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Adjunctive therapies for HIV-1 associated neurologic disease
S W Perry1, J P Norman, H A Gelbard
1Center for Aging and Developmental Biology, Kornberg Medical Research Institute, Rochester, NY 14642, USA.
Neurotoxicity Research
|November 2, 2005
Summary
New therapies are needed to address the rising prevalence of neurologic disease in people with HIV-1. This review explores agents that restore mitochondrial function in the central nervous system (CNS) to improve neuronal health.
Area of Science:
- Neuroscience
- Virology
- Pharmacology
Background:
- Combination chemotherapy has reduced HIV-1 associated dementia (HAD) incidence but not overall neurologic disease prevalence.
- New therapeutic strategies are required, focusing on restoring neuronal and glial homeostasis in the central nervous system (CNS).
Purpose of the Study:
- To review adjunctive therapies for HAD and discuss novel strategies targeting CNS bioenergetics.
- To explore the rationale for investigating agents that restore mitochondrial function in HIV-1 infected CNS.
Main Methods:
- Review of Phase 1 clinical trials for adjunctive HAD therapy.
- Overview of molecular events in HIV-1 neuropathogenesis.
- Discussion of therapeutic agents targeting mitochondrial K-ATP channels and respiratory uncoupling.
Main Results:
- While HAD incidence decreased, overall neurologic disease in HIV-1 patients increased.
- Agents targeting mitochondrial bioenergetics may offer complementary benefits to antiretroviral therapy.
Conclusions:
- Therapeutic agents restoring mitochondrial bioenergetics show promise for improving CNS function in HIV-1 patients.
- These agents could help meet increased bioenergetic demands in the CNS, complementing existing treatments.
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