Evaluation of sofosbuvir, velpatasvir plus voxilaprevir as fixed-dose co-formulation for treating hepatitis C.

The fixed-dose combination of three direct-acting antivirals (DAA), namely sofosbuvir, velpatasvir and voxilaprevir is the first pangenotypic, single tablet regimen developed for the treatment of HCV infection. Areas covered: The pharmacokinetics, pharmacodynamics, efficacy and safety of the co-formulation are reviewed. Information on drug absorption, distribution, metabolism and excretion of each of the three antivirals is evaluated.

Drug interactions in HIV-infected patients treated for hepatitis C.

The introduction of direct-acting antivirals (DAA) has revolutionized the hepatitis C field. Most hepatitis C patients can now be cured, including those coinfected with HIV. However, drug-drug interactions (DDI) between DAA and antiretrovirals (ARV) should be known to prevent either toxicity due to drug overexposure or treatment failures due to low drug concentrations.

Treatment of hepatitis C with new fixed dose combinations.

The advent of oral direct-acting antivirals (DAA) has revolutionized the hepatitis C virus (HCV) therapeutic landscape providing cure rates over 90%. However, a subset of patients remains at higher risk for treatment failure, including those infected with: i) genotype 3 and cirrhosis; ii) resistance-associated substitutions (RAS) occurring either as natural polymorphisms or selected after prior DAA failure; and iii) poor drug adherence associated with social disabilities (homeless, psychiatric illnesses, injection drug use, alcoholism, etc.).

Dual antiretroviral therapy for HIV infection.

For two decades, triple combinations of antiretrovirals have been the standard treatment for HIV infection. The challenges of such lifelong therapy include long-term side effects, high costs and reduced drug adherence. The recent advent of more potent and safer antiretrovirals has renewed the interest for simpler HIV regimens.

New antivirals for the treatment of chronic hepatitis B.

Current treatment with oral nucleos(t)ides entecavir or tenofovir provide sustained suppression of HBV replication and clinical benefit in most chronic hepatitis B virus (HBV) infected persons. However, HBV rebound generally occurs upon drug discontinuation due to persistence of genomic HBV reservoirs as episomic cccDNA and chromosomic integrated HBV-DNA. There is renewed enthusiasm on HBV drug discovery following recent successes with antivirals for hepatitis C and immunotherapies for some cancers.

Decline and changing profile of hepatitis delta among injection drug users in Spain.

Background: Roughly 15 million people worldwide have hepatitis delta, the most severe form of chronic viral hepatitis that often leads to cirrhosis and liver cancer. Injection drug users (IDUs) are the largest HDV reservoir. Their resurgence in North America and Europe may represent a new opportunity for HDV to spread more widely.

Impact of ITPA gene polymorphisms on the risk of ribavirin-induced haemolytic anaemia using interferon-free antivirals for chronic hepatitis C.

Background: Single nucleotide polymorphisms (SNPs) at the ITPA gene are associated with haemolytic anaemia in chronic hepatitis C patients treated with pegylated interferon-ribavirin (RBV). Information in patients treated with interferon-free, direct-acting antivirals (DAA) is scarce.

Methods: Median haemoglobin (Hb) levels were compared at baseline and at week 4, when ribavirin concentration achieves steady state, in all consecutive chronic hepatitis C patients treated with oral DAA plus RBV at our clinic.

Risk of HIV Escape using Sub-Optimal Antiretroviral Dual or Monotherapy.

Budget constrictions have pushed some researchers to explore whether antiretroviral therapy with one or two drugs instead of the well-established triple-drug regimens may be able to maintain undetectable viremia in HIV-infected individuals, at least used as simplification in patients already with viral suppression under standard triple therapy. With the advent of co-formulations and the improved safety of the newest antiretroviral agents, there is no other reason than cost to justify moving from triple to dual or monotherapy.

Drug-Induced Lung Injury in a Liver Transplant Patient Treated With Sofosbuvir.

New direct-acting antivirals (DAAs) have dramatically improved sustained virologic response (SVR) rates in patients treated for chronic hepatitis C. Although the safety of these agents has been very good in registration trials, unexpected side effects have been reported after much broader use of DAAs on marketing. We retrospectively examined all liver transplant recipients with chronic hepatitis C that received sofosbuvir-based regimens at our clinic.

HIV: Test and Treat, Please!

Despite the fact that HIV infection can still not be eradicated from carriers, tremendous advances in antiretroviral therapy have led to achieving sustained suppression of HIV replication in most treated individuals. This translates into huge benefits for both patients and their sexual partners. This message was emphasized during the last IAS Conference, held in Durban, South Africa, at the end of July 2016.

Short-term atorvastatin therapy improves arterial stiffness of middle-aged systemic lupus erythematosus patients with pathological pulse wave velocity.

Objectives Statins have been proposed as a potential treatment for systemic lupus erythematosus (SLE) due to their immunomodulatory properties, their role restoring endothelial function and preventing atherosclerosis. We evaluate the effect of a short period treatment with a low dose of atorvastatin and its withdrawal on early stage subclinical atherosclerosis. Methods Thirty-seven SLE females received 20 mg/day atorvastatin during eight weeks.

Rate and predictors of treatment failure to all-oral HCV regimens outside clinical trials.

Background: Cure rates above 90% have been reported in most Phase III clinical trials using distinct all-oral direct-acting antivirals (DAAs) in chronic hepatitis C patients. Preliminary results in real-world patients have confirmed this, although efficacy tends to be lower.

Methods: All consecutive chronic hepatitis C patients treated with all-oral DAA regimens at three hepatitis clinics in Spain were retrospectively examined.

Does HIV Influence Hepatitis C Cure Rates Using Direct-Acting Antivirals?

Approximately one-third of people living with HIV are coinfected with hepatitis C virus (HCV). Coinfected individuals experience more rapid liver disease progression on average, and in the era of interferon-based therapy they do not respond as well to antiviral treatment. However, recent studies have suggested that this disparity in treatment response does not apply to interferon-free direct-acting anti-viral (DAA) regimens.

Prevention and management of treatment failure to new oral hepatitis C drugs.

Introduction: Chronic hepatitis C virus (HCV) infection has become a curable disease. Sustained virologic response rates above 90% have been achieved with recommended direct-acting antiviral (DAA) combinations in most registration trials. However, outcomes in real-world patients are lower.

High serum HCV RNA in chronic hepatitis C patients coinfected with HIV despite successful antiretroviral therapy.

Background: Baseline serum HCV RNA predicts treatment success in chronic hepatitis C patients. Thresholds at 0.8, 2, 4 and 6 million IU/ml discriminate treatment outcomes using distinct antiviral regimens.

The Burden of Neglected HIV-2 and HTLV-1 Infections in Spain.

HIV-2 and HTLV-1 infections are globally less frequent than those produced by HIV-1, the classical AIDS agent. In Spain and up to the end of 2014, a total of 310 cases of HIV-2, 274 of HTLV-1, and 776 of HTLV-2 infections had been reported. No cases of HTLV-3 or HTLV-4 infections have been identified so far in Spain.

New hepatitis C therapies for special patient populations.

Introduction: Chronic hepatitis C virus (HCV) infection has become a curable disease. More than 90% sustained virologic response rates have been obtained with 8-24 weeks of treatment with distinct combinations of direct-acting antivirals (DAA) in most registration trials. However, outcomes in real-world patients tend to be lower and treatment of special patient populations is often challenging.

Hepatitis C virus coinfection independently increases the risk of cardiovascular disease in HIV-positive patients.

Patients infected with HIV are at increased risk for cardiovascular disease despite successful antiretroviral therapy. Likewise, chronic hepatitis C virus (HCV) infection is associated with extrahepatic complications, including cardiovascular disease. However the risk of cardiovascular disease has not been formally examined in HIV/HCV-coinfected patients.

Metabolic syndrome is associated with decreased circulating endothelial progenitor cells and increased arterial stiffness in systemic lupus erythematosus.

Objectives: Metabolic syndrome (MetS) is highly prevalent in patients with systemic lupus erythematosus (SLE) and it has been associated with increased cardiovascular risk. We examined the contribution of MetS to inflammatory markers, arterial stiffness and circulating endothelial progenitor cells (EPCs) as surrogates of subclinical atherosclerosis.

Methods: Cardiovascular risk factors, SLE-specific factors and peripheral blood EPCs were assessed in 50 female SLE patients.

Rate and predictors of serum HCV-RNA >6 million IU/mL in patients with chronic hepatitis C.

Background: Baseline serum HCV-RNA predicts sustained virological response in chronic hepatitis C patients treated with antiviral therapy. A threshold at 6 million IU/mL has been proposed to best discriminate treatment outcomes on sofosbuvir-based regimens. In comparison with the general population, immunosuppressed individuals exhibit greater viral load values.

Dolutegravir for the treatment of HIV-2 infection.

Background: Therapeutic options are limited for HIV-2 infected persons, largely in part due to the lack of susceptibility to HIV-1 non-nucleoside reverse transcriptase inhibitors and poor susceptibility to some HIV-1 protease inhibitors. This is particularly worrisome for HIV-2 patients with prior antiretroviral failure.

Objectives: Report the virological response to dolutegravir in HIV-2-infected individuals.