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

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

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

                                                                              

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)

The Population Dynamics of HIV-Associated Tuberculosis

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

                                                                              

                                                                              

                                                                              

                                                                              

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

Age-specific, HIV-Negative Tuberculosis Incidence Rates, South African Gold Mines, 1991-2000. 1991-4 1995-7 1998-9 99-2000

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)

Tuberculosis Trends in Abidjan, 1981-1991

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

Incidence, Prevalence, and Duration of Smear-Positive Tuberculosis in South African Goldminers HIV-Pos HIV-Neg Ratio Incidence 2869 497 6.0 (per 105/yr) Prevalence 0.44 0.55 0.8 (%) Mean 0.15 1.15 0.13 duration (years) (Corbett et al, 2003)

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

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

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

                                                                              

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 [0.08-0.95]) (AIDS 2002;16:75) 549 in Spain with EPTB TB as 1st AIDS dx: Prior to 1993 47% 3 year survival 1995-96 72.6% Since 1996 84.6% (Barcelona 2002 ThPeC7459)

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

Impact of HAART on TB Risk Study Rate of TB in non-HAART group RR Reference US, Adult Spectrum of Disease (16.032 py) 1.9/1000 py 0.2 (0.1-0.5) Int J Tuberc Lung Dis 2000; 4:1026 Italy, 1360 patients being considered for IPT, wide range CD4s .79/100 py 0.08 (0.01-.88) AIDS 2000; 14:1985 Brazil, 255 people with advanced HIV 8.4/100 py 0.19 (0.03-1.09) Clin Inf Dis. 2002; 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

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.

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

The Need to Scale Up HIV Testing UN Declaration of Commitment (UNGASS 2001): - 20% 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)

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

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

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

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

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

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