raltegravir-potassium and telaprevir

With the development of effective therapies against human immunodeficiency virus (HIV), hepatitis C virus (HCV) infection has become a major cause of morbidity and mortality among patients with both infections (coinfection). In addition to the high prevalence of chronic HCV, particularly among HIV-infected injection drug users, the rate of incident HIV infections is increasing among HIV-infected men who have sex with men, leading to recommendations for education and screening for HCV in this population. Liver disease is the second leading and, in some cases, a preventable cause of death among coinfected patients. Those at risk for liver disease progression are usually treated with a combination of interferon (IFN) and ribavirin (RBV), which is not highly effective; it has low rates of sustained virologic response (SVR), especially for coinfected patients with HCV genotype 1 and those of African descent. Direct-acting antivirals might overcome factors such as immunodeficiency that can reduce the efficacy of IFN. However, for now it remains challenging to treat coinfected patients due to interactions among drugs, additive drug toxicities, and the continued need for combination therapies that include pegylated IFN. Recently developed HCV protease inhibitors such as telaprevir and boceprevir, given in combination with pegylated IFN and RBV, could increase the rate of SVR with manageable toxicity and drug interactions. We review the latest developments and obstacles to treating coinfected patients.

Topics: Adenine; Anti-HIV Agents; Antiviral Agents; Coinfection; Deoxycytidine; Dideoxynucleosides; Disease Progression; Drug Administration Schedule; Drug Interactions; Drug Therapy, Combination; Emtricitabine; Hepatitis C, Chronic; HIV Infections; Homosexuality, Male; Humans; Interferon-alpha; Lamivudine; Liver Cirrhosis; Liver Diseases; Male; Oligopeptides; Organophosphonates; Polyethylene Glycols; Proline; Pyrrolidinones; Raltegravir Potassium; Recombinant Proteins; Ribavirin; Serine Proteinase Inhibitors; Substance Abuse, Intravenous; Tenofovir; Treatment Outcome

Topics: Antiretroviral Therapy, Highly Active; Antiviral Agents; Coinfection; Drug Therapy, Combination; Female; Hepatitis C; HIV Infections; HIV Integrase Inhibitors; HIV Protease Inhibitors; Humans; Interferon-alpha; Liver Cirrhosis; Male; Middle Aged; Oligopeptides; Polyethylene Glycols; Proline; Pyrrolidinones; Raltegravir Potassium; Recombinant Proteins; Ribavirin

Although different factors have been implicated in the CD4/CD8 T-cell ratio recovery in HIV-infected patients who receive effective antiretroviral therapy (ART), limited information exists on the influence of the regimen composition. A longitudinal study carried out in a prospective, single-center cohort of HIV-infected patients. ART regimens including non-nucleoside reverse transcriptase inhibitors (NNRTI), protease inhibitors (PI), or integrase strand transfer inhibitors (INSTI) from patients who achieved long-term (≥6-month duration) virological suppression (HIV-RNA < 400 copies/mL) from January 1998 to June 2014 were analyzed. The impact of ART composition on the changes of the CD4/CD8 T-cell ratio was modeled using a mixed linear approach with adjustment for possible confounders. A total of 1068 ART regimens from 570 patients were analyzed. Mean (SD) age of the patients was 42.15 (10.68) years and 276 (48.42%) had hepatitis C virus (HCV) coinfection. Five hundred fifty-eight (52.25%) regimens were PI-based, 439 (40.10%) NNRTI-based, and 71 (6.65%) INSTI-based; 487 (45.60%) were initial regimens, 476 (44.57%) simplification, and 105 (9.83%) salvage regimens. Median (IQR) number of regimens was 1 (1-2) per patient, of 29 (14-58) months duration, and 4 (3-7) CD4/CD8 measurements per regimen. The median baseline CD4/CD8 ratio was 0.42, 0.50, and 0.54, respectively, with the PI-, NNRTI-, and INSTI-based regimens (P = 0.0073). Overall median (IQR) increase of CD4/CD8 ratio was 0.0245 (-0.0352-0.0690) per year, and a CD4/CD8 ratio ≥1 was achieved in 19.35% of the cases with PI-based, 25.97% with NNRTI-based, and 22.54% with INSTI-based regimens (P = 0.1406). In the adjusted model, the mean CD4/CD8 T-cell ratio increase was higher with NNRTI-based regimens compared for PI-based (estimated coefficient for PI [95% CI], -0.0912 [-0.1604 to -0.0219], P = 0.009). Also, a higher CD4/CD8 baseline ratio was associated with higher CD4/CD8 increase in the adjusted model (P = 0.001); by contrast, higher age (P = 0.020) and simplification of ART regimen (P = 0.003) had a negative impact on the CD4/CD8 ratio. Antiretroviral regimen composition has a differential impact on the CD4/CD8 T-cell ratio; NNRTI-based regimens are associated with enhanced CD4/CD8 T-cell ratio recovery compared to PI-based antiretroviral regimens.

Topics: Adult; Age Factors; Alkynes; Atazanavir Sulfate; Benzoxazines; CD4-CD8 Ratio; Coinfection; Cyclopropanes; Drug Therapy, Combination; Female; Hepatitis C; HIV Infections; HIV Integrase Inhibitors; HIV Protease Inhibitors; Humans; Interferon Type I; Male; Middle Aged; Oligopeptides; Raltegravir Potassium; Reverse Transcriptase Inhibitors; Ribavirin; Ritonavir