Judith A. Aberg, MD The International AIDS Society–USA Management of AIDS-Related Opportunistic Infections JA Aberg, MD. Presented at IAS–USA/RWCA Clinical Conference, August 2004.

Slide #2 JA Aberg, MD. Presented at IAS–USA/RWCA Clinical Conference, August 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

Slide #3 JA Aberg, MD. Presented at IAS–USA/RWCA Clinical Conference, August PCP Prophylaxis CD4 + T cell count 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

Slide #4 JA Aberg, MD. Presented at IAS–USA/RWCA Clinical Conference, August Treatment TMP/SMX for 21 days Pentamidine TMP plus dapsone Clindamycin plus primaquine Atovaquone Trimetrexate plus leucovorin Corticosteroids : pO 2 35 mm Hg

Slide #5 JA Aberg, MD. Presented at IAS–USA/RWCA Clinical Conference, August 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

Slide #6 JA Aberg, MD. Presented at IAS–USA/RWCA Clinical Conference, August 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 mg po bid or levofloxacin 500 mg qd –Amikacin mg/kg IV qd

Slide #7 JA Aberg, MD. Presented at IAS–USA/RWCA Clinical Conference, August 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

Slide #8 JA Aberg, MD. Presented at IAS–USA/RWCA Clinical Conference, August 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 million infected and 50,000 die annually

Slide #9 JA Aberg, MD. Presented at IAS–USA/RWCA Clinical Conference, August 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

Slide #10 JA Aberg, MD. Presented at IAS–USA/RWCA Clinical Conference, August 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

Slide #11 JA Aberg, MD. Presented at IAS–USA/RWCA Clinical Conference, August 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 days Neuro: Combined IV FOS and GCV

Slide #12 JA Aberg, MD. Presented at IAS–USA/RWCA Clinical Conference, August 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

Slide #13 JA Aberg, MD. Presented at IAS–USA/RWCA Clinical Conference, August 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

Slide #14 JA Aberg, MD. Presented at IAS–USA/RWCA Clinical Conference, August 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

Slide #15 JA Aberg, MD. Presented at IAS–USA/RWCA Clinical Conference, August 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

Slide #16 JA Aberg, MD. Presented at IAS–USA/RWCA Clinical Conference, August 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??