title: Short communication: Interferon/ribavirin treatment for HCV is associated with the development of hypophosphatemia in HIV/hepatitis C virus-coinfected patients.
abstract: One-third of all HIV-infected individuals in the United States are estimated to be coinfected with the hepatitis C virus (HCV). Treatment of chronic hepatitis C in patients coinfected with HIV is a complex problem associated with toxicities and drug interactions between HIV antiretrovirals and interferon and ribavirin. In recent HCV treatment studies, we observed a previously unreported development of hypophosphatemia in HIV/HCV-coinfected patients treated with interferon/ribavirin (IFN/RBV). To further investigate this observation, we retrospectively reviewed 61 HIV/HCV-coinfected patients on antiretrovirals (ARVs) during treatment with IFN/RBV as well as 154 HIV-infected patients treated with ARVs alone. We found that HIV/HCV-coinfected patients on IFN/RBV therapy were more likely to develop frequent (57% vs. 13%, IFN/RBV-treated patients vs. no IFN/RBV; χ(2)=0.001) and higher-grade hypophosphatemia (67.0% Grade 2, 33.3% Grade 3 vs. 94.7% Grade 2, 5.3% Grade 3, IFN/RBV-treated patients vs. no IFN/RBV; χ(2)<0.001) than untreated patients. In addition, we found that the new onset of hypophosphatemia after IFN/RBV treatment initiation was followed by a diminished frequency of this toxicity upon cessation of IFN/RBV, supporting the idea that a drug-drug interaction may increase the risk of this toxicity. To understand the risks of developing this toxicity, we evaluated the association between individual ARV use and hypophosphatemia incidence. Our data suggest that concomitant tenofovir (TDF) use may be a risk factor for the development of hypophosphatemia in HIV/HCV-coinfected patients treated with IFN/RBV. Although the etiology of this abnormality is likely multifactorial, clinicians should be aware of hypophosphatemia as a potential marker of renal toxicity in HIV/HCV-coinfected patients being treated with IFN/RBV regimens.
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Emily K
authors.initials: EK
authors.lastname: Funk
authors.forename: Ashton
authors.initials: A
authors.lastname: Shaffer
authors.forename: Bhavana
authors.initials: B
authors.lastname: Shivakumar
authors.forename: Michael
authors.initials: M
authors.lastname: Sneller
authors.forename: Michael A
authors.initials: MA
authors.lastname: Polis
authors.forename: Henry
authors.initials: H
authors.lastname: Masur
authors.forename: Laura
authors.initials: L
authors.lastname: Heytens
authors.forename: Amy
authors.initials: A
authors.lastname: Nelson
authors.forename: Richard
authors.initials: R
authors.lastname: Kwan
authors.forename: Shyam
authors.initials: S
authors.lastname: Kottilil
authors.forename: Anita
authors.initials: A
authors.lastname: Kohli
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D000998:Antiviral Agents / Q000009:adverse effects* / Q000627:therapeutic use; D060085:Coinfection / Q000821:virology; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy; D016174:Hepacivirus / Q000187:drug effects; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D017674:Hypophosphatemia / Q000150:complications / Q000209:etiology*; D007372:Interferons / Q000009:adverse effects* / Q000627:therapeutic use; D007674:Kidney Diseases / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000627:therapeutic use; D012189:Retrospective Studies; D012254:Ribavirin / Q000009:adverse effects* / Q000627:therapeutic use; D012307:Risk Factors; D000068698:Tenofovir
chemical_list: D019380:Anti-HIV Agents; D000998:Antiviral Agents; D063065:Organophosphonates; D012254:Ribavirin; D007372:Interferons; D000068698:Tenofovir; D000225:Adenine