REFLECTIONS ON HIV/AIDS AND MDR PAHO/WHO Dr. Andrea Luna Heine Resident/Consultant, USAID/PAHO Training Program SupraNational Reference Laboratory, Chile

2. Evidence Found: Conclusive? 3. Getting Closer to an Answer 1. Current Situation 2. Evidence Found: Conclusive? 3. Getting Closer to an Answer Workshop on TB/HIV Co-Infection, San Pedro Sula, Honduras, August 2003

1. Current Situation Workshop on TB/HIV Co-Infection, San Pedro Sula, Honduras, August 2003

Estimated Total Population Living with HIV/AIDS (end of 2001) Eastern Europe and Central Asia 1 million Western Europe 560,000 North America 940,000 East Asia and Pacific 1 million North Africa and Mideast 440,000 Central America 420,000 South East Asia 6.1 million South America 1.4 million Sub-Saharan Africa 28.1 million Australia 15,000 Total: 40 million

The highest estimated rates for TB are found in Africa 25–49 50–99 100–299 < 10 10–24 300+ No estimate per 100,000 pop. Workshop on TB/HIV Co-Infection, San Pedro Sula, Honduras, August 2003

Growing Tendency of TB Incidence (African and Eastern European Countries) 200 180 Africa, low HIV 160 Africa, high HIV 140 Post-communist countries 120 Notification Rates per 100,000 100 80 60 40 20 1980 1985 1990 1995 2000 Workshop on TB/HIV Co-Infection, San Pedro Sula, Honduras, August 2003

Estimated Distribution of Adults Infected with HIV and Tuberculosis, 2000 100,000 50,000 50,000 400,000 150,000 South East Asia 2.3 million Sub-Saharan Africa 9.5 million 450,000 5,000 Global Total : 13 million Workshop on TB/HIV Co-Infection, San Pedro Sula, Honduras, August 2003

In Africa, more HIV means more TB; however, the MDR rate is relatively low. Zimbabwe MDR=1.9% Malawi MDR=0.3% Kenya MDR=0.5% Tanzania MDR=0.9% Ivory Coast MDR=5.3% Workshop on TB/HIV Co-Infection, San Pedro Sula, Honduras, August 2003

Impact of HIV on Tuberculosis (USA, 1980–1992) Cases (thousands) 35 30 observed 25 57,000 more cases 20 15 foreseen 10 5 79 80 81 82 83 84 85 86 87 87 88 89 90 91 92 93 Year Workshop on TB/HIV Co-Infection, San Pedro Sula, Honduras, August 2003

Estimated Percentage of MDR among New TB Cases, 2000 3 - 4.9 5 - 6.9 7 + 0 - 0.9 1 - 2.9 No estimate Workshop on TB/HIV Co-Infection, San Pedro Sula, Honduras, August 2003

Prevalence of HIV Infection among TB Patients (Selected Countries, Region of the Americas, 2001) NY 1997 26% English Caribbean (2000)*: BAH 38% BEL 14% GUY 32.4% JAM 16% SUR 14% TRT 32% DOR 1997 17% HON 2001 8.0% MEX 1990-1994 3.1% GUT 2000 8.0% ELS 1996 2.8% NIC 1999 0.8% Rio de Janeiro BRA 1995-1998 35.6% Sources: Reports from National TB-Control Programs. * Caribbean Epidemiology Centre (CAREC). ARG 1995 2.2% URU 1997 0.7% Workshop on TB/HIV Co-Infection, San Pedro Sula, Honduras, August 2003

Prevalence of MDR among Cases Never Treated (Region of the Americas, 1994–2002) CAN 1.2% - USA 1.2% DOR 6.6% CUB 0.3% MEX: 3 states 2.4% Puerto Rico 2.5% GUT 0.7% VEN 0.3% HON 1.8% ELS 0.3% NIC 1.2% COL 1.47% ECU 6.6% BRA 0.9% PER BOL 3.0% 1.2% No data >= 3% - CHI 0.6% ARG < 3% - 0.9% URU =< 1% - 0.01% Workshop on TB/HIV Co-Infection, San Pedro Sula, Honduras, August 2003

2. Evidence Found: Contradictory? Workshop on TB/HIV Co-Infection, San Pedro Sula, Honduras, August 2003

Is there any association between HIV and TB/MDR ? % of resistance to one or more drugs Dosso 1999 Spellman 1997 Bercion 1995 Ash 1996 Gordin 1996 Workshop on TB/HIV Co-Infection, San Pedro Sula, Honduras, August 2003

Are hospitals a risk factor for HIV ? 10 Odds Ratio (95%CL) 1 0.1 Espinal 2001 Yoshiyama Kenyon 1999 Kenyon 1999 2001 Workshop on TB/HIV Co-Infection, San Pedro Sula, Honduras, August 2003

How reliable are the publications on this How reliable are the publications on this? Certain methodological errors crop up frequently. Non-representative samples Samples not randomized. Methodological defects in sample design (descriptive estimates, small size) Subproducts (Designed with other objectives in mind.)

How reliable are the publications on this How reliable are the publications on this? Certain methodological errors crop up frequently. Biases Information Bias Fails to report previous treatment. Fails to report contacts (MDR). Memory Bias Fails to remember medication given (incorrectly reported as 'never treated'). Selection Bias Serious or uncompensated percentages. Hospital reports. Informed consent.

Factors Creating Confusion How reliable are the publications on this? Certain methodological errors crop up frequently. Factors Creating Confusion No DOTS Flexibility in observed treatment. Irregularity in treatment. Exposure to MDR Strains Less time in hospitals with a greater probability of MDR contact.

How reliable are the publications on this How reliable are the publications on this? Certain methodological errors crop up frequently. Non-TB micobacteria Late diagnosis Diagnosis Existence of outbreaks? Differentiated behavior Outbreaks? Can become generalized among the general population (Cluster: RFLP)

HIV/AIDS High Prevalence of MDR Workshop on TB/HIV Co-Infection, San Pedro Sula, Honduras, August 2003

Lack of Control in the DOTS Strategy HIV/AIDS High Prevalence of MDR Workshop on TB/HIV Co-Infection, San Pedro Sula, Honduras, August 2003

Workshop on TB/HIV Co-Infection, San Pedro Sula, Honduras, August 2003

Source: New York City Department of Health. MDR in New York (1992–2000) The percent of MDRTB cases that are HIV-infected has dropped from 63% in 1992 to 8% in 2000. The decrease in HIV-infected MDRTB patients has been especially dramatic since 1998. Source: New York City Department of Health. Workshop on TB/HIV Co-Infection, San Pedro Sula, Honduras, August 2003

3. Coming closer to an answer ... Workshop on TB/HIV Co-Infection, San Pedro Sula, Honduras, August 2003

Initial Resistance Study (Chile, 2001)   Samples input 939 (737) Samples useful for evaluation 867 Discarded samples 70 (7.5%) 3.2 % due to false report of 'never treated' (30)  1.4 % due to non-TB micobacteria (13)  2.9% for technical reasons (19 with no data y 8 contaminated) Workshop on TB/HIV Co-Infection, San Pedro Sula, Honduras, August 2003

Verifying the Information  Initial survey.  Cross-referencing national TB databases. ENO (EX-RMC14) Epidemiology Registered monthly lab cases ISP Dynamic monthly RNTBC Nursing Review of 100% of the files with >= 1 resistance. Review of a variable percentage of files from sensitive patients x health service from 20% to 100%.  Cross-referencing CONASIDA data on HIV/AIDS. Workshop on TB/HIV Co-Infection, San Pedro Sula, Honduras, August 2003

Trends of Initial and Acquired Resistance: Global-Resistance and Multi-Resistance Forms (1971–2001) Global Initial Resistance Acquired Initial Resistance Initial Multi- Resistance Acquired Multi- Resistance Workshop on TB/HIV Co-Infection, San Pedro Sula, Honduras, August 2003

General Characteristics Analysis of the Impact of HIV/AIDS and the Immigrant Population There is no difference in the characterization of the population as regards sex and age among the resistant and non-resistant population. The population profile is not affected by populations with HIV/AIDS and migrants; but this is the case if there is change within these populations vis-à-vis the national population. Workshop on TB/HIV Co-Infection, San Pedro Sula, Honduras, August 2003

General Characteristics Analysis of the Impact of HIV/AIDS and the Immigrant Population The population co-infected with HIV/AIDS in this sample was 3.4%. Neither of the two subpopulations affects the national resistance profile. Workshop on TB/HIV Co-Infection, San Pedro Sula, Honduras, August 2003

Sample Characterization Regarding HIV/AIDS Patients with HIV/AIDS: 3.3% of all 'never-treated' TB cases. Average age, 37.2 MD 37, 80% of the population is male. 1.1% of the patients are MDR (0.7 national MDR). Regarding being an immigrant Foreign patients = 2.3% of TB cases 'never treated'. Average age, 33.5 MD 29.5; 60% are women. 1.1% of the patients are MDR. Workshop on TB/HIV Co-Infection, San Pedro Sula, Honduras, August 2003

What Other Chilean Studies Show   HIV patients act as an outbreak. 2.4% are MDR among 'never treated' (‘naive’) TB-HIV/AIDS patients (national estimate: 0.7%) 19.8% are MDR among previously treated TB-HIV/AIDS patients (national estimate: 20%) Workshop on TB/HIV Co-Infection, San Pedro Sula, Honduras, August 2003

HIV/AIDS TB MDR

MDR TB HIV/AIDS TB Micobacteria? Misreported as ‘never treated’? DOTS? Outbreak?

Summing Up HIV/AIDS and MDR TB … The global evidence available (Africa, USA, etc.), as well as Regional experiences (Chile), do not indicate any causal association. HIV, however, can be a factor interacting in the generation of MDR TB, above all in the presence of poor tuberculosis control and insufficient biosafety measures. The lack of compliance with strictly supervised anti-TB treatment, as well as exposure to other MDR TB patients, constitute risk factors for drug resistance among this population group. Workshop on TB/HIV Co-Infection, San Pedro Sula, Honduras, August 2003