20 Years of Tears and Triumphs

Size: px

Start display at page:

Download "20 Years of Tears and Triumphs"

Caitlin Parsons
6 years ago
Views:

1 20 Years of Tears and Triumphs A Clinical Research Nurse s Perspective on HIV/AIDS Bobi Keenan, RN, ACRN Clinical Research Nurse UC Irvine Dept. of Medicine/Infectious Diseases

Objectives 1. Understand the Life Cycle of the virus relative to the development of available anti-retroviral therapies. 2. Be familiar with AIDS-defining opportunistic infections 3.

3 Objectives 1. Understand the Life Cycle of the virus relative to the development of available anti-retroviral therapies. 2. Be familiar with AIDS-defining opportunistic infections 3. Be aware of the changing face of the epidemic over time relative to who gets HIV infection. 4. Appreciate the work done by UCIMC laboratory personnel and rightfully share in the pride of the extraordinary work done here in the field of HIV/AIDS Clinical Research. IT COULD NOT HAVE BEEN DONE WITHOUT YOU!

4 HIV

5 HIV Infection Virus enters the body and finds its way to cells in the immune system Targets lymphocytes responsible for protecting the body from outside threats In most people, the immune system is gradually, persistently decimated by the ongoing viral infection 5% to 8% do not progress and maintain immune function, but clearly remain infected

6 HIV Infection To date, there is no way to eliminate the virus from the body Many viral infections remain sequestered throughout a person s lifetime (eg. Herpes) Diagnosis of AIDS is defined by CDC Criteria Average time from infection to AIDS is 10 years

7 Modes of Transmission Must Acquire Fluids with enough Virus to cause infection Sexual Blood/Blood Products Spinal Fluid Laboratory Samples

10 HIV: Spectrum of Disease Asymptomatic Period Minor sx s Major sx s Shingles, Thrush Tuberculosis KS, PCP, Herpes MAC, CMV Crypto, Toxo, CA, Infection YEARS AIDS diagnosis Death

11 Stages of HIV Infection CD4 cell count Baseline, Primary Infection Early HIV Infection > AIDS < 200 Advanced < 50

12 Laboratory Tests CBC w/differential Lymphopenia T-Cell Subsets CD4/mcl and % CD8/mcl and % HIV Viral Load

13 PRIMARY HIV INFECTION

14 Primary HIV Infection Symptoms Fever 87% Rash 68% Pharyngitis 48% Myalgias 42% Headache 39% Diarrhea 32% Abdominal Pain 32% Arthralgias 29% Nausea/Vomiting 29% Nightsweats/Weight loss

15 Primary HIV Infection 80 90% symptomatic Up to 75% will seek medical help 10 15% require hospitalization Median onset of symptoms: 25d Median duration of symptoms: 14d

16 Primary HIV Infection Rapidly Rising Viral Load makes person very contagious Standard HIV Test is negative

17 Time Laboratory Markers in HIV CD 4 cell count HIV antibodies Viral Load

18 Early HIV Infection

19 COMMON MANIFESTATIONS Molluscum Contagiosum Thrush Oral Hairy Leukoplakia Shingles HPV Recurrent, Prolonged Herpes Outbreaks Enlarged Lymph Nodes Malaise Low Grade Fevers

20 Molluscum Contagiosum By Salvatore Marra, from AIDS imaging

21 Oral Hairy Leukoplakia By Salvatore Marra, from AIDS imaging

22 AIDS

23 Pre-1993 AIDS Defining Diagnoses Pneumocystis Pneumonia Candidiasis - Esophageal, Tracheal, Pulmonary Isospora or Cryptosporidial Diarrhea > 1 month Disseminated TB Disseminated Mycobacterium avium or kansasii Coccidiodomycosis, extra-pulmonary Cytomegalovirus, any organ except liver/spleen/ln Herpes Simplex: mucocutaneous ulcer>1 month or bronchitis, pneumonitis, esophagitis Histoplasmosis, extrapulmonary

24 AIDS Defining Conditions (cont.) Kaposi s Sarcoma HIV-associated dementia Lymphoma of brain or non-hodgkins B-cell lymphoma Nocardiosis Progressive Multifocal Leukoencephalopathy Salmonella Septicemia (non-typhoid) Strongyloidosis, extraintestinal Toxoplasmosis of internal organ Wasting

25 CDC AIDS Definition (1993 Revised Classification) HIV + with CD 4 cell count < 200 cells/ml or <14% of total lymphocytes OR AIDS related Opportunistic Infection or cancer Invasive Cervical Cancer Recurrent Pneumonia Pulmonary TB

29 Continued New Infections Transmission by people unaware of their HIV infection Decreased safe sexual practices in those at risk Increased incidence of STD s Decreased use of condoms Risk behaviors continued by those who are HIV+. LA study ( 95 97) of heterosexual, male HIV+ patients attending the HIV clinic showed 37% never used condoms during vaginal intercourse

30 So, What is Causing all this trouble?

34 Antiretroviral Therapy NRTI s AZT, ddi, ddc, D4T, 3TC, Abacavir, FTC Nucleotide Analogues Tenofovir Adefovir (Hep B Tx) NNRTI s Nevirapine Delavirdine Efavirenz Etravirine Rilpivirine ENTRY INHIBITORS Enfuvirtide, Maraviroc Protease Inhibitors Saquinavir, Ritonavir, Indinavir, Nelfinavir, Lopinavir/r, Atazanavir, Amprenavir, Fosamprenavir Tipranavir, Darunavir Integrase Inhibitor Raltegravir

35 CLINICAL TRIAL DESIGN Starts with the question Research plan developed to answer it Controlled Studies Double or Single Blinded Studies Placebo/Standard of Care

36 CLINICAL TRIAL SAFETY Institutional Review Board Data Safety Monitoring Board FDA NIH Informed Consent

37 PHASE I CLINICAL TRIALS Initial studies to determine the metabolism and pharmacologic actions of drugs in humans Side effects associated with increasing doses Gain early evidence of effectiveness May include healthy participants and/or patients. Small Numbers Enrolled

38 PHASE II CLINICAL TRIALS Controlled clinical studies Enroll subjects with condition being studied Intensified look at side effects and toxicities Initial evaluation of efficacy Larger enrollment: enough subjects to determine if studies should continue to Phase III

39 PHASE III CLINICAL TRIALS Expanded Controlled and Uncontrolled Trials Larger numbers enrolled, enough, as determined by statistician to answer the research question Gathers more information on efficacy and side effects Evaluates risk vs benefit Provides adequate basis for treatment recommendations

40 PHASE IV CLINICAL TRIALS Post-marketing studies Collects additional data on risks, benefits, optimal use

41 The Vaxgen Study First Large Scale Phase III Study of a Vaccine to prevent HIV Infection Bivalent gp120 vaccine Prevented SIV in primates Didn t prevent HIV in humans Samples and information collected continue to contribute to research of vaccine development and HIV prevention

43 Reno

44 Opportunistic Infections and Co-morbid Infections

45 Opportunistic Infection Infection with an organism that typically does not cause disease in the normal host. Unusual organisms: Pneumocystis Common organisms that are usually not pathogenic: CMV, toxoplasmosis

46 Co morbid Infection An infection that commonly occurs in a normal host, but occurs with higher frequency among HIV infected patients Tuberculosis Hepatitis C Hepatitis B

47 Selected OIs in Patients With HIV Infection, Pneumocystis carinii pneumonia Mycobacterium avium complex disease Cytomegalovirus retinitis Toxoplasmosis HAART 100 Incidence per 1000 Patient-Years Year Kovacs JA, et al. N Engl J Med. 2000;342: (Based on CDC data.)

48 Adjuvant Steroids for PCP Treatment CCTG Protocol NEJM Nov 1990

50 PCP Use adjuvant steroids if RA po 2 < Prednisone 40 mg BID x 5d 40 mg QD x 5d 20 mg QD for the rest of the course of therapy (3 weeks) Must be started within 72 hours

51 Treatment - PCP Trimethoprim/Sulfamethoxazole 5mg/kg q8h Clindamycin 600 Q8 IV or 450 po q6 Primaquine 30mg qd Atovaquone 750 BID Pentamidine 4mg/kg QD

52 PCP Prophylaxis Primary prophylaxis Risk of PCP if CD4 count = 0.5% Risk of PCP if CD4 < 200 or less than 14% =, 8% History of Oral Candidiasis Secondary prophylaxis Needed to prevent recurrence Recurrence rate without 2 0 prophylaxis: 6m - 18% 9m - 46% 18m - 65%

53 Pneumocystis Pneumonia Matt

54 MYCOBACTERIA

55 TB and HIV Presentation Usual presentation if early HIV disease Unusual presentations are common in late HIV disease mediastinal LN, atypical lung infiltrates, disseminated disease, mycobacteremia, nl CXR

56 Mycobacterium Avium Intracellulare /Complex MAI / MAC KIRK

57 MAC Infection Mycobacterium avium-intracellulare complex Disseminated infection Bone marrow, liver, lymph nodes, GI tract Can be found in the sputum, but doesn t usually cause pneumonia Must differentiate between MAC and TB Diarrhea, fever, night sweats, weight loss, malabsorption, lymphadenopathy, AFB in stool and blood

58 MAC Infection Mycobacterium avium-intracellulare complex Diagnosis Culture: blood Bone Marrow Biopsy Liver Biopsy Treatment combination therapy Clarithromycin or Azithromycin, Rifabutin, Ethambutol, Quinolone

59 Mycobacterium avium complex Prophylaxis CD4 Count < 50 cells/mm Azithromycin 1200 mg PO once weekly Clarithromycin 500 mg PO bid From: 2001 USPHS/IDSA Guidelines

60 Toxoplasmosis John

61 Toxoplasmosis and HIV Often a Reactivation disease Manifests as CNS mass lesions or Ocular lesions Increased incidence with CD4 count < 100.

62 Toxoplasmosis By Salvatore Marra, from AIDS imaging

63 CMV End-Organ Disease Bruce

64 Cytomegalovirus CMV end-organ disease Herpes virus Commonly acquired during childhood, often asymptomatic Reactivation disease in Immunocompromised In HIV occurs when CD4 <100, usually <50 CMV retinitis CMV GI disease CMV CNS disease Host immune response may determine pathology ADCC (Antibody Dependent Cellular Cytotoxic) Response.

65 CNS Manifestations Heidi

66 CNS MANIFESTATIONS HIV Virus enters CNS within minutes Difficult to treat due to blood-brain barrier Persists for life Results in chronic inflammation Responsible for decline in cognitive abilities May affect spinal cord as well

67 CALIFORNIA NEURO-AIDS TISSUE NETWORK Long-term Observational Study of Neurological & Psychological effects of HIV infection Sponsored by NIH/NIMH Consortium of Universities Participating Systematic Evaluation of Subject s Neurological & Psychological Status during lifetime Autopsy and Organ Donation to CNTN Research Tissue Bank upon death

68 Cryptococcal Meningitis Randy

69 Cryptococcal Meningitis Occurs in 10% of untreated patients (prior to HAART) Risk of disease increases when CD4 count falls below 50 cells/ml Associated with pigeon droppings, but usually no risk factor can be elicited

70 Cryptococcal Meningitis Symptoms Fever Headache Mental Status Changes Meningismus

71 Cryptococcal Meningitis Diagnosis Lumbar puncture Head CT/MRI Cryptococcal Antigen - CSF Fungal Blood Cultures Serum Cryptococcal antigen titers

72 Cryptococcal Meningitis Therapy Amphotericin B mg/kg/d + Flucytosine 100mg/kg/d x 14 d (with clinical improvement) Then Fluconazole 400mg qd x wks Maintenance Fluconazole 200mg daily until CD4 >100/mcl for more than 1 year

73 Pilot Study UCI 1990 Published in J.Clinical Infectious Diseases, Oct 1994 Fluconazole 400mg + 5-FC daily (oral regimen) > Success at CST Sterilization at 10 weeks compared to Amphotericin-B or Fluconazole alone

74 Cryptococcal Meningitis Dorothy

75 Thank You! Thank You! Thank You!

Clinical Manifestations of HIV

HIV Symptoms Diane Havlir, MD Professor of Medicine and Chief, HIV/AIDS Division University of California, San Francisco (UCSF) WorldMedSchool; July 2, 2013 1 Clinical Manifestations of HIV! Result from