1. Preventing recurrent TB in high HIV-prevalent areas
What are the options for
TB Control Programmes?

2. DEFINITION OF RECURRENT TB
TB which re-occurs after a patient
has been previously diagnosed with TB
and completed a full course of treatment
Bacteriologically confirmed or based on
clinical criteria
Due to reactivation or reinfection

3. EXTENT OF RECURENT TB: RESULTS OF STUDIES (1)
Systematic review assessing the
influence of HIV and rifampicin therapy
47 studies world wide
17 studies from sub-Saharan Africa
(Korenromp, Scano, Williams, Dye, Nunn. Clin Inf Dis)

4. EXTENT OF RECURENT TB: RESULTS OF STUDIES (2)
Recurrent TB (rate/pa)
HIV-negative %
HIV-positive %
7 months or > Rifampicin 1.4%
5-6 months Rifampicin 2.0%
2-3 months Rifampicin 4.0%
[level of background TB is important]

5. EXTENT OF RECURRENT TB: REPORTS FROM NTPs AND WHO Problems
NTP annual notifications to WHO include “Relapse”, “Failure” and “Rx after DF”
WHO does not include “Failure” or “Rx after DF” in Global TB Reports
NTPs do not notify WHO about recurrent smear-negative TB or EPTB

6. Case History: Malawi High HIV-prevalence country In 2000, 77% of TB patients HIV+ve
2- 4% all cases were relapse sm+ve PTB
Almost no cases of recurrent sm-ve PTB / EPTB
Operational research 1999
12% sm-PTB /EPTB registered as “new” cases had been previously treated for TB

7. From 1999, Malawi improved its registration of patients in terms of new and previously treated cases, especially with smear-ve PTB and EPTB

8. Malawi Case Notifications
Year Total TB New Recurrent
(3%)
(3%)
(8%)
(9%)
(11%)
recurrent TB = relapse, failures, treatment after default
plus recurrent sm-ve PTB and EPTB

9. Why the need to reduce recurrent TB?
Recurrent TB cases:-
consume resources
have a more difficult regimen
increase TB transmission in the community
cause additional morbidity and mortality
erode faith in NTP amongst patients, staff, and community

10. Options to reduce risk of recurrence
Use RH in continuation phase (CP)
Extend duration of CP in HIV+ patients
Give post-treatment isoniazid to HIV+ve patients who complete anti-TB treatment
Treat HIV+ve TB patients with HAART

11. For each option: Evidence of effectiveness Current practice
Operational considerations
[consider especially for sub-Saharan Africa]

12. RH in Continuation Phase (CP) evidence of effectiveness
Systematic review by Korenromp, Scano et al (Clin Inf Dis)
IUATLD Clinical Trial A, RH throughout has lower recurrence than EH in CP
[done mainly in HIV-negative patients]

13. RH in the CP: current practice in Africa
All programmes use RH in IP
Many programmes use EH in CP (6mo)

14. Option: Replace EH with RH in CP for all patients
The dangers:
RH needs distribution to all Rx outlets
RH must be given by DOT
Possible irrational use of RH
If H resistance high, then R as “monotherapy”
Risk of creating MDR-TB
May increase difficulties with use of HAART

15. Extend duration of CP: evidence of effectiveness
In HIV+ve patients:
2RHZE/4RH, then 6RH
recurrent TB = 1.9%
2RHZE/4RH, then placebo
recurrent TB = 9.0%
(Perriens et al, NEJM 1995)

16. Extend duration of CP: current practice in Africa
Not used by any TB programme in Africa

17. Option: Extend duration of CP for HIV+ve patients
Need knowledge of HIV-status and therefore need links with VCT
Evidence only for RH (although may work for EH)
Different lengths of Rx for HIV+ve and HIV-ve patients, and may cause confusion
Long use of RH may delay start of HAART

18. Provide IPT to HIV+ve patients who complete treatment: evidence of effectiveness
Study in Haiti
HIV+ve patients:
2RHZ/4RH, then 12H
recurrent TB = 1.4%
2RHZ/4RH, then placebo
recurrent TB = 7.8%
(Fitzgerald et al, Lancet 2000)

19. Post-treatment isoniazid: current practice in Africa
Not used by any TB programme in Africa

20. Option: IPT to HIV+ve patients who complete Rx
Need knowledge of HIV-status and therefore need links with VCT
Adherence may be better than with 1o IPT
What is the optimal length of 2o IPT ?
Who administers and monitors 2o IPT ?
Will HAART obviate the need for 2o IPT?

21. Treat HIV+ TB patients with HAART: evidence of effectiveness
In West, HAART reduces risk of TB in HIV-positive persons
In South Africa HAART reduces risk of TB in HIV-positive persons (2.4% vs 9.7% pa)
[Risk reduction most in the immunocompromised]
No studies showing effect for recurrent TB

22. HAART to HIV+ve TB patients: current practice in Africa
Not used by any TB programme in Africa

23. Option: HAART to HIV+ve patients with TB
Need knowledge of HIV-status and therefore need links with VCT
Need significant increased funding
Need a structure for safe and secure supply and delivery of HAART

24. WAYS FORWARD
Country TB programmes to determine true burden of recurrent TB
If burden is high, then determine which of the four options is most cost-effective, feasible and least dangerous to do -
Clinical studies / operational research /
philosophy of “learn as we do”