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HIV Update and Review for the Primary Care Physician

HIV Update and Review for the Primary Care Physician. Scott Hendrickson D.O. Assistant Professor Department of Internal Medicine Oklahoma State University Center for Health Sciences. Overview. Epidemiology Testing Primary HIV infection Manifestations of HIV Opportunistic infections

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HIV Update and Review for the Primary Care Physician

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  1. HIV Update and Review for the Primary Care Physician Scott Hendrickson D.O. Assistant Professor Department of Internal Medicine Oklahoma State University Center for Health Sciences

  2. Overview • Epidemiology • Testing • Primary HIV infection • Manifestations of HIV • Opportunistic infections • Antiretroviral therapy • New therapies

  3. Who is Today’s HIV Patient? • HIV patients today are living longer, and new treatment considerations are emerging • Patients frequently present with comorbid conditions, such as hepatitis C (HCV) coinfection, mental illness, and substance abuse 1-4 • The major causes of death in today’s patient are non-opportunistic illnesses, especially hepatic, pulmonary, cardiovascular, and renal complications 5 1. Sulkowski M. Curr Infect Dis Rep. 2001;3:469-476. 2. Centers for Disease Control and Prevention. http://www.cdc.gov/hiv/pubs/facts/HIV-HCV_Coinfection.htm. Accessed September 23, 2004. 3. Kimmel PL, et al. Ann Intern Med. et al. 2003;139:214-226. 4. Bing EG, et al. Arch Gen Psychiatry. 2001;58:721-728. 5. Pallela F, et al. 11th Conference on Retroviruses and Opportunistic Infections, 2004; Poster 872.

  4. 85,000 400,000 Newly diagnosed AIDS cases 1993 Definitionimplementation Deaths 350,000 75,000 Persons living with AIDS 65,000 300,000 55,000 250,000 45,000 No. of cases and no. of deaths No. of persons living with AIDS 200,000 35,000 150,000 25,000 100,000 15,000 50,000 5,000 0 0 1990 2000 1994 1988 1992 1998 2002 1996 1986 Year AIDS Cases, Deaths, and Persons Living with AIDS by Year, 1985-2002–United States CDC HIV/AIDS Surveillance Report, 2002, Vol.14. Adjusted for reporting delays.

  5. Proportion of AIDS Cases and Population, by Race/Ethnicity 2002—United States 1% <1% 4% <1% 17% 13% 31% 13% 69% 51% White, not Hispanic Black, not Hispanic Hispanic Asian/Pacific Islander American Indian/Alaska Native Note. Exclude persons from US dependencies, possessions, and associated nations. *Includes 44 persons of unknown race or multiple races.

  6. Cumulative AIDS Cases Through 2001 – Exposure Category by State http://www.statehealthfacts.kff.org/

  7. HIV Testing • Suspect the Dx of and test for HIV in the following clinical settings • Pneumococcal pneumonia in a person under the age of 55 with no comorbid conditions • New Hep B or Hep C • New TB Dx • Shingles in the adult • Thrush in the adult

  8. HIV Testing • Thrombocytopenia • Fever of unknown origin • Unexplained weight loss • Diffuse lymphadenopathy • Persons in high risk categories presenting with S/Sx of Primary HIV infection

  9. Primary HIV Infection • Acute retroviral syndrome • Occurs 2-4 weeks after infection • Mono-type syndrome • Immunology • Very high viral load • Rapidly falling CD4 count

  10. Primary HIV Infection: Common Signs & Symptoms N = 160 patients with PHI in Geneva, Seattle and Sydney % of patients Vanhems P et al. AIDS 2000; 14:0375-0381. 

  11. PHI: Diagnostic Testing 1 mil HIV RNA 100,000 + HIV RNA HIV-1 Antibodies _ 10,000 Ab 1,000 Exposure 100 Symptoms 10 0 20 30 40 50 Days

  12. Rapid HIV testing

  13. Manifestations of HIV

  14. HIV Seroconversion-macular rash

  15. Persistent generalized lymphadenopathy

  16. Seborrheic dermatitis

  17. Herpes zoster

  18. Tuberculosis

  19. Oral candidiasis

  20. Kaposi’s Sarcoma

  21. HIV Wasting Syndrome

  22. Bacillary angiomatosis

  23. HIV-associated psoriasis

  24. Secondary syphilis

  25. Secondary syphilis

  26. Opportunistic Infections • Pneumocystis pneumonia • Disseminated mycobacterium avium complex • Toxoplasmosis encephalitis • Crypotococcal meningitis • Disseminated histoplasmosis • Cytomegalovirus infections

  27. Pneumocystis jiroveci pneumonia • Pneumocystis is a fungi that produces pneumonia in immunosuppressed patients • Wide range of severity • It is the most frequent form of presentation of AIDS • Usually CD4 count less than 200 cells/mm3 • Diagnosis: clinical, induced sputum, BAL

  28. Treatment • TMP/SMX for 21 days • Pentamidine • TMP plus dapsone • Clindamycin plus primaquine • Atovaquone • Trimetrexate plus leucovorin • Corticosteroids : pO2< 70 mm/Hg or A-a gradient > 35 mm Hg

  29. PCP Prophylaxis • CD4+ T cell count < 200 ; H/O oral candidiasis; Unexplained fever > 2 weeks; Previous episode of PCP • TMP/SMX DS 1 tablet po daily • Dapsone 50 mg po b.i.d. or 100 mg daily • Atovaquone 1500 mg po daily • Pentamidine aerosol 300 mg monthly

  30. Disseminated Mycobacterium avium • Usually late in the course of AIDS (CD4 <50) • Persistent fevers, night sweats, fatigue, weight loss, and anorexia • Hepatosplenomegaly, lymphadenopathy, and (rarely) jaundice • Anemia, leukopenia, elevated alkaline phosphatase levels are common

  31. Mycobacterium avium complex • Improved survival with 3 drugs vs 2: • CLR 500 mg po bid (AZ 500 mg daily) • EMB 15 mg/kg po qd • RBT 300 mg po qd (adjust for ART) • Failure to response/relapse • Susceptibility testing • Ciprofloxacin 500-750 mg po bid or levofloxacin 500 mg qd • Amikacin 10-15 mg/kg IV qd

  32. Acquisition of Toxoplasmagondii • Cat Feces • Undercooked Red Meat DHS/HIV/PP

  33. Toxoplasmosis • Presentation as encephalopathy • Gradual to acute onset • CD4 count <200 • Ring enhancing lesions on CT/MRI

  34. Toxoplasmosis • Standard therapy is pyrimethamine plus sulfadiazine • Sulfadiazine may not be available • Pyrimethamine 200 mg load the 50 mg daily plus clindamycin 600 mg qid plus leucovorin 10 mg daily. • SMX/TMP (based on 5 mg/kg TMP) bid • If no clinical/radiographic improvement in 2 weeks or clinical decline in one week: BIOPSY

  35. Cryptococcal meningitis • Fever and Headache • 25% of patients present with nuchal rigidity • Cryptococcal antigen on the CSF • CD4 <200 • Treatment is with IV AmphoB until the CSF is cleared of antigen or the maximal total dose is given • Minimum of 8 weeks of consolidation therapy with fluconasol 400mg daily • Fluconasol 200mg daily suppressive therapy

  36. Antiretroviral Drugs • Nucleoside reverse transcriptase inhibitors • Nonnucleoside RTI’s • Protease inhibitors • Integrase Inhibitors (T20) • ~20 different aproved drugs or combination drugs • Compact regimens have evolved • 2 pills once daily

  37. HIV Replication Cycle and Sites of Drug Activity Protease New HIV particles Capsid proteins and viral RNA CD4 Receptor Viral RNA Reverse Transcription Attachment Translation Uncoating Integration Transcription • NRTIs • NNRTIs Attachment Inhibitors • Protease Inhibitors Cellular DNA Nucleus HIV Virions Reverse Transcriptase Integrase Unintegrated double stranded Viral DNA gag-pol polyprotein Integrated viral DNA Viral mRNA CCR5 or CXCR4 co-receptor 1 3 4 5 2 6 Assembly and Release Adapted:Levy JA. HIV and the Pathogenesis of AIDS. 2nd ed. Washington, DC: American Society for Microbiology; 1998:9-11 .

  38. Improvement of quality of life Reduction of HIV-related morbidity and mortality Restoration and/or preservation of immunologic function Maximal and durable suppression of viral load Selection of ARV regimen Preservation of future treatment options Rational sequencing of therapy Maximizing adherence Use of resistance testing in selected clinical settings Goals of Antiretroviral Therapy & Tools to Achieve Goals

  39. Before Initiating ART • Confirm HIV results • Complete H&P • CBC, chemistry profile • CD4 cell count • Plasma HIV RNA measurement • Consider resistance testing • Assess “readiness” for treatment and adherence

  40. RPR or VDRL PPD Chest X ray Hepatitis A,B,C serology Toxoplasma IgG Fasting glucose and lipids Gynecologic exam with pap smear Testing for chlamydia and gonorrhea Ophthalmology exam (CD4+ T cell count <100 cells/µL) Before Initiating ART: Additional Tests

  41. Indications for ART in the Chronically HIV-Infected Patient Treat all (regardless of viral load): • Symptomatic (AIDS, severe symptoms) • Asymptomatic, CD4 count <200 cells/µL

  42. Considerations in Initiating ART: Chronically HIV-Infected Patient, Asymptomatic • Strong evidence of decreased mortality and morbidity with ART if CD4 <200 cells/µLor symptomatic • Theoretical benefit of treatment at higher CD4 • Few data establish clinical benefit for treatment if CD4 >200 cells/µL; optimal point to initiate ART is unknown • Individualize treatment decisions

  43. BENEFITS Avoid negative effects on quality of life Avoid drug-related toxicity Preserve future drug options Delay development of drug resistance Decrease total time on medications RISKS Possibility of irreversible immune system depletion Increased possibility of progression to AIDS Possible increased risk of HIV transmission Benefits and Risks of Deferred Therapy

  44. NRTI Abacavir ABC Didanosine DDI Emtricitabine FTC Lamivudine 3TC Stavudine D4T Zidovudine ZDV Zalcitabine DDC Tenofovir TDF NNRTI Delavirdine DLV Efavirenz EFV Nevirapine NVP PI Amprenavir APV Atazanavir ATV Fosamprenavir FPV Indinavir IDV Lopinavir LPV Nelfinavir NFV Ritonavir RTV Saquinavir SQV soft gel SGC hard gel HGC Fusion Inhibitor Enfuvirtide T-20 Current Antiretroviral Medications

  45. Initial Treatment: Preferred Regimens *Avoid in pregnant women and women with pregnancy potential. NNRTI-Based # pills/day PI-Based

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