abacavir and Hepatitis-C

There is no known reason to suspect an adverse drug interaction between dolutegravir-based antiretroviral therapy and sofosbuvir, simeprevir, or ledipasvir. There is a paucity of clinical data for this combination.. Prospective, open-label study of patients with HIV well controlled on dolutegravir, abacavir, and lamivudine, who were co-infected with HCV genotype 1, and required therapy with simeprevir plus sofosbuvir or sofosbuvir/ledipasvir single-tablet regimen (STR) for 12 weeks. The two primary endpoints were percentage of patients achieving sustained virologic response (SVR) at 12 weeks post-treatment and percentage of patients with a HIV-1 viral load <50 copies/ml at end of the combination therapy.. Twenty-eight subjects were enrolled from August 2014 to September 2015. Thirteen patients were treated with simprevir plus sofosbuvir, and 15 subjects were treated with sofosbuvir/ledipasvir. 23 genotype 1a, and 5 genotype 1b were included. Nineteen were treatment naïve, and 2 patients had compensated cirrhosis. The mean age was 59 years (95% CI 58.21-59.78 years). The mean age was 59 years (95% CI: 58.21-59.78 years), and 25 patients were black. Out of the 28 patients who completed this study, SVR 12 was achieved in 27 of 28 patients (96%, 95% CI 89.6-100.0%), and all patients had an HIV virus load <50 copies/ml at week 12 of therapy, for an intent-to-treat rate of 100%. No patients ended therapy secondary to adverse events.. Our study suggests a good safety and efficacy for the combination of a dolutegravir, abacavir, and lamivudine with sofosbuvir-based DAA therapy.

Topics: Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; Coinfection; Dideoxynucleosides; Drug Therapy, Combination; Female; Hepacivirus; Hepatitis C; Heterocyclic Compounds, 3-Ring; HIV Infections; HIV-1; Humans; Lamivudine; Male; Middle Aged; Oxazines; Piperazines; Pyridones; Sofosbuvir; Treatment Outcome; Viral Load

Dolutegravir (DTG) is recommended as part of first-line antiretroviral therapy (ART) for people living with HIV(PLHIV). We sought to determine the rate of adverse events (AEs) and discontinuations among Thais treated during acute HIV infection (AHI) and switched to DTG-based regimens.. Thai participants in the SEARCH010/RV254 cohort who initiated ART during AHI and switched to DTG for at least 48 weeks were prospectively observed and included in the analysis. Rates and characteristics of DTG-related AEs and discontinuations were described.. A total of 313 Thai participants were included in the analysis. The median age was 29 years, 96% were male, 64% had a Bachelor's degree or higher and 16% had a body mass index (BMI) <18.5 kg/m. DTG was well tolerated with few discontinuations in this cohort of young men. Incident hepatitis C virus infection was a driver of liver-related AEs leading to discontinuations. In populations at risk, regular testing for hepatitis C virus during ART is recommended to anticipate possible AEs, guide management and improve safety.

Topics: Adult; Anti-HIV Agents; Cohort Studies; Dideoxynucleosides; Female; Hepatitis C; Heterocyclic Compounds, 3-Ring; HIV Infections; HIV-1; Humans; Male; Middle Aged; Oxazines; Piperazines; Pyridones; Risk Factors; Thailand; Young Adult

Fibroblast growth factor 23 (FGF23) has been associated with cardiovascular mortality. We estimate associations between the level of plasma FGF23 and exposure to abacavir (ABC) and to other components of antiretroviral therapy in patients co-infected with HIV and hepatitis C.. Both intact and c-terminal FGF23 were measured in plasma using commercial assays for a sub-cohort of 295 patients selected at random from the 1150 patients enrolled in the Canadian Co-infection Cohort. The multiplicative effects of antiretroviral drug exposures and covariates on median FGF23 were then estimated using a hierarchical Bayesian model.. The median level of intact FGF23 was independent of either past or recent exposure to abacavir, with multiplicative ratios of 1.00 and 1.07, 95% credible intervals 0.90-1.12 and 0.94-1.23, respectively. Median intact FGF23 tended to increase with past use of both nonnucleoside reverse-transcriptase inhibitors and protease inhibitors, but tended to decrease with recent use of either tenofovir, efavirenz or lopinavir. There were no obvious associations between the median level of c-terminal FGF23 and individual drugs or drug classes. Age, female gender, smoking and the aspartate aminotransferase to platelet ratio index were all associated with a higher median c-terminal FGF23 but not with a higher median intact FGF23.. The level of FGF23 in plasma was independent of exposure to ABC. Lower levels of intact FGF23 with recent use of tenofovir, efavirenz or lopinavir may reflect their adverse effects on bone and vitamin D metabolism relative to other drugs in their respective drug classes.

Topics: Adult; Alkynes; Anti-Retroviral Agents; Bayes Theorem; Benzoxazines; Canada; Coinfection; Cyclopropanes; Dideoxynucleosides; Female; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Hepatitis C; HIV Infections; Humans; Lopinavir; Male; Middle Aged; Prospective Studies; Risk Factors; Tenofovir

Contradicting results on the effect of abacavir (ABC) on hepatitis C virus (HCV) treatment responses in HIV/HCV co-infected patients have been reported. We evaluated the influence of ABC on the response to pegylated interferon (pegIFN) and ribavirin (RBV)-containing HCV treatment in HIV/HCV co-infected patients in a large European cohort collaboration, including data from different European countries.. HIV/HCV co-infected patients were included if they were aged ≥16 years, received pegIFN alfa-2a or 2b and RBV combination treatment and were enrolled in the COHERE cohort collaboration. Logistic regression was used to evaluate the impact of abacavir on achieving a sustained virologic response (SVR) to HCV treatment.. In total 1309 HIV/HCV co-infected patients who had received HCV therapy were included, of whom 490 (37 %) had achieved an SVR. No statistically significant difference was seen for patients using ABC-containing regimens compared to patients using an emtricitabine + tenofovir (FTC + TDF)-containing backbone, which was the most frequently used backbone. In the multivariate analyses, patients using a protease inhibitor (PI)-boosted regimen were less likely to achieve an SVR compared to patients using a non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based regimen (OR: 0.61, 95 % CI: 0.41-0.91). The backbone combinations zidovudine&lamivudine (AZT + 3TC) and stavudine&lamivudine (d4t + 3TC) were associated with lower SRV rates (0.45 (0.24-0.82) and 0.46 (0.22-0.96), respectively).. The results of this large European cohort study validate that SVR rates are generally not affected by ABC. Use of d4T or AZT as part of the HIV treatment regimen was associated with a lower likelihood of achieving an SVR.

Topics: Adult; Anti-HIV Agents; Cohort Studies; Coinfection; Dideoxynucleosides; Drug Combinations; Emtricitabine; Europe; Female; Hepacivirus; Hepatitis C; HIV Infections; Humans; Interferon-alpha; Lamivudine; Male; Middle Aged; Polyethylene Glycols; Recombinant Proteins; Reverse Transcriptase Inhibitors; Ribavirin; Tenofovir; Zidovudine

Abacavir hypersensitivity is a rare, yet significant adverse reaction that results in a spectrum of physical and laboratory abnormalities, and has been postulated to stem from a variety of aetiological factors. The major histocompatibility complex haplotype human leucocyte antigen (HLA)-B5701 is a significant risk factor in development of hypersensitivity reactions, yet only 55% of HLA-B5701+ individuals develop such reactions, suggesting a multifactorial aetiology. Nevertheless, prospective screening and avoidance of abacavir in these patients has limited adverse events. Within this spectrum of adverse events, abacavir-induced liver toxicity is exceedingly rare and reported events have ranged from mild elevations of aminotransferases to fulminant hepatic failure. We report the case of a 50-year-old Caucasian woman with a history significant for HIV, hepatitis C virus and a HLA-B5701+ status, transferred to our emergency department in a hypotensive state and found to have acute liver failure, acute renal failure and significant rhabdomyolysis following a change of highly active antiretroviral therapy regimen.

Topics: Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Coinfection; Dideoxynucleosides; Female; Hepatitis C; HIV Infections; HLA-B Antigens; Humans; Liver Failure, Acute; Middle Aged; Prospective Studies; Risk Factors

In human immunodeficiency virus-hepatitis C virus (HIV-HCV) co-infected patients, steatosis has been independently associated with a number of antiretroviral drugs, including stavudine, especially in patients with non-3 HCV genotypes. We retrospectively investigated the presence of steatosis among HIV-HCV co-infected and HCV mono-infected patients, and the role of tenofovir disoproxil fumarate (TDF) or abacavir (ABC) in determining hepatic steatosis.. Liver steatosis was retrospectively evaluated in all consecutive biopsies performed in the period 2000-2008 in HCV mono-infected and HIV-HCV co-infected patients. A steatosis rate of >5 % was considered to be significant, and a multivariate logistic analysis was performed to evaluate factors associated with steatosis.. In total, 393 HCV-infected patients underwent liver biopsy during the study period, of whom 205 (52.2 %) were co-infected with HIV. A steatosis rate of >5 % was diagnosed in 33.0 % of HCV mono-infected and in 47.8 % of HIV-HCV co-infected patients (P = 0.003). The rate of steatosis was higher in patients resuming antiretroviral therapy (54.7 %) than in naïve patients (33.3 %; P = 0.006). When the overall population was considered, steatosis was associated to HCV genotype 3 [odds ratio (OR) 4.53, 95 % confidence interval (CI) 2.71-7.58; P < 0.001]. In terms of the use of nucleos(t)ide drugs in HIV co-infected patients, multivariate analysis showed that only in patients with HCV genotypes other than genotype 3 was steatosis related to the use of stavudine (OR 5.38, 95 % CI 1.18-24.53; P = 0.03). The use of TDF (OR 1.07, 95 % CI 0.39-2.88; P = 0.898) or ABC (OR 0.592, 95 % CI 0.09-4.07; P = 0.594) was not associated with steatosis.. In HCV mono-infected and HIV-HCV co-infected patients, steatosis appears to be a virus-mediated effect of HCV genotype 3. In HIV patients infected with HCV genotypes other than genotype 3, the risk of developing steatosis was higher in those patients resuming antiretroviral regimens containing old drugs rather than the new antiretrovirals.

Topics: Adenine; Adult; Anti-HIV Agents; Coinfection; Dideoxynucleosides; Fatty Liver; Female; Genotype; Hepatitis C; HIV Infections; Humans; Liver; Male; Multivariate Analysis; Organophosphonates; Prevalence; Retrospective Studies; Reverse Transcriptase Inhibitors; Risk Factors; Tenofovir

Topics: Anti-HIV Agents; Antiviral Agents; Bilirubin; Chi-Square Distribution; Dideoxynucleosides; Drug Interactions; Drug Therapy, Combination; Hepatitis C; HIV; HIV Infections; Humans; Interferon alpha-2; Interferon-alpha; Multivariate Analysis; Randomized Controlled Trials as Topic; Recombinant Proteins; Ribavirin; RNA, Viral; Time Factors; Treatment Failure; Viral Load

Topics: Acyclovir; Anti-HIV Agents; Circumcision, Male; Cyclohexanes; Dideoxynucleosides; Drug Interactions; Female; Hepatitis C; HIV Fusion Inhibitors; HIV Infections; Humans; Male; Maraviroc; Multicenter Studies as Topic; Nitriles; Organic Chemicals; Pyridazines; Pyrimidines; Pyrrolidinones; Raltegravir Potassium; Randomized Controlled Trials as Topic; Triazoles

Topics: Adult; Anorexia; Anti-HIV Agents; Anxiety; Central Nervous System; Depression; Dideoxynucleosides; Female; Hallucinations; Hepatitis B; Hepatitis C; HIV Infections; Humans; Mental Disorders; Migraine Disorders; Mood Disorders; Reverse Transcriptase Inhibitors; Sleep Wake Disorders

Ribavirin (Rebetol) is Schering Corporation's newly approved drug. It is used in combination with interferon for treatment of chronic hepatitis C in patients whose compensated liver disease has not been treated or who have relapsed after interferon monotherapy. Results of clinical trials are summarized, and dosing options and side effects are detailed. Similar information is provided for abacavir (Ziagen), Glaxo-Wellcome's new nucleoside analog reverse transcriptase inhibitor (NRTI) that is used in combination therapy to treat HIV.

Topics: Anti-HIV Agents; Antiviral Agents; Clinical Trials as Topic; Dideoxynucleosides; Drug Combinations; Drug Hypersensitivity; Drug Resistance, Microbial; Hepatitis C; HIV Infections; Humans; Ribavirin

DuPont Pharmaceuticals and Glaxo Wellcome began marketing two new drugs, and the pricing of the drugs started a controversy. DuPont's efavirenz (Sustiva) was priced 60 percent higher than any other nonnucleoside reverse transcriptase inhibitor (NNRTI), with an annual retail price close to $5,000. In response, an ad hoc coalition called the Fair Price Working Group circulated a consensus statement demanding that the drug be priced like other drugs in that category. DuPont refused to reconsider, citing potency, once-daily dosing, and development costs. Several of the largest AIDS Drug Assistance Programs (ADAPs) also refused to add efavirenz to their formularies even though Dupont offered ADAPs a 5 percent rebate on the drug. Glaxo Wellcome learned from this dispute and priced its nucleoside analog abacavir at a level that ADAPs could afford, even though it is at the high end for its class of drugs. The coalition commended Glaxo for fairness in its pricing decision. Agouron and Bristol-Myers Squibb have also been criticized for repeatedly raising prices on their drugs. A continuing dialog, prior to price setting, will lead to greater understanding of a company's costs and may improve a company's reputation.

Topics: Alkynes; Anti-HIV Agents; Antiviral Agents; Benzoxazines; Cyclopropanes; Dideoxynucleosides; Drug Packaging; Drug Therapy, Combination; Hepatitis C; HIV Infections; HIV Protease Inhibitors; Humans; Interferon alpha-2; Interferon-alpha; Oxazines; Recombinant Proteins; Reverse Transcriptase Inhibitors; Ribavirin; United States