The New Patient Entering HIV Care:

Transcription

1 The New Patient Entering HIV Care: What You Need to Know and Do in 2013 Rajesh T. Gandhi, M.D. Disclosures: grant support from Tibotec (now Janssen), Abbott and Viiv

2 Learning Objectives Complete a plan to comprehensively evaluate a patient with newly diagnosed HIV infection. Apply current guidelines to the assessment of a patient with newly diagnosed HIV infection. There are no off-label discussions included in this presentation.

3 Case 69 yo M is tested for HIV as part of a life insurance evaluation HIV ELISA and Western blot are reactive No previous HIV testing

4 Testing for HIV HIV EIA. If +, confirmatory western blot (WB) False-pos. EIA: ~1/250,000 Risk factors: autoimmune disease, MS, parity, recent immunization, IDU, HIV vaccine recipient False-negative EIA or WB Agammaglobulinemia Technical problem Window (median 4 wks) To close the window, new testing algorithm: 4 th gen. Ag/Ab If pos., HIV-1/-2 differentiation assay If neg., HIV RNA Branson B M, Stekler J D JID. 2012

5 Linkage to HIV Care: More to be Done In U.S., only 40% of all HIV+ persons are both aware of their infection and receiving ongoing care Only 25% have a suppressed virus load Without improvements, 1.2 million new infections anticipated in US over next 20 yrs at estimated cost of $450 billion MMWR, Dec. 2, 2011; Hall et al, International AIDS Conference, 2012, abstract FRLBX05 Have a suppressed viral load

6 Approach to the HIV+ Patient: 4 Steps Step 1: History and Examination Step 2: Lab tests Step 3: Antiretroviral therapy and, if indicated, opportunistic infection prophylaxis Step 4: Preventive care

7 History Step 1 Risk behaviors Symptoms Exposures: TB, endemic fungi, sexually transmitted infection (STIs) Family history, e.g. of cardiac disease (MI in 1 st degree relative (male <55 yo, female <65 yo)) Tobacco use Medications, including alternative meds, illicit drugs

8 Common Drug Interactions PPI, H2 blockers reduce atazanavir and rilpivirine absorption PIs increase sildenafil & other PDE5i levels Efavirenz decreases methadone and buprenorphine levels (40-50%); atazanavir increases buprenorphine levels (66%) PIs increase IV midazolam levels but may be given safely for procedural sedation in outpatients with close monitoring Backman E, HIV Med, 2013 Useful site:

9 Drug Interactions: Exogenous Steroids Injectable steroids: levels increased by PIs 10% of patients on PIs who received a steroid injection developed clinical evidence of steroid excess or adrenal insufficiency (Hyle E, submitted) Fluticasone 1 & budesonide 2 levels increased by PIs Cushing s syndrome, adrenal insufficiency reported Beclomethasone appears to be a safer alternative 3 1 DHHS guidelines for use of antiretroviral agents in HIV-1-infected adults and adolescents. Feb 12, Boyd S, CROI 2012, Abstract N-139

10 Physical Exam Step 1 Skin Fundoscopic exam. Refer to ophthalmologist if CD4 cell count <50 Oropharynx Lymph nodes Anogenital exam Rectal exam; anal, prostate masses Cervical pap Consider anal cytology. If abnormal, highresolution anoscopy, biopsy of visible lesions

11 Dermatologic Findings Herpes Zoster Prurigo nodularis Proximal subungal oncyhomycosis Images courtesy of Drs. Anisa Mosam & Richard Johnson

12 Dermatologic Findings: Kaposi s Sarcoma Image courtesy of Dr. Richard Johnson

13 Oropharyngeal Findings Aphthous ulcers Oral candidiasis Oral hairy leukoplakia Medscape

14 Approach to the HIV+ Patient: 4 Steps Step 2 Step 1: History and Examination Step 2: Lab tests Step 3: Antiretroviral therapy and, if indicated, opportunistic infection prophylaxis Step 4: Preventive care, including vaccines

15 Lab Evaluation: General Tests Chemistries, BUN/Cr, LFTs CBC/diff Fasting lipids and glucose Urinalysis Serologies: toxoplasma, CMV, varicella IgG, hepatitis (A, B, C), syphilis PPD or interferon-gamma release assay G6PD: blacks; Mediterranean, India, SE Asia men GC, chlamydia: if sexually-active DHHS guidelines for use of antiretroviral agents in HIV-1-infected adults and adolescents. Feb 12, Aberg J, CID, 2009

16 HCV Testing HCV Antibody (Ab) Sexual transmission of HCV in HIV+ MSM is an increasing problem High-risk patients should have serial screening: annual HCV Ab or every 3-month LFTs If HCV Ab negative but suspicion high (e.g. unexplained elevated LFTs, recent exposure), check HCV RNA Linas B et al, CID, 2012

17 Lab Evaluation: HIV-specific Tests CD4 cell count HIV RNA ( viral load or VL) HIV drug resistance test (genotype) HLA-B5701: if considering abacavir Tropism test (phenotypic or genotypic): if considering maraviroc DHHS guidelines for use of antiretroviral agents in HIV-1-infected adults and adolescents. 2/12/13.

18 CD4 Cell Count and Percentage CD4 cell count = WBC count x % lymphs x % CD4 Variability of ~30% in absolute count CD4 cell count CD4 percentage % % <200 <14% Count affected by changes in WBC count or % lymphs Leukopenia: liver disease (hypersplenism/hcv) 1,2, acute illness, myelosuppressive meds (e.g. IFN-a) Misleadingly high CD4 cell counts: splenectomy and HTLV-1 infection 1. McGovern, CID, 44:431; 2. Gandhi, CID 44:438.

19 How often do you check CD4 counts in stable HIV+ patients on ART? A. Every 3 months B. Every 6-12 months C. Never

20 Monitoring: CD4 Cell Count DHHS guidelines recommend testing every 6-12 mo. in patient with stable HIV infection on ART 1 Even less frequent testing reasonable Pts with VL <200 and CD4 >300: 99% likelihood that CD4 will stay >200 2 Substantial cost saving 1 DHHS guidelines for use of antiretroviral agents in HIV-1- infected adults and adolescents. 2/12/ Gale, CID, 2013

21 Resistance Testing Patient Resistance Test 1 Newly Diagnosed or Treatment Naive Virologic Failure to 1 st or 2 nd Lines of Therapy Genotype (Transmitted Resistance 16% 2 ; NNRTI (8%); NRTI (7%); PI (4.5%) Genotype (Integrase genotype if failing INSTI) Suspected Complex Resistance Phenotype and Genotype Stanford HIV Drug Resistance: 1 DHHS guidelines for use of antiretroviral agents in HIV-1-infected adults and adolescents. 2/12/ Kim D et al, CROI 2013, Abs #149

22 Approach to the HIV+ Patient: 4 Steps Step 1: History and Examination Step 2: Lab tests Step 3: Antiretroviral therapy and, if indicated, opportunistic infection prophylaxis Step 4: Preventive care, including vaccines

23 Case - Continued 69 yo MSM with newly diagnosed HIV Past medical history Gastroesophageal reflux disease (GERD) Allergic rhinitis Hyperlipidemia (not on therapy) Medications: omeprazole, fluticasone Family History: father died of MI in his 60s Smokes 1 ppd Exam: BP normal. BMI 40. Peri-anal condyloma Cr: 0.5. Total cholesterol 210, LDL 165, HDL 35, TG 200 CD4 cell count 181, HIV RNA 178,000 HIV genotype: no resistance mutations

24 Case - Continued 69 yo MSM with newly diagnosed HIV Past medical history Gastroesophageal reflux disease (GERD) Allergic rhinitis Hyperlipidemia (not on therapy) Medications: omeprazole, fluticasone Family History: father died of MI in his 60s Smokes 1 ppd Exam: BP normal. BMI 40. Peri-anal condyloma Cr: 0.5. Total cholesterol 210, LDL 165, HDL 35, TG 200 CD4 cell count 181, HIV RNA 178,000 HIV genotype: no resistance mutations

25 Managing Dyslipidemia Screening: fasting lipids At HIV diagnosis Start of ART Change of ART Every 6-12 months Lipid management: NCEP guidelines 1, HIV lipid guidelines 2 New guidelines for general population expected this year Statin Level with PI Pravastatin -- Atorvastatin Simvastatin Lovastatin Rosuvastatin Use Safe (caution with DRV/r) Use with caution/low dose 20 mg/d atorva with DRV 3 10 mg/d rosuva with ATV 3 Contraindicated 1 Aslangul AIDS 2010;24:77-83; ATPIII JAMA 2001;285: Dube CID 2003;37: ; 3

26 Opportunistic infection prophylaxis PCP prophylaxis (trim/sulfa DS daily) if: CD4 cell count <200 (CD4 percentage <14) History of thrush MAI prophylaxis (azithromycin 1200 mg weekly) if CD4 cell count <50 Aberg J, CID, 2009 MMWR;58 (No. RR-4) April 10, 2009:

27 Antiretroviral Therapy ART is recommended for all HIV+ patients to reduce the risk of disease progression and for prevention of HIV transmission Stayed tuned for upcoming talk on When, What and How to Start by Monica Gandhi DHHS guidelines for use of antiretroviral agents in HIV-1-infected adults and adolescents. Feb 12,

28 Which of these regimens would not interact with his current medications? Current meds: omeprazole, fluticasone A. Atazanavir/ritonavir and TDF/FTC B. Cobicistat/elvitegravir and TDF/FTC C. Raltegravir and TDF/FTC D. Rilpivirine and TDF/FTC

29 Regimen Choice and Drug Interactions Omeprazole: impairs atazanavir & rilpivirine absorption. Rilpivirine should not be used; atazanavir should be avoided or used with caution (staggered dosing) 1 Fluticasone: drug interaction possible with PIor cobicistat-containing regimens 1,2 1 DHHS guidelines for use of antiretroviral agents in HIV-1-infected adults and adolescents. Feb 12, andaidsactivities/ucm htm

30 Approach to the HIV+ Patient: 4 Steps Step 1: History and Examination Step 2: Lab tests Step 3: Antiretroviral therapy and, if indicated, opportunistic infection prophylaxis Step 4: Preventive care

31 Survival Preventive Care: Smoking Cessation Counseling In HIV+ patients, smoking is more deadly than HIV Loss of life-years associated with smoking is twice as high as that associated with HIV In HIV+ patients, 60% of deaths attributable to smoking Helleberg, CID, 2012

32 Preventive Care: Aspirin (ASA) USPTF recommends ASA in men ages and in women when CVD benefit outweighs risk of GI bleeding 1 Only 17% of patients in UAB HIV clinic who met criteria prescribed ASA 2 Recent study questions whether ASA is effective at reducing MI in HIV+ pts 3 Calculate the Framingham risk score for your patient Risk level at which CVD benefit exceeds GI harms Men 10-yr CHD risk Women 10-yr stroke risk Age % Age % Age % Age % Age % Age % Not taking NSAIDs; no upper GI pain; no history of GI ulcers 1 uspsasmi.htm 2 Burkholder, CID, Suchindran, CROI, 2013 hp2010.nhlbihin.net/atpiii/calculator.asp

33 Vaccinations in HIV+ Patients Recommended if other risk factors present ACIP. Recommended Adult Immunization Schedule: US Annals of Int Med. 2013

34 Influenza vaccine Influenza vaccine yearly High dose vaccine (Fluzone High-dose, 60 mcg) more immunogenic than standard dose (15 mcg) Not known whether it s more effective; not yet recommended by ACIP Standard Dose (n = 93) High Dose (n = 97) P *Seroprotection H1N1 87% 96% H3N2 92% 96% B 80% 91% 0.03 Seroconversion McKittrick N, et al. Annals of Int Med, 2013 H1N1 59% 75% 0.018

35 Vaccinations Varicella vaccine if IgG neg and CD4 count >200 Immigrants from tropical areas more likely to be VZV IgG-negative: 5-10% susceptible at age 30 HPV vaccine through age 26 for females (HPV2 or HPV4) and males (HPV4) Ongoing ACTG study of HPV4 in HIV+ MSM and women >26 yo Merrett, CID, 2007 ACIP. Recommended Adult Immunization Schedule: US Annals of Int Med, Feb. 5, 2013

36 HBV vaccination All HIV+ patients should be screened for HBV infection (HBsAg, anti-hbs, +/- anti-hbc) HBsAg a-hbs a-hbc Vaccinate Yes If not previously anti-hbs+, check HBV DNA; if negative, consider vaccination 1 If vaccine series interrupted, does not need to be restarted 2. Give 2 nd & 3 rd doses at least 8 wk apart Check anti-hbs 1-2 mo. after vaccine series 1 Gandhi et al, JID (2005) 191:1435; 2

37 HBV Vaccine Non-Responders ART improves response rates In patients with CD4 count >350, those on ART had higher likelihood of responding than those not on ART 1 Double-dose (DD) vaccine 50% of non-responders responded after reimmunization with DD vaccine 2 In randomized study of primary vaccination, higher response with 4-doses of DD (0, 1, 2 and 6 m) than with 3 doses standard dose (0, 1, 6 m) 3 : 82 vs. 65% 1 Landrum, Vaccine (2009) 27: De Vries-Sluijs, JID (2008) 197: Launay, JAMA, 2011

38 Zoster vaccine (ZV) in HIV+ Patients ZV recommended for non-hiv patients 60 yo In an ACTG study of HIV+ patients on ART with CD4 cell counts >200 and VL <50: ZV safe; no rashes related to vaccine strain ZV elicited antibody responses; T cell responses being evaluated ZV not yet recommended by ACIP for HIV patients Benson C, Lennox J, ACTG 5247 team. CROI 2012, Abstract # 96

39 Pneumococcal Vaccine Invasive pneumococcal disease in HIV+ patients: 173/100,000 (more than 20x higher than for adults without high-risk conditions) ACIP recommends PCV-13 for HIV+ adults History No Previous Pneumococcal Vaccination Previously Received PPSV23 Recommendation PCV-13 followed by PPSV-23 at least 8 wks later PCV-13 1 yr after last PPSV23 Five years later, revaccinate with PPSV-23 (should be >8 wks after PCV-13) ACIP. Recommended Adult Immunization Schedule: US Annals of Int Med, Feb. 5, 2013

40 Approach to HIV+ Patient: 4 Steps Step 1: History and Examination 69 yo M with HIV GERD, allergic rhinitis Medications: omeprazole, fluticasone (interact with several commonly used regimens) BP normal. Obese

41 Step 2: Lab tests Cr: 0.5 Approach to HIV+ Patient: 4 Steps Fasting lipids: total chol. 210, LDL 165, HDL 35 CD4 cell count 181, HIV RNA 178,000 HIV Genotype: no resistance mutations Step 3: ART and OI prophylaxis ART and PCP prophylaxis indicated Requests one-pill once-daily regimen; expresses concern about taking efavirenz

42 Approach to HIV+ Patient: 4 Steps Step 4: Preventive health Anti-HBs & HBsAg negative immunize after he is stable on ART Smoker Framingham risk score: 18%

43 Case Bringing it all back home Trim/sulfa initiated for PCP prophylaxis Initiated TDF/FTC/cobicistat/elvitegravir Fluticasone changed to beclomethasone Vaccines: influenza (standard dose); PCV-13 followed by PPSV-23; HBV vaccine Hyperlipidemia: lifestyle changes; if lipids remain elevated, atorvastatin or rosuvastatin Started on aspirin Smoking cessation and wt. loss counseling

44 Thank you for your attention!