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Management of AIDS-Related Opportunistic Infections. Judith A. Aberg, MD. JA Aberg, MD. Presented at IAS –USA /RWCA Clinical Conference, August 2004. The International AIDS Society–USA. Pneumocystis jiroveci pneumonia.
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Management of AIDS-Related Opportunistic Infections Judith A. Aberg, MD JA Aberg, MD. Presented at IAS–USA/RWCA Clinical Conference, August 2004. The International AIDS Society–USA
Pneumocystis jiroveci pneumonia • Pneumocystis is a fungi that produces pneumonia in immunosuppressed patients • Wide range of severity • It is the most frequent form of presentation of AIDS • Usually CD4 count less than 200 cells/mm3 • Diagnosis: clinical, induced sputum, BAL
PCP Prophylaxis • CD4+ T cell count < 200 ; H/O oral candidiasis; Unexplained fever > 2 weeks; Previous episode of PCP • TMP/SMX DS 1 tablet po daily • Dapsone 50 mg po b.i.d. or 100 mg daily • Atovaquone 1500 mg po daily • Pentamidine aerosol 300 mg monthly
Treatment • TMP/SMX for 21 days • Pentamidine • TMP plus dapsone • Clindamycin plus primaquine • Atovaquone • Trimetrexate plus leucovorin • Corticosteroids : pO2< 70 mm/Hg or A-a gradient > 35 mm Hg
Disseminated Mycobacterium avium • Usually late in the course of AIDS (CD4 <50) • Persistent fevers, night sweats, fatigue, weight loss, and anorexia • Hepatosplenomegaly, lymphadenopathy, and (rarely) jaundice • Anemia, leukopenia, elevated alkaline phosphatase levels are common
Mycobacterium avium complex • Improved survival with 3 drugs vs 2: • CLR 500 mg po bid (AZ 500 mg daily) • EMB 15 mg/kg po qd • RBT 300 mg po qd (adjust for ART) • Failure to response/relapse • Susceptibility testing • Ciprofloxacin 500-750 mg po bid or levofloxacin 500 mg qd • Amikacin 10-15 mg/kg IV qd
Toxoplasmosis • Standard therapy is pyrimethamine plus sulfadiazine • Sulfadiazine may not be available • Pyrimethamine 200 mg load the 50 mg daily plus clindamycin 600 mg qid plus leucovorin 10 mg daily. • SMX/TMP (based on 5 mg/kg TMP) bid • If no clinical/radiographic improvement in 2 weeks or clinical decline in one week: BIOPSY
Differential for Toxo: Chagas • USA has second largest Latino population • Southern US, Latin America to central Argentina • Trypanosoma cruzi • Transmitted by “kissing” (reduviid) bugs, blood transfusions • 1:500 blood donors in LA positive • 1:600 donors positive in 3 SW states • Chagoma: portal of entry • Cardiac, GI, CNS • 16-18 million infected and 50,000 die annually
Chagas Disease • Diagnosis • Serological : limited, not standardized • Buffy coat, GMS • Biopsy • ? Role of T. cruzi IgG: look for chronic carriers. Reactivation similar to toxo • PCR? • Treatment: Nifurtimox 8-10 mg/kg daily
Leishmaniasis • Asia, Mid-East, India, Africa, Brazil, Spain, France, Italy • Sandflies • Weight loss, F/S, anemia, leukopenia, hepatosplenomegaly: weeks to months • Diagnosis: Liver, spleen or BM Biopsy (liver bx least helpful), Buffy coat, EIA and IFA • Treatment: Liposomal AMB drug of choice in HIV. Pentavalent antimonial drugs associated with high relapse and failure
Cytomegalovirus • Immediate vision-threatening: GCV implant plus VGCV 900 mg po qd • Peripheral non-vision threatening: GCV implant • Duration of therapy: continue until immune reconstitution • GI: VGCV for 14-21 days • Neuro: Combined IV FOS and GCV
Fungal Infections • Cryptococcosis and Histoplasmosis: Safe to stop secondary prophylaxis if CD4 >150 • Coccidioidomycosis: Do not stop prophylaxis • Penicilliosis • Asia particularly Thailand • Similar to Histo • AMB ITZ 400 mg
Human papillomavirus • Genital warts usually type 6 or 11 • Podofilox 0.5% solution or gel, apply bid for 3 days, cycle q 4 weeks (50 % response) • Imiquimod 5% cream. Apply at bedtime and wash off in am. Apply 3 non-consecutive nights per week up to 16 weeks (response variable) • Cryotherapy, Surgical Excision, TCA cauterization, cidofovir topical, podophyllin
Anogenital dysplasia • Anal and cervical PAP smears • Colposcopsy indications: • Visible lesion on cervix regardless of PAP results • ASCUS (atypical squamous cells-undetermined significance). Treat for infectious etiology. F/U PAP 2-3 month after treatment. If no infection, repeat PAP q 4-6 months until 3 negative PAP over 2 year period. If second report of ASCUS, do colpo • ASCUS-H (cannot rule out high-grade disease) • ASCUS and previous h/o abnormal • LSIL or HSIL (squamous intraepithelial lesion) • High-resolution anoscopy (HRA) if LSIL or HSIL on anal PAP. Consider ASCUS or ASCUS-H. Biopsy
Effect of ART on OIs • Multiple studies show reduction in OIs on ART • Decreased morbidity/mortality • Improvement in pathogen specific immunity • Parodoxical reactions • Immune reconstitution syndromes • Atypical manifestations
What should we do with ART-naïve? • Risk vs benefit • First line: treat OI • Consider ART • Drug interactions • Drug toxicities • Risk of immune reconstitution syndrome • Consider wait • Consider steroids • If sub-optimal CD4 response??