Fw: NATAP: Formal Neurocogitive Assessments in Studies

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- NATAP: Formal Neurocogitive Assessments in Studies

NATAP http://natap.org/

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Therapy Recommendations for HIV-Associated Neurocognitive Disorders—Reply

In Reply: Dr Zirulnik raises a point that can affect not only the timing of when

to start antiretroviral therapy, but the definition of symptomatic HIV

infection. Since our first report was published in 1996,1 the International AIDS

Society–USA Antiretroviral Guidelines Panel has consistently recommended

beginning therapy in the setting of symptomatic HIV disease. However, at that

time, symptomatic disease was seen more narrowly (AIDS-defining opportunistic

diseases; recurrent mucosal candidiasis; oral hairy leukoplakia; and chronic

unexplained fever, night sweats, and weight loss). It is now recognized that

symptoms and signs of uncontrolled HIV replication, such as subtle

neurocognitive changes, exist even at higher CD4 cell counts.2-3 Although HIV

encephalopathy and dementia would be classified as " classic " symptomatic disease

triggering initiation of therapy, confirmed subtle neurocognitive changes should

also be included in the definition of symptomatic HIV disease, and therapy would

be warranted. Before attributing symptoms and signs to HIV, careful evaluation

should exclude other treatable causes such as depression and substance abuse.

The harder question is whether beginning therapy early in asymptomatic persons

with high CD4 cell counts would prevent the development of subtle CNS

manifestations. As Zirulnik points out, the CNS compartment, particularly the

brain, acts as a sanctuary and reservoir for HIV. Drug-resistant virus in the

CNS, as with other compartments, may not mirror that observed in plasma.4

Differences in blood-brain barrier penetration among antiretroviral drugs, and

thus suppression of virus in the CNS, may not equate with suppression of plasma

viremia.5-6 Although the benefit of early therapy seems likely, systematically

collected data on subtle cognitive function have generally been lacking in

longitudinal cohorts and clinical studies. Future large, prospective cohorts and

clinical trials could provide insight into this question by including formal

neurocognitive assessments in at least a subset of participants.

Financial Disclosures: Dr reported that she has received research

grants for the AIDS Research Consortium of Atlanta from Abbott, Avexa,

Boehringer Ingelheim, Bristol-Myers Squibb, GlaxoKline, Gilead, Koronis,

Merck, Panacos, Pfizer, Progenics, Roche, Serono, TaiMed, Theratechnologies, and

Tibotec; has spoken at events sponsored by GlaxoKline and Serono; and has

served as a consultant to or was on the scientific advisory boards for

GlaxoKline, Gilead, Panacos, Pfizer, Progenics, Serono, and Tibotec. Dr

Hammer reported that he has served as a scientific advisor to Boehringer

Ingelheim, Bristol-Myers

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