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Christopher Mathews, M.D. Director, Owen Clinic University of California, San Diego What Every Internist Should Know About HAART in 2003

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Outline Historical milestones in HIV treatment Current treatment strategies Drug toxicities Resistance testing Drug interactions Medication Adherence Immune Recovery Inflammatory Diseases Resources for staying up to date

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Milestones of Therapy Licensure of antiretroviral agents in the United States Trends in virologic suppression among patients under care Trends in mortality

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Proportion 60,00020 - 60,000 6 - 20,000 1 - 5,000

Considerations in Initiating Therapy HIV Asymptomatic Theoretical benefit No proven long-term clinical benefit for CD4 >200 cells/ml 3 Expert opinion advises initiation of therapy for CD4 350 cells/ml 3 CD4+ T cell The downside of antiretroviral regimens QOL Short- and long-term toxicities

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Risks and Benefits of Delayed Initiation of Therapy Benefits of delayed therapy Avoid negative effects on quality of life (e.g. inconvenience) Avoid drug-related adverse events Delay in development of drug resistance Preserve maximum number of available and future drug options when HIV disease risk is greatest Risks of delayed therapy Possible risk of irreversible immune system depletion Possible greater difficulty in suppressing viral replication Possible increase risk of HIV transmission

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Risks and benefits of early initiation of therapy Benefits of early therapy Control of viral replication easier to achieve and maintain Delay or prevention of immune system compromise Lower risk of resistance with complete viral suppression Possible decreased risk of HIV transmission Risks of early therapy Drug-related reduction in quality of life Greater cumulative drug-related adverse events Earlier development of drug resistance, if viral suppression is suboptimal Limitation of future antiretroviral treatment options

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Goals of Therapy Maximal and durable suppression of viral load Restoration and/or preservation of immunologic function Improvement of quality of life Reduction of HIV-related morbidity and mortality

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Tools to Achieve Goals of Therapy Maximize adherence to the antiretroviral regimen Rational sequencing of drugs Preservation of future treatment options Use of resistance testing in selected clinical settings

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Considerations in Initiating Therapy HIV Asymptomatic Willingness of patient to begin and the likelihood of adherence Degree of immunodeficiency Plasma HIV RNA Risk of disease progression Potential risks and benefits

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Indications for ART in the Chronically HIV-Infected Patient TREAT ALL (regardless of viral load) Symptomatic (AIDS, severe symptoms) Asymptomatic, CD4+ 200/mm 3 but 200/mm 3 but

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Indications for ART in the Chronically HIV-Infected Patient TREATAsymptomatic, CD4+ >350/mm 3 and HIV RNA>55,000(RT-PCR or bDNA)* * Some experts would recommend initiating therapy, recognizing that the 3 year risk of developing AIDS in untreated patients is >30%. In the absence of very high levels of plasma HIV RNA, some would defer therapy and monitor the CD4+ and level of plasma HIV RNA more frequently. Clinical outcomes data after initiating therapy are lacking.

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Indications for ART in the Chronically HIV-Infected Patient DEFER TREATMENT Asymptomatic CD4+ cells > 350/mm 3 HIV RNA