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

2. 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

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

4. 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

5. 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

6. 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

7. 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

8. 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

9. 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

10. Estimated Percentage of MDR among New TB Cases, 2000
7 +
No estimate
Workshop on TB/HIV Co-Infection, San Pedro Sula, Honduras, August 2003

11. Prevalence of HIV Infection among TB Patients (Selected Countries, Region of the Americas, 2001)
NY %
English Caribbean (2000)*:
BAH 38%
BEL 14%
GUY %
JAM 16%
SUR 14%
TRT 32%
DOR %
HON %
MEX %
GUT %
ELS %
NIC %
Rio de Janeiro BRA %
Sources: Reports from National TB-Control Programs.
* Caribbean Epidemiology Centre (CAREC).
ARG %
URU %
Workshop on TB/HIV Co-Infection, San Pedro Sula, Honduras, August 2003

12. 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

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

14. 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

15. 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

16. 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.)

17. 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.

18. 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.

19. 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)

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

21. 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

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

23. 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 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

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

25. Initial Resistance Study
(Chile, 2001)
Samples input (737)
Samples useful for evaluation
Discarded samples (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

26. 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

27. 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

28. 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

29. 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

30. Sample Characterization
Regarding HIV/AIDS
Patients with HIV/AIDS: 3.3% of all 'never-treated' TB cases.
Average age, 37.2 MD 37, % 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

31. 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

32. HIV/AIDS TB
MDR

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

34. 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