Effects of Pegylated Interferon/Ribavirin on Bone Turnover Markers in HIV/Hepatitis C Virus-Coinfected Patients.
HIV/hepatitis C virus (HCV) patients have a 3-fold increased fracture incidence compared to uninfected patients. The impact of HCV therapy on bone health is unclear. We evaluated bone turnover markers (BTM) in well-controlled (HIV RNA <50 copies/ml) HIV/HCV-coinfected patients who received pegylated interferon-α and ribavirin (PEG-IFN/RBV) in ACTG trial A5178. Early virologic responders (EVR: ≥2 log HCV RNA drop at week 12) continued PEG-IFN/RBV and non-EVRs were randomized to continuation of PEG-IFN alone or observation. We assessed changes in C-terminal telopeptide of type 1 collagen (CTX; bone resorption marker) and procollagen type I intact N-terminal propeptide (P1NP; bone formation marker), and whether BTM changes were associated with EVR, complete early virologic response (cEVR: HCV RNA <600 IU/ml at week 12), or PEG-IFN treatment. A total of 192 subjects were included. After 12 weeks of PEG-IFN/RBV, CTX and P1NP decreased: -120 pg/ml and -8.48 μg/liter, respectively (both p < 0.0001). CTX declines were greater in cEVR (N = 91; vs. non-cEVR (N = 101; p = 0.003). From week 12 to 24, CTX declines were sustained among EVR patients who continued PEG-IFN/RBV (p = 0.027 vs. non-EVR) and among non-EVR patients who continued PEG-IFN alone (p = 0.022 vs. Observation). Median decreases of P1NP in EVR vs. non-EVR were similar at weeks 12 and 24. PEG-IFN-based therapy for chronic HCV markedly reduces bone turnover. It is unclear whether this is a direct IFN effect or a result of HCV viral clearance, or whether they will result in improved bone mineral density. Further studies with IFN-free regimens should explore these questions.
1 VA North Texas , Dallas, Texas.
Roger
R
Bedimo
2 Harvard School of Public Health , Cambridge, Massachusetts.
Minhee
M
Kang
3 University of Pennsylvania , Philadelphia, Pennsylvania.
Pablo
P
Tebas
4 University of Alabama at Birmingham , Birmingham, Alabama.
Edgar T
ET
Overton
2 Harvard School of Public Health , Cambridge, Massachusetts.
Kimberly
K
Hollabaugh
5 Case Western School of Medicine , Cleveland, Ohio.
Grace
G
McComsey
6 University of California Los Angeles , Los Angeles, California.
Debika
D
Bhattacharya
7 Oregon Health and Science University , Portland, Oregon.
Christopher
C
Evans
8 Johns Hopkins University , Baltimore, Maryland.
Todd T
TT
Brown
9 Northwestern University , Chicago, Illinois.
Babafemi
B
Taiwo
D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D016723:Bone Remodeling; D060085:Coinfection / Q000188:drug therapy / Q000473:pathology; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy / Q000473:pathology; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000473:pathology*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012254:Ribavirin / Q000627:therapeutic use*; D016896:Treatment Outcome
D000998:Antiviral Agents; D015415:Biomarkers; D016898:Interferon-alpha; D012254:Ribavirin