HIV basics. Katya Calvo Medical Director of Antimicrobial Stewardship

Transcription

1 HIV basics Katya Calvo Medical Director of Antimicrobial Stewardship

2 Learning Objectives 1. Review of HIV epidemiology worldwide and locally 2. Review of recommendations on whom to screen 3. Work up of the newly infected HIV patient 4. Hospitalized patient with HIV: what to look for

3 Epidemiology

4 At the end of 2010: an estimated 34 million people were living with HIV worldwide UNAIDS World AIDS Day Report. Joint United Nations Programme on HIV/AIDS (UNAIDS) 2011

5 Worldwide, the number of people becoming infected with HIV is continuing to fall The HIV epidemic in North America remains stubbornly steady UNAIDS World AIDS Day Report. Joint United Nations Programme on HIV/AIDS (UNAIDS) 2011

6 Year People living with HIV People newly infected with HIV Adult Prevalence (%) N. America million 58, ,000 49, Sub-Saharan Africa million 1.9 million million 2.2 million 5.9 UNAIDS World AIDS Day Report. Joint United Nations Programme on HIV/AIDS (UNAIDS) 2011

7 In New Mexico 1983: AIDS first became reportable in New Mexico By end of 2010, a cumulative total of 6,538 persons with HIV and/or AIDS have been reported In 2010: 3,318 people were known to still be living with HIV in New Mexico 2,025 people were living with AIDS In 2010: 152 new persons infected with HIV were identified Incidence rate of 7.4 per 100,000 population HIV and AIDS annual surveillance report NMDOH. Accessed at

8 HIV Epidemiology in New Mexico (2009 Data) RISK FACTORS DEMOGRAPHICS

9 HIV Epidemiology New Diagnoses in NM Young adults MSM Latinos 43% AIDS at HIV diagnosis Higher rates in Latinos and older adults New Diagnoses in USA Young adults Heterosexual women African Americans 38% AIDS at HIV diagnosis

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11 Screening

12 Case 1 A 24 year old female in a heterosexual monogamous relationship comes to see you in clinic for annual check up. Review of systems unremarkable She tells you that 1 month ago, she had a flulike illness, but otherwise, she has no complains. Do you offer this patient an HIV test?

13 CDC Guidelines Test all patients Test all patients with Tb, STD Test ALL pregnant women Test high risk patients at least annually Pre-test counseling no longer required Need consent, but no longer written Charting should read: Patient has given verbal consent for HIV testing MMWR 2006:55(RR14);1-17

14 Who is high risk? Conventional risk factors IDU MSM Commercial Sex Worker Probable risk groups Substance abuse Psychiatric disorder Prior unprotected sex Partner of IDU, MSM, CSW

15 Opt-in vs Opt-out Testing Opt-in A physician or other healthcare provider asks you if you would like to be tested for a disease at any particular visit Opt-out A physician or other healthcare provider tests you for a disease or condition unless you specifically refuse the test

16 HIV 101 for Patients

17 How does HIV cause AIDS? HIV infects and destroys an important type of cell in the body s immune system known as the T-helper (T H ) cell, also known as the CD 4 cell

18 What is the Viral Load? The HIV viral load is simply a measure of the quantity of HIV in a drop (ml) of a patient s blood, and it is usually measured in copies/ml In general, the higher the viral load, the faster CD4 cells are destroyed

19 HIV Infection is characterized by a steady decline in the number of CD4 cells Acute Infection CD4 Cell Count (cells/mm³) 1, Asymptomatic HIV Infection AIDS CD4 cell count high risk of opportunistic infections 4-8 Weeks Up to 12 Years 2-3 Years Time

20 CD4 Count, Viral Load, and Clinical Course Primary Infection Seroconversion Plasma HIV RNA 10,000,000 1,000, ,000 10,000 1, Viral Load CD4 Cells Intermediate Stage AIDS CD4 Cell Count 1, Weeks Up to 12 Years 2-3 Years

21 New Diagnosis

22 Case 2 A 34 year old male, MSM, had routine lab work done after a clinic visit with you and his HIV screen has returned positive You wait for the confirmatory test to result prior to calling him back to the office What further testing is important to do?

23 HIV Testing Rapid Testing HIV Ab Elisa screen High sensitivity False-positive possible Confirmatory Testing Western blot High specificity Routine Testing HIV Ab Elisa followed by automatic WB confirmation

24 Further Laboratory CBC Leucopenia, thrombocytopenia Electrolytes/LFT s Creatinine important for renal adjustment LFT s may guide you to further work up/treatment choices CD4/HIVRNA Viral load can take about a week to result GART Standard of care to have a baseline genotype prior to initiating ARV May take up to 2 weeks to result

25 Further Laboratory Hepatitis antibodies: A,B,C Hep A total (IgG + IgM) HepBsAg, HepBsAb Hep C Ab Toxo IgG T. pallidum Ab Urine for Gonorrhea and Chlamydia

26 Quick Quiz Patient 1: HepBsAg negative HepBsAb positive Patient 2: HepBsAg positive HepBsAb negative HepB core IgM positive

27 Case 2 Continued CD4 390 Viral load 92,000 copies/ml Immunized to Hep A, but not Hep B Does not have Hep C CBC, Chem7, LFT s normal Toxo IgG positive T. pallidum Ab negative Urine negative for Gonorrhea and Chlamydia Does this patient need prophylaxis?

28 Primary Prophylaxis against Major Infectious Pathogens That Can Cause Complications in the Patient with Newly Diagnosed HIV Infection Hammer S. N Engl J Med 2005;353:

29 When to start ARV

30 Current recommendations HAART for all patients with CD4 <500 cells/µl Randomized control trial (RTC) data support benefit of ART if CD4 350 No RTC data on benefit of ART at CD4 >350, but observational cohort data Guidelines for the Use of Antiretroviral Agents in HIV-1 Infected Adults & Adolescents. DHHS 1/2011.

31 Recommendations for Initiating ART Clinical Category or CD4 Count Recommendation History of AIDS-defining illness CD4 count <350 cells/µl CD4 count cells/µl Pregnant women HIV-associated nephropathy Hepatitis B co-infection* Initiate ART Guidelines for the Use of Antiretroviral Agents in HIV-1 Infected Adults & Adolescents. DHHS 1/2011.

32 Potential Benefits of Early Therapy (CD4 count >500 cells/µl) Cohort study data show survival benefit if ART initiated at CD4 count >500 cells/µl Earlier ART may prevent HIV-related end organ damage; deferred ART may not reliably repair damage acquired earlier Increasing evidence of direct HIV effects on various end organs and indirect effects via HIV-associated inflammation End organ damage occurs at all stages of infection

33 Potential Benefits of Early Therapy (CD4 count >500 cells/µl) Potential decrease in risk of many complications, including: HIV-associated nephropathy Liver disease progression from hepatitis B or hepatitis C Cardiovascular disease Malignancies (AIDS defining and non-aids defining) Neurocognitive decline Blunted immunological response due to ART initiation at older age Persistent T-cell activation and inflammation

34 Can ARV be started while hospitalized? Yes Only in Cryptococcus meningitis should therapy be delayed Tuberculosis is still controversial, but more studies are now showing improved survival with an earlier start Cohen. Curr Opin HIV AIDS Jan;5(1):61-9 Piggot. Clin Dev Immunol. 2011;2011: Epub 2010 Dec 27 but better to do so as an outpatient Patient readiness/willingness for lifelong treatment Insurance issues Adherence issues Patient has had time to think about diagnosis Assess concurrent recreational drug use Unstable shelter

35 Hospitalized Patient with HIV

36 Case 3 A 45 year old male with HIV, CD4 345 on ARV, is admitted with Community Acquired Pneumonia His last VL was undetectable 1 month prior Medications: Atazanavir 300 mg po q day Ritonavir 100 mg po qday Truvada 1 tab po qday What is the most likely etiology for his CAP?

37 Anti-Retrovirals: Crash Course NRTI Abacavir Didanosine Emtricitabine Lamivudine Stavudine Tenofovir Zidovudine (AZT) NNRTI Efavirenz Etravirine Rilpivirine Nevirapine PI Atazanavir Darunavir Fosamprenavir Indinavir Lopinavir Nelfinavir Saquinavir Tipranavir Ritonavir (booster only) Integrase Inhibitor (II) Raltegravir Fusion Inhibitor Enfuvirtide CCR5 Antagonist Maraviroc Current ARV Medications Always include 3 active drugs; > 1 class

38 Initial Preferred Treatment ( 3 drugs included in HAART) NRTI Backbone Tenofovir PLUS Lamivudine/Emtricitabine Additional Class NNRTI Efavirenz Boosted Protease Inhibitor Atazanavir + ritonavir Darunavir + ritonavir Integrase Inhibitor Ralteglavir Avoid tenofovir in renal failure Efavirenz should be avoided in pregnancy Pregnant Women: Zidovudine + Lamivudine + Lopinavir/ritonavir

39 Class Characteristics to Consider Drug Class NNRTI Advantages Once daily dosing Coformulated single pill option Disadvantages Neuropsych side effects Dyslipidemia Rash Low barrier to resistance PI Once daily dosing Dyslipidemia LFT abnormalities GI intolerance II Fewer drug interactions Fewer adverse reactions Lower barrier to resistance Twice daily dosing

40 Drug-Drug Interactions HIV medications are metabolized by the cytochrome P450 mechanism in the liver. These antiretroviral medications have many potential drug interactions with other medications that are also metabolized by this system. Inducers: can decrease levels of other drugs Inhibitors: can increase levels of other drugs ** Check for drug-drug interactions prior to starting any new medication

41 Good resource

42 Case 3- Continued You admit the patient and start Ceftriaxone and Azithromycin. You write to continue Atazanavir, Ritonavir, Truvada (emtricitabine/tenofovir) Orders are also written for Omeprazole 20 mg po qday Due to non-hiv complications, patient remains in-house for 3 weeks and when you check a HIV Viral Load level and returns 30,000 copies/ml Why does the patient have a detectable VL?

43 Hospitalized Patient Summary 1. Important to know immunologic state (CD4?) 2. If patient is on ARV, always look for at least 3 drugs 3. Always think about drug interactions

44 Questions? Thank you

45 Case 4 52 year old male no PMH comes to your office with 2 weeks of fevers, 20 lbs weight loss, and diffuse lymphadenopathy His HIV test returns positive CD4 is 42 What is your differential?

46 DDX prolonged fever in untreated HIV HIV Disseminated MAC Disseminated TB Lymphoma Disseminated fungal infection (coccidiomycosis)