Sofosbuvir and Ledipasvir for 8 Weeks for the Treatment of Chronic Hepatitis C Virus (HCV) Infection in HCV-Monoinfected and HIV-HCV-Coinfected Individuals: Results From the German Hepatitis C Cohort (GECCO-01).

BACKGROUND: Shortening the duration of treatment with HCV direct-acting antivirals (DAAs) leads to substantial cost reductions. According to the label, sofosbuvir and ledipasvir can be prescribed for 8 weeks (SL8) in noncirrhotic women or men with HCV genotype 1 and low viral loads. However, real-world data about the efficacy and safety of SL8 are largely missing. METHODS: Interim results from an ongoing prospective, multicenter cohort of 9 treatment centers in Germany (GECCO). All patients started on treatment with HCV DAAs since January 2014 were included. This report describes safety and efficacy outcomes in 210 patients with HCV monoinfection and 35 with human immunodeficiency virus (HIV)-HCV coinfection given SL8 in a real-world setting. RESULTS: Of 1353 patients included into the GECCO cohort until December 2015, a total of 1287 had complete data sets for this analysis; 337 (26.2%) fulfilled the criteria for SL8 according to the package insert, but only 193 (57.2%) were eventually treated for 8 weeks. Another 52 patients did not fulfill the criteria but were treated for 8 weeks. SL8 was generally well tolerated. The overall sustained virologic response rate 12 weeks after the end of treatment was 93.5% (186 of 199). The on-treatment response rate was 99.4% (159 of 160) in HCV-monoinfected and 96.4% (27 of 28) in HIV-HCV-coinfected patients. Ten patients were lost to follow-up. CONCLUSIONS: SL8 seems highly effective and safe in well-selected HCV-monoinfected and HIV-HCV-coinfected patients in a real-world setting.

Trends of prevalence of primary HIV drug resistance in Germany.

BACKGROUND: Primary HIV drug resistance (PDR) is associated with poor treatment outcome of first-line highly active antiretroviral therapy (HAART). The aim of the study was to observe the trend of prevalence of PDR between 2001 and 2005. METHODS: In a prospective multicentre study in the state of Nordrhein-Westfalen, Germany, 831 treatment-naive chronically HIV-infected patients underwent genotypic resistance testing. RESULTS: Six hundred and forty (77%) of them were male. Two-thirds of the patients (558, 67%) were infected with HIV subtype B. PDR was found in 75 of 831 [9%; 95% confidence interval (CI) 7.1-10.9] cases entering the study between January 2001 and December 2005. An increasing trend of PDR was found from 2001 (4.8%; CI 2.1-9.4) to 2005 (9.0%; CI 5.4-12.6; P = 0.08). A significant tendency to higher PDR was observed for ethnicity other than Caucasian (P = 0.04), HIV subtypes other than B (P = 0.02) and transmission routes other than homosexual (P = 0.03). CONCLUSIONS: A non-significant increase in prevalence of PDR was observed from 2001 to 2005. A significant trend to higher PDR rate was detected in non-Caucasian patients, patients infected with non-B subtypes, and in patients with risk factors for acquisition of HIV other than homosexual transmission. Based on the fact that there is a trend to higher PDR rate, resistance testing in untreated HIV-infected patients starting HAART becomes more important in clinical routine. The identification of patient subgroups with a remarkable risk of PDR makes continuous monitoring of PDR mandatory.

A prospective controlled study of interferon-based therapy of chronic hepatitis C in patients on methadone maintenance.

We examined the feasibility of hepatitis C treatment in patients on opioid maintenance. One hundred patients with chronic hepatitis C, 50 on methadone maintenance, and 50 with no intravenous drug use or opioid maintenance for at least 5 years were prospectively matched for sex, age, hepatitis C virus (HCV) genotype and HCV RNA. The primary end point was undetectable HCV RNA at 24 weeks posttreatment. Treatment with peginterferon alfa-2b (1.5 microg/kg per week) and ribavirin (1000-1200 mg /day) was initiated for 24 weeks (HCV genotype 2, 3) or 48 weeks (HCV genotype 1, 4). Within the first 8 weeks of therapy, discontinuation due to noncompliance or patient request was observed in 22% (11/50) in the methadone group versus 4% (2/50) in the control group (P =.02). After 8 weeks, there was no significant difference in discontinuation due to noncompliance or patient request (4/39 [10%] vs. 4/48 [8%]). There was no difference in discontinuation of therapy because of viral failure or adverse events (10/50 methadone vs. 6/50 control, P =.41). At the end of treatment, 50% (25/50) in the methadone group and 76% (38/50) in the control group had undetectable HCV RNA (P =.01). Sustained viral response was 42% (21/50) in the methadone group and 56% (28/50) in the control group (P =.16). No serious psychiatric event occurred in either group. In conclusion, peginterferon and ribavirin seem reasonably safe and sufficiently effective in patients on methadone maintenance. Patients discontinuing therapy due to noncompliance or request did so early, thereby limiting the cost of an unsuccessful approach to treatment.

Depletion of mitochondrial DNA in liver under antiretroviral therapy with didanosine, stavudine, or zalcitabine.

The "D drug" HIV reverse-transcriptase inhibitors zalcitabine, didanosine, and stavudine are relatively strong inhibitors of polymerase-gamma compared with the "non-D drugs" zidovudine, lamivudine, and abacavir. D drugs deplete mitochondrial DNA (mtDNA) in cultured hepatocytes. This mtDNA depletion is associated with an increased in vitro production of lactate. To investigate the origin of hyperlactatemia in HIV-infected patients and the effects of antiretroviral therapy on liver mtDNA, we biopsied liver tissue from 94 individuals with chronic hepatitis C virus (HCV) infection. Eighty subjects were coinfected with HIV. Serum lactate was measured at the time of biopsy. Hepatic mtDNA and liver histology were centrally assessed. Liver mtDNA content of HIV-infected patients receiving D drugs at the time of biopsy (n = 34) was decreased by 47% (P<.0001) compared with those without D drugs (n = 35). Aside from a possible association between HCV genotype I status and mtDNA depletion in multivariate analysis, there were no other virologic, immunologic, histologic, demographic or treatment-related variables that could explain the mtDNA depletion. Lactate was above the upper limit of normal in only three patients, all of whom were treated with D drugs. The mtDNA in each of them was lower than in any non-D drug patient and significantly (P =.017) depleted compared with D drug patients with normal lactate. In conclusion, D drug treatment is associated with decreased hepatic mtDNA in HIV-infected patients with chronic HCV infection. Moderate mtDNA depletion in liver does not necessarily lead to hyperlactatemia, but more pronounced decreases in hepatic mtDNA may be an important contributor to lactate elevation.