1. Discussion group 1 TB preventive therapy for PLWHA Alasdair Reid for Fabio Scano THD unit Stop TB department WHO

2. What do we know? What do we need to know? What has to be done to fill the knowledge gap? What to do in the meantime?

3. What do we know? Preventing first episode of TB 3 systematic reviews/meta-analyses IPT causes significant reduction of TB incidence (50-60% reduction) in HIV+/PPD+ individuals 40% reduction in HIV+ PPD unknown individuals Duration of effect - limited evidence but likely to decline with time

4. What do we know? Preventing first episode of TB (2) Short course Rifampicin containing regimens as effective as IPT but higher SE No demonstrable effect on mortality Adherence – very variable and may depend on length of treatment and selection criteria Cost-effectiveness – limited data but suggest cost-effective Feasibility - uncertain

5. What do we know? Preventing first episode of TB (3) Simple symptom screening questionnaire as effective as CXR in excluding active TB Use in pregnancy uncertain Use of IPT in settings with high background INH resistance - unclear No evidence that drug resistance increased by PT Breastfeeding infants of sm+ mothers and household contacts <5 plus BCG

6. What do we know? Preventive treatment aimed at preventing recurrent TB Evidence of effect of IPT in preventing recurrent TB in PLWHA

7. Ongoing research CDC: 3/12 INH+RFP vs 9/12 INH 6/12 IPT vs lifelong IPT CREATE: Lifelong IPT in SA mineworkers IPT and ART in Rio Impact of ICF and community interventions including IPT in Zambia & SA

8. Ongoing research South Africa 4 arm study 6/12 INH v lifelong INH v 3/12 RFP/INH v 3/12 RMP/INH Botswana National IPT programme since 2003 Evaluation in 2005 linked to DRS (1995/6, 1999, 2002) USAID - India 6/12 EH vs 3yrs INH NIAID INH to infants of HIV positive mothers

9. What do we need to know? The research questions similar for primary or secondary PT Establish optimal regimens (drugs & duration) & operational feasibility of PT in high HIV prevalence settings Role of PT in developing drug resistance and impact of drug resistance on efficacy of PT What is public health benefit (cost-effectiveness and impact) of large scale PT in high HIV prevalence settings. Incident TB may be higher in HIV-infected patients with a low CD4 count. Should this be a targeted group? Efficacy & safety of routine IPT for HIV+ pregnant women Feasibility of PT programmes in the context of ART scale-up national plans

10. What has to be done to fill the knowledge gap? RCT of ART +/- PT needed to answer the question about added efficacy CREATE project in Brazil Best way of delivering PT in routine setting Development of a valid screening tool Studies looking at the effect of PT programmes on the emergence of anti-TB drug resistance (to any drug) A pilot phase study is needed in order to determine the efficacy and safety of PT for pregnant women

11. What to do in the meantime? IPT should be offered as part of a minimum package of care for PLWH on grounds of its efficacy at individual level. Ongoing studies will show if mass PT will be an adjunctive tool to control TB in high HIV prevalence settings (CREATE). Emergence of drug resistance due to use of PT & implementation of PT programmes in settings with high drug resistance to any drug needs careful evaluation, eg Botswana. Not enough evidence to suggest that PT contributes to drug resistance but high compliance should be encouraged. CXR not necessary to exclude active TB in asymptomatic subjects, symptom screening questionnaire imperative. International guidelines need updating and programmes should develop simple tools and train HCW in use of screening tools. Given limited data, PT cannot be recommended for eligible pregnant women on a routine basis.