Thai hiv guideline

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Thai hiv guideline

  1. 1. New Thai HIV Treatment Guidelines 2010 Wichai Techasathit, MD., MPH. Faculty of Medicine Siriraj HospitalMahidol University, Bangkok, Thailand
  2. 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 87Egger M, et al. CROI 2007. Abstract 62.
  3. 3. Development of Antiretroviral Treatment in ThailandBefore 1992 Treatment of common OI without ARV1992 AZT mono-therapy1995 Dual therapy with AZT + ddI, AZT+3TC1997 Triple therapy through HIV Clinical Research Network2000 Access to Care (ATC) with 8 pre-assigned regimens2004 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. 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. 5. Thai Guideline for ARV 2006-2007 2 NRTIs NNRTI หรือ PI1st line AZT+3TC NVP d4T+3TC EFV IDV/RTV2nd 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
  6. 6. Preferred and Alternative regimens for Initiation of ART - TAS 2008 J Med Assoc Thai 2008;91(12):1925-36
  7. 7. ARV Regimens: NHSO vs. SSO National Health Security Social Security Office Office (NHSO or NAP) (SSO) Effective 1 April 2007 Effective 1 January 20071. 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+EFV2. Group B d4T(AZT)+3TC+IDV/r d4T+3TC+IDV/r AZT+3TC+IDV/r If other regimens needed Consultation for permission3. Group C ddI+3TC or TDF+3TC in cases of lipoatrophy (Expert approval)
  8. 8. 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
  9. 9. 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 ExpertsRegional AIDS Consultants; RAC Group of AIDS ConsultantsBangkok AIDS Consultants; BAC assigned by SSO
  10. 10. National Health Security Social Security Office Office (NHSO or NAP) (SSO)Monitoring Monitoring1. CD4 x 2 times/yr 1. CD4 x 2 times/yr2. VL x 1 time/yr 2. VL x 2 time/yr3. Drug resistance x 1 time/yr 3. Drug resistance x 1 time/yr4. 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”
  11. 11. Who is still taking d4T?90.0% 78.6 77.880.0% d4T-3TC-NVP70.0% d4T-3TC-EFV 62.7 d4T-FTC-EFV60.0% d4T-FTC-NVP50.0% 47.6 45.8 AZT-3TC-NVP AZT-3TC-EFV40.0% TDF-FTC-EFV 28.4 TDF-FTC-NVP30.0% 25.9 24.0 d4T-3TC-LPV/r20.0% Other 11.10 11.2 8.6 8.9 9.110.0% 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 dIvoire Mozambique South Africa Tanzania ZambiaWestreich 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)
  12. 12. 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
  13. 13. NAP Data on ARV Regimens Other regimens Not on ARV Data at 14 JAN 2008
  14. 14. Number of Symptomatic and Asymptomatic AIDSneeding ART in Baseline Scenario(asymptomatics with CD4 < 200)300,000 Not on ART250,000 On ART200,000150,000 2007 = 245,551 UC = 78,365100,000 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
  15. 15. Coverage ARV in Thailand Before and After Universal Coverage (UC) ARV Need Current Receiving300,000250,000 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
  16. 16. When to Start Antiretroviral TherapyLate 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)
  17. 17. CD4+ Count Response Based on Baseline CD4+ Count Johns Hopkins HIV Clinical Cohort ATHENA National Cohort 1000 1000Mean 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.
  18. 18. 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 HAARTSterne J, et al. CROI 2006. Abstract 525.
  19. 19. IAS-USA Guidelines: When to StartYear Recommendation Recommendation to Consider Recommendation to Begin Immediate Therapy to Delay Therapy Immediate Therapy2006 • 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 factors2008 • 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.
  20. 20. DHHS Dec 2009 Guidelines: When to Start TreatmentClinical Category CD4+ Cell Plasma General Guidelines Count HIV-1 RNAAIDS-defining illness or Any value Any value Treatsevere symptoms* (AI)Asymptomatic (AI) < 350 Any value TreatAsymptomatic (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 TreatHIV 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
  21. 21. Half of DHHS Panel Recommended ARTInitiation 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 resistanceDHHS. Available at: http://aidsinfo.nih.gov/contentfiles/AdultandAdolescentGL.pdf.
  22. 22. 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/FTCDHHS. Available at: http://aidsinfo.nih.gov/contentfiles/AdultandAdolescentGL.pdf.
  23. 23. ART and LipoatrophyNRTI Choice: The Major Factor DrivingLipoatrophy Risk Highest Intermediate Lowest Unknown Risk Risk Risk d4T ZDV 3TC ddI + 3TC d4T + ddI ABC FTC TDF
  24. 24. 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 WeeksFTC+TDF+EFV 51 49 48AZT+3TC+EFV 49 44 38‡For change from week 48 within armData on file, Gilead Sciences.
  25. 25. 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 DEXAHaubrich R, et al. CROI 2007. Abstract 38.
  26. 26. 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.
  27. 27. Study 903E: Patients Switching From d4T to TDFMean (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 68Madruga JVR. HIV8, 2006 Glasgow, UK. Poster P120.Cassetti I. HIV8; 2006; Glasgow, UK. Poster P152.Data on file, Gilead Sciences.
  28. 28. NRTIs: Lipid Changes From Baselinein 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 +8.91. 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.
  29. 29. 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/mm3Special 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)
  30. 30. Draft Thai ART Guidelines 2010 (Adult 2) NRTIs NNRTIs PIsPreferred PreferredAZT + 3TC or LPV/rTDF + 3TC/FTC (If can not + EFVAlternative NVP tolerate NNRTIs) AlternativeABC + 3TC ATV/rd4T + 3TC DRV/rddI + 3TC SQV/r**In alphabetic order** Bureau of AIDS,TB, and STIs and Thai AIDS Society (TAS)
  31. 31. Draft d4T Phase-Out Plan1. Patients on d4T or AZT with lipoatrophy d4T or AZT TDF2. 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**
  32. 32. 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)
  33. 33. 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, 4CD4 levels%CD4 or absolute CD4 Treat %CD4 <25 CD4 <350cells/mm3 Bureau of AIDS,TB, and STIs and Thai AIDS Society (TAS)
  34. 34. Case 140 year-old man was diagnosed with HIV in Dec 2001. No other medical history is available. CD4 VLMay 2002 43 - GPOvir (30) (d4T+3TC+NVP)Jan 2003 14 -Jun 2004 55 -Nov 2004 13 -Mar 2005 29 -
  35. 35. Case 140 year-old man was diagnosed with HIV in Dec 2001. No other medical history is available. CD4 VLSep 2005 29 25,631 Do nothing ???Mar 2006 23 -Oct 2006 17 -May 2007 3 -Jul 2007 - 27,000 Do nothing ???
  36. 36. Case 1 CD4 VLNov 2007 4 -May 2008 74 - LipoatrophyJun 2008 - 5,500 GPO (Z250) (AZT+3TC+NVP)Nov 2008 20 - Anemia from AZT (Hb 8 gm) Switched to TDF thenFeb 2009 - 29,000 Genotypic drug resistance ??? M41L, K65R, M184V, T215Y, Y181C, G190A
  37. 37. Case 2 34 yrs male, IVDU, Dx HIV+ May 2002 presented withPulmonary TB CD4 VLSep 03 134Oct 03 - 82,742 Started GPOvirMay 04 289 -Mar 05 351 <50Dec 05 419 -Aug 06 357 33,700 Genotype No MutationFeb 07 415 2,784Jul 07 358 12,367 Genotype M41L, Q151M, M184V, T215Y, Y181C

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