Common AIDS-Related Complications

1. Common AIDS-Related Complications

2. Objective: To understand, identify and be able to manage common AIDS- Related complications

3. AIDS-Related Complications • Infections major cause of morbidity and mortality in persons with HIV • Prevention is key • Diagnosis may be difficult in resource-poor settings • Depends on local epidemiology and immune status of host

4. Diarrheal syndromes Pulmonary complications TB Herpes infections Candida infections Kaposi’s sarcoma Neurologic complications Psychiatric complications Immune reconstitution syndromes Gynecological complications AIDS-Related Complications

5. Diarrheal Syndromes • May be acute or chronic • Often infectious, as people in resource-poor settings lack access to clean water supplies • May be presenting complaint of HIV itslf and of other OIs • Differential diagnosis depends on CD4 count

6. Diarrheal Syndromes • Any CD4: viral, Salmonella species, Shigella species, Campylobacter species, E. coli, Clostridium difficile, M. tuberculosis,Giardia, amebiasis, strongyloides • CD4< 200: M. tuberculosis, M. avium, crypotsporidium, microsporidium, cyclospora, isospora, CMV

7. Protocol 3.16: Approach to Acute Diarrhea History: fever, duration, severity, pain Exam: assess for signs of perforated viscus especially in countries where Salmonella typhi is endemic Laboratory: CBC, malaria smear, Widal test, stool evaluation for fecal leucocytes, ova and parasites, and culture when possible • Observe 2-3 days • Oral rehydration Abdominal pain? Fever? No Yes • Gravely ill: • Hypotension? Acute abdomen? • Inability to drink? No No Stool evaluation positive for ova and parasites? Yes Yes Tenesmus or blood? • Salmonella spp (especially S. typhi), Shigella spp, sepsis, Salmonella typhi with intestinal perforation • IV hydration with normal saline • IV ceftriaxone 1 g OR ampicillin + chloramphenacol • Surgical evaluation Yes No Entamoeba histolytica Metronidazole 500-750 mg 3x/day for 10 days Giardia lamblia Metronidazole 250 mg 3x/day for 7 days Bloating, flatulence? No Yes Cyclospora cayetanensis TMP/SMX 1 DS tablet 2x/day for 14-21 days Shigella spp, Campylobacter spp, Yersinia spp, Salmonella spp TMP/SMX 1DS tablet 2x/day for 10 days

8. Protocol 3.17: Approach to Chronic Diarrhea (>2 Weeks) History: presence of greasy stool, worms, fever, abdominal pain, flatulence, nutritional deficiencies, anorexia/weight loss Exam: weight, nutritional status, evaluation for TB (PPD, CXR, sputum microscopy) Laboratory analysis: CBC, LFT, stool for fecal leukocytes, ova and parasites, acid fast stain Can use antimotility drug, such as Loperamide Pain? Fever? No • Cryptosporidium parvum, Isospora belli, Microsporidia spp, Strongyloides stercoralis: • Albendazole 400 mg 2x/day for 3 weeks (for Microsporidia spp and Strongyloides stercoralis) • TMP/SMX 1 DS 4x/day for 10 days then 2x/day for 3 weeks (for Isospora) Yes Bloating, flatulence? No Yes • Giardia lamblia (seen on ova and parasite exam) • Metronidazole 250 mg 3x/day for 7 days • Cyclospora cayetanensis • TMP/SMX 1DS 2x/day for 14-21 days • Tropical sprue • Malabsorption, macrocytic anemia • TMP/SMX 1 DS 2x/day for 14 days, may require treatment up to one year • Entamoeba histolytica: Metronidazole 500-750 mg 3x/day for 10 days • Tenesmus (pain with passing stool) • Cysts may be seen on ova and parasite exam • Diarrhea may be bloody • Mycobacterium tuberculosis: See Section 3.10 • Presents with persistent fever, weight loss • Stool AFB may be positive • Look for other signs of TB (lymphadenopathy, hepatosplenomegaly, ascites, pulmonary findings) • Mycobacterium avium complex: ethambutol 15-25 mg/kg/day + clarithromycin 500 mg 2x/day (or azithromycin 600 mg/day) + RFB 300 mg/day (see Section 3.10 for RFB interactions with ART) • Seen when CD4 <50 cells/mm3 • Presents with fever, diarrhea

9. Diarrheal Syndromes • Rehydration important • Stool studies if possible • Pathogen-directed therapy • Can use antimotility agents if no fever, bloody stool, or pain • HIV enteropathy as a diagnosis of exclusion

10. Pulmonary Complications • Most common OIs in patients with HIV worldwide • Diagnosis should be based on CD4 count, chest radiograph, sputum analysis and epidemiologic exposure • Most often infectious in nature, but PE and cardiomyopathy also more common in patients with HIV

11. Pulmonary Complications • Any CD4: M. tuberculosis,bacterial pneumonias include S. pneumoniae and H. influenza, viral illnesses • CD4< 200: PCP, fungal pneumonias (e.g. histoplasmosis, crypotcoccosis, CMV)

12. Protocol 3.19: Evaluation of Patients with Shortness of Breath History: acute shortness of breath or chronic presentation Physical examination: respiratory rate, heart rate, pulmonary and cardiac exam, evaluate for clubbing, cyanosis CXR Sputum gram stain and AFB stain and culture to rule out bacterial pneumonia Consider laboratory analyses including LDH, arterial blood gas, blood cultures Elevated respiratory rate (>20 per minute) or other signs of respiratory insufficiency/hypoxia? Yes Consider supplemental oxygen Bronchodilator therapy with albuterol sulfate: 2 inhalations every 4-6 hrs Wheezing heard on physical examination? Yes Evidence of congestive heart failure? Jugular venous distension, pulmonary or peripheral edema third heart sound (S3) Consider furosemide 20 mg Control of blood pressure Yes Evidence of pericarditis? Chest pain, pericardial rub? Jugular venous distension, pulmonary or peripheral edema third heart sound (S3) Consider tuberculous pericarditis, assess lymph nodes, PPD, sputum, CXR Yes CXR with evidence of infiltrate? Yes Initiate therapy based on Protocol 3.20

13. Protocol 3.20: Evaluation of Chest X-ray Findings in HIV-Positive Patients Immunosuppressed? CD4 <200 cells/mm3? Presence of thrush, cachexia, or AIDS-defining illness? No Yes No Bilateral reticular infiltrates on CXR? Rounded infiltrates? No Lobar infiltrates seen on CXR or heard on exam? Yes Upper lobe? No • Fungal pneumonia: histoplasma, aspergillus, blastomycosis, cryptococcus • Treat based on epidemiology of endemic fungi Yes Yes Sputum gram stain positive? AFB seen on sputum smear? No Yes No Yes • Pneumocystis carinii pneumonia • TMP/SMX 2 DS tablet 3x/day for 21 days • If severe shortness of breath, consider prednisone 40 mg po 2x/day and decrease the dose over 21 days • ART should be started after acute infection clears • Patient should be maintained prophylactic TMP/SMX 1 DS tablet/day Tuberculosis Section 2.4 Consider empiric treatment for bacterial pneumonia or TB depending on symptoms Acute bacterial pneumoniaStreptococcus pneumonia, Hemophilus influenzae Ceftriaxone 1 g IV q24 hrs OR oral penicillin OR TMP/SMX (Fluoroquinolone discouraged for empiric treatment in areas where TB is endemic)

14. Pulmonary Complications • Pathogen-directed therapy • Consider isolation if possible until active TB ruled out • Bronchodilators as needed • Adjuvant corticosteroids once patient on appropriate antimicrobial therapy

15. Tuberculosis • Most common OI in persons with HIV • Leading cause of death among person with AIDS • Can occur at any CD4 count • Can have TB multiple times

16. Tuberculosis • Caused by Mycobacterium tuberculosis • Pulmonary symptoms most common, but can affect any organ of the body • Extrapulmonary disease more common in persons with HIV • Diagnosis can be difficult

21. Tuberculosis • Treated with a minimum of 4 drugs for at least six months • Directly observed therapy required • HIV treatment should begin as soon as possible • Drug-drug interactions must be considered

23. Drug-resistant forms of TB • Increasingly common in South Africa • MDR-TB, XDR-TB • Drug susceptibility testing required • Minimum 18 months therapy with 5 drugs, including daily injectable • Suspect in patients with a history of previous treatment, exposure to known MDR-TB, exposure to suspected MDR-TB.

24. Prevention of TB • Isoniazid preventive therapy • Infection control • HIV suppresion • Nutritional support

25. Herpes Infections • Often a presenting sign of HIV infection • Can be local or systemic • Genital lesions may increase likelihood of spread • Include VZV, which causes zoster and HSV which causes oral/gential lesions • Can become disseminated and affect any organ in highly immunosuppressed persons

27. Protocol 3.18: Approach to Herpetic Rash: Varicella Zoster and Herpes Simplex Consider other dermatological conditions Patient with vesicular rash? Tingling or pain? No Yes If history and physical is consistent with oral or genital herpes simplex, acyclovir 400 mg po 5x/day for 10 days for primary episode or severe recurrence No Shingles (dermatomal distribution)? Yes • Localized varicella zoster • Acyclovir 800 mg po 5x/day for 10 days* • Consider ART and TMP/SMX prophylaxis Severe disseminated distribution or more than 2 dermatomes? No Yes • Disseminated varicella zoster • Acyclovir 10 mg/kg IV q8 hours for 14-21 days • Consider ART and TMP/SMX prophylaxis *Analgesia is helpful—NSAIDS, or even narcotics—if pain is severe. While prednisone may decrease pain and the chance of post-varicella pain syndrome (post-herpetic neuralgia), it should be used with great caution in areas where TB is endemic and may be undiagnosed.

28. Candida Infections • Often a presenting sign of HIV infection • Usually occurs in mouth, esophagus or vaginally • Oral candidiasis should prompt initiation of PCP prophylaxis

30. Protocol 3.21: Management of HIV-Positive Patients with Suspected Candidiasis Complete history and physical examination. Assess for other signs of immunosuppression. White plaques in oral cavity that are not removed with gentle scraping? No Creamy white vaginal discharge, vulvar itching? Yes Yes Vaginal candidiasis Fluconazole 200 mg po x 1 dose; if recurrent, treat with fluconazole 200 mg/day and consider suppressive dose of 200 mg/week thereafter Start PCP prophylaxis with TMP/SMX 1 DS tablet/day; consider starting ART Oral candidiasis Fluconazole 200 mg/day for 10-14 days; or nystatin rinse 500,000 units 5x/day Painful swallowing, difficulty swallowing? No Yes Presumed candidal esophagitis Fluconazole 200-400 mg/day po for 2-3 weeks

31. Kaposi’s Sarcoma • Tumor; caused by HHV-8 • Can be seen at any CD4 count • More common in African populations • Suspect anytime there is “bloody fluid” • Visceral versus cutaneous • Requires chemotherapy

35. Neurologic Complications • Common in HIV infection • Include meningitis, encephalitis, and CNS lesions • Differential diagnosis broad and can be difficult in settings in which brain imaging is limited • Work-up should include a lumbar puncture unless signs of increased intracranial pressure

36. Neurologic Complications • Any CD4: M. tuberculosis, lymphoma, bacterial meningitis, cerebral malaria, neurosyphilis, HSV, VZV, HIV • CD4< 100:Toxoplasmosis, crypotococcosis, histoplasmosis, CMV, PML

37. Lumbar Puncture • Should be done unless signs of increased intracranial pressure • Should be sent for cell count and differential, glucose and protein • Should be sent for culture, AFB, and fungal stains; consider viral PCRs in settings where resources permit

38. Protocol 3.14: Approach to HIV-Positive Patientswith Neurologic Changes History: acute or chronic change Clinical exam: vital signs, neurologic exam, evaluate for TB (PPD, sputum, CXR) Laboratory assessment: WBC, serum glucose, malaria smear, LFTs, creatinine, electrolytes Altered sensorium: obtunded, comatose? Yes • 50% dextrose • Check blood sugar • Malaria smear (treat with IV quinine if positive) • If seizure, anticonvulsants No Evidence of focal neurologic deficit* or increased intracranial pressure? Yes • Any CD4 count: If other evidence of TB (CXR, PPD, sputum, or history of TB contact) consider tuberculoma; empiric treatment for tuberculosis • CD4 <150 cells/mm3: Empiric treatment for toxoplasmosis if focal, neurologic deficit and/or seizure • CD4 <50 cells/mm3: Consider CNS lymphoma No • Lumbar puncture: • Opening pressure • Protein • Glucose • Cell count • AFB • Fungal stain • India ink stain • RPR or VDRL • While awaiting CSF analysis: • Empiric antibiotics against bacterial meningitis until diagnosis secured • Consider fluconazole or anti-TB therapy if the patient is gravely ill while results are pending *Focal deficits that suggest basilar meningitis which can be caused by cryptococcus and tuberculosis. These deficits include cranial nerve abnormality and intranuclear ophthalmoplegia.

39. Protocol 3.15a: Evaluation of HIV-Positive Patients with Acute Neurologic Presentations Acute onset of the following: headache, change in mental status, neck stiffness • Aseptic meningitis (HIV, HSV, other viral etiology) • Lumbar puncture • Elevated WBC • Lymphocytic predominance • Protein slightly elevated • Glucose normal Toxic or septic appearance? Elevated peripheral WBC with neutrophil predominance? No Yes • Bacterial meningitis • Ceftriaxone 2 g/day IV for 14 days • OR • Penicillin and chloramphenicol • Lumbar puncture • Opening pressure elevated • WBCs elevated (usually 300-2000 cells/mm3 up to 10,000 cells/mm3) • Neutrophil predominance • Protein elevated • Low glucose <40 mg/dL • Positive gram in 60-90% Peripheral blood smear for malaria positive? No Yes CNS malaria Quinine 20 mg/kg over 4 hrs followed by 10 mg/kg q8 hrs

40. Protocol 3.15b: Evaluation of HIV-Positive Patients with Subacute or Chronic Neurologic Presentations Extra-CNS involvement? No Nausea, vomiting, vision changes, elevated cranial pressure? Yes No Signs or symptoms of TB? (PPD, CXR, sputum) Yes • Tuberculous meningitis • Lumbar puncture • WBC 500 cells/mm3, lymphocytic predominance (neutrophils early) • Protein elevated • Glucose low • AFB stain and culture unreliable • Neurosyphilis • Penicillin G 3-4 million units IV q4 hrs for 10-14 days • Lumbar puncture • WBC elevated, lymphocytic predominance • Protein elevated • Glucose normal • RPR or VDRL positive in lumbar puncture and blood • Cryptococcal meningitis • Amphotericin B 1 mg/kg qd OR fluconazole 400 mg/day for 6-12 weeks with lifelong suppressive regimen fluconazole 200 mg/day • Lumbar puncture • Opening pressure may be very elevated* • India ink with encapsulated yeast (may be seen on a gram stain) • WBC count low, lymphocytic predominance <50 cells/mm3 • Protein and glucose usually normal • Cryptococcus antigen in blood or CSF highly sensitive • *Serial lumbar punctures may be needed to relieve intracranial pressure

41. Neurologic Complications • Pathogen-directed therapy • Consider adjuvant steroids if adequate antimicrobial therapy is instituted

42. Psychiatric Complications • HIV more common in populations with underlying psychiatric disease • HIV also associated with psychiatric complications • Medications may also be associated with psychiatric complications

43. Psychiatric Complications • HIV dementia • Depression • Anxiety

44. Psychiatric complications • Treatment should include HAART, antidepressants, and anxiolytics based on patient presentation • Social and emotional support for patient and family • Rule out underlying infections and metabolic causes in all cases

45. Table 3.12: Clinical Signs and Symptoms of HIV Dementia

46. Table 3.13: Psychological and Psychosocial Issues

47. Immune Reconstitution Syndrome • Paradoxical worsening of symptoms in setting of HAART and therapy • Must consider alternate diagnosis before blaming worsening symptoms on immune reconstitution • Has been reported with almost all OIs

48. Protocol 3.22: Management of Immune Reconstitution Syndrome Patient started on ART in previous 2 weeks to 6 months. Fever? Constitutional symptoms (fatigue, myalgias, etc.)? Suspect drug reaction and consider changing ART (especially NVP) or TMP/SMX Rash? Yes No Previously diagnosed OI for which patient is receiving treatment? No Evaluate for TB and other OIs Yes Neurologic symptoms? No Lymphadenopathy? Pulmonary symptoms? Abdominal symptoms? No Yes Yes Continue OI-specific therapy as in Protocols 3.14, 3.15a, and 3.15b; if evidence of CNS mass effect, consider discontinuing ART Yes Continue OI-specific therapy as in Protocols 3.16 and 3.17 • Continue OI-specific therapy as in Protocols 3.19 and 3.20 and Section 3.10 • Supplemental oxygen if needed • Prednisone 1 mg/kg/day if TB is being treated or has been ruled out • Continue treatment for OI • If evidence of increased intracranial pressure, temporary discontinuation of ART while OI is controlled with specific treatment and with dexamethasone

49. Immune Reconstitution Syndrome • Consider pathogen-directed therapy • If mild, continue HAART and treat with NSAIDS or steroids • If severe, consider suspension of HAART until infection brought under control

50. Gynecological complications • Major cause of morbidity and mortality in women • Most common is invasive cervical cancer • Often overlooked in integrated care settings • Commonly presents as vaginal bleeding