Opportunistic Infections in Persons with HIV

Jimenez

Opportunistic Infections

+what happens after immune system deteriorates, result of ART

unlikely that organisms cause disease

• reactivation vs new exposure

increases risk of annual or infrequent malignancies

incidence and prevalence have decreased since ART

Examples of AIDs-defining illensses

Candidasis (oral or vaginal)

invasive cervical cancer

lymphoma (Burkitt, immunoblastic, or primary CNS)

Pneumonia (> or equal to 2 episodes in 1 year)

wasting syndrome due to HIV

Main and Long term strategy to treat HIV with ART

restore and preserve CD4 count

additionally: vaccines (live contra is <200cells/mm3)

OIs with no effective therapy

crytospoidiosis, microspoidiosis, progressive multifocal leukoenceohalopathy (PML), Kapisi Sarcoma

improve immune function with ART may improve disease outcomes

When to start ART for OIs

early = ≤ 2 weeks

Delay ART treatment in the following OIs

+and why

Cryptococcal Meningitis

TB meningitis

due to increased risk of immune reconstitution inflammatory syndrome (IRIS)

Inflammatory Reconstitution Inflammatory Syndrome (IRIS)

exaggerated inflammatory reaction upon initiating ART

occurs within first weeks/months

• rapid reduction of high loads and very low CD4 counts at baseline

resistant to slide

Inflammatory Reconstitution Inflammatory Syndrome (IRIS) Treatment

+when is ART interruption warranted

symptomatic : NSAIDs or corticosteroids (steroids can increase OI risk)

ART interruption warranted in severe/life-threatening reactions

Pneumocytosis Pneumoniae (PCP)

+pathogen, transmission

vulnerable population, diagnosis, complications, imaging presentation

pathogen: P.jirovecii (fungus)

transmission: spreads airborne route but no person-person

vulnerable: early age → 2-4 years old

Diagnosis:

• can’t culture

• sputum has low sensitivity

• PCR and B-glucan tests are sensitive but not specific

complication: Hypoxemia seen with mod-severe disease

• pO2 <70 mmHg (hypoxic)

• Alveolar-arterial O2 difference >35 mmHg

imaging presentation:

• chest xray: butterfly pattern

• CT scan: “ground-glass opacities

Pneumocytosis Pneumoniai (PCP) Treatment

• ADEs

Trimethoprim-sulfamethoxazoe (TMP-SMX)

• ADEs due to high dose

  • rash* (antihistamines), fever* (antipyretics) ,leukopenia, thrombocytopenia, azotemia, hepatitis, hyperkalemia

• if using as prophylaxis and still develop PCP → still treat with higher TMP-SMX doses

treat with supportive care before discontinuation

Steroids needed mod-severe disease (w/hypoxemia)

• start within 72 hours on PCP therapy

• Prednisone taper

Pneumocytosis Pneumoniai (PCP) Treatment Alternatives

IV Pentamidine

Atovoquone

Treatment Failure

wait at least 4-8 days before switching therapy

deterioration within the first 3-5 days of therapy

Pneumocytosis Pneumoniae (PCP) Prophylaxis

+when to start+stop

Prophylaxis: start if CD4 = <200 cells

• stop when >200 cells for >3 months

drug of choice: TMP-SMX

When to start ART in PCP

ASAP: within 2 weeks

Toxoplasma gondii Encephalitis (TE)

+pathogen, expsoure, transmission

pathogen: Protozoan Parasite

exposure: eating undercooked meat containing csporulated cat feces, ingesting raw shellfish

transmission: no person-person

TE clinical manifestions

+diagnosis

manifestation: focal encephalitis

• headache, confusion, motor weakness, fever

• non-focal manifestations: only H/A and psychiatric symptoms

• disease progression (w/o treatment): seizures, stupor. coma

diagnosis: IgG-positive

• CT or MRI

  • multiple lesion in grey matter associated with edema

• brain biopsy needed for definitive

TE treatment

+duration, ades, alternatives

Pyrimethamine + sulfadiazine + leucovorin

• ADES

  • Pyr: BM suppression, rash, nausea

  • Sulfa: rash, fever, leukopenia, hepatitis, crystalluria

duration: > 6 weeks

alternative: TMP-SMX

TE

+supportive care, chronic maintenance therapy, treatment failure

supportive care

• add corticosteroids (dexamethasone)

• add anticonvulsants

chronic maintenance therapy

• pyrimethamine + sulfadiazine + leucovorin

treatment failure

• clinical/radiological deterioration during the first week

• lack of clinical improvement within 10-14 days

TE prophylaxis

+1°, 2°, ART initiation

1° prophylaxis

• start if CD4 count decreases to <100 cells/uL

• DOC: TMP-SMX

• alt.: atovaquone

• discontinue if CD4 → >200 cells for > 3 months

2° prophylaxis

• same as maintenance therapy

  • lower dose

• alt: TMP-SMX, atovaquone

• discontinue is therapy, asymptotic, CD4 >200 cells/mm3 for > 6 months

Initiate ART within 2-3 weeks of TE

Mycobacterium avian complex (MAC)

+transmission, manifestations, lab findings, diagnosis

not person to person

disseminated multi organ failure

lab findings = anemia, increases phosphorus

diagnosis = clinical picture +culture → Need to rule out TB

MAC treatment

+duration

Azithormycin or clarithromycin + ethambutol + 3rd drug

duration = > 12 months

improves CD4

MAC Prophylaxis

+1°, 2°, initiation of ART therapy

1° prophylaxis: Azithromycin 1220 mg q wk

DO NOT START if on ART immediately

• start if CD4 <50 and not on ART

2° prophylaxis: discontinue treatment regimen if treated more than 1 year, asymptomatic, CD4 >100 cell for > 6 months

Initiate ART 2-3 weeks of TE

Cryptococcosis

+pahtogen, diagnosis, presentation

pathogen: Crytococcus Neoformans

preentation:

• subacute meningitis or meningeonecephalitis

Cryptococcosis Treatment

+induction stage, consolidation, chronic maintenance, supportive care

Induction:

• duration: > 7 days → meningitis, diffuse disease

• DOC: Liposomal AmpB + flucytosine PO 4x a day

  • (flucytosine can cause bone marrow suppression)

do lumbar puncture after; success = negative CSF culture

consolidation:

• duration: > 8 weeks from negative CSF culture

• DOC: fluconazole (high dose)

• If CSF culture + > 2 weeks, give fluconazole PO x 2 weeks

chronic maintenance

• fluconazole (lower dose)

• more more than 1 year from start of therapy)

supportive care

• if elevated ICP

  • removal of CSF with therapeutic lung puncture

Cryptococcosis Treatment Prophylaxis

+ 1°, 2°, ART initiation

1° Prophylaxis

• routine use not shown to improve survival

Starting ART therapy with Cryptococcosis

+monitoring

defer for ~4-6 weeks

monitor for IRIS symptom development

monitor for failure or relapse after clinical response

Amphotericin B

Tox., ADEs+mitigation

Nephrotoxcity

• K+ and Mg2++ wasting

  • consider supplementation

infusion related reactions

• if severe premeidicate 30-60 mins before dose