HIV II

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HIV II

• Update on Opportunistic Infections
• Prevention and Treatment

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Pathophysiology

• Depletion of CD-4 cells (T-helper)
• HIV binds
• Cell entry
• cell death

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CD4-deficiency

• Direct mechanisms  
• Accumulation of unintegrated viral DNA
• Interference with cellular RNA processing
• Intracellular gp 120-CD4 autofusion events
• Loss of plasma membrane integrity because of
  viral budding
• Elimination of HIV-infected cells by
  virus-specific immune responses

• Indirect mechanisms  
• Aberrant intracellular signaling events
• Syncytium formation
• Autoimmunity
• Superantigenic stimulation
• Innocent bystander killing of viral
  antigen-coated cells
• Apoptosis
• Inhibition of lymphopoiesis

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CD4 depletion syndromes

• HIV/AIDS
• idiopathic CD4 T lymphocytopenia
• Iatrogenic
• Corticosteroids
• Immunosuppressants

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Opportunistic infections

• For patients taking potent combination
  antiretroviral therapy (ART), beginning in 1996,
  there has been a dramatic decline in the
  incidence of AIDS-related opportunistic
  infections (OIs) such as Pneumocystis carinii
  pneumonia (PCP), disseminated Mycobacterium avium
  complex (MAC), and invasive cytomegalovirus (CMV)
  disease

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Guidelines for Prevention and Treatment of
Opportunistic Infections in HIV-Infected Adults
and Adolescents Recommendations from CDC, the
National Institutes of Health, and the HIV
Medicine Association of the Infectious Diseases
Society of America Prepared by Jonathan E.
Kaplan, MD1 Constance Benson, MD2 King K.
Holmes, MD, PhD3 John T. Brooks, MD1 Alice Pau,
PharmD4 Henry Masur, MD4 1CDC, Atlanta, Georgia
2 University of California San Diego, San Diego,
California 3University of Washington, Seattle,
Washington 4National Institutes of Health,
Bethesda, Maryland
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However

• Remains a leading cause of morbidity and death in
  HIV patients because
• 1) many patients are unaware of their HIV
  infection and seek medical care when an OI
  becomes the initial indicator of their disease
• 2) certain patients are aware of their HIV
  infection, but do not take ART because of
  psychosocial or economic factors and
• 3) certain patients are prescribed ART, but fail
  to attain adequate virologic and immunologic
  response because of factors related to adherence,
  pharmacokinetics, or unexplained biologic factors

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Furthermore

• The relation between OIs and HIV infection is
  bidirectional.
• HIV leads to immunosuppression that allows
  opportunistic pathogens to cause disease in
  HIV-infected persons.
• OIs and other coinfections that might be common
  in HIV-infected persons, such as sexually
  transmitted infections, can also have adverse
  effects on the natural history of HIV infection
  i.e increase viral load and therefore disease
  progression and transmission.
• chemoprophylaxis and vaccination directly prevent
  pathogen-specific morbidity and mortality, but
  they might also contribute to reduced rate of
  progression of HIV disease.

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Major changes in guidelines

• additional emphasis on the importance of ART for
  prevention and treatment of OIs, especially those
  for which specific chemoprophylaxis and treatment
  do not exist
• information on diagnosis and management of immune
  reconstitution inflammatory syndromes (IRIS)
• information on interferon-gamma release assays
  (IGRAs) for the detection of latent Mycobacterium
  tuberculosis infection
• updated information on drug interactions
  affecting use of rifamycin drugs for prevention
  and treatment of tuberculosis (TB) 5) addition
  of a section on hepatitis B virus (HBV)
  infection and 6) addition of a section on
  malaria to the OIs of geographic interest.

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Rating Strength of the Recommendation

• A Both strong evidence for efficacy and
  substantial clinical benefit support
  recommendation for use. Should always be offered.
  
• B Moderate evidence for efficacy -- or strong
  evidence for efficacy but only limited clinical
  benefit -- supports recommendation for use.
  Should generally be offered.
• C Evidence for efficacy is insufficient to
  support a recommendation for or against use. Or
  evidence for efficacy might not outweigh adverse
  consequences (e.g., drug toxicity, drug
  interactions) or cost of the chemoprophylaxis or
  alternative approaches. Optional.

• D Moderate evidence for lack of efficacy or for
  adverse outcome supports a recommendation against
  use. Should generally not be offered.
• E Good evidence for lack of efficacy or for
  adverse outcome supports a recommendation against
  use. Should never be offered.

Gross PA, Barrett TL, Dellinger EP, et al.
Purpose of quality standards for infectious
diseases. Clin Infect Dis 1994 18(3)421.
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Quality of evidence supporting the recommendation

• I Evidence from at least one properly randomized,
  controlled trial.
• II Evidence from at least one well-designed
  clinical trial without randomization, from cohort
  or case-controlled analytic studies (preferably
  from more than one center), or from multiple
  time-series studies. Or dramatic results from
  uncontrolled experiments.
• III Evidence from opinions of respected
  authorities based on clinical experience,
  descriptive studies, or reports of expert
  committees.

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ART therapy in OI

• Benefits of ART have been demonstrated for
  cryptosporidiosis, PML, microsporidiosis, KS and
  other relatively untreatable OIs
• Recommend begin ART (AIII)
• one recently completed randomized clinical trial
  has demonstrated a clinical and survival benefit
  of starting ART early, within the first 2 weeks,
  of initiation of treatment for an acute OI,
  excluding TB
• However, institution of ART during an OI can
  result in an exuberant immune response (IRIS)
• drug/drug interaction can also be difficult

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ART in acute OI

• Main point In cases of cryptosporidiosis,
  microsporidiosis, PML, KS, PCP, and invasive
  bacterial infections, the early benefits of ART
  outweigh increased risk related to these other
  factors and ART should be started as soon as
  possible

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HIV and fever

• Disseminated MAC
• before HAART, most common cause of FUO in
  advanced AIDS.
• Disseminated histo
• bartonellosis
• CMV
• cryptococcosis

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Mycobacterium avium-intracellulare complex (MAC)

• Disseminated
• FUO
• Fever, night sweats, weight loss, diarrhea
• Anemia, elevated alkaline phosphatase
• GI
• Visceral
• pulmonary

• Localized"immune reconstitution" illnesses
• biopsies show a granulomatous response
• lymphadenitis (mesenteric, cervical, thoracic)
• can mimic Pott's disease with disease presenting
  in the spine
• Pulmonary

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MAC

• Findings
• Adenopathy
• Elevated alk phos
• anemia
• Diagnosis
• Blood culture
• Tissue culture
• Histopathology

• Treatment
• Macrolide ethambutol rifabutin
• Amikacin
• ciprofloxacin

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MAC

• Sources
• Food
• Water
• soil
• Screening not rec b/c no data for benefit,
  although predicts disease
• No recs for avoidance

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MAC prophylaxis

• Primary CD4 lt 50 until gt100 3 mo. (AI)
• Clarithromycin
• Azithromycin
• Rifabutin (not combo-EI)
• Exclude TB
• DIs
• Secondary for 12 mo and until CD4 no sx and CD4
  gt100 6 mo (BCx neg)
• Macrolide ethambutol, /- rifabutin
• High dose clarithromycin asso. W/higher mortality
  (EI)
• Clofazimine too many ADRs (DII)
• Restart at CD4 lt50-100

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Drug Interactions

• Azithromycin not affected by c P450
• Protease inhibitors
• Increase clarithromycin levels
• Some contraindicated w/rifabutin

• NNRTIs (efavirenz)
• Induce clarithromycin metabolism
• Some contraindicated w/rifabutin

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Bartonella

• B. henselae and B. quintana
• Manifestations
• Bacillary angiomatosis (BQ)
• Lymphadenitis (BH)
• Hepatosplenic disease (BH)
• peliosis hepatis
• GI
• Brain
• neuropsych
• bone

• Treatment
• Erythromycin
• Tetracycline deriv.

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Bartonellosis

• HIV-higher incidence
• Older cats less likely to transmit
• Control fleas
• No rec for primary prophylaxis
• Consider long-term suppression (C-III)

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CMV

• Risk groups
• MSM
• IDU
• Childcare exposure
• Test IgG if lower risk group
• Not IDU/MSM
• IgG positive
• Varies by country

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CMV

• Manifestations
• FUO
• pancytopenia
• CNS
• Retinitis
• Blurred vision
• scotomata
• field cuts
• Encephalitis
• Transverse myelitis
• Radiculitis

• pneumonitis
• GI
• Gastritis/GU
• DU
• colitis

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CMV

• Diagnosis
• Serology-not helpful
• Tissue histopathology
• Molecular diagnostics
• Antigen
• PCR

• Treatment
• Valganciclovir
• Ganciclovir 5 mg/kg IV bid 14-21 days
• Foscarnet 60 mg/kg IV q8h or 90 mg/kg IV q12h
  14-21 days
• Cidofovir 5 mg/kg IV weekly 2 then every other
  week
• Implants

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CMVprophylaxis

• Primary
• Can consider if IgG () and CD4 lt50
• Oral ganciclovir or valganciclovir
• Regular optho exams
• Discuss symptoms
• NOT acyclovir/valacyclovir

• Secondary
• Intraocular alone not sufficient
• Valganciclovir
• Consider stopping when CD4gt100-150 6mo
• Continue regular f/u
• CMV-neg or leukopoor irradiated blood if CMV (-)

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HIV and diarrhea

• Cryptosporidium (nls)
• Microsporidiosis
• Isospora
• Giardia (nls)
• Cyclospora (nls)

• bacterial enteric infections
• Salmonella
• Shigella
• campylobacter
• Listeria
• CMV
• Cdiff

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HIV and diarrhea

• Crampy abdominal pain, bloating, and nausea
  suggest small bowel
• Cryptosporidia
• Microsporidia
• Isospora
• Giardia
• cyclospora)
• MAC.
• High-volume, watery diarrhea with weight loss and
  electrolyte disturbance is most characteristic of
  cryptosporidiosis
• bloody stools with abdominal cramping and fever (
  invasive bacterial pathogen)
• Clostridium difficile
• CMV colitis

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HIV and diarrhea

• Stool studies
• OP
• Trichrome
• AFB
• Immunohisto
• Cdiff
• Thorough history
• Medication review
• Low threshold for flex sig

• Given the availability of effective treatment
  more aggressive evaluation that often includes
  endoscopy has replaced the less invasive
  approach.
• Treatment
• Antimotility agents
• Imodium, Lomotil
• Opium
• Calcium
• octreotide

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Bacterial Enteric InfectionsPrevention

• Seek vet care for animals with diarrhea
• WASH HANDS
• Travel precautions
• Bottled beverages
• Avoid fresh produce
• Avoid ice
• Consider prophylaxis or early empiric therapy
• Cipro 500 qd
• Bactrim

• Avoid
• Reptiles, chicks and ducklings
• Raw eggs
• Raw poultry, meat and seafood
• Unpasteurized dairy products/juices
• Raw seed sprouts
• Soft cheeses
• Deli counters unless can reheat
• Refrigerated meat spreads

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Cryptosporidium

• coccidian protozoan (I. belli, C. cayetanensis,
  and Toxoplasma gondii)
• 5-10 of diarrhea in immunocompetent
• Asymptomatic carriers
• mammalian hosts-cattle, horses, rabbits, guinea
  pigs, mice.
• transmission fecal-oral.
• thick-walled, highly resistant oocyst

• Waterborne outbreaks due to contamination of
  drinking water
• excysts in stomach
• sporozoites infect enterocytes and persist at the
  apical pole of intestinal epithelial
  cells-microscopic appearance of extracellular,
  adherent parasite

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Cryptosporidiosisprevention

• biopsy
• fecal examination
• Modifed AFB
• Immunohisto stains
• Treatment
• Azithromycin
• Paromomycin
• Octreotide
• nitazoxanide
• HAART

• Clarithromycin/rifabutin work, but no data.
• Counsel regarding exposure-avoid feces
• Private room
• Diapers
• Animals with diarrhea
• young animals (screen BIII)
• water
• boil water when suggested (AI)
• filters (CIII)
• oysters
• bottled (CIII)

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Microsporidiosis

• observed initially in intestinal biopsy specimens
  in 1982
• No disease in normal hosts
• 2 types
• Enterocytozoon bieneusi, reproduces within
  enterocytes
• Encephalitozoon (Septata) intestinalis infects
  epithelial cells and stromal cells of the lamina
  propria and causes systemic infection

• Diagnosis
• Difficult to see by light microscopy-order
  trichrome stain
• Treatment
• Albendazole (for intestinalis)
• Atovaquone
• metronidazole.
• No recs for prevention

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Isospora

• no other known host
• endemic in Brazil, Colombia, Chile, and parts of
  equatorial Africa and southwest Asia.
• seen rarely in normals
• fecal-oral route

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Isospora

• histologic sections
• Villus atrophy, eosinophil infiltrates, and
  disorganization of the epithelium
• shown better with Giemsa on histo
• Cipro better than Bactrim

• Immunocompetent
• watery diarrhea
• usually clear the infection within about 2 weeks
  
• may persist
• HIV-chronic high-volume watery diarrhea
• Detection in stool samples difficult, and
  concentration or flotation methods. AFB

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Cyclospora

• first reported in the 1980s
• endemic in tropical countries and other areas
  w/poor standards of hygiene and water
  purification
• severity related to the degree of
  immunosuppression
• Rx Bactrim

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Cyclospora

• Epidemics attributed to contamination of water
  supplies, fruits, and vegetables
• similar to Cryptosporidium but larger (8 to 10
  mum versus 4 to 5 mum) and AFB
• fecal-oral route
• intermittent watery diarrhea for 3 gt mo.
• infect enterocytes and proliferate within a
  supranuclear parasitophorous vacuole.

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HIV and pneumonia

• PCP
• histoplasmosis
• cryptococcosis
• rhodococcus
• CMV

• Pneumococcus
• 100-fold risk
• Nontypable H. flu
• Pseudomonas
• 40-fold risk
• Lowest CD4
• HHV-8
• Coccidiodomycosis

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PCP
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PCP

• Symptoms
• Insidious onset
• SOBgtcough
• Pneumothorax
• Before HAART, 70-90 of AIDS pts got PCP, and
  mort was 20-40
• Findings
• diffuse infiltrates in a perihilar or bibasilar
  distribution and a reticular or reticulonodular
  pattern
• No effusion
• Elevated LDH
• SXgtgtgtCXR
• Normal in 26
• Poor air movement

• Microbiology
• P. jiroveci infects human
• P. carinii infects rodents
• 2/3 of kids are infected by 2-4 yo
• Fungus with protozoal properties
• Diagnosis (preferred)
• Expectorated sputum much less sensitive
• Sputum for DFA
• Sputum cytology
• BAL for same
• Histopathology/stains
• Isolation controversial-some rec private room.

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PCP treatment

• TMP 15 mg/kg/d SMX 75 mg/kg/d po or IV 21
  days in 3-4 divided doses for outpatient, 2 DS
  tablets po tid (AI)
• rash, fever, gastrointestinal symptoms,
  hepatitis, hyperkalemia, leukopenia, and
  hemolytic anemia
• Steroid (pO2 lt 70 or A-a gradient gt 35)
• Mortality remains 50 in those requiring ICU or
  mech ventilation
• TMP-dapsone
• Clinda/primaquine
• Atovaquone
• Trimetrexate/folinic acid
• Iv Pentam
• toxicity

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PCP treatment complications

• methemoglobinemia and hemolysis with dapsone or
  primaquine (especially in those with G6PD
  deficiency)
• rash and fever with dapsone
• azotemia, pancreatitis, hypo- or hyperglycemia,
  leukopenia, electrolyte abnormalities, and
  cardiac dysrhythmia with pentamidine
• anemia, rash, fever, and diarrhea with primaquine
  and clindamycin
• headache, nausea, diarrhea, rash, and
  transaminase elevations with atovaquone
• IRIS
• Treatment failure

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PCPprophylaxis

• CD4lt200 or history of oral thrush (AII)
• CD4lt14 or other OI (BII) consider

• Bactrim (AI)
• DS daily (toxo, bacterial pathogens)
• SS daily
• DS TIW (BII)
• rechallenge if rash (desens) - 70 tolerate, can
  use gradual dose increase

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PCPprophylaxis

• Dapsone
• Dapsone pyrimethamine/ leucovorin
• aerosolized pentam (Respirgard II)-pregnancy 1st
  term
• Atovaquone ()

• Other aerosolized Pentam
• parenteral pentam
• oral pyrimethamine/ sulfadoxine
• oral clinda/primaquine
• trimetrexate

All BI
All CIII
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PCPprophylaxis

• Stop when CD4gt200 for 3 mo. (AI)
• Restart if CD4lt200
• Stop secondary prophylaxis if CD4gt200 unless PCP
  occurred at higher CD4

• Children of HIV mothers need prophylaxis
• Children with PCP can not stop secondary
  prophylaxis.

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Typical CAP

• Pulmonary Complications of HIV Infection Study
• incidence 3.97.3 episodes per 100 person-years
• preHAART
• Increased mortality
• Most common Pneumococcal and H. flu
• Increased incidence of Pseudomonas and Staph
• Any age or CD4
• Treatment
• Similar to non HIV but no macrolide alone
• Be cautious about quinolone if TB suspected
• IRIS has not been described

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Typical CAP

• Diagnosis
• c/w PCP, localized findings on exam
• Lower threshold for testing b/c broad diff
• BCx higher yield
• Prevention
• Maintain normal granulocyte count IgG
• Bactrim and macrolide prophylaxis prevent resp
  infections, but not rec solely for this reason
• Stop smoking, excess alcohol or drug use
• Flu vaccine (not live)
• Pneumovax
• BII rec if CD4gt200
• No data for CD4lt200 (less data)
• Repeat in 5 years (even less data)
• Repeat when CD4 gt200

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Tuberculosis

• Low threshold of suspicion
• Lower CD4atypical presentation
• Higher mortality
• Per WHO cause of death in 12 of AIDS cases
• Tuberculin skin testing (TST) negative in 40 of
  patients with disease
• 1/3 of cases are primary in HIV

• 4-drug therapy initially
• Drug interactions major issue
• Associated w/IRIS

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TB-atypical presentation

• In advanced AIDS
• CXR different
• Lower lobe, middle lobe, interstitial, and
  miliary infiltrates common
• Cavitation less common
• Marked mediastinal LAD
• Normal CXR can be smear positive!
• Extrapulmonary more common
• LAD, pleuritis, pericarditis, meningitis.
• Sepsis-like syndrome
• Histopath may not show granulomas

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Tuberculosis prevention

• PPD for all new diagnoses of HIV
• Positive is gt/ 5
• IGRA can be used (but decreasing sens w/CD4)
• Retest when immune reconstitution
• All latent TB in HIV gets treated, as do all
  close contacts w/HIV.
• INH/B6 9 months (AII)
• rifampin 4 months (BIII)
• rif/PZA for 2 months
• hepatic toxicity-no longer recommended
• rifabutin can be subd (less data)
• Consider annual if continued risk
• Employment
• Homeless
• Foreign travel

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Tuberculosis-treatment

• New guidelines
• Emphasize DOT and provider responsibility
• Louis Pasteur once said, "The microbe is
  nothing...the terrain everything"
• Reculture at 2 mo of trx
• Extend if still and cavitary disease
• Everyone gets 2 months 4 drugs, then 4 months 2
  drugs at least
• 3 extra months if cavitary and positive cx

• CNS disease gets 9-12 months
• CD4 cell counts lt100/µl should receive daily or
  three times weekly treatment
• paradoxical flares occur i.e IRIS
• Associated w/HAART
• Effusions, infiltrates, enlargement of CNS
  lesions, nodes, fever
• Steroids used

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Histoplasmosis

• THE MOST common endemic mycosis
• CD4 lt150
• Pulmonary, mucosal, disseminated or CNS
• Respiratory culture
• Blood culture
• Bone marrow biopsy
• Urine Ag
• Some cross reaction
• More sensitive in dissem disease, esp HIV
• Rx ampho, itra
• At least a yr

• Mississippi valley and Ohio valley worldwide
• Normal hosts usually asympto or mild URI-no rx

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Clin Chest Med - 01-DEC-1996 17(4) 725-44
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HistoplasmosisPrevention

• Routine skin testing not predictive
• Avoid
• Creating soil/old building dust
• Cleaning chicken coops
• Disturbing bird roosts
• Exploring caves

• Secondary prophylaxis
• Itraconazole (AII)
• ACTG sudy reported success stopping if ART x 6mo,
  gt1yr rx, neg BCx, histo ag lt2, CD4 gt150
• Resume if fall lt150
• Primary Prophylaxis
• No proven survival benefit
• Consider in high risk and CD4lt100

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Coccidiocomycosis

• Growth is enhanced by bat and rodent droppings.
• Exposure is heaviest in the late summer and fall
• Acute pulm, chronic pulm, dissem, CNS
• Southwestern United States and parts of Central
  and South America
• more severe in immunosuppressed individuals,
  African Americans, and Filipinos
• 2/3 of immunosuppressed have disseminated disease

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Coccidiocomycosis

• Avoid disturbing native soil
• Diagnose by serology or biopsy (spherules)
• Blood cultures not usually positive
• Skin test not predictive
• Treatement
• Amphotericin or azole
• Often refractory to treatment
• Primary px in endemic areas if positive serology
  and low CD4
• Secondary prophylaxis can be stopped after 12
  months of rx if CD4 gt250 and on HAART, and if
  focal PNA. Cant stop if CNS or disseminated.
  High relapse rate (AII)

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Med Clin North Am - 01-Nov-2001 85(6) 1461-91,
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HIV and rash

• Molluscum
• HHV-8 (KS)
• HPV
• VZV
• HSV
• cryptococcus
• Bartonella
• Syphilis

• Candida
• Seborrheic dermatitis
• Folliculitis
• Eosinophilic
• bacterial
• Psoriasis
• Onchomycosis
• Prurigo nodularis
• scabies

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Molluscum contagiosum

• Papular eruption
• Pearly
• umbilicated
• Poxvirus
• Usually CD4 lt 200
• Rx liquid nitrogen

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HHV-8

• Agent of Kaposis sarcoma (HHV8)
• Vertical transmission occurs
• No screening available
• HAART has enormous effect
• May be accelerated if infected after HIV
• Advise about prevention

• Manifestations
• Cutaneous
• Mucosal
• Visceral
• GI
• Pulmonary
• other

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Human papillomavirus

• Manifestations
• Condyloma acuminata
• Plantar warts
• Facial
• Periungual

• Genital epithelial cancer
• Twice yearly screening, then annual in women
• Follow NCI guidelines
• Screening for men being developed

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Herpes

• VZV
• Prior frequent ADI, occurs at CD4 200-500
• Dermatomal, ocular, disseminated
• No effective secondary prevention recs
• Avoid exposure
• Vaccinate relatives
• VZIG if exposed and negative

• HSV
• Very common (gt90 of MSM sero)
• Severe, erosive disease, proctitis
• Some need chronic suppression (acyclovir/famcyclov
  ir)
• Resistance occurs and cross-res w/ganciclovir.

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Candida Infections

• Manifestations
• Oral thrush
• Esophageal candidiasis
• Candidal dermatitis
• vulvovaginal
• Treatment
• fluconazole
• Clotrimazole
• Nystatin
• Itraconazole
• Amphotericin (po or iv)

• Responds quickly to therapy
• Primary prophylaxis not rec
• Secondary is optional, prefer early empiric rx
• Azole resistance is an issue

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HIV and headache

• Cryptococcus-meningitis
• Toxoplasmosis-enhancing
• PML
• lymphoma
• HIV
• CMV (perivent)
• EBV

nonenhancing
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Cryptococcus

• Meningitis
• Headache
• subtle cognitive effects.
• Occaasional meningeal signs and focal neurologic
  findings
• nonspecific presentation is the norm
• Pulmonary disease
• Disseminated disease
• FUO
• Adenopathy
• Skin nodules
• Organ involvement

• Diagnosis
• CSF Ag sens100
• Need opening pressure
• Treatment
• Ampho 5FC (GI, hem toxicity)
• Fluconazole when CSF cx neg, 2wks, and
  improvement clinically

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Forehead ulcer. This is in an HIV-infected host
with Cryptococcus neoformans seen in
histopathology. 
Cytospin CSF preparation of host with
cryptococcal meningitis. This shows an
encapsulated yeast surrounded by a mixed
inflammatory reaction. 
Cryptococcal nodule. This was a previously
healthy, asymptomatic patient with a right lung
nodule.
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Cryptococcal meningitis

• Intracranial pressure management
• gt250 mm H2 O was seen in 119 out of 221 patients
• higher titers of cryptococcal antigen
• more severe clinical manifestations
• headache, meningismus, papilledema, hearing loss,
  and pathologic reflexes
• shortened long-term survival
• Desired OP lt 200 mm H2 O or 50 of the initial
  pressure
• Daily lumbar punctures until the pressure is
  stable
• Lumbar drain
• Ventriculoperitoneal shunting
• Corticosteroids, mannitol and Diamox are not
  recommended

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CryptococcusPrevention

• Primary prophylaxis effective but generally not
  rec
• Secondary until CD4 gt200 6 mo. and no sx (BII)
• Fluconazole (AI) (itra inferior)
• Restart at lt200

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Toxoplasmosis

• Seroprevalence 15 in the United States and
  50--75 in certain European countries
• preART, 1/3 of pts w/advanced AIDS got toxo
  within 12 months
• Usually CD4 lt50, rare for lt200

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Toxoplasmosis

• Encephalitis
• sensorimotor deficits, seizure, confusion,
  ataxia.
• Fever, headache common.
• Multiple ring-enhancing lesions , often w/edema
• Almost always due to reactivation

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Toxoplasmosis diagnosis

• Toxoplasmosis seronegative or toxoplasmosis
  prophylaxis or lesions atypical radiographically
  for toxoplasmosis (single, crosses midline,
  periventricular) CSF exam /- biopsy
• EBV PCR highly correlates with lymphoma
• JCV PCR c/w PML
• toxo PCR diagnostic but insensitive
• Toxo IgG no prophylaxis Empiric Rx
• Clinical response is usually seen within 7 days
  (and often sooner)
• radiographic response in 14 days.

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ToxoplasmaTreatment

• Pyrimethamine 100-200 mg then 50-100 mg/d
  folinic acid 10 mg/d sulfadiazine 4-8 g/d for
  at least 6 weeks
• Or sub clinda, azithro, clarithro or atovaquone
• Steroids if mass effect

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Toxoplasmaprophylaxis

• Screen for IgG (BIII)
• if negative, aggressively counsel regarding
  avoidance of cat litter, raw meat (165 deg)
• wash, wear gloves when gardening
• wash vegetables
• keep cats indoors, avoid raw meat foods
• getting rid of or testing the cat is an EIII
  offense!
• CD4 lt100 if seropositive only

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Toxoplasmaprimary prophylaxis

• For CD4lt100 and seropositive
• Trim/sulfa DS qd (AII)
• dapsone/pyrimethamine plus leucovorin(BI)
• atovaquone (CIII)
• dapsone, macrolides, pyrimethamine dont work
  (DII)
• Aerosolized pentam definitely doesnt work (EII)

79
Toxoplasmaprimary prophylaxis

• Stop primary px when CD4 gt 200 for 3 months
• stop secondary when gt200 6 months
• restart when CD4 drops lt100 again

80
Toxoplasmasecondary prophylaxis

• After initial therapy completed
• Pyrimethamine plus sulfadiazine
• pyrimethamine plus clinda (not for PCP)
• stop when CD4gt200 for 6 months, no symptoms and
  initial therapy completed
• restart if drop below 200

81
Prevention of Exposure

• Currently, there are no recommendations for
  preventing exposure to
• P jiroveci pneumonia (PCP) no data to support
  isolation in hospital
• M avium complex (MAC) no data
• S pneumoniae and H influenzae not practical
• Candidiasis not practical
• Cryptococcosis not practical

82
Review-when to stop prophylaxis
83
Other References

• Opportunistic infections in HIV disease down but
  not out. Sax PE - Infect Dis Clin North Am -
  01-JUN-2001 15(2) 433-55
• Graybill JR, Sobel J, Saag M, et al Diagnosis
  and management of increased intracranial pressure
  in patients with AIDS and cryptococcal
  meningitis. The NIAID Mycoses Study Group and
  AIDS Cooperative Treatment Groups. Clin Infect
  Dis 3047, 2000
• Infectious diarrhea in human immunodeficiency
  virus. Cohen J - Gastroenterol Clin North Am -
  01-SEP-2001 30(3) 637-64
• State-of-the-art review of pulmonary fungal
  infections. Seminars in Respiratory
  Infections.Volume 17 Number 2 June 2002