HIV Update For General Practioners 2013

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Lecture for Genaral practitioners at Hotel Kohinoor Pune on 18th Jan 2012. Organised by Genix Pharma. Chair person -Dr Bharat Purandare

Lecture for Genaral practitioners at Hotel Kohinoor Pune on 18th Jan 2012. Organised by Genix Pharma. Chair person -Dr Bharat Purandare

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  • 1. Dr Madhu OswalSamvad HIV AIDS Helpline
  • 2. Overview  How to diagnose?  How to monitor after diagnosis ?  When to start ART?  What to start?  How to monitor after starting ART?  When to refer?1/19/2013 Samvad HIV Helpline 020-26381234
  • 3. Mayur  Mr Mayur, 24 yr old, called at 10 am on Sunday morning.  H/O Unprotected exposure (condom slipped) night before.  Wants to know if he is HIV infected- TODAY.  What to do?1/19/2013 Samvad HIV Helpline 020-26381234
  • 4. “Window Period” Following HIV Infection Acute HIV syndrome Antibody Primary HIV Asymptomatic infection Viremia ------------------------------------ PCR P24 a.g ELISA a b 0 2 3 4 Years1/19/2013 (Weeks since infection) Samvad HIV Helpline 020-26381234 6 Source: S Conway and J.G Bartlett, 2003
  • 5. Diagnosis in the window period  After 6 weeks-antibody tests Elisa/Rapid  At approx 4 weeks- HIV Duo  At approx 2 weeks- HIV RNA HIV DNA P24 Ag test A POSITIVE RESULT HAS TO BE CONFIRMED BY AN ANTIBODY TEST AFTER THE WINDOW PERIOD1/19/2013 Samvad HIV Helpline 020-26381234
  • 6. HIV DNA or RNA  HIV DNA or RNA tests are NOT recommended for diagnosis in adults  False positive results in almost 20% of patients  Costs around Rs 4000.  The patients have to be subjected to antibody testing for confirmation after 6 weeks.1/19/2013 Samvad HIV Helpline 020-26381234
  • 7. What to do?  Take history: was the risk significant  Any symptoms or signs of STD-Treat  Test for baseline HIV status, Hbs Ag, ? Anti HCV  Explain about window period  Start PEP for HIV if indicated  Start Heb B vaccine course, if not vaccinated and HbS Ag neg.  Risk reduction counseling  If woman( Mayuri), Emergency contraception1/19/2013 Samvad HIV Helpline 020-26381234
  • 8. Post Exposure Prophylaxis1/19/2013 Samvad HIV Helpline 020-26381234
  • 9. Drugs for Post exposure prophylaxis  Basic regimen: 1. Tenofovir 300+ Emtricitabine 200mg OD OR 2. AZT 300 mg + Lamivudine 150 mg BD  Expanded regimen: 1. Above plus Atazanavir 300 + Ritonavir 100 mg OD 2. Lopinavir 400mg +Ritonavir 100 mg BD All for 4 weeks Test after 6 weeks and 3 months for HIV and Hep B1/19/2013 Samvad HIV Helpline 020-26381234
  • 10. After 3 months……..  Mayur ‘s HIV test is Negative  Risk reduction counseling .1/19/2013 Samvad HIV Helpline 020-26381234
  • 11. After 3 months……..  Mayur ‘s HIV test is Positive (……..May be because I didn’t take his call on Sunday )  Now what? 1. Disclose Mayur that he is HIV positive? 2. Do Western Blot test 3. Do HIV DNA/ RNA test? 4. Repeat Elisa test?1/19/2013 Samvad HIV Helpline 020-26381234
  • 12. Ist Rapid / Elisa. NegativePositive Uninfected II nd Rapid / Elisa Negative Positive Uninfected Symtomatic Asymptomatic III rd Rapid / Elisa Infected. Negative Equivocal W.B.1/19/2013 Samvad HIV Helpline 020-26381234
  • 13. Which test would you utilize when you suspect HIV infection?  Elisa test  Rapid test  Western Blot test1/19/2013 Samvad HIV Helpline 020-26381234
  • 14. ELISA for HIV antibody Microplate ELISA for HIV antibody: coloured wells indicate reactivity1/19/2013 Samvad HIV Helpline 020-26381234
  • 15. Elisa report Positive1/19/2013 Samvad HIV Helpline 020-26381234
  • 16. Rapid test  Uses ELISA principle  Takes 10 min to 30 mins to perform  Very simple to perform without any need to special apparatus  Can be used in G.P’ s clinic  Most have sensitivity and specificity comparable to ELISA1/19/2013 Samvad HIV Helpline 020-26381234
  • 17. Rapid tests brands  Determine  Triline  Retroquick HIV  Immunoblot  HIV Tridot  Comb AIDS 1/2,  HIV Comb  Retrocheck HIV1/19/2013 Samvad HIV Helpline 020-26381234
  • 18. Step 1- Do Rapid Test in your clinic. If positive,Step 2- Confirm with ELISA in a standard Lab.
  • 19. WESTERN BLOT TEST1/19/2013 Samvad HIV Helpline 020-26381234 Positive for
  • 20. Western Blot Result Interpretation  Results are interpreted as follows:  Negative: no bands  Positive: reactivity to gp120/160, plus either gp41 or p24  Indeterminate: one reactive band (or anything other than a positive test) should be repeated at a later time, e.g., 1-3 months later  Repeatedly indeterminate: no HIV infection1/19/2013 Samvad HIV Helpline 020-26381234
  • 21. Western Blot test – Not a “gold standard” test in India  Indeterminate results  High cost1/19/2013 Samvad HIV Helpline 020-26381234
  • 22. Mayur has confirmed HIV test  Now what?  Don’t know how to break the news, so keep silent  Refer to HIV specialist  Manage further1/19/2013 Samvad HIV Helpline 020-26381234
  • 23. Mayur goes into depression  Don’t turn up for 5 to 6 years.  Then one fine day…..he comes with Herpes Zoster1/19/2013 Samvad HIV Helpline 020-26381234
  • 24. Initial evaluation: history  Fever, night sweats, weight loss, cough (any duration): TB  Other OI’s: herpes zoster, chronic diarrhoea  ARV exposure with response  Co-morbidities: DM, HTN, CKD, Jaundice  Smoking, alcohol  High risk behaviour  Ask if he has any sexual partner, marital status , children1/19/2013 Samvad HIV Helpline 020-26381234
  • 25. Initial evaluation: physical examination  Weight  Lymphadenopathy  Oral cavity  Hepato-splenomegaly, doughy feel of abdomen  Fundoscopic  Dermatological exam 1/19/2013 Samvad HIV Helpline 020-26381234
  • 26. Initial evaluation: Laboratory workup  CBC with differential  Urinanalysis, creatinine  Blood sugar  Liver enzymes (optional)  Chest Xray/USG abdomen(before starting ART)  CD4 Count  Serologic  VDRL, TPHA  HbsAg, anti-HCV  sCRAG (in pts with CD4<200)  Cervical PAP smear in Mayuri 1/19/2013 Samvad HIV Helpline 020-26381234
  • 27. Tests NOT recommended  Exceptional situations only  Plasma viral load  ARV resistance testing  Fasting lipids  CMV, Toxo serology  TB tests  TB ELISA  Tuberculin testing  IGRA assays( TB Gold, Quantiferon)1/19/2013 Samvad HIV Helpline 020-26381234
  • 28.  Mayur has never married (He feels he won’t live long anyway).  He has a girlfriend, whom he has not disclosed his status.  He has taken to smoking and alcohol  All report s normal.  CD4 count 325 cells/ml1/19/2013 Samvad HIV Helpline 020-26381234
  • 29. What to do next? 1. Start ART? 2. Wait till CD4 falls upto 250 and start Septran 3. Start ayurvedic treatment or Amway products? 4. Refer?1/19/2013 Samvad HIV Helpline 020-26381234
  • 30. Reassurance!! Reassurance!!!!Reassurance !!!!!!!  HIV is a chronic manageable disease like Diabetes, like Hypertension, like asthma.  One can expect a near NORMAL lifespan with HIV infected individuals  There is no cure, but with regular medicines one can lead a normal life 1/19/2013 Samvad HIV Helpline 020-26381234
  • 31. More than just medicines…  Mental health  Diet  Hygiene-water, air  Exercise  Lifestyle  Addictions  Financial security  Disclosure / testing of partner, if indicated1/19/2013 Samvad HIV Helpline 020-26381234
  • 32. Chemoprophylaxis Medication Dose Indication Benefit TMP-SMX 1 DS qd CD<200 PCP Toxo Isospora, cycospora Typhoid Malaria Community UTI Dapsone 1 qd CD4<200 PCP TMP_SMX HSR Pyrimethamine 50 mg qwk CD4<200 Toxo With dapsone Azithromycin 1.2 qwk CD4<50 MAC INH 300 mg qd Rule out active TB MTB Hepatitis B vaccine to all Hbs Neg1/19/2013 Samvad HIV Helpline 020-26381234
  • 33. When to start ART?  All Pt with hx of AIDS-defining condition  All patients with CD4 T-cell count of <350 cells/mm3  All Pt that are pregnant, HIV nephropathy, HBV co- infection when HBV Rx is needed  Recommended for all Pt with 350-500 cells/mm3  Optional for Pt with >500 cells/mm3DSHS,January 10, 20111/19/2013 Samvad HIV Helpline 020-26381234
  • 34. Benefits of ART  The survival after development of advanced HIV disease increased from 18 months to over 25 years for those who can access medicines.  Prevention of transmission  Secondary prevention  Post-exposure prophylaxis  Occupational and non-occupational  Mother to child transmission  Pre-exposure prophylaxis1/19/2013 Samvad HIV Helpline 020-26381234
  • 35. What to start? Fusion ENF Viral protease CCR5 antag. maraviroc SQV RNA RNA RTV Proteins IDV Reverse RT NFV transcriptase RNA fAPV RNA LPVZDV, ddI, DNA ATVddC, d4T, RT DRV3TC, ABC, TPVTDF, FTC DNADLV, NVP, DNA Provirus IntegraseEFV, ETV raltegravir 1/19/2013 Samvad HIV Helpline 020-26381234
  • 36. Nucleoside ReverseTranscriptase Inhibitors( NRTIs)  Tenofovir (TDF)-  Zidovudine (AZT)  Lamivudine (3TC)  Emtricitabine (FTC)  Stavudine (d4T)  Didanosine (ddI)  Abacavir (ABC)  Zalcitabine (ddC) Helpline 020-263812341/19/2013 Samvad HIV
  • 37. Non-Nucleoside ReverseTranscriptase Inhibitors (NNRTIs)  Nevirapine (NVP)  Efavirenz (EFV)  Etravirive  Delaverdine1/19/2013 Samvad HIV Helpline 020-26381234
  • 38. First line regimens  Preferred  TDF/XTC/EFV or NVP( Trustiva, Effoday, )  Alternative  AZT/3TC/EFV or NVP  No options available  d4T/3TC/EFV or NVP1/19/2013 Samvad HIV Helpline 020-26381234
  • 39. How to monitor when on ART? 1. Look for IRIS: Immune reconstitution inflammatory syndrome 2. Look for adverse effects- clinical and lab investigations 3. Watch for drug drug interaction 4. Monitor response to ART: CD4 and Viral load1/19/2013 Samvad HIV Helpline 020-26381234
  • 40. How to monitor when on ART? IRIS: Immune reconstitution inflammatory syndrome  Iris is occurrence or manifestations of new OIs within six weeks to six months after initiating ART; with increase in CD4 count  Two types: Unmasking and Paradoxical1/19/2013 Samvad HIV Helpline 020-26381234
  • 41. IRIS 3 weeks after ART (TDF+3TC+EFV)1/19/2013 Source: Dr.Rajasekaran, Superintendent, GHTM,Chennai Samvad HIV Helpline 020-26381234 41
  • 42. IRIS1/19/2013 Samvad HIV Helpline 020-26381234 42 Source: GHTM,Chennai
  • 43. How to monitor when on ART?  TDF: Renal, bone( Do urine R, S creat)  AZT: Anemia( Hb)  EFV: CNS  Nev: HSR, Hepatitis( LFT if symptomatic)  d4T: Neuropathy, lactic acidosis1/19/2013 Samvad HIV Helpline 020-26381234
  • 44. Nevirapine (NVP)  Rash  Hepatitis Risk is greatest in first 6 weeks of therapy   Could be benign or fatal  Increased risk if started in women with CD4 above 250 and men with CD4 above 400  Not to use in concomitant Anti TB drugs1/19/2013 Samvad HIV Helpline 020-26381234
  • 45. Nevirapine-Induced Rash1/19/2013 Samvad HIV Helpline 020-26381234 Courtesy of HIV Web Study, www.hivwebstudy.org
  • 46. Efavirenz Toxicity  CNS Changes (excessive sleep or loss of sleep, delusions, nightmares)  Rash  Hepatotoxicity (  Contraindicated during pregnancy  Teratogenic—Class D?  Useful in TB with HIV  Useful when stsrting ART in higher CD4 count1/19/2013 Samvad HIV Helpline 020-26381234
  • 47. Long term Toxicity (After fewyears)  Bone Marrow Suppression  Myalgia  Anemia  Myopathy  Neutropenia  Pigmentation of nail  Peripheral Neuropathy beds  Lipoatrophy  Lactic acidosis, fatty liver  Fat accumulation  Pancreatitis  Osteoporosis  Cardiovascular side effects  Metabolic syndrome  Renal dysfunction  Hepatic dysfunction1/19/2013 Samvad HIV Helpline 020-26381234
  • 48. Facial Lipoatrophy1/19/2013 Samvad HIV Helpline 020-26381234
  • 49. Lipodystrophy1/19/2013 Samvad HIV Helpline 020-26381234
  • 50. Test On starting 2-8 weeks after Every 3 to 6 Every year ART starting ART months Heamogram √ √ (If on ZDV) √ Urine R √ √ (If on TDF, √ esp in DM, HT) BSL -F √ √ALT, AST ,S-bili √ √ √ S. creatinine √ √ √ S elec, S Ca, S √ √ √ Phos, Cr Cl Lipid profile √ √(If last report √ (If last report abnormal) normal) CD4 count √ √ √( If very stable and high counts) Viral load √ √ √( If stable and 1/19/2013 Samvad HIV Helpline 020-26381234 adherent)
  • 51. Knowing about CD4 Count WBCs RBCs platelets PMNs Eos Lymphs Grans Macroph. CD4 (T helper) CD8 (T helper) others1/19/2013 Samvad HIV Helpline 020-26381234
  • 52. Uses of CD4 Cell Count  Decision to initiate ARV  Guide in initiating OI prophylaxis  Assess progression of disease  Measure response to treatment (prognostication)  Detect immunologic treatment failure  Pneumocystis pneumonia  CD4 <200  TLC <1200  Toxoplasmosis  CD4 <100 and positive Toxoplasma serology  Cryptococcal meningitis  CD4 <1001/19/2013 Samvad HIV Helpline 020-26381234
  • 53. CD4 COUNT  Normal CD4 count is 800-1050 cells/cu.mm  CD4 decreases at a rate of 40-60 cells per yr in an HIV infected person.  Diurnal variation.  Treat OI before testing for CD4 count.  Sample :3 ml in EDTA bulb  CD4 count increases > 50 cells/mm3 at 4-8 weeks after ART and then increases an additional 50 – 100 cells / mm3 per year thereafter.  Change more than 30% is significant.  Ideally CD4 count to be measured every 6 months.1/19/2013 Samvad HIV Helpline 020-26381234
  • 54. CD4 COUNT 1481/19/2013 Samvad HIV Helpline 020-26381234
  • 55. Viral Load test of RNA PCR test  Commercial methods/kits in use:  Amplicor  B-DNA  NASBA  Preferable use the same kit/ method for repeat testing  Sample :3 ml in EDTA bulb  Viral load should be below detectable level after 6 months of effective ART1/19/2013 Samvad HIV Helpline 020-26381234
  • 56. Viral Load Monitoring  Where available, PCR or NASBA monitoring provide valuable information about ART effectiveness  Viral load should be checked:  Every 3-6 months when not on ART  6 months after starting ART  Every 6 -12 months in stable ART patients1/19/2013 Samvad HIV Helpline 020-26381234
  • 57. 1/19/2013 Samvad HIV Helpline 020-26381234
  • 58. Detection of Treatment Failure  Immunological failure: If the CD4 cell count fail to rise, increase < 25-50 in 1st yr, decline after previous increase; return to pre-ART baseline.  Viral load testing : Failure to achieve undetectable viral load within first 4-6 months of ART or rise after achieving a stable, low level of persistent virus  In cases of 1st line treatment failure, refer to HIV specialist.1/19/2013 Samvad HIV Helpline 020-26381234
  • 59. 1/19/2013 Samvad HIV Helpline 020-26381234
  • 60. 3 years after starting ART…..  Mayur has undetectable viral load, CD4 945 cells/cu mm  No toxicity  Mayur comes with Mayuri, his girl friend who wants to marry him , pretty well knowing his positive status. She is HIV negative.1/19/2013 Samvad HIV Helpline 020-26381234
  • 61. What would you ADVISE? 1. Its illegal. They cannot marry. 2. She would get infected 3. They won’t have an option of having children 4. They can marry provided they are ready to adopt safer methods.1/19/2013 Samvad HIV Helpline 020-26381234
  • 62.  HPTN O52: The effectiveness of antiretroviral drugs in reducing sexual transmission of HIV, by up to 96% in serodiscordant couples.  Prep trials ((iPrEx study, Partners PrEP, and TDF2, FEM- PrEP)  Circumcision : Male circumcision is associated with lower risk for HIV. May reduce female to male transmission( 50 to 60 %).1/19/2013 Samvad HIV Helpline 020-26381234
  • 63. Advise for discordant couplewho want to have a child  If male positive  Undetectable viral load  Sperm washing with IUI  Timed intercourse with Prep  If female positive  Undetectable viral load  IUI or Timed intercourse with Prep  ART at-least from 14th weeks of pregnancy, till she stops breast feeding her child  ART drugs for newborn for 4 to 6 weeks1/19/2013 Samvad HIV Helpline 020-26381234
  • 64. Mayur and Mayuri have a cutelittle baby girl  To test or not to test?  When to test and which tests to use? 1/19/2013 Samvad HIV Helpline 020-26381234
  • 65. Diagnosis in child born to HIV +vemother  After 18 months- Antibody tests (Elisa/Rapid/WB)  Before 18 months- Antigen test (HIV DNA PCR)1/19/2013 Samvad HIV Helpline 020-26381234
  • 66. Advise for PPTCT  ART throughout pregnancy  If viral load undetectable close to labour, no need of Caesarian section  Breast feeding advisable , but mother should continue ART  ART drugs for newborn for 4 to 6 weeks Chances of baby getting infection below 5% . AIDS FREE GENERATION1/19/2013 Samvad HIV Helpline 020-26381234
  • 67. Ending AIDS: AIDS 20121/19/2013 Samvad HIV Helpline 020-26381234
  • 68. Will AIDS really end?  Most unlikely.  No.s will fall for some time  It will restrict itself again among those who practice risky behaviour, eg People practicing risky behaviour; Sex workers; MSM  But complacency will bring it back again as our track record against any STD is poor.1/19/2013 Samvad HIV Helpline 020-26381234
  • 69. 2012: HIV IS STILL AN ISSUE  350 lakh people are infected with HIV worldwide  More than 96% are in low and middle income countries- in Asia and Africa  India has 25 lakh people infected with HIV- stands third after Sub Saharan Africa and Nigeria  Still 26 lakh new infections occur every year around the world and 18 lakh deaths from HIV/AIDS.  6000 young people are dying of HIV every day1/19/2013 Samvad HIV Helpline 020-26381234
  • 70. HIV estimates in India1/19/2013 Samvad HIV Helpline 020-26381234
  • 71. HIV prevalence among differentpopulation groups, 2007-2008 8 7.4 7.2 % 7 6 5.1 5 3.6 4 3.6 3 2.5 2 1 0.5 0 MSM IDU FSW STD Migrants Truckers ANC patients attendeesSource: HIV sentinel surveillance and HIV estimation in India, 2007-2008 1/19/2013 Samvad HIV Helpline 020-26381234
  • 72. So in HIV management, we as GPs are not extinct species1/19/2013 Samvad HIV Helpline 020-26381234
  • 73. Thank You1/19/2013 Samvad HIV Helpline 020-26381234