Transcript HIV 1993-2008 Jeffrey P. Nadler, MD, FACP

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
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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
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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?