1. Kevin M De Cock MD CDC Kenya Nairobi, September 21, 2003
The New Tuberculosis (Again): The Rationale for Collaborative TB/HIV Activities
Kevin M De Cock MD
CDC Kenya
Nairobi, September 21, 2003

3. The New Tuberculosis (Again)
Descriptive Epidemiology
Interactions with HIV
Transmission and Disease
Interventions
Future Prospects

4. Acknowledgements
Dr Liz Corbett, London School of Hygiene and Tropical Medicine, UK
Dr Gavin Churchyard, Anglo Gold, Welkom, South Africa
Dr Barbara Marston, CDC Kenya
Dr Doris Macharia, CDC Kenya
Dr Joseph Odhiambo, CDC Kenya
Dr Elizabeth Marum, CDC Kenya
Dr Dorothy Mbori-Ngacha, CDC Kenya
Dr Richard Chaisson, Johns Hopkins University

6. Tuberculosis Is Not One Disease
“Old” tuberculosis (low HIV prevalence developing countries)
Tuberculosis in industrialized countries
Primary multi-drug resistant tuberculosis (former Soviet Union)
HIV-associated tuberculosis (sub-Saharan Africa, parts of Asia)

7. The Population Dynamics of HIV-Associated Tuberculosis

8. Interactions Between HIV and Tuberculosis
Increased relative risk for TB in HIV-infected, therefore high HIV prevalence in TB patients
TB manifestations are influenced by the severity of immune deficiency
Co-morbidity
Increased mortality
Increased recurrence

13. Trends in Tuberculosis Case Notification Rates (per 100,000) in South African Goldminers

14. Age-specific, HIV-Negative Tuberculosis Incidence Rates, South African Gold Mines, 1991-2000.

15. Trends in Tuberculosis in South African Goldminers, 1991-2000
Overall tuberculosis incidence has increased four-fold to >4000/100,000 per year
Age, silicosis, and HIV were independent risk factors for tuberculosis
In HIV-negative persons, age-specific tuberculosis incidence did not change significantly
A strong, DOTS-based programme contained tuberculosis incidence in HIV-negative persons
Interpretation of tuberculosis trends requires stratification by HIV status
(Corbett et al, 2003)

16. Tuberculosis Trends in Abidjan, 1981-1991

17. Tuberculosis Epidemiology
Incidence - new cases/population/time
(eg n cases TB/100,000/year)
Prevalence – cases/population
(eg n cases HIV/100)
Prevalence = incidence x duration
Tuberculosis transmission is predominantly from persons with smear-positive disease

18. Incidence, Prevalence, and Duration of Smear-Positive Tuberculosis in South African Goldminers
HIV-Pos HIV-Neg Ratio
Incidence
(per 105/yr)
Prevalence
(%)
Mean
duration (years) (Corbett et al, 2003)

19. Proportional Distribution by HIV Status of Smear-Positive Tuberculosis Incidence and Duration in South African Goldminers

20. Tuberculosis Transmission and Disease in Relation to HIV
In high HIV prevalence settings:
Most tuberculosis disease occurs in HIV-positive persons
Much or most tuberculosis transmission is from HIV-negative persons

21. Requirements for Tuberculosis Control in the Era of HIV/AIDS
Effective treatment of active cases to reduce transmission of Mycobacterium tuberculosis
Effective HIV prevention
Reduction in vulnerability to TB of HIV-infected
- Preventive therapy
- Highly active antiretroviral therapy

23. Treatment of HIV-Associated Tuberculosis
Acceptable “cure” rates with rifampin-based Rx
Mortality 3-4x increased; highest in first month
HAART reduces mortality (3/85 [3.5%] vs. 13/103 [12.6%], RR 0.28 [ ]) (AIDS 2002;16:75)
549 in Spain with EPTB TB as 1st AIDS dx:
Prior to 1993
47% 3 year survival
72.6%
Since 1996
84.6%
(Barcelona 2002
ThPeC7459)

24. HAART in Patients with Tuberculosis – Practical and Clinical Considerations
Challenges
Drug interactions
Pill burden
Drug toxicity
Adherence
Monitoring
Immune reconstitution
Supervision and care delivery, cost
Approaches
Delay ARVs till rifampicin completed
Efavirenz if early Rx essential
Clinical monitoring

25. Impact of HAART on TB Risk
Study
Rate of TB in non-HAART group RR
Reference
US, Adult Spectrum of Disease ( py)
1.9/1000 py
0.2 ( )
Int J Tuberc Lung Dis 2000; 4:1026
Italy, 1360 patients being considered for IPT, wide range CD4s
.79/100 py
0.08 ( )
AIDS 2000; 14:1985
Brazil, 255 people with advanced HIV
8.4/100 py
0.19 ( )
Clin Inf Dis ; 34:543
South Africa—HIV+ cohort not on ARVs (n=770), participants in ARV trials (n=264)
9.7/100 py
0.19 (0.09 – 0.38)
Lancet 2002;359:2059

26. HIV-Related TB Associated with HAART in Rio de Janeiro
TB/HIV Cases
1995 – 159 cases
1996 – 148 cases
1997 – 105 cases
1998 – 100 cases
1999 – 42 cases
In Brazil, HIV-related TB has declined substantially at the major HIV and TB treatment center in Rio de Janeiro where the number of HIV-related TB cases declined from approximately 160 to 40 cases per year with the introduction of HAART. The proportion of TB cases that were HIV-related fell by almost 50%.
In Europe and the US, published studies have shown an 80-90% reduction in the incidence of TB in patients receiving HAART when compared to patients who do not receive HAART. In South Africa, the incidence of TB is reduced by about 85% with HAART, although patients who get HAART still have a 10-fold increased risk of TB compared with HIV-negative patients.
Source: Mello et al 2000.

27. Impact of HAART on Tuberculosis Incidence--Summary
HAART reduces risk of TB by about 80%
TB incidence remains higher than in HIV-negative
Numbers of cases averted depend on incidence of TB, stage of HIV, treatment effectiveness (adherence etc)
Potential exists for TB and HIV drug resistance
Potential exists for worsening of TB incidence

28. The Need to Scale Up HIV Testing
UN Declaration of Commitment (UNGASS 2001): % reduction in MCT by 2005
- 50% reduction in MCT by 2010
Almost 40 million women become pregnant annually in sub-Saharan Africa
3 million HIV-infected persons to receive HAART by 2005 (WHO)
175 million globally require HIV testing (WHO, 2002)

29. Rapid Testing for HIV
Two different, rapid, simple whole blood tests are used for every client
Done on site by trained Counselor
Confirmed results in 15 to 20 minutes
Tests used in Kenya:
Abbott Determine
Trinity Biotech UniGold

30. Tuberculosis and HIV, 2003
Persons positive for one of these diseases should be tested for the other

31. Expectations of Tuberculosis Programs in the HIV/AIDS Treatment Era
Aim to reduce transmission, disease, death
Provide TB treatment in the context of AIDS care to HIV-positives
Provide TB treatment to HIV-negatives
Decentralize provision of services
Define responsibilities and functioning of TB and HIV/AIDS care programs

32. Models of TB Program Functioning in the HAART Era
Limit TB Program Responsibilities
- Policy
- Quality control
- Care of HIV-negative TB only
- Registration and outcome evaluation
2. Provide all necessary care, including TB, HAART, and OI prophylaxis

33. Should TB Programs Administer HAART?
Probably best equipped to manage HAART (experience with long term follow-up, adherence, monitoring)
Overlapping populations
Clinical considerations
Con —
HAART would overwhelm most TB programs
Infection control
Drug interactions

34. Interventions for Effective Tuberculosis Control in the Era of HIV
Widespread HIV testing
Analysis of TB trends by HIV status
DOTS expansion
Active case finding (household contacts, HIV-positive persons)
Preventive therapy in HIV-infected
HAART in HIV-infected