Initial Approach to the Patient Newly Diagnosed with HIV

Transcription

1 Activity Code TM809

2 Initial Approach to the Patient Newly Diagnosed with HIV Rajesh T. Gandhi, M.D. Massachusetts General Hospital Disclosures: grant support from Tibotec (now Janssen), Abbott and Viiv

3 Learning Objectives Upon completion of this presentation, learners should be better able to: Describe the initial evaluation of the newlydiagnosed HIV+ patient Discuss when, what and how to start ART Summarize preventive care for the HIV-infected patient

4 Case 69 yo man who has sex with men (MSM) is tested for HIV as part of a life insurance evaluation HIV ELISA and Western blot are positive No previous HIV testing

5 Approach to the HIV+ Patient: Step 1: History, Examination and Lab Tests Step 2: Opportunistic infection prophylaxis (if indicated)* Step 3: Antiretroviral therapy: when and what to start; how to monitor* Step 4: Preventive care 4 Steps *More on these in upcoming sessions

6 Aberg J et al, CID, Nov. 13, 2013

7 Step 1: History Step 1 Risk behaviors; approximate date of infection Symptoms Exposures: tuberculosis, endemic fungi, sexually transmitted infection (STIs) Psychiatric history (prevalence of depression twice as high in HIV+ women as in infected men) Family history: cancer; myocardial infarction in 1 st degree relative (male <55 yo, female <65 yo) Tobacco, alcohol, illicit drug use; sexual history Medications, including alternative meds

8 Physical Exam Step 1 Skin Fundoscopic exam ophthalmologist if CD4 <50 Oropharynx Lymph nodes consider biopsy if dominant, focal node or rapid enlargement Anogenital exam Cervical pap Rectal exam; anal, prostate masses

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

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

11 Oropharyngeal Findings Aphthous ulcers Oral candidiasis Oral hairy leukoplakia Source: Medscape

12 Lab Tests Routine tests Screening tests for infection HIV-specific tests

13 Which test should you order in all HIV+ patients? A. G6PD B. HIV tropism C. HLA-B5701 D. HIV genotype E. HIV phenotype 20% 20% 20% 20% 20% A. B. C. D. E. 8

14 Lab Evaluation: Routine Tests Chemistries, BUN/Cr, liver function tests CBC/diff Fasting lipids and glucose G6PD: blacks; males from Mediterranean, India, SE Asia Urinalysis (U/A) DHHS guidelines for use of antiretroviral agents in HIV-1-infected adults and adolescents. Feb 12, Aberg J et al, CID, 2013

15 Lab Evaluation: Screening for Infection Serologic testing for infections that can reactivate: toxoplasma IgG, CMV IgG Hepatitis serologies (A, B, C) PPD or interferon-gamma release assay (IGRA) If negative and patient s CD4 count is <200, repeat PPD or IGRA after immune reconstitution STI screening: syphilis serology; gonorrhea (GC), chlamydia (CT) DHHS guidelines for use of antiretroviral agents in HIV-1-infected adults and adolescents. Feb 12, Aberg J et al, CID, 2013

16 HCV Testing HCV antibody (Ab) at care initiation and then annually for high-risk MSM, IDU Increasing sexual transmission of HCV in HIV+ MSM At Fenway Health in Boston, HCV incidence 1.6/100 person-yrs If HCV Ab negative but suspicion high (elevated LFTs, recent exposure), check HCV RNA Window period until seroconversion may be up to 12 wks Garg S et al, CID, 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 8% of US whites 1 ~2% of US African-Americans and Hispanics 1 Tropism test (phenotypic or genotypic): if considering maraviroc DHHS guidelines for use of antiretroviral agents in HIV-1-infected adults and adolescents. 2/12/ E Phillips, CID, 2006

18 Resistance Testing Patient Resistance Test 1 Newly Diagnosed or Treatment Naive Virologic Failure to 1 st or 2 nd Lines of Therapy Genotype (RT and PR) (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 Kim D et al, CROI 2013, Abs #149

19 Which test should you order in all HIV+ patients? A. G6PD B. HIV tropism C.HLA-B5701 D.HIV genotype E. HIV phenotype

20 Approach to the HIV+ Patient: 4 Steps Step 2 Step 1: History, Examination and Lab Tests Step 2: Opportunistic infection prophylaxis (if indicated)* Step 3: Antiretroviral therapy and monitoring Step 4: Preventive care, including vaccines *More on this topic in upcoming sessions

21 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 Smokes 1 ppd Exam: Blood pressure normal. Body mass index 40. Cr 0.5. Total cholesterol 210, LDL 165, HDL 35 CD4 count 181, HIV RNA 178,000 HIV genotype: no resistance mutations HLA-B5701 positive

22 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 Smokes 1 ppd Exam: Blood pressure normal. Body mass index 40. Cr 0.5. Total cholesterol 210, LDL 165, HDL 35 CD4 count 181, HIV RNA 178,000 HIV genotype: no resistance mutations HLA-B5701 positive

23 Pneumocystis pneumonia (PCP) prophylaxis (trim/sulfa DS daily) if: CD4 count <200 (CD4 percentage <14) History of thrush Mycobacterium avium complex prophylaxis (azithromycin 1200 mg weekly) if CD4 count <50

24 Approach to the HIV+ Patient: 4 Steps Step 3 Step 1: History, Examination and Lab Tests Step 2: Opportunistic infection prophylaxis (if indicated)* Step 3: Antiretroviral therapy: when and what to start; how to monitor* Step 4: Preventive care, including vaccines *More in tomorrow morning s session: Treatment Guidelines Update

25 When to Start ART recommended for all HIV+ individuals. Strength of recommendation varies based on CD4 count: CD4 Cell Count >500 Recommendation AI AII BIII AI: strong recommendation, data from randomized clinical trials AII: strong recommendation, non-randomized or observational cohort studies BIII: moderate recommendation, expert opinion Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. Available at US DHHS Guidelines, January 2011.

26 What to start DHHS guidelines NNRTI + 2 NRTI PI + 2 NRTI May 1, 2014 Recommended Regardless of VL, CD4 count Efavirenz/tenofovir/emtricitabine Darunavir/ritonavir + tenofovir/emtricitabine Atazanavir/ritonavir + tenofovir/emtricitabine Raltegravir + tenofovir/emtricitabine INSTI + 2 NRTI Elvitegravir/cobicistat/tenofovir/emtricitabine Dolutegravir + tenofovir/emtricitabine Dolutegravir + abacavir/lamivudine

27 Recommended but only for patients with pretherapy VL <100,000 NNRTI- Regimen What to start DHHS guidelines May 1, 2014 Rilpivirine/tenofovir/emtricitabine* Efavirenz + abacavir/lamivudine * PI Regimen Atazanavir/ritonavir + abacavir/lamivudine * Only if patient s CD4 count is >200

28 Choosing an Antiretroviral Regimen: Two decisions Step 1: Decide which NRTI to use Step 2: Decide on which drug to use within the NNRTI, PI or INSTI class

29 TDF/FTC or ABC/3TC ABC/3TC TDF/FTC NRTI PROS CONS TDF/FTC Single pill options available (with EFV, RPV, EVG/cobi) Active vs. HBV Nephrotoxicity (particularly in those receiving other nephrotoxic agents, PIs) Increased loss of bone mineral density ABC/3TC Not nephrotoxic When combined with DTG, superior to TDF/FTC/EFV Coformulation with DTG may be available this year Must confirm HLA-B5701 negative VL >100 K: more virologic failures with ABC/3TC than TDF/FTC when used with ATV/r or EFV Some studies, but not all, show association with MI

30 Individualizing Therapy: Choosing Between NRTIs Factor Renal Disease CV disease Hyperlipidemia Bone disease Pre-ART VL >100 K Preferred Therapy ABC/3TC Possibly TDF/FTC Possibly TDF/FTC Possibly ABC/3TC If using with EFV or ATV/r TDF/FTC Cost 3TC patent expired in 2010 ABC patent expired in 2012

31 Individualizing Therapy: Choosing a 3 rd drug: NNRTI, PI, INSTI Factor Need to start ART before resistance results known (acute HIV, OI) or uncertain adherence Pre-ART VL >100 K, CD4<200 Food requirements Considerations Drug with low rate of TDR, high genetic barrier to resistance: PI, possibly DTG Avoid RPV EFV: empty stomach RPV with meal (>400 kcal); EVG/cobi/TDF/FTC: with food DTG: no food requirements Drug-drug interactions Acid-lowering therapy Polyvalent cations CYP3A4-metabolized meds Caution with or avoid RPV, ATV/r Careful with INSTIs Avoid PIs, cobi (CYP inhibitors)

32 Choosing 3 rd drug: NNRTI, PI, INSTI (cont.) Factor Comorbidities Depression Dyslipidemia Considerations Avoid EFV Favor RPV, DTG, EVG/cobi, RAL Preference for SPC EFV, RPV, EVG/cobi (with TDF/FTC) Future: DTG with ABC/3TC; PI SPC Cost/copayments EFV to come off patent soon Possibly fewer co-pays with SPCs SPC = Single-pill combinations

33 How should you monitor a patient receiving ART? 33

34 Monitoring after Starting ART Chemistries, BUN/Cr, LFTs: wk 2-8 after starting ART, then every 3-6 mo. CBC/diff: every 3-6 mo. Fasting glucose or HbA1c: every 3-6 mo. if previously abnormal; every 12 mo. if normal Lipids: if abnormal, every 6 mo; normal: every 12 mo. U/A annually; every 6 mo. if receiving tenofovir DHHS guidelines, ; Aberg J et al, CID, 2013

35 Monitoring after Starting ART HIV RNA 2-4 wks after starting ART; then every 4-8 wks until undetectable First 2 yrs of ART: every 3-4 mo. After 2 yrs of virologic suppression, can extend to every 6 mo CD4 count: 3 mo. after initiating ART First 2 yrs of ART: every 3-6 mo After 2 yrs of virologic suppression, CD : every 12 mo.; CD4 >500, optional DHHS guidelines, ; Aberg J et al, CID, 2013

36 Approach to the HIV+ Patient: 4 Steps Step 4 Step 1: History, Examination and Lab Tests Step 2: OI prophylaxis (if indicated) Step 3: Antiretroviral therapy Step 4: Preventive care Screening for cervical and anal cancer Endocrine issues Cardiovascular disease prevention Vaccines

37 Screening for Cervical and Anal Cancer (CA) Cervical and anal cancer incidence much higher in HIV+ patients than in the general population Cervical CA Anal CA Robbins H et al, AIDS, 2014

38 Cervical cytology Cervical pap at initiation of care, repeat at 6 mo. and then annually if normal In women with high CD4 counts, consider increasing screening interval to 3 years if both Pap and HPV testing are negative Aberg J et al, CID, Nov. 13, 2013

39 Anal cytology Recommended by HIVMA/IDSA guidelines for: Men who have sex with men (MSM) Women with history of receptive anal intercourse or abnormal cervical pap All patients with genital warts If abnormal high-resolution anoscopy, biopsy of visible lesions Aberg J et al, CID, 2013

40 Endocrine Issues Bone densitometry in postmenopausal women and men age 50 years Fasting blood glucose and/or HbA1c HbA1c >6.5% twice: diabetes mellitus (DM) HbA1c cutoff of 5.8% may improve sensitivity for DM diagnosis in patients on ART Males with fatigue, weight loss, loss of libido, erectile dysfunction or reduced bone mineral density check morning (before 10 AM) serum testosterone (T) Calculate free T from total T and sex-hormone binding globulin ( Free testosterone by equilibrium dialysis Aberg J et al, CID, 2013

41 Cardiovascular Disease Prevention: Lipid Management Screening: fasting lipids At HIV diagnosis Start of ART Change of ART Every 6-12 months Statin Level with PI Pravastatin -- Atorvastatin Simvastatin Lovastatin Use Rosuvastatin Lipid management Beware of drug interactions between statins and PIs or cobicistat Safe (caution with DRV/r) Use with caution/low dose 20 mg/d atorva with DRV 1 10 mg/d rosuva with ATV 1 Contraindicated 1

42 Lipid Management 2013 AHA guidelines for general population LDL-C >190, DM, 7.5% risk of atherosclerotic CV disease statins No lipid targets Risk calculator controversy How to apply to HIV+ pts is uncertain Stone NJ et al, Circulation, 2013

43 A Walk in the Park? Italian study on effect of walking in 50 sedentary HIV+ pts on ART 35 pts completed the program Improved 6-min walking test, strength exercises, BMI Significant reductions in d-dimer, IL-6, IL-18, myostatin, T cell activation Longo V et al, CROI 2014, #763

44 Vaccines 44

45 Which of following vaccines is NOT recommended for all susceptible HIV+ patients? A. Pnemococcal conjugate vaccine B. Pneumococcal polysaccharide vaccine C. Meningococcal vaccine D. Influenza vaccine E. Human papillomavirus vaccine (if 26 years 20% 20% 20% 20% 20% of age) A. B. C. D. E. 8

46 Vaccinations in HIV+ Patients Recommended if other risk factors present Advisory Committee on Immunization Practices (ACIP): Recommended Adult Immunization Schedule: US 2014.

47 HBV vaccination All HIV+ patients should be screened for HBV infection (HBsAg, anti-hbs, +/- anti-hbc) If non-immune HBV vaccine at 0, 1, 6 mo. If vaccine series interrupted, does not need to be restarted 1. Give 2 nd & 3 rd doses at least 8 wk apart Check anti-hbs after completing primary series If anti-hbs <10 second series of HBV vaccinations Consider revaccinating with a double dose 1

48 # of patients HBV Response: DD vs. SD Vaccine In retrospective study, double-dose (DD) vaccine associated with higher response rate than standard-dose (SD) vaccine 59% 85% Psevdos, AIDS Patient Care & STDs (2010) 24: 403.

49 What about the primary HBV vaccine series? Some experts recommend a double dose of HBV vaccine for the primary vaccine series In a French study, higher response rate to primary vaccination with 4-doses of DD (40 mcg) vaccine (0, 1, 2 and 6 m) than with 3 doses of SD vaccine (0, 1, 6 m): 82 vs. 65% Vaccine used was different than the one used in US Did not compare 3 doses of DD to 3 doses of SD Launay, JAMA, 2011

50 Isolated anti-hbc HIV+ pts with isolated anti-hbc are at risk for acquiring HBV 1 Most HIV+ pts with isolated anti-hbc do not have an anamnestic anti-hbs response after HBV immunization 2,3, suggesting they may benefit from vaccination Check HBV DNA to rule out occult HBV (rare) If negative, vaccination should be considered 4 1 French CID (2009) 49:148 2 Gandhi et al, JID (2005) 191: Chakvetadze, CID (2010) 50:1184; 4 Aberg J et al, CID, 2013

51 Geometric Mean Titer Zoster vaccine (ZV) in HIV+ Patients In HIV pts on ART with CD4 >200 and VL <50 1 : ZV safe; no rashes related to vaccine strain ZV elicited antibody responses Consider ZV in pts > 60 yo with CD4 count > Benson C, Lennox J, ACTG 5247 team. CROI 2012, Abstract # 96; 2 Aberg J et al, CID, 2013

52 HPV Vaccine Recommended for females and males through age 26 HPV4 safe and immunogenic in HIV-infected women years old 1 Ongoing ACTG study of HPV4 in HIV+ MSM and women >26 yo 1 Milunka Kojic et al, CID, 2014

53 Pneumococcal Vaccine Invasive pneumococcal disease in HIV+ patients: 173/100,000 (more than 20x higher than for adults without high-risk conditions) 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 ACIP. Recommended Adult Immunization Schedule: US 2014

54 Approach to HIV+ Patient: Step 1: History, Examination, Labs 69 yo M with HIV GERD, allergic rhinitis. Meds: omeprazole, fluticasone (interact with several commonly used regimens) BP normal. Obese Total chol. 210, LDL 165, HDL 35 CD4 cell count 181, HIV RNA 178,000 HIV Genotype: no resistance mutations HLA-B5701 positive 4 Steps

55 Step 2: OI Prophylaxis CD4 count 181: PCP prophylaxis indicated Step 3: ART individualizing therapy Requests one-pill once-daily regimen Abacavir contraindicated (pt is HLA-B5701 positive) Step 4: Preventive health Anti-HBs & HBsAg negative needs vaccination Smoker Approach to HIV+ Patient: 4 Steps Framingham risk score: 18%; AHA 10 year atherosclerotic CVD risk: 25%

56 Case Bringing it all back home Trim/sulfa initiated for PCP prophylaxis Initiated TDF/FTC/elvitegravir/cobicistat Fluticasone changed to beclomethasone Vaccines: influenza; PCV-13 followed by PPSV- 23 (>8 wks later); HBV vaccine Hyperlipidemia: lifestyle changes; atorvastatin or rosuvastatin Focusing on smoking cessation and wt. loss counseling

57 Thank you for your attention!

58 Activity Code TM809