1. Initiating Antiretroviral Therapy in Treatment-Naive Patients Charles B. Hicks, MD Associate Professor of Medicine, Division of Infectious Diseases and International Health, Duke University Medical Center Associate Director, Duke AIDS Research and Treatment Center, Durham, NC

2. Clinical Evaluation for Newly Diagnosed Chronic HIV Infection: Focal Points Medical history –HIV symptoms, opportunistic infections –STIs, substance use, mental health Physical exam –Oral, skin, ocular, genital exams Laboratory tests –Viral load and CD4 count –CBC, screening chemistries, lipids, hepatitis serologies, PPD HIV-1 resistance genotype CBC = complete blood count; PPD = purified protein derivative; STI = sexually transmitted infection.

3. Indications for Initiating Antiretroviral Therapy Symptomatic HIV infection regardless of CD4 count or HIV RNA level (viral load): should be treated Asymptomatic HIV infection with CD4 count < 200 cells/mm 3 : should be treated Asymptomatic HIV infection with CD4 count 200– 350 cells/mm 3 : consider treatment Asymptomatic HIV infection with CD4 count > 350 cells/mm 3 : consider pros and cons of treatment HIV RNA >100,000 copies/mL: possible indicator of higher risk DHHS. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Available at http://aidsinfo.nih.gov.

4. Considering Treatment at Higher CD4 Counts: Data from the SMART Study Event Rate (per 100 PY) End Point Episodic Treatment (n = 2720) Continuous Treatment (n = 2752) HR (95% CI) OI or death from any cause 3.31.32.6 (1.9–3.7) Death from any cause 1.50.81.8 (1.2–2.9) Major CV, renal, hepatic disease 1.81.11.7 (1.1–2.5) Grade 4 adverse event 5.04.21.2 (1.0–1.5) CI = confidence interval; CV = cardiovascular; HR = hazard ratio; OI = opportunistic illness; PY = person-years. Strategies for Management of Antiretroviral Therapy (SMART) Study Group. N Engl J Med 2006;355:2283–96.

5. Antiretroviral Regimen for Treatment- Naive Patients: Current DHHS Guidelines Column A: NNRTI or PIColumn B: Dual NRTIs Preferred therapy NNRTI Efavirenzor PI Atazanavir + ritonavir Fosamprenavir + ritonavir Lopinavir / ritonavir + Tenofovir / emtricitabine Zidovudine / lamivudine Alternative therapy NNRTI Nevirapineor PI Atazanavir Fosamprenavir Fosamprenavir + ritonavir Lopinavir / ritonavir + Abacavir / lamivudine Didanosine + (emtricitabine or lamivudine) NNRTI = nonnucleoside reverse transcriptase inhibitor; NRTI = nucleoside reverse transcriptase inhibitor; PI = protease inhibitor. DHHS. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Available at http://aidsinfo.nih.gov.

6. BPI = ritonavir-boosted protease inhibitor; NNRTI = nonnucleoside reverse transcriptase inhibitor; NRTI = nucleoside reverse transcriptase inhibitor; PI = protease inhibitor. Bartlett JA, et al. AIDS 2006;20:2051–64. Triple-Therapy Options: Bartlett Meta-analysis

7. Triple-Therapy Options: ACTG 5142 ACTG = AIDS Clinical Trials Group; BPI = ritonavir-boosted protease inhibitor; NNRTI = nonnucleoside reverse transcriptase inhibitor; NRTI = nucleoside reverse transcriptase inhibitor. Riddler SA, et al. XVI International AIDS Conference, 2006. Abstract no. THLB0204.

8. Triple-Therapy Options: Once-Daily vs Twice-Daily Regimens AEs = adverse events; LAs = laboratory abnormalities. Pozniak AL, et al. J Acquir Immune Defic Syndr 2006;43:535–40.

9. Goals of Antiretroviral Therapy Sustained suppression of HIV replication Regeneration of CD4 cells Decrease in opportunistic infections Improvement in immune function

10. Improving Adherence: Patient-Related Factors Readiness for and commitment to therapy –Able to comply with multiple medications over the long term? –Need for a simpler or once-daily regimen? –Discuss pros and cons of various options Mental health issues Substance abuse Social challenges Funds for medications DHHS. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Available at http://aidsinfo.nih.gov.

11. Improving Adherence: Strategies for Providers Educate patient about the treatment regimen Simplify the treatment regimen Provide tools to assist with adherence Discuss potential adverse effects; have a management plan before starting therapy Involve significant others Involve entire clinic staff; encourage patient to contact staff about any problems DHHS. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Available at http://aidsinfo.nih.gov.

12. Treatment Monitoring Evaluate treatment response –Primary outcome: viral load < 50 copies/mL within 6 months –Secondary outcome: increase in CD4 count Monitor long-term suppression of viral load –Related to adherence, regimen, pretreatment indices Assess adverse effects (AEs) –Related to treatment regimen or another cause? –Can the AEs be treated or is a change in the regimen needed?

13. Conclusions Treat HIV-positive patients: –Symptomatic, regardless of CD4 count –Asymptomatic, depending on CD4 count (? higher levels) Initiate a triple-agent regimen: –2 NRTIs + NNRTI or –2 NRTIs + boosted PI Individualize treatment: –Evaluate patient’s readiness and related health issues –Determine patient’s treatment preferences Maximize adherence : –Simplify the regimen –Educate about dosing and adverse effects –Foster a trusting doctor-patient relationship Monitor virologic/immunologic response and toxicity NNRTI = nonnucleoside reverse transcriptase inhibitor; NRTI = nucleoside reverse transcriptase inhibitor; PI = protease inhibitor.

14. CRIXIVAN ® (indinavir sulfate) Indication –CRIXIVAN in combination with other antiretroviral agents is indicated for the treatment of HIV infection. This indication is based on 2 clinical trials of approximately 1 year’s duration that demonstrated: 1)a reduction in the risk of AIDS-defining illnesses or death 2)a prolonged suppression of HIV RNA Contraindication –CRIXIVAN is contraindicated in patients with clinically significant hypersensitivity to any of its components.

15. Before prescribing CRIXIVAN (indinavir sulfate), please read the accompanying Prescribing Information. CRIXIVAN is a registered trademark of Merck & Co., Inc. 20705951(2)-08/07-CRX