novel regimens for tb prevention: epidemiologic...
TRANSCRIPT
Novel Regimens for TB Prevention: Epidemiologic Considerations
C. Robert Horsburgh, Jr, MD, MUS
Boston University School of Public Health
Outline
• Prevention of “Reactivation” TB Disease
• Prevention of Primary TB Disease
• Prevention of M.tb Infection
• Effects of HIV and ART on TB prevention
• Prevention of “Reactivation” TB Disease
J Infect Dis 2011;204:S1160
Natural History of Tuberculosis
Prevention of reactivation in HIV+, TST+ Persons in Rio de Janeiro
CID 2015;60:643
Prevention of reactivation in HIV+, TST+ Persons in Uganda
NEJM 1998;337:805
Prevention of reactivation in HIV+, TST+ Persons in Uganda: Long Term Follow-up
AIDS 2001;15:2141
• Prevention of Primary TB Disease
J Infect Dis 2011;204:S1160
• Prevention of M.tb Infection
J Infect Dis 2011;204:S1160
Is longer LTBI Treatment for HIV-infected Persons in Sub-Saharan Africa Better?
HR=0.57, 0.33-0.99
Lancet 2011;377:1593
Is there a Post-treatment Effect?
AIDS 2015;29:356
IPT Effect is not
Discernable under High
FOI Pressure
NEJM 2014;370:301 (Suppl)
• Effects of HIV and ART on TB prevention
Increased Susceptibility of the Exposed HIV-infected Person
In two studies, HIV-infected household contacts (HHC) were more likely to be TST-positive than HIV-uninfected HHC in multivariate analysis
OR = 6.11 (0.89-42)
RR = 2.84 (1.73-4.65)CID 2016;63:10-20
AJRCCM 2016;194:1152-63
Increased Primary TB Disease among HIV-infected Persons
In two studies, HIV-infected household contacts (HHC) were more likely to develop primary TB disease than HIV-uninfected HHC
OR = 8.6 (5.8-13)
RR = 6.94 (3.54-13.6)AJRCCM 2000;162:2033-8
AJRCCM 2016;194:1152-63
Lancet 2001;
358:1687-93
Relapse
and
Reinfection
by
HIV Status
Increased Reactivation TB Diseaseamong HIV-infected Persons
In one prospective cohort study, HIV-infected TST+ homeless persons were more likely to develop TB disease than HIV-uninfected TST+ homeless persons
RR = 9.5 (3.6-25)
AJRCCM 2000;162:460-4
STAGES OF TUBERCULOSIS
HIV -
HIV +
70%
30%
5%
95%
5%
95%
30%
70%
40%
60%
45%
55%
Prevention of TB Disease in HIV+, Anergic Persons in Uganda
AIDS 2001;15:2142
TEMPRANO trial: IPT or ART?
Factorial design comparing early vs. late ART and IPT vs. no IPT
• ART reduced TB, HR = 0.50 (0.32-0.79)
• IPT reduced TB, HR = 0.44 (0.28-0.69)
• TB in ART-/IPT- = 8.0%
• TB in ART-/IPT+ = 3.1%
• TB in ART+/IPT- = 4.2%
• TB in ART+/IPT+ = 2.6%
NEJM 2015;373:808-22
IPT adds to ART
Lancet 2014;384:685
Effectiveness of Oral TB Drugs Against Nonreplicating Bacilli
• Likely highly effective: Rifamycins, Delamanid, Bedaquiline, Linezolid, Clofazimine
• Likely partially effective: Isoniazid, Fluoroquinolones
• Likely ineffective: Ethambutol, Cycloserine,
• Effectiveness unknown: PZA, Ethionamide
Conclusions
• “Latency” is only one of several states that precede TB disease
• Prevention of TB disease can occur by interruption of the natural history of progression at several steps along the pathway
• HIV and ART have strong influence on the ability of the host to drive bacteria into a non-replicating state
• TB drugs have varying efficacy against non-replicating bacilli