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Opportunistic infections (Bacterial infections (Mycobacterium tuberculosis…

- - - - Sub acute onset
        Nonproductive cough
        Fever
        Progression of exertional dyspnea
        Symptoms lasting for weeks
    - - Hypoxemia with reduced pO2
        X-ray: bilateral, symmetrical interstitial infiltrates /but may be normal in 20% of cases/
        Thin-section CT scan: ground glass attenuation /negative thin-section CT scan does not exclude PCP
    - - cytology / histopathology of induced sputum (sensitivity up to 80%), bronchoalveolar lavage (sensitivity > 95%) or bronchoscopic tissue biopsy (sensitivity > 95%)
        Immunofluorescent stains /higher yield/
        Positive stains remain positive for weeks after treatment so treatment can be initiated before specimen collection
      - Definitive diagnosis
        Cough and dyspnoea on exertion AND diagnosis by cytology / histopathology of induced sputum (sensitivity up to 80%),
        bronchoalveolar lavage (sensitivity > 95%) or
        bronchoscopic tissue biopsy (sensitivity > 95%)
      - Presumptive diagnosis
        CD4 count < 200 cells/ μL AND dyspnoea / desaturation on exertion and cough AND radiology compatible with PcP AND no evidence for bacterial pneumonia AND response to PcP treatment
    - - Preferred regimen:
        Trimetoprim 3x5mg/kg/day + Sulfometoxazol 3x25mg/kg/day PO or IV x 21 days.
        
        Alternative regimen:
        Pentamidine 1x4mg/kg/day IV x21 days
        Hypoxemia: patients with moderately severe or severe disease /pO2<70mm/ should receive corticosteroids /Prednisone 40mg PO bid x 5 days, then 40mg PO qd x 5 days, then 20mg/day 10 days/. Efficacy of corticosteroids for hypoxemia is established. Benefit of corticosteroids if started within 72 hours after start of treatment
        Treat at least 21 days, then secondary prophylaxis until CD4 count > 200 cells/μL and HIV-VL undetectable over 3 months
      - Adverse reactions to TMP-SMX
        Rash 30-55%
        Fever 30-40%
        Leukopenia 30-40%
        Hepatitis 20%
        Thrombocytopenia 15%
      - prophylaxis
        
        Primary if CD4<200 no symptoms of PcP
        
        Secondary after PcP treatment
        
        Preferred regimen:
        TMX-SMX 1 ds. tablet (800/160mg)/3x week or 1 ss tablet (400/80mg)1x/day or 1 ds. tablet (800/160mg) a day
        
        Discontinuation
        Patients who have increased in CD4 to >200/mm3 and HIV VL undetectable > 3 months may safely discontinue primary and secondary PCP prophylaxis
  - - - Definitive diagnosis:
        macroscopic inspection at endoscopy, OR histology of biopsy, OR cytology of specimen from the mucosal surface
        Presumptive diagnosis:
        if 1. Recent onset of dysphagia AND 2. Oropharyngeal candidiasis
    - - Usually empirically
        Characteristic rapid response
        Preferred regimen:
        Fluconazole 400mg loading dose then 200mg po 10-14 days
        Itraconazol 100-200mg/day 10-14 days (drug drug interactions with ARVs)
        Voriconazol 2x200mg/day
        In cases of refractory disease, treat according to resistance testing.
  - - - Usual presentation is sub acute meningitis
        Fever, Headache
        Malaise, CD4 count < 100/mm3
        Many have non-meningeal sites ex. skin with vesicular or papular lesions that may resemble molluscum or pneumonitis which may be difficult to distinguish from PcP
    - - Primary prophylaxis:
        One large RCT in Africa (the REALITY trial suggests that an enhanced infection prophylaxis in severely immunosuppressed persons (< 50 CD4 cells/μL) including INH 12 weeks, fluconazole 100 mg/day for 12 weeks, azithromycin 500 mg/day for 5 days and albendazole 400 mg single dose may decrease overall opportunistic infections (including cryptococcal meningitis) and mortality.
      - Pre-emptive therapy:
        Early stages of disseminated cryptocccal infections may be oligosymptomatic. Newer data from mainly resource limited settings support determination of serum cryptococcal antigen in all newly diagnosed HIV-positive persons with CD4 counts < 100 cells/μL. If cryptococcal antigen is detected, CSF should be examined to rule out cryptococcal meningitis. If meningitis is ruled out, pre-emptive therapy with fluconazole 800 mg/day po for two weeks is recommended before starting cART to reduce the risk of unmasking IRIS.
      - Diagnosis
        
        CSF analysis:
        elevated opening preasure />200mmH2O in 75%/
        increased protein
        decreased glucose level
        mononuclear pleocytosis /5-100 mg/dL/
        
        Positive CSF culture: >95%
        Positive CSF cryptococcal antigen : >95%
        Positive CSF india ink: 60-80%
        Positive blood cultures: 50-70%
        Positive serum cryptococcal antigen: >95%
      - treatment
        
        Induction therapy – 14 days: Liposomal amphotericin B 0,7mg/kg/day IV + 5-FC 4x25mg/day po
        
        Then perform lumbar puncture (LP): if CSF culture is sterile, switch to oral consolidation therapy – 8 weeks: Fluconazole 400mg/day
        
        Maintenance therapy at least 12 months – Fluconazole 200mg po , consider to stop if CD4 > 100 cells/µl and HIV VL undetectable for over 3 months
- - - - CD4 count <100/mm3
        
        Focal neurological deficits
        
        Headache
        
        Confusion
        
        Fever
    - - CNS imaging: MRI - >2 ring enhancing lesions
        
        Positive anti T.gondii IgG >90% /serology/
        
        CSF T.gondii PCR 50% sensitive, >96% specific
        
        Most patients respond to therapy with clinical and MRI improvement in about 2 weeks, which is diagnostic
        
        Brain biopsy HE stain rarely obtained or necessary
      - Definitive diagnosis:
        clinical symptoms, typical radiology of the cerebrum AND cytological / histological detection of organism
      - Presumptive diagnosis:
        clinical symptoms, typical radiology AND response to empirical treatment. It is the standard in most clinical settings.
    - - Preferred regimen /for 6 weeks/
        Pyrimethamine 50-75mg/day po
        Sulfadiazine 2x2000-3000mg/day po
        Folinic acid 1x 10-15mg/day po
        Monitor for myelotoxicity of pyrimethamine, mostly neutropenia
        Sulfadiazine is associated with crystalluria and may lead to renal failure and urolithiasis. Good hydration is essential.
      - maitenance therapy:
        Pyrimethamine 25-50mg/day po
        Sulfadiazine 2x1000-1500mg
        Folinic acid 1x 10-15mg/day po
        Discontinue when: CD4>200 cells/µl and HIV VL undetectable over 6 months
      - prophylaxis
        
        Start: if CD4 count < 200 cells/μL, or CD4 percentage < 14%
        Stop: if CD4 count > 200 cells/μL over 3 months or CD4 count 100-200 cells/μL and HIV-VL undetectable over 3 months
        TMP-SMX 1 ds. tablet (800/160mg) 3x week or 1 ss tablet (400/80mg) 1x/day
- - - - Pulmonary, drug susceptible TB: 6 months
        
        Pulmonary TB and positive culture at 8 weeks of TB treatment: 9 months
        
        Extrapulmonary TB with CNS involvement or disseminated TB: 9-12 months
        
        Extrapulmonary TB with bone/joint involvement: 9 months
        
        Extrapulmonary TB in other sites: 6-9 months
  - - - Preferred regimens
        Claritromycin 500mg bid po + EMB 15mg/kg/day po + Rifabutin 300mg/day po (Rifabutin can be replaced by Amikacin, Levofloxacin)
        
        Alternative regimens
        Azitromycin 500-600mg/day + EMB 15mg/kg/day PO
      - prophylaxis
        
        When CD4<50 cells/µl
        
        Clarithromycin 500mg bid po
        
        Azyhtromycin 1200mg/week po
        
        Rifabutin 300mg/day po
        
        Discontinuation of prophylaxis when CD4>100/mm3 for>3months and person on effective ART
- - - - Clinical features
        Floaters, field defects, decreased acuity
        CD4<50/mm3
      - Diagnosis
        Clinical appearance of typical retinal lesions AND response to therapy. PCR of aqueous and vitreous humor optional
        Fundoscopic exam - perivascular yellow-white retinal infiltrates + intraretinal hemorrhage /”cottage cheese and ketchup”/
      - treatment
        
        Retinitis, immediate sight-threatening lesions
        Ganciclovir 2 x 5 mg/kg/day iv
        21 days, then secondary prophylaxis
        
        Retinitis, small peripheral retinal lesions
        Valganciclovir 2 x 900 mg/day po (with food)
        14-21 days, then secondary prophylaxis
        
        Secondary prophylaxis / Maintenance therapy
        Valganciclovir 1 x 900 mg/day po (with food)
        Stop: if CD4 count > 200 cells/μL and HIV-VL undetectable over 3 months
- - - - Induced by an infection with human herpesvirus-8 (HHV-8) or Kaposi’s sarcoma associated herpesvirus (KSHV)
        
        Purple to brown-black macules, patches, nodules, popules that are usually asymptomatic – neither pruritic, nor painful
        
        Usually on legs, face, oral cavity and genitalia
        
        Complications include lyphedema especially mouth, legs, face, genitalia
        
        More advanced forms - visceral involvment mouth,, gastrointestinal tract, lungs
        
        HAART reduces frequency of KS
    - - Skin and oral cavity- biopsy of one typical lesion.
        
        Lung: X ray to detect effusion, nodules or infiltrate. Bronchoscopy to detect typical raised lesions, biopsy unnecessary and may cause bleeding.
        
        GI tract: suspect with cutaneus lesions plus unexplained GI symptoms usually pain, bleeding or obstruction. Diagnosis: upper and lower endoscopy to detect typical raised, red mocosal lesion.Zmiany
    - - In not advanced KS HAART is effective and chemotherapy is rarely required
        
        Systemic therapy is required in:
        Pulmonary KS
        Visceral KS
        Rapidly progressive cutaneous KS associated with lyphedema
        
        Liposomal doxorubicin
        
        Paclitaxel (Taxol)
  - - - treatment
        -The prognosis is significantly better with HAART
        -Chemotherapy
        CHOP (Cyclophosphamide, doxorubicin, vincristine, prednison)
        CDE (Cyclophpsphamide, doxorubicin, etoposide)
      - symptoms:
        CD4<100cells/mm3 and EBV (50-80%)
        Sparse lymphnode involvement
        Fever, night sweats
        Hepatic dysfunction
        Marrow involvement
        Lung disease (effusions, multinodular infiltrates, mass lesions, hilar adenopathy)
        GI involvement (any level - pain, weight loss)
        CNS (aseptic meningitis, CNS mass lesions)
        Diagnosis - histopathological examination