection during the second trimester of her pregnancy. She had achieved virologic suppression on an HIV protease inhibitor-based regimen and had recurrent genital herpes simplex virus infection managed with antivirals. Given the risk of perinatal transmission of HCV and to avoid performing a caesarean section, after multidisciplinary consultations and consideration of the limited data on safety on HCV direct-acting antivirals (DAAs) in pregnancy, she consented to and was successfully treated with a 6-week lead-in course of sofosbuvir (SOF) alone followed by a 6-week course of SOF and velpatasvir postpartum. This resulted in cure of her HCV infection. The neonate tested negative for HCV at birth and was healthy without birth defects 2 years postdelivery. Our case highlights a successful HCV treatment approach in a pregnant woman with newer DAAs.

Topics: Adult; Antiretroviral Therapy, Highly Active; Antiviral Agents; Carbamates; Female; Hepatitis C; Herpes Genitalis; Heterocyclic Compounds, 4 or More Rings; HIV Infections; Humans; Infectious Disease Transmission, Vertical; Postpartum Period; Pregnancy; Pregnancy Complications, Infectious; Sofosbuvir

Treatments for Hepatitis C virus (HCV) infection have vastly improved over the past few decades with current regimens now offering pangenotypic activity with excellent cure rates reported in clinical trials, including in the HIV-HCV coinfected population. However, there is some concern that stringent inclusion and exclusion criteria in the trials may lead to results that are not achievable in real-world populations.. Our study evaluated a real-world HIV-HCV coinfected population and compared them to the eligibility criteria for trials of two of the most recent approved HCV agents; sofosbuvir/velpatasvir and glecaprevir/pibrentasvir.. Our study included 219 HIV-HCV coinfected patients and found that 89% met exclusion criteria for the sofosbuvir/velpatasvir trial and 90% met exclusion criteria for the glecaprevir/pibrentasvir trial. The majority of patients met more than one exclusion criteria with the most frequent criteria for exclusion being a non-approved ART regimen (58 and 47% respectively), having a psychiatric disorder (52%), active alcohol or injection drug use (27%), having an HIV viral load > 50 copies/ml (15%), a CrCl < 60 ml/min (13%) and a history of decompensated cirrhosis (13%).. Although the newer Hepatitis C treatments are very effective, the real world HIV-HCV coinfected population often have comorbidities and other characteristics that make them ineligible for clinical trials, such that they are barriers to treatment. These barriers need to be recognized and addressed in order to optimize treatment outcomes in the HIV patient population.

Topics: Adult; Aged; Aminoisobutyric Acids; Anti-Retroviral Agents; Antiviral Agents; Benzimidazoles; Carbamates; Coinfection; Cyclopropanes; Drug Interactions; Female; Hepacivirus; Hepatitis C; Heterocyclic Compounds, 4 or More Rings; HIV Infections; Humans; Lactams, Macrocyclic; Leucine; Liver Cirrhosis; Male; Middle Aged; Proline; Pyrrolidines; Quinoxalines; Sofosbuvir; Sulfonamides; Treatment Outcome; Viral Load

Data on anti-HCV therapy in patients on dialysis is still evolving. Sofosbuvir is mainly eliminated through the renal route and there is controversy about its use in these patients.. We describe a 53-year-old male patient with HCV genotype 3 and human immunodeficiency type 1 (HIV) infection on chronic dialysis. HIV infection was diagnosed in 1987 and since July 2007 the patient was compliant with his antiretroviral therapy (ART) and had an undetectable plasma HIV viral load on all follow-up measurements. The patient was known to have HCV infection since 1997 but has never been treated for chronic hepatitis C. Because of progressive renal impairment dialysis started in 2005.. Before anti-HCV treatment commenced the patient liver transient elastography (FibroScan) indicated F3 fibrosis (stiffness, 11.6 kPa) and his HCV RNA viral load was 320,798 IU/mL (Abbott RealTime HCV assay).. Fixed dose combination of sofosbuvir/velpatasvir (400 mg/100 mg) for 11 weeks.. Twelve weeks after treatment cessation HCV RNA was undetectable, hence the patient achieved a sustained virologic response. The drugs were well tolerated and the patient did not report any side effects.. Sofosbuvir/velpatasvir may be an option for HCV genotype 3 infection in patients coinfected with HIV on long-term dialysis.

Topics: Antiviral Agents; Carbamates; Coinfection; Hepatitis C, Chronic; Heterocyclic Compounds, 4 or More Rings; HIV Infections; Humans; Male; Middle Aged; Renal Dialysis; Sofosbuvir