Transcript ART in HIV-Infected TB Patients: Research Priorities

ART in HIV-Infected Patients
with TB: Research Priorities
Group II
Facilitator: David Cohn
Rapporteur: Soumya Swaminathan
ART for HIV-infected patients
with TB
• Delay ART till TB treatment is completed,
depending on stage of HIV disease
• Use any ART with non-Rifampicin antituberculosis treatment (ATT) regimen
• Use ART with ATT including Rifampicin
 Triple drug with 2 NRTI and 1 NNRTI
 Triple nucleoside
 Boosted PI
Major Questions in Treatment
• Nevirapine (NVP) vs Efavirenz: Equivalent
efficacy against HIV, different adverse event
(AE) profile. No comparative studies in HIV/TB
pts
• Nevirapine and Rifampicin (RIF): Concerns
about resistance, efficacy and toxicity risk
• Risk factors for toxicity: Black race, female, high
CD4, HBV/HCV co-infection
• Current recommendations: Use NVP and RIF
with caution with close monitoring
Efavirenz in HIV/TB co-infection
(600 mg vs 800 mg)
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Reduction in EFV levels by RIF: 13-33%
AEs dose-related
Inter-patient variability, effect of ethnicity
600mg effective, especially in pts < 60kg
Patients weighing > 60kg: Need more
evaluation
• ? Impact of food/high fat meal
• ? Correlation with stage of HIV disease
Protease Inhibitors and Rifampicin:
Safety and Efficacy
• Impact of RIF on PI levels: 80-90% reduction
• Pharmacologic boosting with ritonavir (SQV or
LPV + RTV): May increase AEs (hepatotoxicity)
• SQV/r 1600/200 mg: AUC of reduced 50% by
RIF, but clinical efficacy maintained
• SQV/r 1000/100 mg: In HIV-, high rate of clinical
hepatitis; unknown in HIV+
• SQV/r 400/400 mg: Limited data
• More studies needed...
IRIS/IRD
• Incidence of IRIS in HIV-related TB: Europe,
USA 11-43%; Africa 41%; India 15.2/100 p-y;
Higher in pts with active TB at start of ART
• Risk factors: ART within 6 weeks, disseminated
TB, low baseline CD4, rise in CD4%, fall in VL, ?
high bacillary burden
• Clinical: Fever, abscesses, LN enlargement,,
arthritis, GI, CNS, radiographic worsening, other
manifestations
• Reaction to mycobacterial antigens vs live
bacilli?
Research Issues: Treatment
• When and how to start ART in TB co-infected patients on
ATT: Clinical and laboratory parameters?
• Patients on standard 3-drug ART regimens: Monitoring
efficacy and toxicity, PK studies
• Special emphasis on NVP when used with anti-TB
drugs, e.g., hepatotoxicity, drug interactions
• Alternative regimens: od vs bid (split-dose Efavirenz?),
triple/quadruple nucleosides, SQV/r in HIV+ ? (in light of
new findings in HIV-), new drugs
• Simplification of regimens, including use of fixed-dose
combinations (ART and ATT)
• Use of rifabutin in developing countries, as it becomes
available
Research Issues: IRIS
• What is the best clinical definition for IRIS for use in
resource-constrained settings?
- need for validation studies
• Define incidence in different settings and by disease
stage
• Risk factors and predictors for IRIS
• Role of corticosteroids and other anti-inflammatory drugs
in prevention and treatment of IRIS
• Laboratory/immunological parameters for diagnosis
• Pathophysiology
Research Issues: Other
• Developing simpler outcome definitions
• Monitoring: Clinical vs laboratory for AEs
(minimal requirements)
• Strategies for drug delivery: DOT, mDOT
• Emergence of TB and HIV drug resistance
• Strategies for measuring and enhancing
adherence for patients on ATT and ART
Research Issues: Health Systems
• Cost-effectiveness of different regimens
and treatment strategies
• Different strategies of collaboration and
integration: Settings, type of clinic,
personnel, level of training
• Nosocomial transmission of TB
Special Populations
• All these issues to be evaluated in special
populations:
 Pregnant women
IDUs (Hep B and C, methadone,
buprenorphine?)
Children
Summary - 1
• What is the optimal time to start ART in TB co-infected
patients on ATT (in order to improve efficacy and
decrease toxicity)?
- relative risk of mortality and morbidity vs complications of
treatment, stratified by stage of disease
• What are best ART regimens to use with ATT?
• In patients on standard 3-drug ART regimens, how to
best monitor efficacy and toxicity
- Need for PK studies
- Special emphasis on Nevirapine when used with ATT, e.g.,
hepatotoxicity, drug interactions
• What are alternative regimens (e.g., dosing)?
• Would Rifabutin-containing ATT with ART be more
advantageous than Rifampicin-containing regimens?
Summary - 2
• What is the best clinical definition for IRIS for use in resourceconstrained settings (validation studies)?
• What are the risk factors and predictors for IRIS and how best to
prevent and treat IRIS?
• What are the optimal treatment delivery strategies, e.g., DOT,
modified-DOT?
• What are the different strategies of collaboration and integration in
TB and HIV programmes, by settings, types of clinic, and
personnel?
• What is the cost-effectiveness of different regimens and strategies?
• What are the minimal requirements for clinical and laboratory
monitoring for outcomes related to efficacy and safety?
• What are the best strategies for measuring and enhancing
adherence for patients on ATT and ART?
• For all above questions, consideration in special populations,
including their co-morbidities and unique charactersitics.