Antiretroviral therapy in HIV infection - Are neurologically active drugs important?
ABSTRACT The effect on neuropsychological function of antiretroviral drugs that are able to penetrate into the brain in effective concentration (neuroactive drugs) remains unclear.
To investigate whether highly active antiretroviral therapy (HAART) containing neuroactive drugs is associated with better neuropsychological performance in patients with human immunodeficiency virus disease.
Tertiary referral hospital outpatient clinics.
The study population consisted of 97 individuals positive for human immunodeficiency virus (stage C3, 1993 Centers for Disease Control and Prevention classification) whose condition had been stable on their current HAART regimen for a mean +/- SD of 18.5 +/- 16.5 months and who were aged 48.14 +/- 9.38 years. The patient groups were analyzed according to whether their regimen contained 3 or more neuroactive drugs (neuroHAART group; n = 41) or not (HAART group; n = 56). Thirty seronegative men matched for age and education were recruited as controls.
Neuropsychological performance on 7 cognitive domains.
The neuroHAART and HAART groups did not differ from one another on neuropsychological performance, but both patient groups were impaired compared with controls. Impaired patients in each treatment group were compared, and the neuroHAART group showed significantly better memory performance, unrelated to plasma viral load, than the HAART group.
No direct benefit of neuroactive HAART therapy was found in patients with advanced human immunodeficiency virus infection. However, in neuropsychologically impaired patients, there was a benefit in memory function. This suggests that a threshold of neuropsychological impairment is required for the benefit of neuroactive HAART.
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ABSTRACT: The role of brain HIV load in the pathogenesis of HIV-associated neurocognitive disorders (HAND) is unclear. To try and determine if the amount of HIV drives the severity of pathology, a severe combined immunodeficient (SCID) mouse model of HIV encephalitis (HIVE) was utilized to determine the effectiveness of a systemically administered combined antiretroviral (cART) regimen. SCID mice were inoculated intracerebrally with HIV-infected or uninfected (control) human macrophages and treated subcutaneously with cART or saline for 10 days. Immunohistochemistry was then used to examine gliosis and neuronal damage. Drug levels were measured in brain and plasma using high-performance liquid chromatography. Peak plasma and brain levels of atazanavir, tenofovir, and emtricitabine were determined to be 1 h post-injection of cART therapy. cART significantly reduced neuropathological features of HIVE, including astrogliosis and the presence of mononuclear phagocytes, and ameliorated reduced MAP2 (neuronal integrity) staining. However, cART did not eradicate HIV from the brain. Using this animal model of HIVE, these data indicate effective penetration of cART reduces brain viral loads and HIV pathology, possibly by eliminating the production of HIV proteins, virus infected cells, or both. Importantly, these data suggest that viral load directly affects the extent of pathology seen in the brain, particularly neuronal damage, which implies that more effective suppression of HIV in the CNS could reduce currently highly prevalent forms of HAND. However, these data also strongly suggest that cART will not eliminate HIV from the brain and that adjunctive therapies must be developed.Journal of NeuroVirology 01/2014; 20(1). DOI:10.1007/s13365-013-0223-5 · 3.32 Impact Factor
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