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. CONCLUSION: 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.
Subject(s)
AIDS-Related Opportunistic Infections/drug therapy , Antibiotics, Antitubercular/therapeutic use , Coinfection/drug therapy , HIV Infections/drug therapy , HIV Protease Inhibitors/therapeutic use , HIV-1/drug effects , Mycobacterium tuberculosis/drug effects , Rifabutin/therapeutic use , Tuberculosis/drug therapy , AIDS-Related Opportunistic Infections/diagnosis , AIDS-Related Opportunistic Infections/economics , AIDS-Related Opportunistic Infections/microbiology , Adult , Antibiotics, Antitubercular/adverse effects , Antibiotics, Antitubercular/economics , Antiretroviral Therapy, Highly Active , Coinfection/diagnosis , Coinfection/economics , Cost-Benefit Analysis , Drug Costs , Drug Interactions , Evidence-Based Medicine , HIV Infections/diagnosis , HIV Infections/economics , HIV Infections/virology , HIV Protease Inhibitors/adverse effects , HIV Protease Inhibitors/economics , HIV-1/enzymology , HIV-1/isolation & purification , Humans , Mycobacterium tuberculosis/isolation & purification , Rifabutin/adverse effects , Rifabutin/economics , Time Factors , Treatment Outcome , Tuberculosis/diagnosis , Tuberculosis/economics , Tuberculosis/microbiologyABSTRACT
Ultrafast optical pulses shorter than 20 fs with 400-mW average power at a 110-MHz repetition rate have been generated by a Cr(4+):YAG laser with only double-chirped mirrors for dispersion compensation. The corresponding pulse spectrum has a peak intensity at 1450 nm and extends from 1310 to 1500 nm full width at half-maximum (FWHM). These pulses, which are believed to be the shortest generated to date from a Cr(4+):YAG laser, are only four optical cycles within the FWHM intensity width.
