HIV Testing. HIV Symposium Patient Jane. Outline: 4/13/2010. What are your primary concerns for this patient?

Transcription

1 Patient Jane HIV Symposium 2010 Jess Fogler Waldura, MD Mina Matin, MD National HIV AIDS Clinicians Consultation Center San Francisco General Hospital University of California, San Francisco Referral from a family medicine resident to the Family HIV Clinic: Jane is a 24 yo with 2 children (7 yo and 5 mo girls). She recently found out that her FoB, who is in and out of prison, tested HIV positive in prison. His release date is in a couple of months and he ll be coming home. Her last exposure to him was 6 months ago prior to his most recent incarceration. What are your primary concerns for this patient? Outline: Testing Serodiscordant partners Mother to child transmission Prevention with positives HIV Basics Updated DHHS Guidelines (December 2009) Primary care for HIV-positive patients Post exposure prophylaxis HIV Testing 1

2 Some terminology CDC testing guidelines 2006 Opt-in: patient consents to HIV screening, usually in writing. Opt-out: patient notified that an HIV screening will be done unless s/he specifically refuses. CDC recommendations for patients in all health-care settings One-time opt-out HIV screening for all patients years old High risk patients screening at least annually Separate written consent for HIV testing not required Prevention counseling not required Source: CDC; CDC testing guidelines 2006 For pregnant women Opt-out HIV screening with routine 1 st trimester labs Repeat screening in 3 rd trimester in areas with high rate of HIV infection among pregnant women Rapid HIV test in labor if no documented prenatal test National HIV/AIDS Clinicians Consultation Center Warmline, PEPline, Perinatal HIV Hotline UCSF San Francisco General Hospital State HIV Testing Laws Compendium Descriptions of each state s HIV testing laws Definitions of commonly used terms Links to helpful resources HRSA AIDS ETC Program & Community Based Programs, HIV/AIDS Bureau & Centers for Disease Control and Prevention (CDC) 2

3 Patient Jane Which test to use? Jane was potentially exposed 6 months ago. Which test is indicated? Standard HIV antibody tests Screening test confirmatory test ELISA (EIA) IFA, Western blot (WB) Very sensitive and specific 30 days: 85-90% sensitive 8 weeks: 95-98%+ sensitive 6 months: approaching 100% sensitive Close to 100% specific at all time points Which test to use? The Window Period Rapid HIV Tests EIA antibody screening test Results in < 1hr % sensitive and specific Need confirmatory Western blot Acute HIV viral load: a bad test for screening Use to diagnose acute HIV False positives not uncommon Some people with HIV have undetectable viral load 3

4 The Window Period Acute vs Chronic HIV HIV antibody HIV RNA Acute HIV Negative (or indeterminate) Positive (usually >100,000) Chronic HIV Positive Positive (but can be undetectable) Patient Jane The Indeterminate test What f/u is now indicated? Per CDC: EIA at 6 wks, 3 mos, 6 mos post exposure (She tests negative) Jane is lucky. EIA screening tests Very, very sensitive May pick up some false positives Western blot tests Very specific evolve over weeks to months Need to see a full complement of bands to identify true HIV Indeterminate tests not uncommon 4

5 Western Blot Bands Western Blot Criteria for HIV The Indeterminate test Optional: send an HIV viral load test now If VL high = acute HIV If VL undetectable = no HIV If VL low =? (false positive?) Prevention with Positives Repeat HIV EIA and WB in 4 weeks If HIV+, should show evolution of bands 5

6 Prevention with Positives Exposures and associated risk MTCT IVDU Serodiscordant partners MTCT (~ 1/4 vaginal births) IVDU (~ 1/150 1/100 episodes) Sexual exposures stay tuned Estimated Number of Perinatally Acquired AIDS Cases in United States, by Year of Diagnosis, (Source: Centers for Disease Control and Prevention ) MTCT 6

7 Impact of prenatal HAART on MTCT Instrumentation intrapartum is associated with increased MTCT IVDU risk reduction Drug-Related Risk Behavior: Percent of HIV-infected IDU entering a methadone maintenance program who reported risk behavior within the prior month. 7

8 Factors Associated with High-Risk Sexual Behavior Serodiscordant Partners Partner notification: Risk of HIV transmission per sexual exposure: Mechanism of exposure Risk of transmission per episode of exposure Receptive rectal ~ 1/200 1/100 Receptive vaginal ~ 1/1000 1/500 Insertive vaginal ~ 1/2000 1/1000 Insertive rectal ~ 1/2000 1/1000 Receptive oral ~ 1/10,000 1/1000 Insertive oral Very low risk, difficult to quantify 8

9 Importance of STD Tx among serodiscordant partners Importance of STD Tx among serodiscordant partners Mucous membrane exposure and subsequent infection in relation to time post exposure Patient Jane Jane s HIV positive FoB, Jim, is now reintegrated back into the family. At Jane s encouragement he sees you and you begin Prevention with Positives efforts. Notification of partners. Discussion of risks of exposure for Jane. Treatment? 9

10 HIV Clinical Course HIV Basics Plasma HIV RNA 10,000,000 1,000, ,000 10,000 1, Primary Infection Seroconversion Intermediate Stage Plasma RNA Copies CD4 Cells AIDS CD4 Cell Count 1, Weeks Years Apx 2-3 Years Acute HIV and viral syndrome Signs Fever Rash Lymphadenopathy Pharyngitis Wt loss Symptoms Acute HIV Symptoms start 2-6 weeks after exposure High levels of viremia before antibody production starts Viral syndrome Rapid CD4 decline Opportunistic infections Myalgias / Arthralgias Fatigue Sore throat headache 10

11 Acute HIV treat now or wait? Chronic HIV- When to Start? Clinical trial information limited Potential benefits May slow disease progression by improving the immunologic and virologic set points Potential risks Exposure to ARV toxicity without clear benefit Unknown if can stop acute treatment after a time (e.g. 6 or 12 month) or if therapy needs to be lifelong. New guidelines 2009 Definitely start antiretrovirals in pts with: Hx of AIDS-defining illness, or CD4 count <350 cells/mm3 (AI) And in patients with: Pregnancy HIV- associated nephropathy Hepatitis B virus (HBV) coinfection when treatment of HBV is indicated (AIII). Chronic HIV- When to Start? Goals of Therapy Recommended, but weaker evidence CD4 counts between 350 and 500 cells/mm3 Still controversial CD4 counts >500 cells/mm3, Undetectable viral load Improved quality of life Less illness, death Prevent HIV transmission 11

12 Antiretroviral Medications HAART = highly active antiretroviral therapy ARV = Antiretroviral medication Usually a combination of 3 or more drugs 5 classes of ARVs now Abacavir (ABC) Didanosine (ddi) Emtricitabine (FTC) Lamivudine (3TC) Stavudine (d4t) Tenofovir (TDF) Zidovudine (ZDV) 3TC/ABC 3TC/ABC/ZDV 3TC/ZDV FTC/TDF Non-nucleoside Reverse Transcriptase Inhibitors Delavirdine (DLV) Efavirenz (EFV) Etravirine (ETR) Nevirapine (NVP) Antiretroviral Treatment Nucleoside Reverse Transcriptase Inhibitors Multiple Class Combinations EFV/FTC/TDF Protease Inhibitors Atazanavir (ATV) Darunavir (DRV) Fosamprenavir (FPV) Indinavir (IDV) Lopinavir/ritonavir (LPV/RTV) Nelfinavir (NFV) Ritonavir (RTV) Saquinavir (SQV ) Tipranavir (TPV) Entry Inhibitors Enfuvirtide (ENF) Maraviroc (MVC) Integrase Inhibitors Raltegravir (RAL) Integrase Inhibitors Starting ARV Regimens Protease Inhibitors TDF/FTC (2 NRTIs) + one agent from another class Drug Sites of Action Entry Inhibitors Reverse Transcriptase Inhibitors NRTI NNRTI NNRTI-based Regimen EFV + TDF/FTC PI-based Regimens ATV/r + TDF/FTC DRV/r + TDF/FTC INSTI-based Regimen RAL + TDF/FTC Twice daily regimen Drug-drug interactions 12

13 Adverse Drug Reactions Common Drug-drug Interactions All ARVs are toxic to the liver Most can cause GI upset Remember: AZT: anemia ABC: hypersensitivity reaction NNRTI: rash, psych PIs: metabolic syndrome (lipids, glucose) Anti-hypertensives Anti-convulsants Psychiatric medications Warfarin Hormonal Contraceptives Proton Pump Inhibitors Cholesterol-lowering agents Viagra and friends Intake visit: Primary Care for Patients with HIV olabs: HIV Viral Load CD4 (will inform stage of HIV disease) HIV resistance testing (Genotype) ojim s results: Wild-type virus No resistance mutations detected 13

14 Patient Jim Jane is now negative, and her partner is HIV positive. Jim s results: HIV VL 100,000 with CD What to do? You discuss the options with Jane and Jim. Jim wants to protect Jane. In addition to using condoms correctly and consistently, he opts for treatment and believes he can commit to life-long HAART. Benefits of Treatment Reducing HIV-associated morbidity and mortality Decreasing non-aids related complications Reducing HIV-associated inflammation Decreasing sexual transmission of HIV Risks of Treatment Drug toxicity from long-term use Potential development of antiretroviral resistance Cost (?) Patient Jane Virologic Response on HAART Jim starts Atripla (EFV + TDF/FTC). Baseline labs: HIV VL 100,000 At 4 wks of HAART: VL 1000 At 8 wks of HAART: VL undetectable (< 50 copies/ml) He denies missed doses. You provide adherence counseling, emphasize concern for resistance with suboptimal adherence and schedule him for f/u in 4 wks. This graph shows desired virologic response to HAART, with HIV RNA levels decreasing to less than 50 copies/ml within 16 weeks. 14

15 > 500 Health Care Maintenance < 200 Candida Cx CA Papsmears AIDS defining Conditions Primary Prophylaxis for Pneumocystis Pneumonia TB PCP PNA PPD / IGRA, Tx LTBI Pneumococcal vaccine 15

16 Toxoplasma gondii Life Cycle and Human Infection PCP Toxo PCP ppx CD4 < 200 Toxo ppx CD4 < 100 Septra Primary Prophylaxis for Toxoplasma Encephalitis MAC MAC ppx CD4 < 50 Azithromycin Q wk 16

17 Primary Prophylaxis for Disseminated MAC CMV Annual Retinal Exam CD4 < 50 Vaccinations October 2009 FDA approved for males 17

18 Recommended dose, route, and schedule for hepatitis A vaccines and hepatitis B vaccines: Acknowledgements for previous slide: 20mcg/mL 40mcg/mL 2 ml 1 ml History at intake: ohistory needed to inform future infectious complications past and current sexual practice HBV RPR GC/CT HPV past or current IVDU? h/o TB: personal or contact history? animal contact? h/o chicken pox, zoster? serologies h/o residence in endemic areas for fungal organisms? Other labs at intake: oqft (IGRA) or PPD (TST) orpr or VDRL o GC/CT (urine) ohav IgG o HBsAg, HBsAb, HBcAb ohcv IgG o Toxoplasma IgG ovzv IgG ocmv IgG 18

19 Patient Jim Jim starts Atripla. Baseline labs: HIV VL 100,000 At 4 wks of HAART: VL 100 At 8 wks of HAART: VL undetectable (< 50 copies/ml) Adherence counseling provided, he denies any missed doses. Jim didn t show up for 16 wk f/u visit and labs At 24 wks he makes a f/u appt. He and Jane have had stress with the kids at home and they ve lost their jobs. VL is now 10,000 He admits to poor adherence. It s been 2 months since his last dose of Atripla. Benefits of Treatment Reducing HIV-associated morbidity and mortality Decreasing non-aids related complications Reducing HIV-associated inflammation Decreasing sexual transmission of HIV Risks of Treatment Drug toxicity from long-term use Potential development of antiretroviral resistance Cost (?) Post-exposure Prophylaxis for HIV Exposure 19

20 What Is An Exposure? a percutaneous injury or contact of mucous membrane or non-intact skin with blood, tissue or other body fluids that are potentially infectious. What Isn t An Exposure? General Principles BBP transmission does not occur Through intact skin Via inhalation Updated Public Health Service Guidelines for the management of Occupational Exposures to HBV, HCV and HIV and Recommendations for PEP. June 29, Beltrami, et al. ClinMicroRev July 2000 Definitely Infectious Body Fluids Blood Semen Pre-ejaculate Vaginal secretions Any visibly bloody fluid Non-Infectious Body Fluids Feces Urine Sputum or nasal secretions Saliva (except HBV) Sweat Tears Vomitus If Not Visibly Bloody 20

21 Potentially Infectious Body Fluids Cerebrospinal fluid Synovial fluid Pleural fluid Peritoneal fluid Pericardial fluid Amniotic fluid Pus Is PEP Needed? Two Components of Risk Nature of exposure Source patient status Occupational Transmission Risk Estimates Percutaneous 0.3% Mucocutaneous 0.09%? Conjunctival exposures riskier HBV percutaneous % HCV percutaneous 1.8% MMWR 6/29/01 Non-Occupational Transmission Risk Estimates Exposure Type HIV HCV HBV Receptive anal 0.1 5%?/Very low High Insertive anal < 0.06%?/Very low High Receptive vaginal %?/Very low High Insertive vaginal %?/Very low High Receptive oral (MSM) < 0.06%?/Very low High Insertive oral? 1 case report?/very low High WSW Case reports?/very low High Needle sharing High Very high Very high 21

22 Exposure Severity Affects Transmission Risk Percutaneous exposure Type of needle Superficial vs. deep puncture Visible blood on device Device used in intravascular space Device used recently vs. remotely Mucous membrane and non-intact skin exposure Volume of infectious fluid Duration of contact Source Patient Factors Influence HIV Transmission Risk If source is HIV+ Viral load Stage of disease If HIV status is unknown Risk behavior history Signs/symptoms suggestive of primary HIV infection Prior testing history If source is unknown Background prevalence Occupational Exposure Percutaneous MMWR Vol. 54,

23 Occupational Exposure Mucous Membrane MMWR Vol. 54, 2005 Non-Occupational Exposure Substantial Exposure Risk Negligible Exposure Risk 72 hrs since exposure >72 hrs since exposure HIV+ SP SP of unknown HIV status PEP for HIV: General Principles Most exposures do not result in HIV infection, even without PEP Antiretroviral medications are not benign Potential benefits of PEP must be weighed against potential risks npep recommended Case-by-case determination npep not recommended 23

24 When Should PEP Be Started? Start as soon as possible Efficacy decreases as time passes But time when efficacy completely lost is unknown < 72 hours Do not delay PEP until source evaluation is complete Make best empiric choice Reassess and adjust later PEP for HIV: Regimen Selection Basic regimen (2 drug) Expanded regimen (3 drug) Other Basic PEP Regimens Expanded PEP Regimens Usual AZT+3TC =Combivir one tab PO BID or TDF+FTC = Truvada one tab PO once daily Basic regimen PLUS: Occ and non-occ exposures: Lopinavir/r (Kaletra ) 2 tabs PO BID Non-occ exposures Efavirenz 600mg QD (can use as combination with TDF/FTC in Atripla ) 24

25 Antiretroviral Toxicity Monitoring Baseline LFTs (everyone) CBC w/diff + platelets (if AZT) BUN/Creatinine (if TDF) Repeat at 2 weeks Post-Exposure Follow-Up HIV antibody testing Baseline, 6 wks, 3 mos, 6 mos HCV antibody testing & ALT Baseline, 3 mos, 6 mos HCV RNA: consider at 4-6 weeks for earlier diagnosis HBV testing As clinically indicated Acknowledgements: National HIV/AIDS Clinicians Consultation Center UCSF San Francisco General Hospital National HIV/AIDS Clinicans Consultation Center Warmline (800) National HIV Telephone Consultation Service Consultation on all aspects of HIV testing and clinical care PEPline (888) National Clinicians Post-Exposure Prophylaxis Hotline Recommendations on managing occupational exposures to HIV and hepatitis B & C Perinatal HIV Hotline (888) National Perinatal HIV Consultation & Referral Service Advice on testing and care of HIV-infected pregnant women and their infants Referral to HIV specialists and regional resources HRSA AIDS ETC Program & Community Based Programs, HIV/AIDS Bureau & Centers for Disease Control and Prevention (CDC) 25