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Hiv 2007 Family Practice

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HIV management for family practice residents

Publicada em: Saúde e medicina
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Hiv 2007 Family Practice

  1. 1. HIV Infection and AIDS 2007 Family Practice Board Review Miguel G. Madariaga, MD Assistant Professor of Medicine University of Nebraska Medical Center
  2. 2. HIV epidemiology in a capsule
  3. 3. The natural history of HIV
  4. 4. Acute HIV infection <ul><li>Fever 96% </li></ul><ul><li>Adenopathy 74% </li></ul><ul><li>Pharyngitis 70% </li></ul><ul><li>Rash 70% </li></ul><ul><li>Myalgias 54% </li></ul><ul><li>Diarrhea 32% </li></ul><ul><li>Headache 32% </li></ul><ul><li>Nausea and vomiting 27% </li></ul><ul><li>Hepatosplenomegaly 14% </li></ul><ul><li>Weight loss 13% </li></ul><ul><li>Thrush 12% </li></ul><ul><li>Neurologic symptoms 12% </li></ul><ul><li>Dx: HIV RNA > 10,000 copies + indeterminate or negative HIV serology or recent seroconversion </li></ul>
  5. 5. Case definition of HIV infection C3 B3 A3 < 200 mm 3 (<14%) C2 B2 A2 200-499 mm 3 (14 to 28%) C1 B1 A1 > 500 mm 3 (>29%) AIDS indicator condition (Category C) Symptomatic, but not with AIDS indicator condition (Category B) Asymptomatic (Category A) CD4 cell categories
  6. 6. Conditions that define AIDS: infections <ul><li>Bacterial infections </li></ul><ul><ul><li>Disseminated MAC </li></ul></ul><ul><ul><li>Pulmonary or EP Tuberculosis </li></ul></ul><ul><ul><li>Recurrent bacterial pneumonia </li></ul></ul><ul><ul><li>Salmonella sepsis </li></ul></ul><ul><li>Fungal infections </li></ul><ul><ul><li>Candidiasis (esophageal, airway) </li></ul></ul><ul><ul><li>EP coccidiodomycosis </li></ul></ul><ul><ul><li>EP cryptococcosis </li></ul></ul><ul><ul><li>EP histoplasmosis </li></ul></ul><ul><ul><li>Pneumocysts pneumonia </li></ul></ul><ul><li>Parasitic infections </li></ul><ul><ul><li>Cryptosporidiasis c chronic diarrhea </li></ul></ul><ul><ul><li>Isosporiasis c chronic diarrhea </li></ul></ul><ul><ul><li>Toxoplamosis </li></ul></ul><ul><li>Viral infections </li></ul><ul><ul><li>CMV (no liver, spleen or nodes) </li></ul></ul><ul><ul><li>Herpes simplex (chronic ulcer, esophagus, airway) </li></ul></ul>
  7. 7. But remember it is not just infections <ul><li>Neoplasias </li></ul><ul><ul><li>Invasive cervical cancer </li></ul></ul><ul><ul><li>Kaposi´s sarcoma </li></ul></ul><ul><ul><li>Lymphoma (Burkitt´s, immunoblastic, primary CNS) </li></ul></ul><ul><li>Other </li></ul><ul><ul><li>HIV dementia </li></ul></ul><ul><ul><li>PML </li></ul></ul><ul><ul><li>HIV wasting </li></ul></ul><ul><li>Suggestive of HIV infection </li></ul><ul><ul><li>Bacilary angiomatosis </li></ul></ul><ul><ul><li>Recurrent mucosal candidiasis </li></ul></ul><ul><ul><li>Cervical dysplasia or carcinoma in situ </li></ul></ul><ul><ul><li>Constitutional symptoms </li></ul></ul><ul><ul><li>Hairy leukoplakia </li></ul></ul><ul><ul><li>Herpes zoster </li></ul></ul><ul><ul><li>ITP </li></ul></ul><ul><ul><li>Listeriosis </li></ul></ul><ul><ul><li>PID </li></ul></ul><ul><ul><li>Peripheral neuropathy </li></ul></ul>
  8. 8. HIV serology: who to test? <ul><li>For patients in all health-care settings </li></ul><ul><ul><li>Opt-out screening. </li></ul></ul><ul><ul><li>Persons at high risk should be screened at least annually. </li></ul></ul><ul><ul><li>Separate written consent should not be required. </li></ul></ul><ul><ul><li>Prevention counseling should not be required. </li></ul></ul><ul><li>For pregnant women </li></ul><ul><ul><li>HIV screening should be included in routine prenatal care. </li></ul></ul><ul><ul><li>Opt-out screening. </li></ul></ul><ul><ul><li>Separate written consent for HIV testing should not be required. </li></ul></ul><ul><ul><li>Repeat screening in the third trimester if there is elevated rates of HIV infection among pregnant women. </li></ul></ul>
  9. 9. What test to order and how to interpret results? <ul><li>Consider rapid testing, but always confirm with standard test </li></ul><ul><li>Positive WB: reactivity to gp120/160 plus either gp41 or p24. </li></ul><ul><li>False positive results </li></ul><ul><ul><li>HIV vaccines </li></ul></ul><ul><ul><li>Factitious HIV infection </li></ul></ul><ul><ul><li>Technical or clerical error </li></ul></ul><ul><li>False negative results </li></ul><ul><ul><li>Window period </li></ul></ul><ul><ul><li>Seroreversion </li></ul></ul><ul><ul><li>Agammaglobulinemia </li></ul></ul><ul><ul><li>Type N or O strains or HIV-2 </li></ul></ul><ul><ul><li>Technical or clerical error </li></ul></ul><ul><li>Indeterminate results </li></ul><ul><ul><li>Most commonly is process of seroconversion </li></ul></ul><ul><ul><li>Cross reactivity </li></ul></ul><ul><ul><li>Infection with strain O or HIV-2 </li></ul></ul><ul><ul><li>Technical or clerical error </li></ul></ul>
  10. 10. Other tests used in HIV infection <ul><li>Quantitative plasma HIV RNA </li></ul><ul><ul><li>HIV RNA PCR or branched chain DNA or nucleic acid sequence-based amplification (NABSA) </li></ul></ul><ul><ul><li>Used routinely every 3-4 mo </li></ul></ul><ul><ul><li>Goal is to have it undetectable </li></ul></ul><ul><ul><li>Viral load is increased by progressive disease, treatment failure, active infections and immunizations </li></ul></ul><ul><li>CD4 cell count </li></ul><ul><ul><li>Diurnal and seasonal changes </li></ul></ul><ul><ul><li>Infections, surgery and steroids may decrease it </li></ul></ul><ul><li>CD4 percentage </li></ul><ul><ul><li>200 cells - <14%, 500 cells - > 30% </li></ul></ul><ul><li>Total lymphocyte count </li></ul>
  11. 11. Resistance testing I doubt you have to remember funny numbers, but M184V is a “popular” mutation
  12. 12. Routine lab tests in HIV infection <ul><li>Serologic tests </li></ul><ul><ul><li>Hepatitis serology </li></ul></ul><ul><ul><li>Syphilis </li></ul></ul><ul><ul><li>Toxoplasma </li></ul></ul><ul><ul><li>Consider varicella IgG and CMV IgG </li></ul></ul><ul><li>Chemistry </li></ul><ul><ul><li>Liver and renal function tests </li></ul></ul><ul><ul><li>Glucose </li></ul></ul><ul><ul><li>Lipid profile </li></ul></ul><ul><ul><li>G6PD </li></ul></ul><ul><li>Hematology </li></ul><ul><ul><li>CBC </li></ul></ul><ul><li>Other </li></ul><ul><ul><li>CXR </li></ul></ul><ul><ul><li>PAP smear (consider anal smear in male patients) </li></ul></ul><ul><ul><li>PPD skin test </li></ul></ul><ul><ul><li>Urine NAAT for N. gonorrhoeae and C. trachomatis </li></ul></ul><ul><ul><li>Wet mount for Trichomonas </li></ul></ul>
  13. 13. Disease prevention: prophylaxis <ul><li>Pneumocystis jiroveci </li></ul><ul><ul><li>CD4 < 200, oral trhush or unexplained fever for 2 weeks </li></ul></ul><ul><ul><li>TMP-SMX 1 tab PO qd </li></ul></ul><ul><ul><li>Alternatives: TMP-SMX qod, dapsone, pentamidine, atovaquone </li></ul></ul><ul><li>M. tuberculosis </li></ul><ul><ul><li>PPD is positive at 5 mm in HIV infected patients </li></ul></ul><ul><ul><li>INH 300 mg PO qd x 9 mo plus vitamin B6 </li></ul></ul><ul><ul><li>Alternatives: RFP + PZA x 2 mo (hepatotoxic) or RFP x 4 mo </li></ul></ul><ul><li>Toxoplasma gondii </li></ul><ul><ul><li>CD4 less than 100 </li></ul></ul><ul><ul><li>Usually PCP prophylaxis is enough </li></ul></ul><ul><li>MAC </li></ul><ul><ul><li>CD4 less than 50 </li></ul></ul><ul><ul><li>Clarithromycin 500 bd or azithromycin 1200 mg qweek </li></ul></ul><ul><li>VZV, histoplasmosis, coccidiodomycosis </li></ul>
  14. 14. Disease prevention: vaccines <ul><li>Streptococcus pneumoniae </li></ul><ul><ul><li>Preferably use when CD4 > 200 </li></ul></ul><ul><ul><li>Revaccinate every 3-5 years </li></ul></ul><ul><li>Hepatitis A </li></ul><ul><ul><li>Use in MSM, IVDA and patients with chronic liver disease </li></ul></ul><ul><li>Hepatitis B </li></ul><ul><li>Influenza </li></ul><ul><li>Do not use live vaccines: MMR, varicella, BCG, polio (in other countries) </li></ul>
  15. 15. Probability of developing AIDS based on CD4 cell count and viral load
  16. 16. When to start antiretroviral therapy? Defer treatment <100,000 <ul><li>350 </li></ul>Asymptomatic Some may consider treatment >100,000 >350 Asymptomatic Treatment offered Any value 200-350 Asymptomatic Treat Any value <ul><li>200 </li></ul>Asymptomatic Treat Any value Any value Symptomatic Reccomendation Plasma HIV RNA CD4 cell count Clinical category
  17. 17. HIV life cycle and potential pharmacological targets
  18. 18. Available antiretroviral agents <ul><li>Nucleoside reverse transcriptase inhibitors (NRTI) </li></ul><ul><ul><li>Abacavir </li></ul></ul><ul><ul><li>Didanosine </li></ul></ul><ul><ul><li>Lamivudine or emtricitabine </li></ul></ul><ul><ul><li>Tenofovir </li></ul></ul><ul><ul><li>Zidovudine </li></ul></ul><ul><ul><li>*Stavudine </li></ul></ul><ul><ul><li>*Zalcitabine </li></ul></ul><ul><li>Non nucleoside reverse transcriptase inhibitors (NNRTI) </li></ul><ul><ul><li>Efavirenz </li></ul></ul><ul><ul><li>Nevirapine </li></ul></ul><ul><ul><li>*Delavirdine </li></ul></ul><ul><li>Protease inhibitors </li></ul><ul><ul><li>Atazanavir </li></ul></ul><ul><ul><li>Fosamprenavir </li></ul></ul><ul><ul><li>Lopinavir/ritonavir </li></ul></ul><ul><ul><li>Nelfinavir </li></ul></ul><ul><ul><li>Ritonavir </li></ul></ul><ul><ul><li>*Indinavir </li></ul></ul><ul><ul><li>*Saquinavir </li></ul></ul><ul><ul><li>**Darunavir </li></ul></ul><ul><ul><li>**Tipranavir </li></ul></ul><ul><li>Fusion inhibitors </li></ul><ul><ul><li>**Enfuvirtide </li></ul></ul>* Rarely used or discontinued due to adverse effects or pill burden ** Not used as initial therapy but for treatment experienced patients
  19. 19. What to start? <ul><li>1 NNRTI plus 2 NRTI </li></ul><ul><ul><li>Efavirenz </li></ul></ul><ul><ul><li>plus </li></ul></ul><ul><ul><li>Tenofovir/ emtricitabine or zidovudine/ lamivudine </li></ul></ul><ul><li>Alternative: </li></ul><ul><ul><li>Use nevirapine instead of efavirenz </li></ul></ul><ul><li>1boosted PI plus 2 NRTI </li></ul><ul><ul><li>Atazanavir/ritonavir or Fosamprenavir/ritonavir bid or Lopinavir/ritonavir bid </li></ul></ul><ul><ul><li>plus </li></ul></ul><ul><ul><li>Tenofovir/ emtricitabine or zidovudine/ lamivudine </li></ul></ul><ul><li>Alternative: </li></ul><ul><ul><li>Use unboosted atazanavir or unboosted fosamprenavir </li></ul></ul><ul><ul><li>Use boosted fosamprenavir or lopinavir/ritonavir once a day </li></ul></ul>Remember that NRTI come in fixed combinations. There is even a one pill once a day: tenofovir/emtricitabine/efavirenz Never use together emtricitabine and lamivudine or zidovudine and stavudine
  20. 20. Adherence is key to success <ul><li>Always assess readiness before starting treatment </li></ul><ul><li>Entire team should reinforce adherence </li></ul><ul><li>Health care staff predicts adherence poorly </li></ul><ul><li>Patients overreport adherence </li></ul><ul><li>Adherence worsens with time </li></ul><ul><li>Most likely regimen to succeed is first </li></ul><ul><li>Recommendations to improve adherence: </li></ul><ul><ul><li>Treatment simplification </li></ul></ul><ul><ul><li>Improvement in knowledge </li></ul></ul><ul><ul><li>Devices may help to remember </li></ul></ul><ul><ul><li>DOT may be difficult, but brief interventions may be beneficial </li></ul></ul>
  21. 21. What is failure and what can be done about it? <ul><li>Failure can be virological, immunological or clinical </li></ul><ul><li>Assess for: </li></ul><ul><ul><li>Adherence </li></ul></ul><ul><ul><ul><li>Access: social worker evaluation </li></ul></ul></ul><ul><ul><ul><li>Psychiatric comorbidity: mental health referral </li></ul></ul></ul><ul><ul><ul><li>Substance abuse: abstinence, abuse treatment </li></ul></ul></ul><ul><ul><ul><li>Tolerability: use symptomatics </li></ul></ul></ul><ul><ul><ul><li>Convenience: choose once a day regimens </li></ul></ul></ul><ul><ul><ul><li>Comprehension: teaching </li></ul></ul></ul><ul><ul><li>Resistance: use genotyping and phenotyping </li></ul></ul><ul><ul><li>Pharmacokinetic interactions: evaluate food and drug interactions </li></ul></ul><ul><li>Stopping ART is not a good idea </li></ul>
  22. 22. Interclass adverse effects Symptomatic treatment Treat osteoporosis Surgery? XR followed by MRI if symptoms present Any agent Osteopenia, osteonecrosis Switch antiretrovirals Liver function tests every 3-6 months Nevirapine, efavirenz, stavudine, zidovduine, didanosine, tipranavir Hepatitis Check for associated metabolic complications Cosmetic treatment? Consider switching antiretrovirals Question patient Imaging not recommended routinely Stavudine, zidovudine, protease inhibitors (lipoatrophy) Efavirenz (lipohyperthrophy) Lipodistrophy Use insulin sensitizing agents Consider switching antiretrovirals Fasting glucose every 3-6 months Mainly protease inhibitors Insulin resistance Use National Cholesterol Educational Program guidelines Consider switching antiretrovirals Fasting lipid profile every 3-6 months Stavudine Protease inhibitors (except atazanavir) Hyperlipidemia Treatment Testing Agents Toxicity
  23. 23. Lipodystrophy <ul><li>Fat accumulation (abdominal cavity, breast and central SC tissue) </li></ul><ul><li>Fat atrophy (loss of SC fat in face, extremities and buttocks) </li></ul><ul><li>Metabolic syndrome may be associated </li></ul><ul><li>Stavudine, zidovudine and PI </li></ul><ul><li> </li></ul><ul><li>Usually self diagnosed and confirmed on physical exam </li></ul><ul><li>Waist-hip ratio, DEXA, US, CT could be used </li></ul><ul><li>Treatment: diet, growth hormone, thiazolidinones, metformin, surgery, regimen change </li></ul>
  24. 24. Class and specific adverse effects Discontinue medication Never rechallenge Abacavir Hipersensitivity Discontinue medication Didanosine, zalcitabine, stavudine Peripheral neuropathy Discontinue medication Didanosine, zalcitabine Pancreatitis Erythropoietin, switch agent Zidovudine Bone marrow supression, especially anemia Discontinue medication NNRTI Rash including Steven Johnson’s syndrome Symptomatic PI, NRTI GI toxicity Treatment Agents Toxicity
  25. 25. Class and specific adverse effects Actually not adverse effects, but some physicians and patients get excited about them (they are “markers” of adherence) Reassure patient Atazanvir Indirect hyperbilirrubinemia (Gilbert’s syndrome) Reassure patient Zidovudine Macrocytosis without anemia Good hydration Avoid other nephrotoxic agents Indinavir (stones), tenofovir Nephrotoxic Avoid during pregnancy Efavirenz Teratogenicity Consider switching agent Efavirenz CNS toxicity Treatment Agents Toxicity
  26. 26. Drug interactions <ul><li>All PIs and NNRTIs are metabolized by the cytochrome P450 system (particularly CYP3A4 isoenzyme). </li></ul><ul><li>Drugs with potential interactions with PIs and/or NNRTIs: “statins”, benzodiazepines, Ca channel blockers, immunosuppressants, anticonvulsants, rifamycins, erectile dysfunction agents, ergot derivatives, azole antifungals, macrolides, oral contraceptive, and methadone. </li></ul><ul><li>All PIs are substrates of CYP3A4 and some PIs may also be inducers or inhibitors of other CYP isoenzymes. Ex: rifampin significantly reduces concentration of most PIs and NNRTIs. </li></ul><ul><li>The NNRTIs are also substrates of CYP3A4 and can act as an inducer (nevirapine), an inhibitor (delavirdine), or a mixed agent (efavirenz). </li></ul><ul><li>Low doses of ritonavir are used in clinical practice as a pharmacokinetic enhancer . </li></ul>
  27. 27. HIV in Pregnancy <ul><li>All pregnant women should be treated regardless of their CD4 count </li></ul><ul><li>Resistance testing is recommended </li></ul><ul><li>Avoid efavirenz and didanosine plus stavudine </li></ul><ul><li>Preferred combination is zidovudine, lamivudine and nelfinavir or boosted saquinavir </li></ul><ul><li>Nevirapine is recommended in developing countries </li></ul><ul><li>C-section reduces risk of perinatal transmission if viral load is detectable at the time of delivery </li></ul><ul><li>Breast feeding: not recommended in developed countries. Used in developing countries and good if used exclusively </li></ul>
  28. 28. Postexposure prophylaxis <ul><li>Risk for percutaneous exposure is low (0.33%) and lower for mucosal exposure (0.09%). Ten times higher risk for hepatitis C and 100 times for hepatitis B. </li></ul><ul><li>Prophylaxis depends on the source (seropositivity and viral load) and on the type of exposure (severe or not). </li></ul><ul><li>For high risk sources (with any type of exposure) and low risk sources with severe exposure three drugs are recommended. </li></ul><ul><li>For low risk sources with non-severe exposure two drugs are recommended. </li></ul><ul><li>Choice of drugs is similar to drugs used to treat for HIV. Preferred combination AZT + lamivudine + lopinavir/ritonavir </li></ul><ul><li>PEP should e started within 24 hours and kept for 4 weeks </li></ul><ul><li>Testing is required in 6 weeks, 3 months and 6 months </li></ul><ul><li>Advice about sexual precautions, pregnancy and breast feeding </li></ul><ul><li>In occasions non-occupational exposures may also require prophylaxis </li></ul><ul><li>HBV PEP depends on vaccine status of the health worker and the HBsAg status of the source. If indicated use HBIG x 1 and vaccine series within 7 days </li></ul><ul><li>There is no PEP available for hepatitis C </li></ul>
  29. 29. Cardiovascular complications <ul><li>Dilated cardiomyopathy </li></ul><ul><ul><li>Cause: mitochondrial toxicity, deficiency of selenium or carnitine </li></ul></ul><ul><ul><li>Causes CHF, arrythmia </li></ul></ul><ul><ul><li>TX:ART, treat CHF, control other CV risk factors </li></ul></ul><ul><li>Cardiovascular disease associated with ART </li></ul><ul><ul><li>DAD study showed that ART increases CV risk </li></ul></ul><ul><ul><li>Tx: diet exercise, smoking cessation, weight loss, treatment of HTN and DM </li></ul></ul><ul><ul><li>Use statins (pravastatin, fluvastatin, rosuvastatin, atorvastatin) for hypercholesterolemia and gemfibrozil or fenofibrate for hypertrygliceridemia </li></ul></ul><ul><ul><li>Switch PI </li></ul></ul><ul><li>Pulmonary hypertension </li></ul><ul><li>Tricuspid valve endocarditis </li></ul>
  30. 30. Dermatologic complications <ul><li>Bacillary angiomatosis </li></ul><ul><ul><li>B. henselea, B quintana </li></ul></ul><ul><ul><li>Resembles KS </li></ul></ul><ul><ul><li>May also cause lytic bone lesions, peliosis hepatis and endocarditis </li></ul></ul><ul><ul><li>Dx: using Warthin Starry silver stain </li></ul></ul><ul><ul><li>Tx: macrolide or doxycycline </li></ul></ul><ul><li>Cryptococosis </li></ul><ul><ul><li>Always consider invasive disease and obtain serum antigen and culture </li></ul></ul><ul><ul><li>Consider lumbar puncture </li></ul></ul><ul><ul><li>Differntial is limited: molluscum, penicillum, smallpox </li></ul></ul><ul><li>Folliculitis </li></ul><ul><ul><li>Eosinophilic </li></ul></ul><ul><ul><li>MRSA related </li></ul></ul>
  31. 31. Dermatologic complications <ul><li>Herpes simplex </li></ul><ul><ul><li>Papule-vesicle-ulcer-crust </li></ul></ul><ul><ul><li>Dx: clinical, but also culture, Tzanck preparation </li></ul></ul><ul><ul><li>Tx: acyclovir, famciclovir, valacyclovir </li></ul></ul><ul><ul><li>If resistant high dose acyclovir, foscarnet, cidofovir </li></ul></ul><ul><ul><li>It may also cause esophagitis, pneumonitis, hepatitis, encephalitis, keratitis </li></ul></ul><ul><li>Purigo nodularis </li></ul><ul><ul><li>May be related to arthropod bite </li></ul></ul><ul><ul><li>Hyperpigmented, hyperkeratotic, hyperpruritic </li></ul></ul><ul><ul><li>Tx: interrupt cycle pruritus-scratch </li></ul></ul>
  32. 32. Dermatologic complications <ul><li>Herpes zoster </li></ul><ul><ul><li>More than one dermatome suggest HIV infection </li></ul></ul><ul><ul><li>Risk factors include age and immunosuppression </li></ul></ul><ul><ul><li>Diagnosis is clinical. Remember painful prodrome </li></ul></ul><ul><ul><li>Other complications: encephalitis, transverse myelitis, PORN, ARN, vasculitis </li></ul></ul><ul><ul><li>Tx: famcyclovir, valacyclovir, IV acyclovir. Pain control: trycyclic antidepressants, gabapentin, narcotics, lidocaine patch. Steroids not used </li></ul></ul><ul><ul><li>Prevention: No vaccine. Use VZIG within 96 hours if exposed and susceptible. Do not forget isolation. </li></ul></ul><ul><li>Molluscum contagiosum </li></ul><ul><ul><li>Caused by poxvirus </li></ul></ul><ul><ul><li>Tx: curetage, cryotherapy, electrocauterization </li></ul></ul>
  33. 33. Dermatologic complications <ul><li>Kaposi’s sarcoma </li></ul><ul><ul><li>Caused by HHV-8 </li></ul></ul><ul><ul><li>Either dermic or visceral (mouth, GI and resp tract) </li></ul></ul><ul><ul><li>Tx: ART. If advanced may need local tx (cryosurgery, laser, radiatio, liquid nitrogen, vinblastin injection) or systemic tx (liposomal anthracyclines, paclitaxel) </li></ul></ul><ul><li>Scabies </li></ul><ul><ul><li>Look for burrows in interdigital spaces, wrists, axillas, buttocks </li></ul></ul><ul><ul><li>Dx: scraping </li></ul></ul><ul><ul><li>Tx: permethrin, lindane ivermectine </li></ul></ul><ul><ul><li>Consider Norwegian scabies in HIV </li></ul></ul><ul><li>Seborrheic dermatitis </li></ul><ul><ul><li>Tx is topical with steroids or shampoos containing zinc or selenium </li></ul></ul>
  34. 34. Gastrointestinal complications: chronic diarrhea <ul><li>Consider medication induced particularly PI </li></ul><ul><li>Cryptosporidum </li></ul><ul><ul><li>Watery diarrhea with nausea an vomiting </li></ul></ul><ul><ul><li>Dx: acid fast stain, IFA, EIA </li></ul></ul><ul><ul><li>Tx: ART, paromomycin, nitazoxanide </li></ul></ul><ul><li>Cyclospora </li></ul><ul><ul><li>Watery diarrhea </li></ul></ul><ul><ul><li>Dx: acid fast stain. Resembles cryptosporidium </li></ul></ul><ul><ul><li>Tx: TMP-SMX </li></ul></ul><ul><li>Isospora </li></ul><ul><ul><li>Watery diarrhea, abdominal pain and wasting </li></ul></ul><ul><ul><li>Dx: acid fast stain </li></ul></ul><ul><ul><li>Tx: TMP-SMX, quinolones </li></ul></ul><ul><li>Microsporidium (Septata intestinalis, Enterocitozoon bieneusi) </li></ul><ul><ul><li>Watery diarrhea </li></ul></ul><ul><ul><li>Dx: calcoflour white </li></ul></ul><ul><ul><li>Tx: ART, fumagilin, albendazole </li></ul></ul>
  35. 35. Gastrointestinal complications: chronic diarrhea <ul><li>CMV </li></ul><ul><ul><li>Associated with CD4 count < 50 </li></ul></ul><ul><ul><li>Colitis or enteritis with fecal WBC and or/blood </li></ul></ul><ul><ul><li>Biopsy with inclusion bodies </li></ul></ul><ul><ul><li>Treatment similar to retinitis </li></ul></ul><ul><li>Mycobacterium avium intracellulare </li></ul><ul><ul><li>It is a rare cause of pulmonary disease in HIV </li></ul></ul><ul><ul><li>Instead it causes disseminated disease with fever, night sweats, weight loss, diarrhea in patients with CD4 < 50 </li></ul></ul><ul><ul><li>Dx: AFB blood cultures </li></ul></ul><ul><ul><li>Tx: clarithromycin plus ethambutol. Some add rifabutin </li></ul></ul><ul><ul><li>Always r/o active disease before starting prophylaxis </li></ul></ul>
  36. 36. Other gastrointestinal complications <ul><li>Esophagitis </li></ul><ul><ul><li>Dysphagia and odynophagia are presenting symptoms </li></ul></ul><ul><ul><li>Empiric treatment with fluconazole is reasonable </li></ul></ul><ul><ul><li>If no improvement consider a biopsy: it can be HSV or CMV or an aphtous ulcer </li></ul></ul><ul><li>Pancreatitis </li></ul><ul><ul><li>Caused by didanosine or stavudine, as a consequence of mithocondrial toxicity, hence may be asscoiated with lactic acidosis </li></ul></ul><ul><ul><li>PI induced hypertrygliceridemia may be another cause </li></ul></ul><ul><ul><li>CMV is a rare causal agent. </li></ul></ul><ul><ul><li>Lipase is always more sensitive than amylase </li></ul></ul><ul><ul><li>Treatment is supportive </li></ul></ul>
  37. 37. Liver disease <ul><li>Hepatitis A </li></ul><ul><ul><li>Acute, self-limited, oral-fecal transmission </li></ul></ul><ul><ul><li>Common among MSM </li></ul></ul><ul><ul><li>May cause cholestasis (rarely) </li></ul></ul><ul><ul><li>Never becomes chronic </li></ul></ul><ul><li>Hepatitis B </li></ul><ul><ul><li>HBsAg (-), anti-HBc (-), anti-HBs (-): susceptible </li></ul></ul><ul><ul><li>HBsAg (-), anti-HBc (+), anti-HBs (+): immune due to natural infection </li></ul></ul><ul><ul><li>HBsAg (-), anti-HBc (-), anti-HBs (+): immune due to vaccination </li></ul></ul><ul><ul><li>HBsAg (+), anti-HBc (+), IgM anti HBc (+) anti-HBs (-): acute infection </li></ul></ul><ul><ul><li>HBsAg (+), anti-HBc (+), IgM anti HBc (-) anti-HBs (-): chronic infection </li></ul></ul><ul><ul><li>HBsAg (-), anti-HBc (+), anti-HBs (-): several interpretations </li></ul></ul>
  38. 38. Liver disease: hepatitis B <ul><li>HBeAg and HBV DNA levels are markers of viral replication </li></ul><ul><li>Follow LFT, but also albumin, PT, platelets, bilirrubin </li></ul><ul><li>Check AFB and liver US every 6-12 months </li></ul><ul><li>Always vaccinate patients if susceptible </li></ul><ul><li>If infected avoid ETOH, vaccinate against HAV </li></ul><ul><li>Tx indicated if ALT is levated and/or biopsy shows inflammation and there is evidence of viral replication </li></ul><ul><li>If ART indicated use lamivudine, emtricitabine, tenofovir </li></ul><ul><li>If ART not indicated use peg-interferon gamma, adefovir. </li></ul><ul><li>Entecavir may select for HIV resistance </li></ul>
  39. 39. Liver disease: hepatitis C <ul><li>Dx with antibody, confirmation with HCV RNA. If HCV RNA is negative repeat in 6 months, because viremia can be intermittent </li></ul><ul><li>Neither HCV viral load nor LFT correlate with disease progression </li></ul><ul><li>Initial management: alcohol abstinence, use of condoms, avoidance needle sharing, HAV and ABV vaccines </li></ul><ul><li>Liver biopsy is usually indicated (except genotypes 2 & 3) before tx </li></ul><ul><li>Tx: peginterferon alpha + ribavirin if HIV stable and no contraindications </li></ul><ul><li>Monitor for neutropenia, anemia, thyroid dysfunction, depression, flu like symptoms </li></ul><ul><li>HCV RNA at 12 weeks is a good predictor of outcome, but sustained virologic response is the goal </li></ul><ul><li>Always treat for 48 weeks </li></ul>
  40. 40. Other causes of liver disease in HIV infection <ul><li>Alcohol </li></ul><ul><li>Antiretroviral therapy </li></ul><ul><ul><li>Nevirapine hepatitis </li></ul></ul><ul><ul><li>PI/NNRTI transaminitis </li></ul></ul><ul><ul><li>Hepatosteatosis with zidvudine, stavudine and didanosine </li></ul></ul><ul><li>Cholangiopathy </li></ul><ul><ul><li>RUQ pain and cholestasis </li></ul></ul><ul><ul><li>CD4 usually below 100 </li></ul></ul><ul><ul><li>Causes: cryptosporidium, CMV, Cyclospora </li></ul></ul><ul><ul><li>Resembles sclerosing cholangitis </li></ul></ul><ul><ul><li>Tx: sphinterectomy </li></ul></ul>
  41. 41. Hematologic complications <ul><li>Anemia: </li></ul><ul><ul><li>HIV infection of marrow progenitor cells </li></ul></ul><ul><ul><li>Infiltrating tumor such as lymphoma, rarely KS </li></ul></ul><ul><ul><li>Infiltrating infection: TB, MAC, histoplasma </li></ul></ul><ul><ul><li>Parvovirus B19: dx with serology and PCR. Usually CD4 < 100. Tx: ART and IVIG </li></ul></ul><ul><ul><li>Nutritional and iron deficiency </li></ul></ul><ul><ul><li>G6PD deficiency: dapsone, ribavirin, primaquine </li></ul></ul><ul><li>ITP </li></ul><ul><ul><li>Mostly HIV related. TMP-SMX? </li></ul></ul><ul><ul><li>Tx: ART, sometimes preednisone, IVIG, splenectomy </li></ul></ul>
  42. 42. Neurologic complications: Cryptococcus <ul><li>Port of entry: lungs </li></ul><ul><li>Skin lesions resemble molluscum </li></ul><ul><li>One of the “less” symptomatic aseptic meningitis </li></ul><ul><li>Dx: serum cryptococcal antigen (90%), blood cultures (70%) </li></ul><ul><li>CSF: do not forget opening pressure. Other findings are similar to aspetic meningitis, but cells may be low or zero </li></ul><ul><li>India ink is rarely used any longer </li></ul><ul><li>Antigen is not useful for follow up, cultures are </li></ul><ul><li>Tx: amphotericin B + 5FC x 14 days followed by high dose of fluconazole for 1o weeks, followed by chronic supression. Premedicate patients and monitor Cr, K, Mg, LFT Repeat LP as needed or use lumbar drain. </li></ul>
  43. 43. Neurologic complications <ul><li>Toxoplasmic encephalitis </li></ul><ul><ul><li>Nearly always represents reactivation </li></ul></ul><ul><ul><li>Fever, headache, confusion and focal neurologic deficits </li></ul></ul><ul><ul><li>Dx: clinical, imaging, Toxoplasma IgG </li></ul></ul><ul><ul><li>Tx: sulfadiazine + pyrimethamine + leucovorin for 6 weeks plus manteinance </li></ul></ul><ul><li>PML </li></ul><ul><ul><li>Caused by JC virus </li></ul></ul><ul><ul><li>Cognitive impairment, visual field defects, hemiparesis, speech defects, no fever. CD4 < 200 </li></ul></ul><ul><ul><li>CSF is normal but JC PCR may be positive. MRI with hypodense lesions without edema or enhancement </li></ul></ul><ul><ul><li>Tx: ART, cidofovir? </li></ul></ul>
  44. 44. Neurologic complications <ul><li>Primary CNS lymphoma </li></ul><ul><ul><li>EBV associated </li></ul></ul><ul><ul><li>Focal symptoms, confusion, headache, memory loss, hemiparesis, seizures </li></ul></ul><ul><ul><li>CD4 usually below 50 </li></ul></ul><ul><ul><li>Single or multiple isodense or hypodense lesions, sometimes with ring enhancement. May affect corpus callosum </li></ul></ul><ul><ul><li>Dx: failure to respond to toxo treatment, negative toxo IgG, lack of fever, SPECT with thallium uptake </li></ul></ul><ul><ul><li>Tx: radiation and steroids </li></ul></ul><ul><li>CMV neurologic disease </li></ul><ul><ul><li>It can present as dementia, ventriculitis or ascending polyradiculomyelopathy </li></ul></ul><ul><ul><li>Dx is clinical plus PCR in CSF or brain </li></ul></ul><ul><ul><li>Treatment is with ganciclovir and foscarnte but tolerability and prognosis are poor </li></ul></ul>
  45. 45. Cytomegalovirus retinitis <ul><li>Asymptomatic or floaters, field defects or decreased visual acuity </li></ul><ul><li>CD4 count usually below 50 </li></ul><ul><li>Cottage cheese and ketchup on fundoscopy is diagnostic </li></ul><ul><li>Tx: for vision threatening lesion intraocular gancyclovir implant plus oral valgancyclovir. Only valgancyclovir if peripheral lesions. Alternatives: ganciclovir, foscarnet, cidofovir. </li></ul><ul><li>Implant does not protect contralateral eye </li></ul>
  46. 46. Oral complications <ul><li>Apthous ulcer </li></ul><ul><ul><li>HSV, CMV, drugs </li></ul></ul><ul><ul><li>Consider biopsy </li></ul></ul><ul><ul><li>Treat with topical lidocaine. triamcinolone </li></ul></ul><ul><li>Candidiasis </li></ul><ul><ul><li>Not an AIDS defining illness unless invasive </li></ul></ul><ul><ul><li>Not necessarily a white plaque. It white differentiate with hairy leukoplakia </li></ul></ul><ul><ul><li>Dx: KOH </li></ul></ul><ul><ul><li>Tx: topical clotrimazole, nystatin, fluconazole. If resistant: itraconazole, oral or IV amphotericin </li></ul></ul><ul><ul><li>Tx duration: vaginitis 1 day, oral 10 days, esophagitus 14 days </li></ul></ul><ul><li>Herpes simplex </li></ul><ul><li>Kaposi’s sarcoma </li></ul><ul><li>Oral hairy leukoplakia </li></ul><ul><li>Salivary gland enlargement </li></ul>
  47. 47. Pulmonary complications: Pneumocytis jirovecii <ul><li>Previously called P. carini, but PCP acronym remains </li></ul><ul><li>Subacute respiratory disease </li></ul><ul><li>Labs: hypoxemia, elevated LDH </li></ul><ul><li>CXR: “atypical pattern”, normal CXR, pneumothorax. Pleural effusion or consolidation are rare. “Cysts” are seen on CT. </li></ul><ul><li>Dx: Sputum, induced sputum or bronchosocpy. Giemsa, Diff-Quick, Gomori-methenamine silver, Gram-Weigert. </li></ul><ul><li>Tx: TMP-SMX 15-20 mg/kg plus prednisone (if hypoxemia is present) </li></ul><ul><li>Improvement takes several days. Resistance is rare </li></ul><ul><li>Alternatives: pentamidine, clindamycin+ primaquine, atovaquone (moderate cases), trimethexate, but TMP-SMX is best choice (treat thru rash) </li></ul>
  48. 48. Pneumocystis jirovecii pneumonia
  49. 49. Pulmonary complications: M. tuberculosis <ul><li>HIV increases the risk of HIV infection 100 times </li></ul><ul><li>TB can happen at any CD4 count. With high CD4 presentation is typical. With low CD4 disease may be disseminated, extrapulmonary or atypical </li></ul><ul><li>Now there is MDR and XDR M.tuberculosis (even in the USA) </li></ul><ul><li>Dx: AFB, culture in liquid media particularly MODS (microscopic observation drug susceptibilty), role of interferon gamma assays? </li></ul>
  50. 50. Pulmonary complications: M. tuberculosis <ul><li>Tx: isoniazid, rifampin, ethambutol, pyrazinamide for 4 months plus isoniazid and rifampin for 4 months. Add vitamin B6 </li></ul><ul><li>Do not use rifampin with protease inhibitors </li></ul><ul><li>Do not start TB treatment and ART at the same time </li></ul><ul><li>Prophylaxis (now called treatment of latent tuberculosis) is given to patients with PPD > 5. </li></ul><ul><li>Isoniazid is the best choice. Short course of rifampin + pyrazinamide is hepatotoxic </li></ul>
  51. 51. Renal complications <ul><li>Mixed cryglobulinemia: hepatitis C realted. With purpura, decreased complement and nephrotic syndrome </li></ul><ul><li>Heroin nephropathy: probably associated with impure drug. May resemble HIVAN, but usually associated with hypertension </li></ul><ul><li>HIVAN or HIV associated nephropathy causes collapsing focal glomerulosclerosis, particularly in african-american. Tretament is with ART, ACE inhibitorsd and steroids. It may go into ESRD </li></ul><ul><li>Nephrotoxic drugs: indinavir (renal calculi), tenofovir (Fanconi's syndrome), amphotericin, TMP-SMX, cidofovir, foscarnet </li></ul><ul><li>TTP: anemia, thrombocytopenia, hemolysis, kidney failure, neurologic changes. Cause unknown. Tx is plasma exhange an steroids </li></ul>
  52. 52. Syphilis <ul><li>Darkfield and DFA test are useful in primary disease </li></ul><ul><li>For late syphilis use non-treponemal tests (VDRL or RPR) and confirm with treponemal tests (FTA) </li></ul><ul><li>Non-treponemal tests behave atypically in HIV </li></ul><ul><li>LP is indicated if there is evidence of neurologic , ocular or auditory findings; treatment failure, late latent syphilis (> 1 year duration), non-penicillin treatment for VDRL > 1:32, but some recommend it in everybody with HIV </li></ul><ul><li>Neurosyphilis is diagnosed by pleocytosis, elevation of protein or positive VDRL </li></ul><ul><li>Treatment of choice is penicillin </li></ul>
  53. 53. Fungal infections <ul><li>Coccidioides immites </li></ul><ul><ul><li>Usual presentation is disseminated disease or meningitis </li></ul></ul><ul><ul><li>If disseminated: fever, generalized adenopathy, skin nodules or ulcers, hepatitis, bone lesions. </li></ul></ul><ul><ul><li>Dx: positive culture, biopsy with spherules, serology > 1/16 </li></ul></ul><ul><ul><li>Tx: amphotercin for diseminated, fluconazole for meningitis </li></ul></ul><ul><li>Histoplasma capsulatum </li></ul><ul><ul><li>Usual presentation is disseminated disease with fever, weight loss, fatigue, often lung and CNS compromise </li></ul></ul><ul><ul><li>Dx: stain of tissue, urinary histoplasma antigen </li></ul></ul><ul><ul><li>Tx: amphotericin for severe cases,itraconazole for moderate cases </li></ul></ul>
  54. 54. Immune reconstitution syndrome <ul><li>Atypical inflamatory disorder associated with immune recovery </li></ul><ul><li>It happens in temporal relation with starting antiretrovitral therapy and particularly in people with low CD4 as baseline </li></ul><ul><li>It causes unmasking of a previously unidentified disease or paradoxical worsening of a recognized and treated disease. </li></ul><ul><li>Example (right): Patient asymptomatic is started on ART due to low CD4 count. Two weeks later develops cough, fever and an infiltrate in the CXR and has AFB + in sputum. Dx: TB IRIS (umasking) </li></ul><ul><li>Example (below): Patient with AIDS and TB is started on treatment for both. Three weeks later remains symptomatic, CXR is worse. Dx: TB IRIS (paradoxical reaction) </li></ul>
  55. 55. Immune reconstitution syndrome <ul><li>It can happen with any opportunistic infection, but specially with M. tuberculosis, MAC and Crypto. </li></ul><ul><li>The manifestations are usually atypical and there is a significant inflammatory component with formation of granulomas </li></ul><ul><li>Treatment is to continue ART, start or continue specific treatment for opportunistic infection, use steroids </li></ul><ul><li>To prevent it, avoid using ART at the same time of treatment of opportunistic infection. Wait until antigen load diminishes </li></ul>Hypercalcemia may be a manifestation of IRIS!
  56. 56. Good luck!