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Clinical Aspects of HIV

Clinical Aspects of HIV. Rachel Gallen , Eduardo Cortez-Garcia, Kelli Chaviano , Amber Childers, James Barr April 5, 2012. Objectives. Discuss diagnosis of HIV Discuss screening infected individuals for other chronic infections

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Clinical Aspects of HIV

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  1. Clinical Aspects of HIV Rachel Gallen, Eduardo Cortez-Garcia, Kelli Chaviano, Amber Childers, James Barr April 5, 2012

  2. Objectives • Discuss diagnosis of HIV • Discuss screening infected individuals for other chronic infections • Discuss common diseases of HIV positive adults and elaborate on those for which screening is recommended • Discuss adult immunizations for HIV infected patients

  3. HIV General Information • Blood-borne virus • Transmitted via sexual intercourse, IV drug use, and mother to child (at birth or through breast milk) • Co-infection with other viruses that share similar routes of transmission is common • Hepatitis B, Hepatitis C, HHV-8 (Kaposi sarcoma) • Causes a cellular immune deficiency (depletion of helper T lymphocytes/ CD4 cells) • Leads to development of opportunistic infections and neoplastic processes

  4. Clinical Presentation of HIV • Patient history is very important!! • Unprotected sexual intercourse • Large number of sexual partners • Prior or current STDs • IV drug use • Receipt of blood products (before 1985 in the US) • Contact with infected blood/ needle-stick injuries • Maternal HIV infection

  5. Clinical Presentation of HIV • Patient may present with • Flulike illness (ie. Fever, malaise, generalized rash) • Generalized lymphadenopathy • Weight loss • HIV should always be suspected in a healthy appearing individual who present with an unusual/recurrent infection (opportunistic infection)

  6. Diagnosis of HIV

  7. Diagnosis of HIV • ELISA followed by Western Blot • ELISA (enzyme-linked immunosorbent assay) • Used for screening for HIV • Looks for antibodies to viral proteins • Sensitive test • Western blot assay • Performed following a positive ELISA • Confirmatory test • Looks for antibodies to viral proteins • Specific test • Problems • Tests may be falsely negative in the first 1-2 months of HIV infection • Tests may be falsely positive initially in babies born to infected mothers (anti-gp120 crosses placenta)

  8. Diagnosis of HIV • ELISA followed by Western Blot • HIV PCR/viral load tests • Increasing in popularity • Allow the physician to monitor the effect of drug therapy on viral load • Used in newborns since ELISA/ Western Blot can give false positives due to presence of maternal antibodies

  9. Diagnosis of HIV • CD4 T cell count • Indicates risk of acquiring opportunistic infections • Reference range: 500-2000 cells/ μL • CD4 count < 200/ μL is a diagnosis of AIDS • Increased risk of opportunistic infections • Genotyping of viral DNA/RNA • Allows you to choose antivirals that are most likely to respond

  10. Screening HIV infected individuals for chronic infections

  11. Screening HIV+ Individuals • Initial workup of a patient diagnosed with HIV should include screening for: • Tuberculosis (PPD skin test) • Cytomegalovirus (Serology for anti-CMV IgG) • Syphilis (RPR testing) • Gonorrhea and Chlamydia (Rapid amplification testing) • Hepatitis A, B and C (Serology) • Toxoplasma gondii (Serology for anti-toxoplasma antibody) • Patients also should receive an ophthalmologic examination • For CMV retinitis

  12. Common diseases of HIV positive adults and screening for those diseases

  13. Systemic Diseases of HIV Positive Adults • Clinical Presentation • Low-grade fever, cough, hepatosplenomegaly, tongue ulcer • Remember from case patient had: • low grade fevers • cough • Findings/ labs • Oval yeast cells within macrophages, CD<100 • Pathogen • Histoplasmacapsulatum

  14. Systemic Diseases of HIV Positive Adults • Histoplasmacapsulatum • In healthy people it causes only pulmonary symptoms • Mostly found in Mississippi and Ohio River Valleys. • “Histo Hides (within Macrophages)” • Pic: Macrophage filled with histoplasmacapsulatum • Smaller then the RBC

  15. Neurologic Diseases of HIV Positive Adults • Encephalopathy • Findings/ labs • Due to reactivation of latent virus; results in demyelization, CD4 <200 • Pathogen • JC virus reactivation • Abscesses • Findings/ labs • Many ring-enhancing lesions on imaging, CD4<100 • Pathogen • Toxoplasma gondii • Screening is done for toxoplasma gondii in HIV positive adults • Test • Measure Anti- toxoplasma antibody to determine whether patients have had toxoplasmosis, and thus are at risk for reactivation of infection in the event of immunocompromise. • Drug prophylaxis: TMP-SMX • Patients with prior Toxoplasma infection require prophylaxis if their CD4+ T-cell counts drop below 100/µL.

  16. Neurologic Diseases of HIV Positive Adults • Meningitis • Findings/ labs • India ink stain reveals yeast with narrow-based budding and large capsule • CD4 < 50 • Pathogen • Cryptococcus neoformans(in case) • Cryptococcus neoformans • Heavily encapsulated yeast • Found in soil and pigeon droppings • Acquired through inhalation and with hematogenous spread • Culture on Sabouraud’s agar • Stain with India Ink • Latex agglutination test detect polysaccharide capsular antigen and is more specific

  17. Neurologic Diseases of HIV Positive Adults • Retinitis • Findings/ labs • Cotton-wool spots on fundoscopic exam • Associated with esophagitis • CD4<50 • Pathogen • CMV • Screening is done for CMV in HIV positive adults • Test • Serology looking for the presence of anti-CMV IgG • Ophthalmologic examination is used to evaluate for CMV retinitis in people with very low CD4 T-cell counts. • Dementia • Directly associated with HIV • Must be differentiated from other causes

  18. Dermatologic diseases of HIV Positive Adults

  19. Oncologic diseases of HIV positive adults

  20. Oncologic diseases of HIV positive adults

  21. Tree Man??! Indonesian Tree Man: HPV + Epidermodysplasiaverruciformis (rare autoimmune)

  22. Gastrointestinal Diseases of HIV Positive Adults • Pathogen • Cryptosporidium spp. • Clinical Presentation • Chronic, watery diarrhea in immunocompromised patients • Mild-watery diarrhea in non- immunocompromised • Findings/ labs • Acid-fast cysts seen in stool especially when CD4 < 200 • Transmission • Cysts in water • Treatment • None • Prevention • Filter city water supplies

  23. Respiratory Diseases of HIV Positive Adults • Pathogen • Cytomegalovirus (CMV) • Clinical Presentation • Interstitial pneumonia • Mononucleosis (negative monospot) • Findings/ labs • Cowdry Type A nuclear inclusions (owl’s eyes) in infected cells (seen on biopsy) • Transmission • Congenital • Transfusion, transplant • Sexual contact, saliva, urine • Prevention • Wash hands often • Avoid body fluids • Avoid sharing food • Practice safe sex

  24. Respiratory Diseases of HIV Positive Adults • Pathogen • Aspergillusfumigatus • Clinical presentation • Invasive aspergillosis • Lung cavity aspergilloma (fungus ball) • May disseminate causing brain abscess. • Findings/ labs • Pleuritic pain, hemoptysis, infiltrates on imaging • Mold with septate hyphae branching at angles less than or equal to 45 degrees. • Not present in the dimorphic form • Culture on Sabouraud’s agar • Transmission • Ubiquitous in manure, compost heaps, soil, damp areas in buildings • Spread likely due to spore spread during renovation/construction. • Treatment • Capsofungin, voriconazole, Amphotericin B

  25. Respiratory Diseases of HIV Positive Adults • Pathogen • Pneumocystis jiroveci • Clinical Presentation • Pneumonia (CD4 < 200 cells/mm3) • Findings/ labs • Microscopic exam of fluid stained with toludine blue, methenamine silver, and Giemsa • thick wall cysts and thin walled trophozoites • Transmission • May be inhaled as air-borne cysts • Or may be part of normal flora • most people acquire organism by 3 years old • Treatment • TMP/SMX

  26. Respiratory Diseases of HIV Positive Adults • Pathogen • Mycobacterium avium- intracellulare • Clinical Presentation • Tuberculosis-like disease (CD4 <50 cells/mm3) • Findings/ labs • Bacilli-weakly gram positive; prominent acid-fast • M. avium complex is a group of closely related sp. • Transmission • Believed to occur via ingestion • Infects multiple bird and mammal species • Found in water and soil • Treatment • AIDS patient- either: • Ethambutol plus clarithromycin • Ethambutol plus azithromycin

  27. Adult Immunizations for HIV Infected Patients

  28. CDC Recommended Vaccinations for HIV Positive Adults • Vaccine Scheduling according to the CDC: • Pneumococcal polysaccharide (PPSV) vaccination • Persons with asymptomatic or symptomatic HIV infection should be vaccinated as soon as possible after their diagnosis • Meningococcal vaccination • HIV-infected persons who are vaccinated should also receive 2 doses • Human papillomavirus (HPV) vaccination • HPV vaccines are not live vaccines and can be administered to persons who are immunocompromised as a result of infection (including HIV infection), disease, or medications • Vaccine is recommended for immunocompromised persons through age 26 years who did not get any or all doses when they were younger • The immune response and vaccine efficacy might be less than that in immunocompetentpersons

  29. CDC Recommended Vaccinations for HIV Positive Adults • Hepatitis B vaccination • Vaccinate persons with any of the following indications and any person seeking protection from hepatitis B virus (HBV) infection: • Persons with end-stage renal disease, including patients with HIV infection and persons with chronic liver disease • Haemophilusinfluenzae type b (Hib) vaccine • 1 dose of Hib vaccine should be considered for persons who have sickle cell disease, leukemia, or HIV infection, or who have anatomic or functional asplenia if they have not previously received Hib vaccine.

  30. NIH Recommended HIV Vaccination Schedule

  31. Immunizations according to FA • It is dangerous to give a live vaccine to an immunocompromised patient and their close contacts • Live vaccines induce a humoral response(Th1) and cell mediated immunity(Th2) • AHIV-infected patient has a low CD4+ count, so the T-cell response would be very weak • There have been reports of live vaccines reverting back to virulence. • MMR= measles, mumps, rubella • ALIVE VACCINE that CAN be given to HIV positive individuals that DO NOT show signs of immunodeficiency

  32. References • http://emedicine.medscape.com/article/211316-overview • First Aid for the USMLE Step 1, 2012. Le, Bhushan, Hofmann. Pg. 192-194. • First Aid for the USMLE STEP 1, 2011. Le, Bhushan, Tolles. • http://www.rightdiagnosis.com/phil/html/cryptosporiosis/7829.html • http://www.asm.org/Division/c/viruses.htm • http://phil.cdc.gov/PHIL_Images/04032002/00002/PHIL_300_lores.jpg • Fungal Pneumonias, B.A. Buxton, Ph D • Infections in the Immune Compromised Host part 1, B.A. Buxton, Ph. D. • pathmicro.med.sc.edu • http://www.cdc.gov/vaccines/recs/schedules/default.htm • www.aidsinfo.nih.gov/.../Recommended_Immunizations_FS_en.pdf • http://articles.latimes.com/2010/jul/16/world/la-fg-indonesia-treeman-20100716

  33. Review Questions

  34. Question 1 • A 47 year old white male presents to his primary care physician complaining of fever, cough and fatigue. On physical exam fluffy, white cottage lesions are seen in the mouth. Seeing that thrush is unusual for a patient of this age and presentation you begin to suspect that the patient may have HIV. On further questioning, you learn that the patient has unprotected sex with both men and women and occasionally uses IV drugs. What test is used to screen for HIV and why? • (A) ELISA, high sensitivity • (B) ELISA, high specificity • (C) RT- PCR, gives viral load • (D) Western Blot, high sensitivity • (E) Western Blot, high specificity

  35. Question 1 • A 47 year old white male presents to his primary care physician complaining of fever, cough and fatigue. On physical exam fluffy, white cottage lesions are seen in the mouth. Seeing that thrush is unusual for a patient of this age and presentation you begin to suspect that the patient may have HIV. On further questioning, you learn that the patient has unprotected sex with both men and women and occasionally uses IV drugs. What test is used to screen for HIV and why? • (A) ELISA, high sensitivity • (B) ELISA, high specificity • (C) RT- PCR, gives viral load • (D) Western Blot, high sensitivity • (E) Western Blot, high specificity

  36. Question 1 Explained • (A) ELISA, high sensitivity • Correct: ELISA is the test used to screen for HIV because it is a sensitive test. When screening for a disease, it is better to have a test with a high sensitivity (probability that a test detects disease when it is present). • (B) ELISA, high specificity • Incorrect: ELISA is the test that is used for screening for HIV. However, ELISA has a high sensitivity, not a high specificity. • (C) RT- PCR, gives viral load • Incorrect: RT-PCR is used to measure viral load in patients with HIV and to determine response to treatment. However this is not the test that is used to screen for HIV. • (D) Western Blot, high sensitivity • Incorrect: Western Blot is used to confirm the diagnosis of HIV once you have a positive screening test (ELISA). Also, Western Blot has a high specificity, not a high sensitivity. • (E) Western Blot, high specificity • Incorrect: Western Blot does have a high specificity (probability that a test indicates non-disease when disease is absent). However, because of its high specificity, Western Blot is used to make a confirmatory diagnosis of HIV once you have a positive screening test (ELISA). Western Blot is not used for screening.

  37. Question 2 • A 32 year-old HIV positive man with a recent CD4+ count of 84/mm^3 and a 3 week history of worsening headaches is brought to the emergency department by ambulance because of acute mental status changes. Upon arrival he is noted to have papilledema, a third cranial nerve palsy, and a rigid neck that cannot be flexed or extended. He subsequently dies from an overwhelming infection involving his nervous system. An autopsy specimen of the patient's brain was performed and acid fast bacilli were found. What is the underlying cause of this patient's symptoms? • (A) Bacterial meningitis • (B) Fungal meningitis • (C) Herpes encephalitis • (D) Myobacterial meningitis • (E) Viral meningitis

  38. Question 2 • A 32 year-old HIV positive man with a recent CD4+ count of 84/mm^3 and a 3 week history of worsening headaches is brought to the emergency department by ambulance because of acute mental status changes. Upon arrival he is noted to have papilledema, a third cranial nerve palsy, and a rigid neck that cannot be flexed or extended. He subsequently dies from an overwhelming infection involving his nervous system. An autopsy specimen of the patient's brain was performed and acid fast bacilli were found. What is the underlying cause of this patient's symptoms? • (A) Bacterial meningitis • (B) Fungal meningitis • (C) Herpes encephalitis • (D) Myobacterial meningitis • (E) Viral meningitis

  39. Question 2 Explained • (A) Bacterial meningitis • Incorrect: Acid-fast bacilli specifically points to TB • (B) Fungal meningitis • Incorrect: This would be associated with Cryptococcus neoformans; however, no yeast was foundindicating that this is not correct • (C) Herpes encephalitis • Incorrect: Encephalitis in HIV is usually associated JC virus not HIV • (D) Mycobacterial meningitis • Correct: The patient suffered from tuberculous meningitis, which is demonstrated by the characteristic acid-fast bacilli present in the patient's brain tissue. Immunocompromised patients are at risk for developing tuberculous meningitis, which occurs after the CNS is seeded with mycobacteria that subsequently produce a thick, gelatinous exudate. This exudate typically collects in the basilar region of the CNS and can cause cranial nerve destruction, commonly in CN 3, 6 and 7, as well as obstruction of basilar cisterns, resulting in obstructive hydrocephalus. • (E) Viral meningitis • Incorrect: Acid-fast bacilli is not viral

  40. Question 3 • A 35 year old female IV drug user was recently diagnosed with HIV and has come to your office with a new complaint. She has recently noticed superficial vascular proliferation on her face. Biopsy reveals that these lesions have neutrophilic inflammation. What is the most likely cause of these lesions, and what is the diagnosis? • (A) Bartonellahenselae, Bacillary angiomatosis • (B) Bartonellahenselae, Kaposi’s sarcoma • (C) HHV-8, Kaposi’s sarcoma • (D) HHV-8, Non-Hodgkin’s lymphoma • (E) HHV-8, Hodgkin’s lymphoma

  41. Question 3 • A 35 year old female IV drug user was recently diagnosed with HIV and has come to your office with a new complaint. She has recently noticed superficial vascular proliferation on her face. Biopsy reveals that these lesions have neutrophilic inflammation. What is the most likely cause of these lesions, and what is the diagnosis? • (A) Bartonellahenselae, Bacillary angiomatosis • (B) Bartonellahenselae, Kaposi’s sarcoma • (C) HHV-8, Kaposi’s sarcoma • (D) HHV-8, Non-Hodgkin’s lymphoma • (E) HHV-8, Hodgkin’s lymphoma

  42. Question 3 Explained • (A) Bartonellahenselae, Bacillary angiomatosis • Correct: It is important to understand that B. henselaeis associated with neutrophilic inflammation and NOT lymphocytic inflammation. • (B) Bartonellahenselae, Kaposi's sarcoma • Incorrect: Kaposi's sarcoma is associated with HHV-8 • (C) HHV-8, Kaposi's sarcoma • Incorrect: HHV-8 is associated with Kaposi's sarcoma. However, it is important to understand that HHV-8 is associated with lymphocytic inflammation and NOT neutrophilic inflammation. • (D) HHV-8, Non-Hodgkin's lymphoma • Incorrect: Non-Hodgkin's lymphoma is more likely to be associated with EBV. • (E) HHV-8, Hodgkin's lymphoma • Incorrect: HIV is not usually associated with Hodgkin's lymphoma, nor is HHV-8.

  43. Question 4 • A 36 year old homosexual female is brought to the ER with severe diarrhea occurring for 3 days. She was diagnosed HIV positive 2 years ago and she states that she is not taking her medications. Upon history and physical, you find that she is living in an old loft who’s water system is undergoing repairs. Stool cultures reveal cysts on acid-fast staining. Lung and neurologic examinations were unremarkable. What would be the most likely source of her infection? • (A) Ingestion of soil • (B) Inhaled • (C) Water supply • (D) Sexual contact, saliva, urine • (E) Part of normal flora

  44. Question 4 • A 36 year old homosexual female is brought to the ER with severe diarrhea occurring for 3 days. She was diagnosed HIV positive 2 years ago and she states that she is not taking her medications. Upon history and physical, you find that she is living in an old loft who’s water system is undergoing repairs. Stool cultures reveal cysts on acid-fast staining. Lung and neurologic examinations were unremarkable. What would be the most likely source of her infection? • (A) Ingestion of soil • (B) Inhaled • (C) Water supply • (D) Sexual contact, saliva, urine • (E) Part of normal flora

  45. Question 4 Explained • (A) Ingestion of soil • Incorrect: Mycobacterium avium is an acid fast rod known to cause tuberculous-like disease • (B) Inhaled • Incorrect: Pneumocystis jiroveci causes pneumonia and is diagnosed using Giemsa, toludine blue and methanaminesilver • (C) Water supply • Correct: This case describes Cryptosporidium spp. Transmission is via cysts in water supplies • (D) Sexual contact, saliva, urine • Incorrect: Cytomegalovirus causes mononucleosis/ pneumonia and is diagnosed by identifying Cowdry Type A nuclear inclusions in infected cells • (E) Part of normal flora • Incorrect: Pneumocystis jiroveci causes pneumonia and is diagnosed using Giemsa, toludine blue and methanamine silver

  46. Question 5 • A 30 year-old woman suffers a tonic-clonic seizure and presents with delirium and hydrophobia. The patient states that she was bitten on the hand by a bat about 1 month ago. The patient subsequently dies of respiratory failure. Viral particles are found throughout the brainstem and cerebellum at autopsy. In addition to direct viral cytotoxicity, the necrosis of virally infected neurons in this patient was mediated primarily by which of the following mechanisms? • (A) Histamine release from mast cells • (B) Humoral and cellular immunity • (C) Neutrophil-mediated phagocytosis • (D) Release of oxygen radicals from macrophages • (E) Vasoconstriction and ischemia

  47. Question 5 • A 30 year-old woman suffers a tonic-clonic seizure and presents with delirium and hydrophobia. The patient states that she was bitten on the hand by a bat about 1 month ago. The patient subsequently dies of respiratory failure. Viral particles are found throughout the brainstem and cerebellum at autopsy. In addition to direct viral cytotoxicity, the necrosis of virally infected neurons in this patient was mediated primarily by which of the following mechanisms? • (A) Histamine release from mast cells • (B) Humoral and cellular immunity • (C) Neutrophil-mediated phagocytosis • (D) Release of oxygen radicals from macrophages • (E) Vasoconstriction and ischemia

  48. Question 5 Explained • (A) Histamine release from mast cells • Incorrect: Histamine release from mast cells is seen in acute inflammation but does not represent an antigen-specific response to viral infections. • (B) Humoral and cellular immunity • Correct: Both humoral and cellular arms of the immune system protect against the harmful effects of viral infections. Thus, the presentation of viral proteins to the immune system immunizes the body against the invader and elicits both killer cells and the production of antiviral antibodies. These arms of the immune system eliminate virus-infected cells by either inducing apoptosis or directing complement-mediated cytolysis. In this patient, the rabies virus entered a peripheral nerve and was transported by retrograde axoplasmic flow to the spinal cord and brain. The inflammation is centered in the brainstem and spills into the cerebellum and hypothalamus. • (C) Neutrophil-mediated phagocytosis • Incorrect: Histamine release from mast cells is seen in acute inflammation but does not represent an antigen-specific response to viral infections. • (D) Release of oxygen radicals from macrophages • Incorrect: Histamine release from mast cells is seen in acute inflammation but does not represent an antigen-specific response to viral infections. • (E) Vasoconstriction and ischemia • Incorrect: Histamine release from mast cells is seen in acute inflammation but does not represent an antigen-specific response to viral infections. • Note: • Diagnosis: Rabies • Although the question is NOT about HIV, it refers to the humoral and cell mediated immune response related to the T cell immunity

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