title: Increased bone resorption during tenofovir plus lopinavir/ritonavir therapy in Chinese individuals with HIV.
abstract: We sought to evaluate the effects of antiretroviral therapy on skeletal metabolism in Chinese individuals with human immunodeficiency virus. Patients switched to tenofovir/lamivudine + lopinavir/ritonavir after treatment failure had an increase in bone resorption marker levels by nearly 60%, which is greater than the magnitude previously described in non-Chinese populations.
  
  
  BACKGROUND
  Few studies have evaluated the effects of antiretroviral therapy on skeletal metabolism in Asian populations infected with human immunodeficiency virus (HIV).
  
  
  METHODS
  We performed a secondary analysis of bone turnover markers (BTM) at baseline and 2 years in stored plasma samples collected from 2/2009 to 1/2013 as part of a multi-center trial. Two groups were compared: (1) treatment-naïve patients initiated on zidovudine (AZT)/lamivudine (3TC) plus nevirapine (NVP) and (2) patients who failed first-line therapy and were switched to tenofovir (TDF)/3TC plus lopinavir/ritonavir (LPVr). Tests included the bone resorption marker, C-terminal cross-linking telopeptide of type-1 collagen (CTX), and the bone formation marker procollagen type 1 N-terminal propeptide (P1NP).
  
  
  RESULTS
  In the TDF/3TC + LPVr group, samples were available from 59 patients at baseline and 56 patients at 2 years. Of these, 36 patients had samples available from both time points. In the AZT/3TC + NVP group, plasma samples were analyzed from 82 participants at baseline and of those, 61 had samples at 2 years. Median change over 2 years was greater in the TDF/3TC + LPVr group for both CTX (+0.24 ng/mL, interquartile ranges (IQR) 0.10-0.43 vs. +0.09 ng/mL, IQR -0.03 to 0.18, p = 0.001) and P1NP (+25.5 ng/mL, IQR 2.4-51.3 vs. +7.11 ng/mL, IQR -4.3 to 21.6, p = 0.012). Differences remained after adjusting for potential confounders in the multivariable analysis.
  
  
  CONCLUSIONS
  Switching to TDF/3TC + LPVr after treatment failure resulted in greater increases in BTMs than initiation with AZT/3TC + NVP in Chinese patients with HIV. Following this change, bone resorption marker levels increased by nearly 60 %, which is greater than the 25-35% increase from baseline described previously in non-Chinese populations. Further studies are warranted to elucidate these findings.
authors.affiliation: Department of Infectious Diseases, Peking Union Medical College Hospital, No. 1 Shuaifuyuan, Wangfujing Street, Beijing, 100730, China.
authors.forename: E
authors.initials: E
authors.lastname: Hsieh
authors.forename: L
authors.initials: L
authors.lastname: Fraenkel
authors.forename: W
authors.initials: W
authors.lastname: Xia
authors.forename: Y Y
authors.initials: YY
authors.lastname: Hu
authors.forename: Y
authors.initials: Y
authors.lastname: Han
authors.forename: K
authors.initials: K
authors.lastname: Insogna
authors.forename: M T
authors.initials: MT
authors.lastname: Yin
authors.forename: J
authors.initials: J
authors.lastname: Xie
authors.forename: T
authors.initials: T
authors.lastname: Zhu
authors.forename: T
authors.initials: T
authors.lastname: Li
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D016723:Bone Remodeling / Q000187:drug effects; D001862:Bone Resorption / Q000097:blood / Q000139:chemically induced*; D024042:Collagen Type I / Q000097:blood; D004338:Drug Combinations; D057915:Drug Substitution; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy*; D015497:HIV-1; D006801:Humans; D061466:Lopinavir / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000097:blood; D019438:Ritonavir / Q000009:adverse effects* / Q000627:therapeutic use; D000068698:Tenofovir / Q000009:adverse effects* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D015415:Biomarkers; D024042:Collagen Type I; D004338:Drug Combinations; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; C558899:lopinavir-ritonavir drug combination; D061466:Lopinavir; D000068698:Tenofovir; D019438:Ritonavir