Lecture 2 - Manifestations of Disease[1]

Protease inhibitor resistance uncommon with failure

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Protease inhibitor resistance uncommon with failure (boosted PI) NNRTI options preserved for future use DISADVANTAGES Metabolic complications (fat maldistribution, dyslipidemia, insulin resistance) GI intolerance Potential for drug interactions (CYP450), especially with RTV
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University of North Carolina 01/10/11 When to Start Therapy? -Hit early, hit hard -Start therapy based on viral load -Defer therapy, then hit hard -Start therapy based on CD4 count Eradication Virologic suppression Immunologic control Decreased transmission Decreased quality of life Long-term toxicity Resistance Lack of demonstrated benefit at higher CD4 counts
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University of North Carolina 01/10/11 Indications for Initiating ART: Chronic Infection (12/1/09) Clinical Category or CD4 Count Recommendation History of AIDS-defining illness CD4 count <350 cells/µL Pregnant women HIV-associated nephropathy Hepatitis B coinfection, when HBV treatment is indicated* Initiate ART * Treatment with fully suppressive drugs active against both HIV and HBV is recommended.
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University of North Carolina 01/10/11 Indications for Initiating ART: Chronic Infection (2) Clinical Category or CD4 Count Recommendation CD4 count of >350 cells/µL, asymptomatic, without conditions listed above Panel recommended but divided on the strength of recommendation CD4 > 500 cells/ul Panel split in terms of recommendation
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University of North Carolina 01/10/11 Prognosis of HIV-Infected Antiretroviral-Naïve Patients Time to AIDS defining events or death 12,040 patients followed at 12 centers starting HAART During follow-up, there were 858 AIDS-defining events and 329 deaths Probability of AIDS-free survival 0.95 0.90 0.85 0.80 0.75 Years from starting HAART 0 1 2 3 ≥5 4-4.99 1.00 3-3.99 >3 1.00 0.95 0.90 0.85 0.80 0.75 Years from starting HAART 0 1 2 3 0-49 50-68 100-198 200-349 350 Egger, et al. 2002 Lancet 360:119. CD4 cell count at baseline Log HIV RNA at baseline
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University of North Carolina 01/10/11 Moore CID 2007 Johns Hopkins Cohort on HAART VL<400 650 Patients
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University of North Carolina 01/10/11 Correlation Between Nonadherence and Virologic Failure 0 20 40 60 80 100 >95% 90–95 80–90 70–80 <70 Adherence (%) Proportion with virologic failure (%) P=0.00001, r=–0.554 Paterson D. 6th CROI, 1999
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University of North Carolina 01/10/11 Resistance Virus mutates (changes) so that medications are no longer effective Occurs when patients do not take medications in the correct manner Does not occur when patients are on no medications or when virus is completely suppressed
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University of North Carolina 01/10/11 Timing of Treatment Switch Accumulation of mutations Time Viral load Early Late First regimen Second regimen
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University of North Carolina 01/10/11 Comparison of clinician estimates vs. objective measures of adherence Adherence as measured by MEMS Clinicians’ estimates of adherence 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% Underestimates Overestimates p< 0.001 Miller et al., JGIM 2001
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University of North Carolina 01/10/11 Non compliance Lack of knowledge about medications Lack of social supports Addiction/psychiatric illness Medication toxicity Confidentiality issues Complex regimens/schedules Does the Dr. really know?
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University of North Carolina 01/10/11
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