Transcript Indications for Initiation of Antiretroviral Therapy

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
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.
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.
Considering Treatment at Higher CD4
Counts: Data from the SMART Study
Event Rate (per 100 PY)
Episodic
Treatment
(n = 2720)
Continuous
Treatment
(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)
End Point
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.
Antiretroviral Regimen for TreatmentNaive Patients: Current DHHS Guidelines
Column A: NNRTI or PI
Column B: Dual NRTIs
Preferred therapy
NNRTI
Efavirenz
or
PI
• Atazanavir + ritonavir
• Fosamprenavir + ritonavir
• Lopinavir / ritonavir
• Tenofovir / emtricitabine
• Zidovudine / lamivudine
+
Alternative therapy
NNRTI
Nevirapine
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.
Triple-Therapy Options:
Bartlett Meta-analysis
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: 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.
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.
Goals of Antiretroviral Therapy
Sustained
suppression
of HIV
replication
Regeneration
of CD4 cells
Improvement
in immune
function
Decrease in
opportunistic
infections
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.
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.
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?
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.
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.
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