reuben granich who hiv/aids department · •reported lupin price for one capsule rifabutin 150 mg:...
TRANSCRIPT
Rifabutin for TB for people on ART
HIV/TB Core Group Meeting Addis Ababa, Ethiopia,
11-12 November 2008
Reuben Granich
WHO HIV/AIDS Department
Nearly one million more people on antiretroviral therapy
54% increase in one year in sub-Saharan Africa.
Access among women is higher than or equal to that among men.
97% of adults and children on therapy in low- and middle-income countries on first-line antiretroviral drug regimens.
First-line antiretroviral drug regimens are increasingly affordable.
Gains in Access to Care and Treatment
Rifabutin and WHO Essential
Medicines List
•Rifabutin is currently not used as standard therapy for TB
•Experience with rifabutin for TB disease in resource-constrained settings is limited
•Limitations in the data have hampered the development of clear WHO policy recommendations regarding the inclusion of rifabutin on the Essential Medicine List (EML).
•Rifabutin on the EML, as a first step toward EOI and PQ, may serve to increase the availability for large scale use and affordable costs
•High cost of rifabutin has rendered it thus far inaccessible to tuberculosis control programs in resource-limited settings
TB and second-line ART demand
assumptions
•UNAIDS/WHO ART roll-out scenario • Around 80,000 per month are placed on ART
•Patients failing first-line ART and needing ritonavir-boosted PI-based therapy: • Annual migration from first to second-line is ~ 2% to 4%
• Annual TB rates during ART around 3-7%
•Estimated 2008-2015 patients on PI-based ART that will develop TB:
• 2% scenario: 221,580 to 508,550
• 4% scenario 392,760 to 901,810
Rifabutin international availability
• Pfizer Inc., NYC, NY, USA; innovator (Mycobutin capsules 150 mg)
• Lupin laboratories Ltd. Mumbai, India; generic capsules 150 mg: not prequalified
• Sichuan Med. Shine Pharmaceuticals, China; generic capsules 150 mg: not prequalified
• Macleods, India; generic capsules 150 mg, not prequalified
Range of costs
•Reported Lupin price for one capsule
rifabutin 150 mg: 0.84 USD. Estimated 6
months rifabutin regimen is around 70 USD,
of with > 95% of the cost is due to rifabutin.
•MedShine (RisingPharm): $3 per dose
(information communicated by the Clinton
foundation)
•The Pfizer product cost is $4.86 per dose.
•Macleods: pricing information not available
Rough costing analysis
Unit values (USD) LPV/r (median) LPV/r (average)
LIC MIC LIC MIC
Estimated cost of the ARV protocol during Rifampicin based TB treatment* (6 months) 453.6 2764.8 939.6 2689.2
Estimated cost of the ARV protocol during Rifabutin based TB treatment* (6 months) 270 1846.8 572.4 1706.4
Next steps
• WHO Essential Medicines List
• Complete costing analysis
• Continue dialogue with manufacturers and
stakeholders
• Scientific advocacy
• Additional research
Edde Loeliger (intern)
Mark O'Connor (intern)
Charlie Gilks (WHO)
Fabio Scano (WHO)
Barbara Milani (WHO)
David Ripin (Clinton)
Renee Ridzon (Gates)
Thank you
TB/HIV—match made in heaven!
Rifampicin and PI background
• Rifampicin essential for short-course chemotherapy
• WHO-recommended anti-retroviral therapy (ART) recommends standardised antiretroviral drugs
• Ritonavir-boosted Protease-Inhibitor (PI) based antiretroviral therapy reserved for second-line therapy:
• patients no longer responding to first-line therapy
• alternative option in those with adverse reactions or contraindications to NNRTI’s used in standard first-line therapy
Rifampin and ART
• Rifampin leads to sub-therapeutic
concentrations of PIs mediated by CYP3A4 • Rifampicin and ATZ/r results in greater than 90%
reduction of plasma levels during co-administration
• Rifampicin can only be used in combination
with LPV boosted with high-doses of ritonavir
(eg. “super-boosting” with ritonavir 400 mg
twice daily),
Advantages of Rifabutin
•Little effect on PI serum concentrations
•Can be used with ritonavir-boosted PIs (no need
for "super-boosting")
•Should be dose-reduced by 75% (150mg QOD)
with boosted-PI-containing at standard dosing
Evidence for rifabutin for TB
•The evidence from the RCTs, dominated by HIV negative individuals, suggests that rifabutin is as effective as rifampicin for the treatment of TB
•The Cochrane review of five RCT found no statistical difference between the two rifamycins with: • RR of 1.00 (95% CI: 0.96 -1.04) for cure of TB
• RR of 1.23 (95%CI: 0.45 – 3.35) favouring rifampicin for relapse
• RR of 1.05 (95% CI: 0.96 – 1.15) favouring rifabutin
• RR 1.00 (95% CI: 0.98 – 1.03), for culture status at 2 and 3 month respectively.
•The only comparative RCT in HIV positive patients found both rifamycins to be safe and effective and demonstrated more rapid clearance of acid-fast bacilli in the rifabutin arm (log rank p< 0.05)
Rifabutin safety and efficacy
• Rifabutin is equally safe and effective as
rifampicin for TB
• However randomised clinical trials include
mostly HIV- negative individuals
• Observational cohort studies including in
HIV-infected patients treated with ART
does not point to inferior performance of
rifabutin