title: Protease inhibitor-containing antiretroviral treatment and tuberculosis: can rifabutin fill the breach?
abstract: OBJECTIVE
  To assess how to best manage co-administration of rifabutin (RFB) and human immunodeficiency virus 1 (HIV-1) protease inhibitor (PI) containing antiretroviral treatment (ART). Recommended for initial anti-tuberculosis treatment, rifampicin (RMP) lowers PI concentrations below therapeutic levels, posing significant challenges for ART. As RFB has little effect on PI concentrations, it could be an alternative to RMP.
  
  
  METHODS
  A review of the scientific literature on the safety and efficacy of RFB for adult tuberculosis (TB) treatment was conducted, focusing on ART-TB co-therapy. A cost comparison was performed between treatment regimens, and estimates of the burden of TB disease in patients on ART were used to model RFB demand in low- and middle-income countries (LMICs).
  
  
  RESULTS
  Eleven clinical studies were identified, comprising 1543 TB patients treated with RFB; 980 (64%) were living with HIV. RFB was as safe and effective as RMP, including in 313 patients receiving co-administered ART (unboosted PIs included indinavir, nelfinavir or saquinavir; a minority received ritonavir [RTV] boosted amprenavir or saquinavir). The total cost for 6 months of all HIV and TB treatment containing RTV-boosted lopinavir (LPV) and RFB is US$410, compared to US$455 if RMP is used with LPV super-boosted with RTV. Our model suggests that demand for RFB in LMICs could be between 10,000 and 18,000 courses by 2012.
  
  
  CONCLUSIONS
  RFB is effective and safe in combination with the PIs studied, cost-saving for co-therapy with currently recommended boosted PIs, and may have a pivotal role in the roll-out of ART. Further research into a daily dose of RFB to simplify dosing regimens and developing fixed-dose combinations can enhance the public sector roll-out of ART.
authors.affiliation: World Health Organization, Geneva, Switzerland.
authors.forename: A
authors.initials: A
authors.lastname: Loeliger
authors.forename: A B
authors.initials: AB
authors.lastname: Suthar
authors.forename: D
authors.initials: D
authors.lastname: Ripin
authors.forename: P
authors.initials: P
authors.lastname: Glaziou
authors.forename: M
authors.initials: M
authors.lastname: O'Brien
authors.forename: F
authors.initials: F
authors.lastname: Renaud-Thery
authors.forename: S
authors.initials: S
authors.lastname: Crowley
authors.forename: B
authors.initials: B
authors.lastname: Williams
authors.forename: R
authors.initials: R
authors.lastname: Ridzon
authors.forename: R
authors.initials: R
authors.lastname: Granich
authors.forename: C
authors.initials: C
authors.lastname: Gilks
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000175:diagnosis / Q000188:drug therapy* / Q000191:economics / Q000382:microbiology; D000328:Adult; D000904:Antibiotics, Antitubercular / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D060085:Coinfection / Q000175:diagnosis / Q000188:drug therapy* / Q000191:economics; D003362:Cost-Benefit Analysis; D016527:Drug Costs; D004347:Drug Interactions; D019317:Evidence-Based Medicine; D015658:HIV Infections / Q000175:diagnosis / Q000188:drug therapy* / Q000191:economics / Q000821:virology; D017320:HIV Protease Inhibitors / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology / Q000302:isolation & purification; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000302:isolation & purification; D017828:Rifabutin / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D014376:Tuberculosis / Q000175:diagnosis / Q000188:drug therapy* / Q000191:economics / Q000382:microbiology
chemical_list: D000904:Antibiotics, Antitubercular; D017320:HIV Protease Inhibitors; D017828:Rifabutin