1. New Thai HIV Treatment
Guidelines 2010
Wichai Techasathit, MD., MPH.
Faculty of Medicine Siriraj Hospital
Mahidol University, Bangkok, Thailand

2. When is Antiretroviral Therapy
Started?
Review of data from 2003-2005 from 176 sites in 42 countries (N = 33,008)
Since 2000, CD4+ cell count at initiation in developed countries stable at
approximately 150-200 cells/mm3, increasing in sub-Saharan Africa from
50-100 cells/mm3
164
200 179
187 163 192
123 157 206
102 103 53 95
125 86
122 100 72 134
97 97 239
181 87
Egger M, et al. CROI 2007. Abstract 62.

3. Development of Antiretroviral Treatment in
Thailand
Before 1992 Treatment of common OI without ARV
1992 AZT mono-therapy
1995 Dual therapy with AZT + ddI, AZT+3TC
1997 Triple therapy through HIV Clinical Research Network
2000 Access to Care (ATC) with 8 pre-assigned regimens
2004 National Access to Antiretroviral Program for PHA
(NAPHA)
2004 ARV program by Social Security Office (SSO)
2006 National AIDS Program (NAP) by National Health
Security Office (NHSO): ART Benefit Package in
Universal Coverage

4. Thai MOPH Guideline 2007 – When to Treat
อาการทางคลินิก ระดับ CD4 (เซลล/ คําแนะนํา
ลบ.มม.)
มีความเจ็บปวยของ เทาใดก็ตาม เริ่มยาตานเอชไอวี
ระยะเอดส
(AIDS-defining
illness)*
มีอาการ** เทาใดก็ตาม เริ่มยาตานเอชไอวี
ไมมีอาการ < 200 เริ่มยาตานเอชไอวี
ไมมีอาการ 200 – 350 ยังไมเริมยาตานเอชไอวี
่
ใหติดตามอาการและตรวจระดับ
CD4 ทุก 3 เดือน
ไมมีอาการ > 350 ยังไมเริมยาตานเอชไอวี
่
ใหติดตามอาการและตรวจระดับ
CD4 ทุก 6 เดือน
แนวทางการดูแลรักษาผูติดเชื้อเอช ไอ วี และผูปวยเอดสในประเทศไทยป พ.ศ. 2549/50
กรมควบคุมโรค กระทรวงสาธารณสุข สมาคมโรคเอดสแหงประเทศไทย สมาคมโรคติดเชื้อในเด็ก

5. Thai Guideline for ARV 2006-2007
2 NRTIs NNRTI หรือ PI
1st line AZT+3TC NVP
d4T+3TC EFV
IDV/RTV
2nd line AZT+ddI SQV/RTV
ddI+3TC NFV
TDF+3TC ATV+RTV
ABC+3TC LPV/RTV
National Guidelines on HIV/AIDS Diagnosis and Treatment: Thailand 2006-2007

7. Preferred and Alternative regimens
for Initiation of ART - TAS 2008
J Med Assoc Thai 2008;91(12):1925-36

8. ARV Regimens: NHSO vs. SSO
National Health Security Social Security Office
Office (NHSO or NAP) (SSO)
Effective 1 April 2007 Effective 1 January 2007
1. Group A 1. Basic regimens
d4T+3TC+NVP (GPOvirS) d4T+3TC+NVP
d4T+3TC+EFV AZT+3TC+NVP
AZT+3TC+NVP(GPOvirZ)
AZT+3TC+EFV 2. Alternative regimens
d4T(AZT)+3TC+EFV
2. Group B d4T(AZT)+3TC+IDV/r
d4T+3TC+IDV/r
AZT+3TC+IDV/r If other regimens needed
Consultation for permission
3. Group C
ddI+3TC or TDF+3TC in cases of
lipoatrophy (Expert approval)

9. National Health Security Social Security Office
Office (NHSO or NAP) (SSO)
4. Group D 3. 2nd line regimens
(After expert approval) (After expert approval)
Boosted PI+OBR LPV/r+OBR
- d4T+3TC ATV/r+OBR (not available)
- ddI+3TC - ddI+3TC
- AZT+3TC - AZT+3TC
- AZT+ddI - AZT+ddI
- AZT+TDF - AZT+TDF
- TDF+3TC - TDF+3TC
Boosted PIs+NVP (or EFV)
in only NRTIs resistance
Boosted PIs+AZT+3TC+TDF
in NNRTIs & multi NRTIs
resistance: Q151M &/or T69Si
&/or TAM>4

10. National Health Security Social Security Office
Office (NHSO or NAP) (SSO)
Choices of boosted-PIs Choices of boosted-PIs
1. IDV/r 1. IDV/r
2. LPV/r 2. LPV/r
3. ATV/r 3. ATV/r (not available)
AIDS Experts AIDS Experts
Regional AIDS Consultants; RAC Group of AIDS Consultants
Bangkok AIDS Consultants; BAC assigned by SSO

11. National Health Security Social Security Office
Office (NHSO or NAP) (SSO)
Monitoring Monitoring
1. CD4 x 2 times/yr 1. CD4 x 2 times/yr
2. VL x 1 time/yr 2. VL x 2 time/yr
3. Drug resistance x 1 time/yr 3. Drug resistance x 1 time/yr
4. CBC, FBS, Cr, TG, TC, SGPT x
2 times/yr
“To do genotypic drug resistance, “To do genotypic drug resistance,
VL must >2,000 copies/ml” VL should >1,000 copies/ml”

12. Who is still taking d4T?
90.0%
78.6 77.8
80.0%
d4T-3TC-NVP
70.0% d4T-3TC-EFV
62.7
d4T-FTC-EFV
60.0%
d4T-FTC-NVP
50.0%
47.6
45.8
AZT-3TC-NVP
AZT-3TC-EFV
40.0% TDF-FTC-EFV
28.4 TDF-FTC-NVP
30.0% 25.9
24.0
d4T-3TC-LPV/r
20.0% Other
11.10 11.2
8.6 8.9 9.1
10.0% 6.1 7.3 6.0
5.2 4.7 4.6 4.6
1.8
2.1 3.5
0.1 0.002 0.1 0.2 1.3 1.3 0.1
0.0%
Cote d'Ivoire Mozambique South Africa Tanzania Zambia
Westreich DJ, et al, Tuberculosis treatment and risk of stavudine substitution in first-line antiretroviral therapy, Clin Infect Dis.
2009 Jun 1;48(11):1617-23
Marlink R et al , IAC 2008 (WEAXO106)

13. Situation in National AIDS Program, Thailand.
Cumulative Patients on 1st and 2nd Line ARV
2nd line
160000 regimens
6,470 4.54%
140000
120000 135,809
100000
80000
2nd line regimens
1st line regimens
60000
40000
20000
0
09
07
08
0
7
8
9
09
06
07
08
09
07
08
.1
.0
.0
.0
n.
n.
n.
c.
c.
c.
c.
p.
p.
p.
ar
ar
ar
ar
De
De
De
De
Ju
Ju
Ju
Se
Se
Se
M
M
M
M
National Health Security Office (NHSO) Thailand Data at 7 Mar 2010

14. NAP Data on ARV Regimens
Other regimens
Not on ARV
Data at 14 JAN 2008

15. Number of Symptomatic and Asymptomatic AIDS
needing ART in Baseline Scenario
(asymptomatics with CD4 < 200)
300,000
Not on ART
250,000
On ART
200,000
150,000
2007 = 245,551 UC = 78,365
100,000 2008 = 255,178 UC = 110,770
2009 = 259,948 UC = 136,704
50,000 2010 = 260,388 UC = 149,590
0
20
00
05
10
15
25
90
95
20
19
20
20
20
20
20
19

16. Coverage ARV in Thailand
Before and After Universal Coverage (UC)
ARV Need Current Receiving
300,000
250,000 77.8 %
ARV-UC 67.1 %
200,000 56.4 %
51.5 %
150,000
42.5 %
100,00032.5 %
50,000
0
2004 2005 2006 2007 2008 2009
Source: UNGASS 2009

17. When to Start Antiretroviral Therapy
Late clinical stages
Late clinical stages Early Clinical Stages
Early Clinical Stages
< 200
< 200 > 500
> 500
200
200 350
350
Any viral load
Any viral load High Viral load
High Viral load
CD4
Schechter, 2004 (JID 2004;190:1043-1045)

18. CD4+ Count Response Based on
Baseline CD4+ Count
Johns Hopkins HIV Clinical Cohort ATHENA National Cohort
1000 1000
Mean CD4+ Count
800 800
(cells/mm3)
600 600
400 400
200 200
0 0
0 1 2 3 4 5 0 48 96 144 192 240 288 336
Years on HAART Weeks From Starting HAART
• Magnitude of CD4+ increase greatest if therapy started at low CD4+
counts, but greater likelihood of CD4+ count normalization with earlier
therapy
Keruly J, et al. CROI 2006. Abstract 529. Gras L, et al. CROI 2006. Abstract 530.

19. Clinical Outcome Improved by Starting
Therapy at Higher CD4+ Cell Count
Cumulative Probability of AIDS/Death by
• Timing of antiretroviral initiation in
treatment-naive subjects (N = CD4+ Cell Count at HAART Initiation
10,885) in Antiretroviral Cohort
Collaboration
101-200 cells/mm3
• HR for progression to AIDS or 201-350 cells/mm3
death by CD4+ cell count at 351-500 cells/mm3
Probability of AIDS or Death
0.12
initiation of therapy
– < 200 vs 201-350 cells/mm3 0.10
HR: 2.93 (95% CI: 2.41-3.57)
0.08
– < 350 vs 351-500 cells/mm3
HR: 1.26 (95% CI: 0.94-1.68) 0.06
• Results suggest a lower risk of
disease progression/death 0.04
when starting between 351-500 0.02
cells/mm3
0.00
1 2 3 4 5
Years Since Initiation of HAART
Sterne J, et al. CROI 2006. Abstract 525.

20. IAS-USA Guidelines: When to Start
Year Recommendation Recommendation to Consider Recommendation
to Begin Immediate Therapy to Delay Therapy
Immediate Therapy
2006 • Active AIDS • No history of active AIDS, but • CD4+ cell count
• No history of CD4+ cell count from 200-350 ≥ 350 cells/mm3
active AIDS, but cells/mm3
CD4+ cell count • CD4+ cell count > 350 cells/mm3
≤ 200 cells/mm3 but rapid CD4+ cell count
decline, HIV-1 RNA > 100,000
copies/mL, CVD risk factors,
other non-AIDS risk factors
2008 • Active AIDS • CD4+ cell count ≥ 350 cells/mm3 • CD4+ cell count
• No history of but rapid CD4+ cell count ≥ 350 cells/mm3
active AIDS, but decline, HIV-1 RNA > 100,000
CD4+ cell count copies/mL, CVD risk factors,
< 350 cells/mm3 other non-AIDS risk factors
Hammer SM, et al. JAMA. 2008;300:555-570.

21. DHHS Dec 2009 Guidelines: When to Start Treatment
Clinical Category CD4+ Cell Plasma General Guidelines
Count HIV-1 RNA
AIDS-defining illness or Any value Any value Treat
severe symptoms* (AI)
Asymptomatic (AI) < 350 Any value Treat
Asymptomatic (A/B-II) 350-500 Any value 55% of panel members voted
for strong recommendation (A)
45% of panel members voted
for moderate recommendation
(B)
Asymptomatic (B/C-III) > 500 Any value 50% of panel members favor
starting ART (B)
50% of panel members view
treatment is optional (C)
Pregnancy (AI) Any value Any value Treat
HIV associated
nephropathy (AII)
HBV co-infection when
HBV treatment is
indicated (AIII)
* Severe symptoms = unexplained fever or diarrhea > 2-4 wks, oral candidiasis, or > 10% unexplained weight loss.
DHHS Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents Dec 1, 2009

22. Half of DHHS Panel Recommended ART
Initiation at CD4+ Cell Count > 500 c/mm3
Arguments in Favor Arguments Against
• Cohort data showing survival • Available data do not definitively
benefit establish benefit of ART in all
patients with CD4+ cell count >
500 cells/mm3
• Untreated HIV infection may be • Benefits of earlier initiation may
associated with higher risk of be outweighed by
non-AIDS conditions • Risks of short- or long-term
• Availability of newer regimens drug-related adverse events
with improved efficacy, • Risk of nonadherence in
convenience, and tolerability asymptomatic patients
• Growing evidence that treatment • Potential for development of
reduces HIV transmission drug resistance
DHHS. Available at: http://aidsinfo.nih.gov/contentfiles/AdultandAdolescentGL.pdf.

23. December 2009 DHHS Guidelines:
Preferred Initial Regimens
Preferred regimens: those with optimal and durable
efficacy, favorable tolerability and toxicity profile, and
ease of use
NNRTI based • EFV/TDF/FTC
Boosted PI • ATV/RTV + TDF/FTC
based • DRV/RTV + TDF/FTC
INSTI based • RAL + TDF/FTC
DHHS. Available at: http://aidsinfo.nih.gov/contentfiles/AdultandAdolescentGL.pdf.

24. ART and Lipoatrophy
NRTI Choice: The Major Factor Driving
Lipoatrophy Risk
Highest Intermediate Lowest
Unknown
Risk Risk Risk
d4T ZDV 3TC ddI + 3TC
d4T + ddI ABC
FTC
TDF

25. Study 934
Median Total Limb Fat (Q1, Q3) Through Week
144 for Patients with Week 48 Data
14
TDF+FTC
12
AZT+3TC
10
Kilograms
8.1†
8 7.4* 8.3†‡
6
6.0* 4.9†‡
5.5†
4
2
*P = 0.035 †P < 0.001 ‡P < 0.001
0
0 48 96 144
Weeks
FTC+TDF+EFV 51 49 48
AZT+3TC+EFV 49 44 38
‡For change from week 48 within arm
Data on file, Gilead Sciences.

26. ACTG 5142: Lipoatrophy at
Week 96
LPV/RTV + 2 NRTIs
Patients With Lipoatrophy (%)
60
EFV + 2 NRTIs
51
45 40 EFV + LPV/RTV
32 33
30
17 16
15 9 12
6
0
Overall d4T ZDV TDF
NRTI-Containing Regimens
Lipoatrophy defined as > 20% loss of extremity fat by DEXA
Haubrich R, et al. CROI 2007. Abstract 38.

27. ACTG 5142: Drug-Associated
Risk for Lipoatrophy
Drug-Associated Risk for Lipoatrophy at Week 96
(Logistic Regression)*
Factor OR (95% CI) P Value
EFV vs LPV/RTV 2.7 (1.5-4.6) < .001
d4T vs ZDV 1.9 (1.1-3.5) .029
TDF vs ZDV 0.24 (0.12-0.50) < .001
*Excludes NRTI-sparing arm.
Haubrich R, et al. CROI 2007. Abstract 38.

28. Study 903E: Patients Switching From d4T to TDF
Mean (95% Cl) Total Limb Fat – Years 2-6
10 P=0.04
8.8
8.0 8.1 8.0 8.2
Mean Limb Fat in kg
8
5.5 5.8
6 5.0 5.0
4.6
P<0.001
4
TDF+3TC+EFV
2
d4T+3TC+EFV
0
1 2 3 4 5 6
Year
n= 69 69 65 61 58
n= 74 74 74 71 68
Madruga JVR. HIV8, 2006 Glasgow, UK. Poster P120.
Cassetti I. HIV8; 2006; Glasgow, UK. Poster P152.
Data on file, Gilead Sciences.

29. NRTIs: Lipid Changes From Baseline
in Recent Prospective Clinical Trials
Study and Drugs TC, TG,
Conclusion
Compared mg/dL mg/dL
GS 934 (144 wks)[1]
ZDV/3TC ↑ TC (P = .005) and TG
• EFV + TDF + FTC +24 +4
(P = .047) more than TDF + FTC
• EFV + ZDV/3TC +36 +36
SWEET (24 wks)[2]
ZDV/3TC ↑ TC (P = .008) and TG
• TDF/FTC -13 -22
(P < .001) more than TDF/FTC
• ZDV/3TC -1 +22
BICOMBO (48 wks)[3] ABC/3TC ↑ TC (P = .001), HDL
• ABC/3TC +12 +0 (P < .0001), LDL (P < .0001), and
TG
• TDF/FTC -9 -16 (P = .01) more than TDF/FTC
RAVE (48 wks)[4]
ABC ↑ TC (P < .0001) more than
• TDF -19.3 -26.6
TDF
• ABC +7.7 +8.9
1. Arribas JR, et al. IAS 2007. Abstract WEPEB029. 2. Moyle G, et al.
IAS 2007. Abstract WEPEB028. 3. Martinez E, et al. IAS 2007.
Abstract WESS102. 4. Moyle GJ, et al. ICAAC. Abstract H-340.

30. Draft Thai ART Guidelines 2010 (Adult 1)
Clinical CD4
Recommendations
Presentations (cells/mm3)
AIDS-defining illness Any Treat
HIV-related Symptomatic Any Treat
Asymptomatic <350 Treat
Defer Rx, follow clinical status and CD4
Asymptomatic >350
every 6 months
Treat, discontinue ARV after delivery if
Pregnancy Any
pre-treat CD4 >350 cells/mm3
Special consideration for ART initiation
• HBV or HCV co-infection: any CD4 if treatment of HBV or HCV needed
• Age >50: CD4 350-500 with at least one of these following conditions
(DM, HT, Dyslipidemia)
Bureau of AIDS,TB, and STIs and Thai AIDS Society (TAS)

31. Draft Thai ART Guidelines 2010 (Adult 2)
NRTIs NNRTIs PIs
Preferred Preferred
AZT + 3TC or LPV/r
TDF + 3TC/FTC (If can not
+ EFV
Alternative
NVP tolerate NNRTIs) Alternative
ABC + 3TC ATV/r
d4T + 3TC DRV/r
ddI + 3TC SQV/r
**In alphabetic order**
Bureau of AIDS,TB, and STIs and Thai AIDS Society (TAS)

32. Draft d4T Phase-Out Plan
1. Patients on d4T or AZT with lipoatrophy
d4T or AZT TDF
2. Patients on d4T without lipoatrophy
d4T AZT
• 1st priority: patients with the longest
duration on d4T
• If patients could not tolerate AZT or start
to develop lipoatrophy (after 6 months of
AZT) then switch to TDF
**Viral load <50 before switching to TDF**

33. Draft Thai ART Guidelines 2010 (PMTCT)
CD4 Timing
Regimen
(cells/mm3) Start After delivery
<350 AZT+3TC+LPV/r immediate Continue ARV
(could be switched to NNRTI-based
(all q 12 hrs) regimens)
>350 AZT+3TC+LPV/r After 14 wks Discontinue ARV
(all q 12 hrs) gestation
Bureau of AIDS,TB, and STIs and Thai AIDS Society (TAS)

34. Draft Thai ART Guidelines 2010 (Pediatric)
Age < 1 ป Age 1-5 ป Age > 5 ป
Clinical Presentations Treat CDC category B, C CDC category B, C
or WHO stage 3, 4 or WHO stage 3, 4
CD4 levels
%CD4 or absolute CD4 Treat %CD4 <25 CD4 <350cells/mm3
Bureau of AIDS,TB, and STIs and Thai AIDS Society (TAS)

35. Case 1
40 year-old man was diagnosed with HIV in Dec 2001. No other
medical history is available.
CD4 VL
May 2002 43 - GPOvir (30)
(d4T+3TC+NVP)
Jan 2003 14 -
Jun 2004 55 -
Nov 2004 13 -
Mar 2005 29 -

36. Case 1
40 year-old man was diagnosed with HIV in Dec 2001. No other
medical history is available.
CD4 VL
Sep 2005 29 25,631 Do nothing ???
Mar 2006 23 -
Oct 2006 17 -
May 2007 3 -
Jul 2007 - 27,000 Do nothing ???

37. Case 1
CD4 VL
Nov 2007 4 -
May 2008 74 - Lipoatrophy
Jun 2008 - 5,500 GPO (Z250)
(AZT+3TC+NVP)
Nov 2008 20 - Anemia from AZT
(Hb 8 gm)
Switched to TDF then
Feb 2009 - 29,000 Genotypic drug
resistance ???
M41L, K65R, M184V, T215Y, Y181C, G190A

38. Case 2
34 yrs male, IVDU, Dx HIV+ May 2002 presented with
Pulmonary TB
CD4 VL
Sep 03 134
Oct 03 - 82,742 Started GPOvir
May 04 289 -
Mar 05 351 <50
Dec 05 419 -
Aug 06 357 33,700 Genotype
No Mutation
Feb 07 415 2,784
Jul 07 358 12,367 Genotype
M41L, Q151M, M184V, T215Y, Y181C