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HIV 1993-2008. Jeffrey P. Nadler, M.D., FACP Acting Director, Therapeutics Research Program DAIDS, NIAID, NIH. Historical Perspective. Disease described 1981 Life expectancy 6-9 months Classic opportunistic infections (OI) limiting survival No antiretroviral therapy
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HIV 1993-2008 Jeffrey P. Nadler, M.D., FACP Acting Director, Therapeutics Research Program DAIDS, NIAID, NIH
Historical Perspective • Disease described 1981 • Life expectancy 6-9 months • Classic opportunistic infections (OI) limiting survival • No antiretroviral therapy • Delayed (clinical) diagnosis • No validated surrogate lab markers • Early improvement in clinical recognition and prophylaxis and treatment of OIs extended life expectancy to several years
Opportunistic Infection (OI) • These are often severe illnesses that are rarely encountered unless the immune system is considerably compromised (by conditions such as HIV) • Medical advances have substantially improved the prognosis of many (but not all) OIs • OI may still result in persistent illness or death unless there is significant immune improvement, such as is often seen in HIV with HAART (though this is not necessarily a rapid process)
Therapy • 1987 was the dawn of ART, with ZDV • Monotherapy, serially (ZDV, then ddI, etc.) • Limited effect • 1992/3 combination therapy proposed and studied • Limited benefit due to adverse effects of Rx • Still applied in advanced HIV
Major Advance: HAART • 1995/96 PI HAART • 1996/97 NNRTI Rx • Huge decrease mortality, morbidity followed • Coupled with new lab diagnoses, disease monitoring
HAART Issues • Incremental improvements in HAART from 1996 • Prominent adverse effects of therapy: GI intolerance, anemia, disfigurement, wasting, “mitochondrial toxicity” • Subsequent (2001) major improvements in HAART - reduced toxicity, better tolerability • More potent agents with improved durability of response • Further lab monitoring improvements
Disease Issues • Viral resistance compromising response • Selected OI emergence • Hepatitis C • Premature death may be due to HIV itself, acceleration of natural processes (CVD, malignancies)?
US HIV Demographic Changes • Fewer MSM’s • Increasingly, infected women, especially minority women • More people living with HIV • CDC now estimates new infection annual undercount by 40% • Life expectancy decades, approaching the HIV-uninfected population
HIV in an Aging Population • Elevated lipids (due to Rx and HIV) - increased CVD? • Persistent morphologic changes - disfigurement • Higher rates of glucose intolerance/diabetes • Decreased bone mineral density, more frailty, fractures? • Persistent neuropathy • Chronic hepatitis C • Increased malignancy, AIDS and non-AIDS? • Subtle cognitive impairment? Depression?
Additional Considerations • HIV interactions with aging? • Polypharmacy and drug interactions • Complicate management • Increase inconvenience and cost • Potential for adverse effects • Key: Disproportionate effect on minorities and lower socioeconomic groups • Key: Benefit shortage, discrimination?