4. Major Targets of Antiretroviral Agents HIV RNA DNA ds DNA RT Integrase Transcription Proviral DNA Spliced mRNA mRNA Genomic RNA Polyprotein Protein Protease Protease Inhibitors SQV,RTV, IDV, NFV, AMV, LPV/rtv, ATV, DRV RT Inhibitors NRTI : AZT, ddI, ddC, d4T, 3TC, ABC NNRTI : NVP, DLV, EFV NTRTI: Tenofovir 1 2 3 4 5 6 Entry Inhibitors CXCR4: AMD3100, T22 CCR5: SCH-C, D; TAK779 Fusion gp41 : T20 vpr Integrase Srtand Transfer Inhibitor INSTI, RAL
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6. Accum_Register Current Register Accum. Death New Register National AIDS Program (NAP) Data at 7 Mar 2010 Courtesy Dr. Wicahi Thechasatit
7. CD4+ Count Response Based on Baseline CD4+ Count Johns Hopkins HIV Clinical Cohort ATHENA National Cohort Mean CD4+ Count (Cell/mm 3 ) Years on HAART Week From Starting HAART Greater likelihood of CD4+ count normalization with earlier therapy Keruly J, et al. CROI 2006.Abstract 529. Gras L, et al. CROI 2006. Abstrac 530
8. Improved Clinical Outcome by Starting ARV Rx at Higher CD4 Sterne J, et al. CROI 2006. Abstract 525. Years Since Initiation of HAART Morbidity/Mortality
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10. Thai ART Guidelines 2010 Bureau of AIDS,TB, and STIs and Thai AIDS Society (TAS) NRTIs + NNRTIs or (If can not tolerate NNRTIs) P I s Prefer red EFV NVP Preferred AZT + 3TC TDF + 3TC/FTC LPV/r Alternative Alternative ABC + 3TC d4T + 3TC ddI + 3TC ATV/r DRV/r SQV/r
11. Currently available ARVs in Thailand and recommended dosages. 300mg every 12 hours, or 600mg every 24 hours 250mg 1 hour before meal every 24 hours for weight <60 Kg., or 400mg 1 hour before meal every 24 hours for weight ≥ 60 Kg. 300 mg Chewable buffered tablets (125,200 mg), enteric coated Capsule (250,400mg) Abacavir (ABC) Didanosine (ddI) 300mg every 24 hours, or 150mg every 12 hours 30mg every 12 hours 300mg every 24 hours 150,300mg 30mg 300mg Lamivudine(3TC) Stavudine (d4T) Tenofovir (TDF) Dosages Preparations Drugs
12. One tablet every 24 hours 200-300mg every 12 hours 600mg every 24 hours before bedtime 200mg every 12 hours 200mg every 12 hours 300mg + RTV 100mg every 24 hours with food* 600mg + RTV 100mg every 12 hours with food, or 800mg+RTV 100mg every 24 hours with food** 300/200mg 100,250,300mg 200,600mg 100mg 200mg 300 mg 300mg, 400mg TDF/emtricitabine (FTC) Zidovudine (AZT) Efavirenz (EFV) Etravirine (ETR) Nevirapine (NVP) Atazanavir (ATV) Darunavir (DRV) Dosages Preparations Drugs
13. *when used with TDF or EFV, use with RTV only; avoid taking with antacid, H2-blocker or proton pump inhibitors. **once daily dosing is recommended for ARV-na ve patients only 400/100mg every 12 hours with food, or 800/200mg every 24 hours with food** Only used as PI booster in the regimen 100mg + RTV 100mg every 12 hours with food, or 1500mg+RTV 100mg every 24 hours with food** 400mg every 12 hours 100/25, 200/50mg 100mg 500mg 400mg Lopinavir/ritonavir (LPV/r) Ritonavir (RTV) Saquinavir (SQV) Raltegravir (RAL) Dosages Preparations Drugs
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16. Side effect of ARV Neuropathy Lipodystrophy Dyslipidemia( โดยเฉพาะ TG) Lactic acidosis d4T Anemia, neutropenia, BM suppression *Myopathy(CPK, LDH สูง ) Black nail AZT Side effect ARV
17. Renal failure Fanconi syndrome Nephrogenic diabetes insipidus *Weight loss (unexplained) *Osteopenia TDF Neuropathy *Alopecia 3TC Neuropathy Pancreatitis Alopecia DDI Side effect ARV
18. CNS symptoms Depression Skin rash Elevated liver enzyme Hyperlipidemia *Gynecomastia, *False positive cannabinoid test Teratogenicity EFV Skin rash Steven Johnson syndrome TEN DRESS Hepatitis NVP Side effect ARV
19. GI symptom Elevated indirect hyperbilirubinemia Nephrolithiasis *Integument adverse events Hyperlipidemia Elevated plasma glucose Bleeding in hemophiliac patient IDV GI symptom Hyperlipidemia (esp. TG) Elevated plasma glucose Elevated liver enzyme Bleeding in hemophiliac patient Lipodystrophy LPV/r Side effect ARV
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21. Indications for initiation of ART in patients with HIV and tuberculosis (TB) co-infection. Start ART 2-8 weeks after the initiation of TB treatment Start ART 2 months after the initiation of TB treatment Defer ART Follow up clinical status and monitor CD4 + T- cell count every 6 months <200 200- <350 ≥ 350 Recommendation CD4 + T cell counts (cells/mm 3 )
34. Recommended laboratory monitoring after initiation of ART Strongly recommended if TDF is used every 6 months at 6 and 12 months Creatinine* should be performed at 3 months if NNRTI is used every 6 months at 6 and 12 months ALT should be performed before switching of ARVs due to adverse effects every 6 months every 12 months (every 6 months is preferred ) Every 12 months at 6 and 12 months First regimen: at 6 and 12 months The next regimens: at 3 and 6 months CBC, CD4+T-cell count Plasma VL every 6 months at 6 and 12 months FBS Following years First year of ART Note Recommended time for the test Laboratory tests
35. * for calculation of creatinine clearance. Perform when clinical status indicates every 12 months at 12 months Pap smear Perform when clinical status indicates - - CXR every 6 months at 6 and 12 months Lipid profile (TC,TG,LDL,HDL) should be performed 12 months if TDF is used - - Urinalysis Following years First year of ART Note Recommended time for the test Laboratory tests
43. Perinatal Transmission Rate In Surveillance Province (Birth cohort Jan 2001-Dec 2006 N=3,687) Tx% Bureau of Epidemiology(PHOMS); December 2006
44. Triple-antiretroviral prophylaxis during pregnancy and breastfeeding compared to short-ARV prophylaxis to prevent mother-to-child transmission of HIV the Kesho Bora randomized controlled clinical trail in five sites in Burkina Faso, Kenya and South Africa I. De Vincenzi. 5 th IAS 2009. Cape town, South africa. Trial registration number ISRCTN71468401.
45. Number pediatric AIDS aged 0-4 years who born to HIV positive mother during 1984-2009 Epidemiology Division, July 2009 http://203.157.15.4/reportaids/2009/T2_090731160851.pdf AZT short course AZT 28 wks + SD NVP or HAART
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50. ช่วงเวลาในการถ่ายทอดเชื้อเอชไอวีสู่ลูก : Non-breastfeeding population จำนวนเด็ก จำนวนที่ติดเชื้อ ช่วงเวลา % ที่ติดเชื้อ <14 weeks 14-36 weeks 36 weeks Through labour Delivery 75 uninfected 25 infected 100 95 99 1 17% 3% 4 12 83 8 30% 50% Athens PK, et al. Mother-to-child transmission of HIV-1: timing and implication for prevention Lancet infect Dis 2006; 6:726-32.
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52. หญิงตั้งครรภ์ ไม่เคยกินยา ARV ฝากครรภ์ ผล Anti HIV Positive CD4 count ถ้าหาก LPV/r ไม่ได้ให้ EFV แทนหลังไตรมาส 2 หลังคลอด ปรึกษาอายุรแพทย์ GPOvirZ 250 หรือ AZT/3TC/EFV หลังคลอด หยุด ARV ( หากได้ NNRTI AZT+3TC 1 สัปดาห์ ) บุตร AZT 4 mg/kg m6d 12 ชม . 4 สัปดาห์ ≤ 350 AZT+3TC+LPV/r เริ่มยาทันที > 350 AZT+3TC+LPV/r เริ่มยา 14-24 สัปดาห์ ระหว่างเจ็บครรภ์คลอด AZT q 3 hr. จนคลอด New Thai PMTCT Guidelines 2010
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54. New Thai PMTCT Guidelines 2010 หญิงตั้งครรภ์ที่กินยา ต้านไวรัสอยู่ก่อน - ไม่ต้องหยุดยา - ปรับสูตรยาให้มี AZT ด้วยถ้าเป็นไปได้ - หากกิน EFV และอยู่ในช่วงไตรมาสแรก ให้เปลี่ยนยา แต่หากพ้นไตรมาสแรก ให้กินต่อได้ ระหว่างเจ็บครรภ์คลอด AZT ทุก 3 ชม . จนคลอด ( แม้ว่าจะเคยดื้อยา AZT มาก่อนก็ตาม ) หลังคลอด ปรึกษาอายุรแพทย์ เพื่อปรับสูตรยาตามความเหมาะสม บุตร AZT 4 mg/kg ทุก 12 ชม . 4 สัปดาห์
Accum regis เคยลงทะเบียนใน NAP Current regis ยังคงมาติดตามการรักษาย้อนหลัง 12 เดือน New regis ผืที่มาลงใหม่ ใน ไตรมาสนั้นๆ
CI, confidence interval; HR, hazard ratio. One cohort study that helps to inform us on when to start therapy comes from the Antiretroviral Therapy Cohort Collaboration. In this particular 2006 analysis, the hazard ratio of progression to AIDS or death was determined for more than 10,000 antiretroviral-naive patients who started therapy within 3 different CD4+ cell count strata. The 3 CD4+ cell count categories were 100-200 cells/mm^3, 201-350 cells/mm^3, and 350-500 cells/mm^3. The results demonstrated a strong trend in favor of starting therapy with a CD4+ cell count > 350 cells/mm^3. For more information about this study, go online to: http://clinicaloptions.com/HIV/Conference%20Coverage/Retroviruses%202006/Tracks/First%20Line/Capsules/525.aspx
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