HIV/AIDS Update 2007

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HIV/AIDS Update 2007 Joanne J. Orrick, Pharm.D., BCPS Clinical Assistant Professor University of Florida Faculty, Florida/Caribbean AIDS Education and Training Center orricjj@ufl.edu

www.faetc.org orricjj@ufl.edu 352-273-6365

Legal/Legislative Issues: HIV Testing Florida Statutes Title XXIX Chapter 381.004

Global summary of the HIV and AIDS epidemic, 2006 Number of people living with HIV in 2006 Total Adults Women Children under 15 years 39.5 million [34.1 47.1 million] 37.2 million [32.1 44.5 million] 17.7 million [15.1 20.9 million] 2.3 million [1.7 3.5 million] People newly infected with HIV in 2006 AIDS deaths in 2006 Total 4.3 million [3.6 6.6 million] Adults 3.8 million [3.2 5.7 million] Children under 15 years 530 000 [410 000 660 000] Total 2.9 million [2.5 3.5 million] Adults 2.6 million [2.2 3.0 million] Children under 15 years 380 000 [290 000 500 000] www.unaids.org

A global view of HIV infection 38.6 million people [33.446.0 million] living with HIV, 2005 www.unaids.org

HIV Natural Progression

Prevention of Vertical Transmission Rapid HIV testing recommended by CDC for all HIV-infected pregnant women who do not have an HIV test result available at the time of delivery Goal is to reduce the number of infants infected perinatally in US from 200-300/year to 0/year Public Health Service Taskforce. Recommendations for the Use of Antiretrovirals in Pregnant HIV-1 Infected Women for Maternal Health and Interventions to Prevent Perinatal HIV-1 Transmission in the United States.-October 12th, 2006. Available online at www.aidsinfo.nih.gov

Numberofcases

Postexposure Prophylaxis Guidelines U.S. Public Health Service Guidelines for the Management of Occupational Exposure to HIV and Recommendations for Postexposure Prophylaxis-September 30, 2005 Available online at www.aidsinfo.nih.gov PEPLine National Clinicians Postexposure Prophylaxis Hotline 1-888-HIV-4911 Consultation available 24 hours per day

Patient Case JB JB is a 32 year old male admitted to the hospital with a 3 week history of shortness of breath, nonproductive cough and fever. He has a known diagnosis of HIV infection x 3 years. He previously was started on Combivir 1 po bid, Efavirenz 600 mg qhs but only took these meds intermittently and has not seen his HIV care provider in > 6 months Lab data: O2 Sat=85%, Arterial Blood Gas: ph=7.4, PO2=61, PCO2=42, HCO3=24, CD4 25 cells/mm 3, viral load pending, (other labs WNL) Chest x-ray: diffuse interstitial bilateral infiltrates

Patient Case JB Patient is admitted with a presumptive diagnosis of PCP (pneumonia due to Pneumocystis jiroveci (formerly Pneumocystis carinii) Patient is started on Septra DS 1 tab po bid, prednisone 40 mg po bid, gatifloxacin 400 mg po qd The team also decides to restart the patients ART but instead initiates (lamivudine/zidovudine) Combivir 1 po bid + (stavudine) Zerit 40 mg po bid

Patient Case JB What changes do you recommend to the patient s regimen? Dose of Septra is too low for treatment of PCP Recommended dose is 15 mg/kg/day divided q8h to q6h (usual po dose 2 DS tabs tid) Zidovudine and stavudine should not be combined DC stavudine and add NNRTI or boosted PI regimen Add azithromycin 1200 mg po qweek for MAI prophylaxis Treating Opportunistic Infections Among HIV- Infected Adults and Adolescents - Recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association/Infectious Diseases Society of America December 17, 2004 (Available online at www.aidsinfo.nih.gov)

CD4 + -Based Guidelines for Opportunistic Infection Prophylaxis in HIV-infected Patients Infection Pneumocystis jiroveci (formerly carinii) pneumonia (PCP) CD4+ Count < 200 cells/mm 3 Prophylaxis TMP/SMX DS 1 po qd or MWF Toxoplasmic encephalitis (TE) * < 100 cells/mm 3 TMP/SMX DS 1 po qd Mycobacterium avium complex (MAC) < 50 cells/mm 3 Azithromycin 1200 mg po qweek *Patient positive Toxoplasma IgG antibody 2001 USPHS/IDSA Guidelines for the Prevention of Opportunistic Infections in Persons Infected with Human Immunodeficiency Virus. Available at www.aidsinfo.nih.gov

HIV/AIDS Treatment Guidelines October 10th, 2006 Department of Health and Human Services Guidelines for the Use of Antiretroviral Agents in HIV-infected Adult and Adolescents Available at www.aidsinfo.nih.gov

Treatment of Asymptomatic HIV Infection CD4 + Cell Count < 200 Viral Load Any Recommendation Treat 200-350 Any Most treat > 350 > 100,000 Some treat > 350 < 100,000 Defer therapy

Trends in Antiretroviral Therapy McNaghten, et al. AIDS. 1999; 13(13):1687-1695

Source: WHO/UNAIDS. Available online at http://www.who.int/hiv/facts/en/

Impact of AIDS on life expectancy in five African countries, 1970 2010 70 Life expectancy at birth (years) 65 60 55 50 45 40 35 30 25 20 1970 1975 1980 1985 1990 1995 2000 2005 1975 1980 1985 1990 1995 2000 2005 2010 Botswana South Africa Swaziland Zambia Zimbabwe Source: United Nations Population Division (2004). World Population Prospects: The 2004 Revision, database. 4.1

Fusion Inhibitors HIV Life Cycle Protease inhibitors (PIs) NRTIs and NRTIs NNRTI and NNRTIs From The Immunodeficiency Clinic - University Health Network Website, www.tthhivclinic.com

Timeline of ARV Approvals 1987: 1 st NRTI Approved 1987: Zidovudine 1991: Didanosine 1992: Zalcitabine 1995: 1 st PI 1996: 1 st NNRTI 1994: Stavudine 1995: Lamivudine, Invirase 1996: Nevirapine, Ritonavir, Indinavir 1997: Delavirdine, Nelfinavir, Fortovase 1998: Abacavir, Efavirenz 1999: Amprenavir 2000: Lopinavir/ritonavir 2003: 1 st Fusion Inhibitor 2001: Tenofovir 2003: T-20, Atazanavir, Emtricitabine, Fosamprenavir The Future: Entry inhibitors, Integrase inhibitors 2005: Tipranavir 2006: Darunavir

Protease Inhibitors (PI s) Agent Approved Saquinavir-HGC (SQV-HGC, Invirase ) 12/95 Ritonavir (RTV, Norvir ) 3/96 Indinavir (IDV, Crixivan ) 3/96 Nelfinavir (NFV, Viracept ) 3/97 Saquinavir-SGC (SQV-SGC, Fortovase ) 11/97 Amprenavir (APV, Agenerase ) 4/99 Lopinavir/ritonavir (KAL, Kaletra ) 9/00 Atazanavir (ATV, Reyataz ) 6/03 Fosamprenavir (fos-apv, Lexiva ) 10/03 Tipranavir (TPV, Aptivus ) 6/05 Darunavir (DRV, Prezista ) 6/06

One Pill Once Daly! Atripla (emtricitabine/tenofovir/efavirenz) Emtricitabine/tenofovir (Truvada ) + efavirenz (Sustiva ) Approved July 12, 2006 First collaborative effort between 2 companies to develop combination pill for HIV treatment Not new drugs!

Case Study LJ

Patient Case MJ CF is a 58 yo male diagnosed with HIV in June of 2003, he returns to the ID clinic for routine follow up of his HIV. He was started on ARVs in August 2004 (CD4 220, viral load 158,000) Current Meds: lamivudine/abacavir (Epzicom ) 1 tab po qd, atazanavir (Reyataz ) 300 mg po qd, ritonavir (Norvir ) 100 mg qd, lisinopril 10 mg po qd, ezetimibe/simvastatin (Vytorin ) 10/40 mg po qd, metformin 500 mg po bid

Patient Case MJ He was recently discharged from the hospital where he was treated for communityacquired pneumonia. Additional medications on discharge: pantoprazole 40 mg po qd, gatifloxacin 400 mg po qd Viral load: < 50 copies/ml, CD4 + cell count 345 cells/mm 3 (3 months ago) Recent labs show a total bilirubin of 3.8 mg/dl

Patient Case MJ Which medication(s) should be discontinued due to a significant drug interaction with the patients ARVs? Metformin Simvastatin Pantoprazole Gatifloxacin

Drugs That Should Not Be Given With PIs Simvastatin Lovastatin Astemizole Terfenadine Cisapride Pimozide Bepridil St. John s Wort Garlic supplements Rifampin (except ritonavir) Rifapentine Midazolam Triazolam Ergot alkaloids Additionally the following should not be given with ritonavir: amiodarone, flecainide, propafenone, quinidine, voriconazole, alfuzosin, fluticasone Proton pump inhibitors and Irinotecan should not be used with atazanavir Carbamazepine, phenobarbital, phenytoin can levels of PIs/NNRTIs

Web Sources of HIV Information www.aidsinfo.nih.gov www.cdc.gov www.hiv-druginteractions.org http://hivinsite.ucsf.edu www.hopkins-aids.edu www.thebodypro.com www.faetc.org