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Title: HIV II


1
HIV II
  • Update on Opportunistic Infections
  • Prevention and Treatment

2
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3
Pathophysiology
  • Depletion of CD-4 cells (T-helper)
  • HIV binds
  • Cell entry
  • cell death

4
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

5
CD4 depletion syndromes
  • HIV/AIDS
  • idiopathic CD4 T lymphocytopenia
  • Iatrogenic
  • Corticosteroids
  • Immunosuppressants

6
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

7
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
8
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

9
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.

10
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.

11
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.
12
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.

13
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

14
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

15
HIV and fever
  • Disseminated MAC
  • before HAART, most common cause of FUO in
    advanced AIDS.
  • Disseminated histo
  • bartonellosis
  • CMV
  • cryptococcosis

16
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

17
MAC
  • Findings
  • Adenopathy
  • Elevated alk phos
  • anemia
  • Diagnosis
  • Blood culture
  • Tissue culture
  • Histopathology
  • Treatment
  • Macrolide ethambutol rifabutin
  • Amikacin
  • ciprofloxacin

18
MAC
  • Sources
  • Food
  • Water
  • soil
  • Screening not rec b/c no data for benefit,
    although predicts disease
  • No recs for avoidance

19
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

20
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

21
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.

22
Bartonellosis
  • HIV-higher incidence
  • Older cats less likely to transmit
  • Control fleas
  • No rec for primary prophylaxis
  • Consider long-term suppression (C-III)

23
CMV
  • Risk groups
  • MSM
  • IDU
  • Childcare exposure
  • Test IgG if lower risk group
  • Not IDU/MSM
  • IgG positive
  • Varies by country

24
CMV
  • Manifestations
  • FUO
  • pancytopenia
  • CNS
  • Retinitis
  • Blurred vision
  • scotomata
  • field cuts
  • Encephalitis
  • Transverse myelitis
  • Radiculitis
  • pneumonitis
  • GI
  • Gastritis/GU
  • DU
  • colitis

25
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

26
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 (-)

27
HIV and diarrhea
  • Cryptosporidium (nls)
  • Microsporidiosis
  • Isospora
  • Giardia (nls)
  • Cyclospora (nls)
  • bacterial enteric infections
  • Salmonella
  • Shigella
  • campylobacter
  • Listeria
  • CMV
  • Cdiff

28
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

29
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

30
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

31
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

32
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)

33
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

34
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

35
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

36
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

37
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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39
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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41
PCP
42
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.

43
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

44
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

45
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

46
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
47
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.

48
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

49
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

50
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

51
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

52
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

53
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55
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

56
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

57
Clin Chest Med - 01-DEC-1996 17(4) 725-44
58
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

59
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

60
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)

61
Med Clin North Am - 01-Nov-2001 85(6) 1461-91,
62
HIV and rash
  • Molluscum
  • HHV-8 (KS)
  • HPV
  • VZV
  • HSV
  • cryptococcus
  • Bartonella
  • Syphilis
  • Candida
  • Seborrheic dermatitis
  • Folliculitis
  • Eosinophilic
  • bacterial
  • Psoriasis
  • Onchomycosis
  • Prurigo nodularis
  • scabies

63
Molluscum contagiosum
  • Papular eruption
  • Pearly
  • umbilicated
  • Poxvirus
  • Usually CD4 lt 200
  • Rx liquid nitrogen

64
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

65
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

66
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.

67
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

68
HIV and headache
  • Cryptococcus-meningitis
  • Toxoplasmosis-enhancing
  • PML
  • lymphoma
  • HIV
  • CMV (perivent)
  • EBV

nonenhancing
69
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

70
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.
71
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

72
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

73
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

74
Toxoplasmosis
  • Encephalitis
  • sensorimotor deficits, seizure, confusion,
    ataxia.
  • Fever, headache common.
  • Multiple ring-enhancing lesions , often w/edema
  • Almost always due to reactivation

75
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.

76
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

77
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

78
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
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