judith a. aberg, md the international aids society–usa management of aids-related opportunistic...

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.

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Pneumocystis jiroveci pneumoniaPneumocystis 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

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PCP ProphylaxisPCP 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

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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

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Disseminated Mycobacterium aviumDisseminated 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

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Mycobacterium avium complex 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

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ToxoplasmosisToxoplasmosis

• 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

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Differential for Toxo: ChagasDifferential 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

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Chagas DiseaseChagas 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

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LeishmaniasisLeishmaniasis

• 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

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CytomegalovirusCytomegalovirus

• 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

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Fungal InfectionsFungal 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

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Human papillomavirusHuman 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

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Anogenital dysplasiaAnogenital 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

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Effect of ART on OIsEffect 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

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What should we do with ART-naïve?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??

judith a. aberg, md the international aids society–usa management of aids-related opportunistic...

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