individualized triple-therapy using boceprevir in hiv-positive patients with hepatitis c

Conditions: Hepatitis C, Chronic; HIV

Summary: response-guided triple-therapy with boceprevir (boc) in combination with pegylated interferon (pegifn) and ribavirin (rbv) is the current standard of care for hiv-negative patients infected with hepatitis c genotype (hcv-gt) 1. in contrast, in hiv-positive patients, a fixed treatment duration of 48 weeks is used. the aim of this study is to assess efficacy and safety of response-guided triple-therapy with boc in combination with pegifn and rbv in hiv-positive patients. thus, treatment duration will be individualized based on hcv-rna negativity at treatment week 8 (w8). all patients will receive 4 weeks of pegifn/rbv lead-in. patients with undetectable hcv-rna at w8 will be treated with 24 weeks of boc/pegifn/rbv triple-therapy resulting in a total treatment duration of 28 weeks, while patients with detectable hcv-rna at w8 will receive 44 weeks of boc/pegifn/rbv triple-therapy and a total treatment duration of 48 weeks.


Eligibility criteria:
inclusion criteria: * confirmed hiv infection (anti-hiv1/2 antibody positive). * chronic hcv infection (anti-hcv positive, hcv-rna detectable for \>6 months). * hcv-gt 1 infection. * age ≥18 years and ≤65 years. * no prior treatment with boc/pegifn/rbv. * cd4+ cell count \>200 cells/µl. * stable antiretroviral therapy (art) including tenofovir/emtricitabine (truvada®, gilead) and raltegravir (isentress®, msd) with hiv-rna \<50 copies/ml. * valid result on transient elastography or liver biopsy within 6 months prior to enrollment. * female patients of childbearing potential must agree to use an effective contraceptive during treatment and for 4 months after treatment has been concluded. * male patients or their female partners must agree to use an effective contraceptive during treatment and for 7 months after treatment has been concluded. exclusion criteria: * hcv-gt other than hcv-gt 1. * cirrhotic patients (as defined by metavir f4 in liver biopsy or liver stiffness \>12.3 kpa) with decompensated liver disease (child-pugh stage b/c). * chronic liver diseases other than hepatitis c virus infection (hepatitis b virus infection: hbsag positivity, nonalcoholic steatohepatitis, autoimmune hepatitis, primary biliary cirrhosis, hemochromatosis, wilson's disease, alpha-1 antitrypsin deficiency, cystic fibrosis). * significant cardiac disease (ejection fraction \<40% at echocardiography). * significant pulmonary disease (copd stage gold iii/iv). * significant renal disease (serum creatinine \>1.5 mg/dl). * subjects taking medication(s) that is/are highly dependent on cyp3a4/5 for clearance, and for which elevated plasma concentrations are associated with serious and/or life-threatening events such as but not limited to, orally administered midazolam, pimozide, amiodarone, flecainide, propafenone, quinidine, and ergot derivatives (dihydroergotamine, ergonovine, ergotamine, methylergonovine). * contraindications for boceprevir (victrelis®, msd), pegylated interferon alpha-2a (pegasys®, roche) or ribavirin (copegus®, roche), as listed in section 4.3 of the respective summary of product characteristics (smpcs). * ongoing alcohol abuse (average daily alcohol consumption \>50g). * ongoing illicit drug abuse. * unwillingness to give written informed consent. * pregnancy and breastfeeding. * women wishing to become pregnant.

Keywords: boceprevir hiv/hcv-coinfection hiv/hcv coinfection hiv/hcv response-guided therapy