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Initiating Antiretroviral Therapy in Treatment-Naive Patients
Charles B. Hicks, MDAssociate Professor of Medicine, Division of Infectious Diseases
and International Health, Duke University Medical Center
Associate Director, Duke AIDS Research and Treatment Center, Durham, NC
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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 genotypeCBC = complete blood count; PPD = purified protein derivative; STI = sexually transmitted infection.
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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/mm3: should be treated
• Asymptomatic HIV infection with CD4 count 200–350 cells/mm3: consider treatment
• Asymptomatic HIV infection with CD4 count > 350 cells/mm3: 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.
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Considering Treatment at Higher CD4 Counts: Data from the SMART Study
Event Rate (per 100 PY)
End PointEpisodic
Treatment (n = 2720)
ContinuousTreatment(n = 2752)
HR (95% CI)
OI or death from any cause
3.3 1.3 2.6 (1.9–3.7)
Death from any cause
1.5 0.8 1.8 (1.2–2.9)
Major CV, renal, hepatic disease
1.8 1.1 1.7 (1.1–2.5)
Grade 4 adverse event
5.0 4.2 1.2 (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.
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Antiretroviral Regimen for Treatment-Naive Patients: Current DHHS Guidelines
Column A: NNRTI or PI Column B: Dual NRTIs
Preferred therapy
NNRTIEfavirenz or
PI• Atazanavir + ritonavir• Fosamprenavir + ritonavir• Lopinavir / ritonavir
+
• Tenofovir / emtricitabine• Zidovudine / lamivudine
Alternative therapy
NNRTINevirapine or
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.
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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
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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.
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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.
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Goals of Antiretroviral Therapy
Sustained suppression
of HIV replication
Regeneration of CD4 cells
Decrease in opportunistic
infections
Improvement in immune function
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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.
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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.
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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?
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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.
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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 death2) a prolonged suppression of HIV RNA
• Contraindication– CRIXIVAN is contraindicated in patients with
clinically significant hypersensitivity to any of its components.
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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