Transcript Granich Rifabutin talk_FIN []

Rifabutin for TB for people on ART
Reuben Granich
WHO HIV/AIDS Department
HIV/TB Core Group Meeting
Addis Ababa, Ethiopia,
11-12 November 2008
Towards Universal Treatment Access
Gains in Access to Care and Treatment
 Nearly one million more people on
antiretroviral therapy
 54% increase in one year in subSaharan 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.
Rifabutin and WHO Essential
Medicines List
•Rifabutin is currently not used as standard therapy for TB
•Experience with rifabutin for TB disease in resourceconstrained 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
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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)
LIC
MIC
Estimated cost of the
ARV protocol during
Rifampicin based TB
treatment* (6 months)
453.6
Estimated cost of the
ARV protocol during
Rifabutin based TB
treatment* (6 months)
270
LPV/r (average)
LIC
MIC
2764.8
939.6
2689.2
1846.8
572.4
1706.4
Next steps
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WHO Essential Medicines List
Complete costing analysis
Continue dialogue with manufacturers and
stakeholders
Scientific advocacy
Additional research
Thank you
Edde Loeliger (intern)
Mark O'Connor (intern)
Charlie Gilks (WHO)
Fabio Scano (WHO)
Barbara Milani (WHO)
David Ripin (Clinton)
Renee Ridzon (Gates)
TB/HIV—match made in heaven!
Rifampicin and PI background
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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
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Rifampin leads to sub-therapeutic
concentrations of PIs mediated by CYP3A4
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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:
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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)
Thank you
WHO Three I's Meeting,
Geneva, April 2-4, 2008
Rifabutin safety and efficacy
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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
Side effects
•Neutropenia
•Leucopenia
•ALAT/ASAT elevations
•Rash and upper gastrointestinal complaints
•More rarely uveitis