1. Ensuring ART for TB patients: experience from Thailand
Praphan Phanuphak, M.D., Ph.D.
The Thai Red Cross AIDS Research Centre

2. TB/HIV in Thailand
700,000 Thais are currently living with HIV/AIDS with 50,000 new AIDS cases/year
25% of Thai AIDS patients at any moment have TB
100,000 new TB in Thailand each year (42% are infectious cases), 20% of these occur in HIV patients
16% of Thai TB patients in 1996 were HIV-positive as compared to 5.6% in 1991
Positive PPD was found in 20% of Thai HIV patients in the MTCT-Plus program (N=500)
1ry INH resistance 6.2%, Rifam 2%, MDR 1%

3. Reducing drug-resistant tuberculosis among HIV-positive TB patients, Chiang Rai
MDR-TB p
primary % 4.1% %
secondary 38.6% % % <0.001
Prevalence of primary MDR-TB was associated with
-HIV positive status (OR 2.2, 95%CI )
-being treated at provincial referral hospital in
(OR 2.6, 95%CI )
Possible due to DOTS and control of nosocomial TB
H. Yanai et al,:XV IAC: MoPeB3217

4. ART in Thailand
A national commitment to treat 50,000 new patients in 2004 because of the World AIDS Conference, the cheaper generic ARV and the Global Fund
Social security insurance scheme (for insured workers) provides ARV since July 2004
AZT, 3TC, AZT/3TC, d4T, ddI, NVP, d4T/3TC/NVP (GPO-vir), NFV are the available generic drugs
53 out of 76 provincial hospitals have CD4 facility in 2004, an increase from 19 Flow cytometer in 2002
Large scale training of doctors and nurses
Thus, it looks like ART is not a problem in Thailand!

5. ARV budget 1992-2003 and expected to 2006, Thailand
million baht

6. Healthcare infrastructure for ART in Thailand (2004)
ARV sites expanded from 110 to 800 hospitals
CD4 facility expanded from 19 to 53 hospitals with US$1.25M for reagents
Viral load only in Bangkok, Chiang Mai, Khon Kaen and Udorn Thani
Genotypic resistance only in 3 university hospitals in Bangkok
TDM only at HIV-NAT (Bangkok)
Accelerated training of ARV prescribers

7. Challenges of ART in TB/HIV co-infected patients at the policy level
Although HIV, TB and STD are merged into the same bureau and although TB/HIV services are supposed to be integrated, it has not yet happened in real life.
TB service has more manpower but personnel are older, less active and has much less budget. Thus, the HIV service has the control over the TB service.
We have to make the TB service more dynamic and more powerful.

8. Challenges of HIV screening in TB patients
TB doctors (GP, internist) have low awareness on HIV co-infection and on the perceived risk as well as have no skill of HIV counseling
Regulation by Thai law that HIV testing needs consent and pre- and post-test counseling, i.e., additional effort and facility, thus, why to bother & low uptake!
HIV testing is not free
Thus, the existing VCT services should be more proactive & more accessible for TB patients

9. Challenges of CD4 testing in co-infected patients
CD4 is rarely ordered by TB doctors and there is no national guideline for CD4 follow-up in HIV-infected patients, thus, frequently neglected
Accessibility to CD4 service such as the combined VCT & CD4 services of the Thai Red Cross Anonymous Clinic
CD4 testing is not free either, US$10

10. Challenges on ART in co-infected patients: Diverse guidelines
When to start HAART?
-2 weeks – 2 months vs. 6 months
What ARV to be used?
- 3NRTI vs. EFV (up dose?) vs. NVP
Methods of delivery HAART?
-DOTS like TB Rx?
Docs are confused! Thus, single guideline for TB & HIV programs is needed.

11. Weerawat Manosuthi, Somnuek Sungkanuparph, Ammarin Thakkinstian,
A Randomized Controlled Trial of Efavirenz mg/day versus 800 mg/day in HIV-infected Patients with Tuberculosis Receiving Rifampicin
Weerawat Manosuthi, Somnuek Sungkanuparph, Ammarin Thakkinstian,
Asda Vibhagool, Sasisopin Kiertiburanakul, Wisit Prasithsirikul, Jongkol Sankote,
Apicha Mahanontharit, Sasivimol Rattanasiri, Kiat Ruxrungtham
Faculty of Medicine Ramathibodi Hospital, Mahidol University;
HIV-NAT Research Collaboration, Thai Red Cross AIDS Research Center;
Bamrasnaradura Institute, MOPH, Thailand: XV IAC: MoOrB1013

12. Baseline characteristics
Parameter
EFV 600 mg
n = 42
M/F = 27/15
Age = 35.1 (6.9)
BW = 50.6 (7.4)
EFV 800 mg
M/F = 35/7
Age = 35.1 (9.4)
BW = 52.9 (9.4)
p value
CD4 count, median (range)
%CD4, median (range)
HIV RNA (copies/ml),
median (range)
HIV RNA log,
32 ( )
3.5% (0 - 20)
326,000
(7, ,000)
5.47 ( )
37.5 ( )
3% (0 - 17)
412,000
(10, ,000)
5.62 ( )
0.799
0.443
0.525
0.343

13. Distribution of plasma EFV levels between EFV 600 and 800 mg groups
3.02 ( )

14. Proportion of Patients with EFV level
Number of patients 25 20
Plasma EFV level 15
p = 0.274 10
กราฟนี้ไม่แน่ใจ ถ้า wee จะใช้ ช่วย label ให้ด้วยนะ ว่าเป็น graph ของอะไร 5
p = 0.274
EFV 600 mg
EFV 800 mg

15. Time to virologic success
Probability of HIV RNA <50 copies/mL
1.00
p = 0.848
0.75
0.50
0.25
0.00 10 20 30 40
Weeks
EFV = 600
EFV = 800

16. ARV therapy in advanced HIV-infected patients with active tuberculosis
A retrospective study in CD4< 200 cells/mm3 with active TB at Ramathibodi Hosp.
N= 23
CD4, cells/mm
HIV RNA > 100,
Median time in starting ART, weeks 8 (4-12)
EFV (56.5%)
NVP (43.5%)
Clinical improved 23(100%)
At 48 week HIV RNA < (83%)
HIV RNA< (78%)
Sungkanuparph S, et al,:XV IAC:MoOrB1015

17. Percentage of patients with undetectable HIV RNA after HAART
<400 copies/mL
65.2%
78.3%
87.0%
82.6%
<50 copies/mL
69.6%

18. CD4 response (mean) after HAART
EFV group 77
103
166
212
196
NVP group 41 91
133
179
181
Total 61
100
157
190
185

19. HAART regimens in patients taking rifampicin
Triple NRTI should be avoided.
EFV containing regimen is preferred and up dosing of EFV is not needed.
In resource-limited setting where only NVP-containing regimen is available, it still can be used. However, large pharmacokinetic and clinical outcome studies are urgently needed.
Such firm guidelines should come out from CDC or WHO.

20. Challenges for ART in Thailand
Weakness in management system
Limited resources & continued political commitment
How to improve adherence in view of limited laboratory monitoring?
Drug resistance and higher cost of salvage regimens eg. what after GPO-Vir failure?
VCT as entry point for care & ART
NVP in PMTCT with 20% NVP resistance and with unavoidable future use of NVP-containing regimens
Negative message for 1ry & 2ry prevention