Clinical Case #25 Yvonne Josephine Banarez Pharmacology -A- October 12, 2006

- History- 32 Year Old Man (Homosexual) 3 month history of:  Weight Loss  Fatigue Intermittent Fever Intermittent Lymphadenopathy Progressive Increase of Diarrhea (1mo period) Occurrences of Severe SOB Non-Productive Cough: 3days

-Physical- Patient is Febrile at 102˚F (38.9˚C) All Other Reports are Omitted

-Lab Orders- CBC w/ Differential CXR

-Lab Results- Blood work: -CD4 Count: 180 u/mm³ Chest X-Ray -Diffused Interstitial Infiltrate ** These were the only given results. ** All values omitted are assumed within normal range.

-Radiograph of Diffuse Interstitial Infiltrate- Nodular Densities are Seen Throughout Both Lungs

-Differential Dx- HIV/AIDS - Based on lifestyle - Hx. Of sudden weight loss and fatigue - Hx. of lymphadenopathy **Diagnostic: CD4 Count = 180!! <500 reveals late stage HIV infection. <200 indicative of AIDS. Set Values Based on US Center for Disease Control

Pneumonia - Fever, SOB, Non-Productive Cough, CXR revealed Diffuse Interstitial Filtrate Types:Those closely related to AIDS - Pneumocystis carinii (PCP) - Cryptococcal neoformans (CNP) Mycobacterial Infection Types:Tuberculosis -Differential Dx-

-Discussion- AIDS: coincides with patient’s symptoms, CD4 count, rapid Ig test, p24 Antigen Test or PCR may be used to confirm CNP: common w/ AIDS, but X-Ray of lungs do not show infiltrates TB: common w/ AIDS, shows infiltrates, but mycobacterium infected coughs have phlegm and/or blood. Patient states dry cough. Absence of systemic symptoms also make Dx less likely PCP: common w/ AIDS, shows infiltrates, coincides w/ dry cough

-AIDS Treatment- Protease Inhibitors (PIs) Highly Active Antiretroviral Therapy (HAART) Consists of combination or “cocktail” of 3 or more drugs from the 4 categories 1.Protease Inhibitors (PIs) 1.cleave precursor molecules results in production of immature viral particles 2.Nucleoside Reverse Transcriptase Inhibitors (NRTIs) 1.competitively inhibit HIV reverse transcriptase 2.incorporated into the growing viral DNA chain to cause termination 3.Non Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) 1.bind to HIV reverse transcriptase and block RNA and DNA dependent DNA polymerase activities 2.Different binding site from NRTIs 4.Entry Inhibitors 1.Prevents the penetration of the virus into the host cell

DrugAdult Dosing AptivusAptivus® (tipranavir), by Boehringer IngelheimBoehringer Ingelheim Two 250mg capsules plus two 100mg Norvir capsules, twice a day (a total of 8 pills a day).Norvir CrixivanCrixivan® (indinavir), by Merck & Co.Merck & Co.Two 400mg capsules, every 8 hours (a total of 6 pills a day), or two 400mg Crixivan capsules with either one or two 100mg Norvir capsules twice a day (preferred dosing). InviraseInvirase® (saquinavir), by Hoffmann-La RocheHoffmann-La Roche Invirase must be used in combination with Norvir. The approved dose is two 500mg Invirase tablets plus one 100mg Norvir capsule, twice a day (a total of 6 pills a day).Norvir KaletraKaletra®* (lopinavir + ritonavir), by Abbott LaboratoriesAbbott Laboratories * Also sold as Aluvia in some parts of the world. Two tablets, twice a day (a total of 4 pills a day), or, if starting therapy for the first time, four tablets once a day (see Notes for exceptions). Each tablet contains 200mg lopinavir + 50mg ritonavir. LexivaLexiva® (fosamprenavir), by GlaxoSmithKline GlaxoSmithKline Two 700mg tablets, twice a day (a total of 4 pills a day), or two 700mg tablets plus two 100mg Norvir capsules, once a day (a total of 4 pills a day), or one 700mg tablet plus one 100mg Norvir capsule twice a day (a total of 4 pills a day). This last dosing option should be used for patients who have tried and failed other protease inhibitors in the past.Norvir Norvir® (ritonavir), by Abbott LaboratoriesAbbott LaboratoriesSix 100mg capsules, twice a day* (a total of 12 pills a day). Start with 3 capsules, twice a day, and increase to full dose over 14 days. Note: the full dose of Norvir is rarely used any more. Norvir is most often used at much lower doses to "boost" the levels of other protease inhibitors in the body. PrezistaPrezista™ (darunavir) by TibotecTibotecPrezista must be used in combination with Norvir. The approved dose is two 300mg Prezista tablets plus one 100mg Norvir capsule, twice a day (a total of 6 pills a day).Norvir ReyatazReyataz® (atazanavir), by Bristol-Myers SquibbBristol-Myers Squibb Two 200mg capsules, once a day (a total of 2 pills a day), or two 150mg capsules plus one 100mg Norvir capsule, once a day (a total of 3 pills a day).Norvir ViraceptViracept® (nelfinavir), by PfizerPfizerTwo 625mg tablets, two times a day (a total of 4 pills a day), or five 250mg tablets, twice a day, or three 250mg tablets, three times a day (a total of 9-10 pills a day). Protease Inhibitors

DrugAdult Dosing Atripla™ (Sustiva* + Viread + Emtriva), by Gilead Science and Bristol-Myers Squibb One tablet (contains 600mg Sustiva + 300mg Viread + 200mg Emtriva), once a day (a total of one pill a day). Combivir® (Retrovir + Epivir), by GlaxoSmithKline One tablet (contains 300mg Retrovir + 150mg Epivir), twice a day (a total of 2 pills a day) Emtriva® (emtricitabine), by Gilead Sciences One 200mg capsule once a day. Epivir® (lamivudine; 3TC), by GlaxoSmithKline One 300mg tablet, once a day, or one 150mg tablet, twice a day* (a total of 1 or 2 pills a day) Epzicom™* (Ziagen + Epivir), by GlaxoSmithKline * Also sold as Kivexa in some parts of the world. One tablet (contains 600mg Ziagen + 300mg Epivir), once a day Retrovir® (zidovudine; AZT), by GlaxoSmithKline One 300mg tablet, twice a day* (a total of 2 pills a day) Trizivir® (Retrovir + Epivir + Ziagen), by GlaxoSmithKline One tablet (contains 300mg Retrovir + 150mg Epivir + 300mg Ziagen), twice a day (a total of 2 pills a day) Truvada® (Viread + Emtriva), by Gilead Sciences One tablet (contains 300mg Viread + 200mg Emtriva), once a day Videx® (didanosine; ddI): buffered versions, by Bristol- Myers Squibb Two 100mg tablets twice a day* (a total of 4 pills a day), or two 200mg tablets, once a day (a total of 2 pills a day). For patients weighing less than 133 lbs. (60 kg), click here. Videx® EC (didanosine; ddI): delayed-release capsules, by Bristol-Myers Squibb One 400mg capsule once a day. For patients weighing less than 133 lbs. (60 kg), the dose is one 250mg capsule once a day. Viread® (tenofovir DF), by Gilead Sciences One 300mg tablet once a day. Zerit® (stavudine; d4T), by Bristol-Myers Squibb One 40mg capsule, every 12 hours (a total of 2 pills a day). For patients weighing less than 133 lbs. (60 kg), click here. Ziagen® (abacavir), by GlaxoSmithKline One 300mg tablet twice a day, or two tablets once a day (a total of 2 pills a day) NNRTIs

DrugAdult Dosing AtriplaAtripla™ (Sustiva + Viread* + Emtriva*), by Gilead Science and Bristol-Myers SquibbGilead ScienceBristol-Myers Squibb * Viread and Emtriva are nucleoside reverse transcriptase inhibitors (NNRTIs) nucleoside reverse transcriptase inhibitors (NNRTIs) One tablet (contains 600mg Sustiva + 300mg Viread + 200mg Emtriva), once a day (a total of one pill a day). RescriptorRescriptor® (delavirdine), by Pfizer Pfizer Two 200mg tablets, three times a day (a total of 6 pills a day) SustivaSustiva®* (efavirenz), by Bristol-Myers Squibb Bristol-Myers Squibb * Also sold as Stocrin in some parts of the world. One 600mg tablet once a day (just 1 pill a day) ViramuneViramune® (nevirapine), by Boehringer Ingelheim Boehringer Ingelheim One 200mg tablet per day for 14 days, then one 200mg tablet, twice a day* (a total of 2 pills a day) NNRTIs DrugAdult Dosing FuzeonFuzeon® (T-20), by Trimeris and Hoffmann-La RocheTrimerisHoffmann-La Roche Two 90mg (in 1-ml solution) subcutaneous (under the skin) injections a day. Fusion/ Entry Inhibitors

-Diagnostic Procedures- CD4 count of 180 implies AIDS. Standard retroviral treatments can begin, that inhibit further replication of HIV. Unfortunately, AIDS in not curable, and can only be slowed down – not stopped. Pneumocystis carinii pneumonia (PCP) is the most common cause of an interstitial infiltrate in an HIV-infected patient with a CD4 count less than 200/mm3. The patient was started on presumptive therapy for PCP with trimethoprim-sulfamethoxazole and prednisone. However, his clinical condition remained unchanged during treatment, indicating a possible misdiagnosis! More lab tests need to be ordered to be conclusive.

-Further Lab Testing- A Bronchioscopy was ordered to visualize any lesions or macroscopic structures possibly causing respiratory distress. Upon inspection, a transbronchial lung biopsy was ordered. Pathological reports will then be issued, possibly revealing the agent causing pneumonia. PCP can now be ruled out.

-Conclusion- Since the exercise did not provide a report on the last two tests ordered, a definitive diagnosis could not be obtained. However, the fact that the authors included the order for a lung biopsy, highly suggests that Malignancy is a strong consideration. A bothersome cough is a common feature of Kaposi's sarcoma (KS), which, along with the symptoms and the X-Ray findings, is most probable with homosexual men with AIDS. Non Hodgkin’s Lymphoma is also a malignancy to be considered with AIDS, but the X-Ray does not indicate such.

Should those assumptions be correct, the patient was started on vinca alkaloids – mitotic spindles Paclitaxel – mitotic spindles Etoposide - topoisomerase Anthracyclines - topoisomerase bleomycin Which are all systemic chemotherapy drug used to treat KS associated with HIV. A combination of these drugs is also a possible treatment.

-Question 1 & 2- What are the most likely infectious agents that are causing the patient’s pneumonia? What are the therapeutic options for each agent? PCP  trimethoprim-sulfamethoxazole and prednisone Mycobacterial Infection  Broad spectrum antibiotics and amphotericin B Kaposi’s Sarcoma  vinca alkaloids, Paclitaxel, Etoposide, Anthracyclines, bleomycin

-Question 3- What are the most likely etiologic agents causing the patients diarrhea? What are the therapeutic options? Malabsorptive Syndrome  AIDS treatment Fungi – cryptosporidium, isosporabelli or microsporidia  Amphotericin B Bacteria – salmonella, shingella  Broad spectrum antibiotics

THANKS…