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HIV, Dementia & HAART
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HIV, Dementia & HAART. "Evidence for a change in AIDS dementia complex in the ....Whether this leads in the long term to brain damage and a chronic form of
www.natap.org/2004/HIV/hiv_aging_03.htm
".....it therefore seems very likely that the introduction of HAART has changed the very nature of ADC (AIDS dementia complex). It is now not so strongly linked to the CD4 cell count, there may be inactive and chronic forms of ADC, and patients are living longer making them vulnerable to the possible cognitive effects of hitherto unappreciated disorders. Chief among these is the large body of evidence that points, theoretically at least, to an increased risk of Alzheimer's disease. Verification of these concepts is clearly required, but equally clearly such confirmation will take several years. In the mean time, clinicians and researchers should be open to these possibilities in order to avoid their confounding effects on understanding HIV neuropathogenesis.
HAART may also be associated with a chronic form of ADC....ADC may also be 'transformed' in the era of HAART....nadir CD4 cell count may be a new important risk factor for ADC.....testosterone deficiency can lead to a cognitive deficit at least in non-HIV-infected individuals. The extent to which this can be reversed by replacement is unknown....it is still unknown whether in the long term HAART-treated patients may develop brain mitochondrial toxicity....It is now becoming increasingly apparent that hepatitis C in conjunction with HIV may lead to more profound cognitive deficits. In an individual patient this may also lead to a 'layering' of one deficit (hepatitis C) on top of another (ADC)..... The HIV regulatory protein tat may play a role in increasing the risk of Alzheimer's disease.
.....Raised cholesterol concentrations have repeatedly been shown to be a risk factor for Alzheimer's disease......perhaps most importantly, ADC non-ADC patients may be at an increased risk of developing Alzheimer's disease. Although this is also speculative there are several reasons for suspicion: increased age, high lipids, axonal injury, and the effects of tat and quinolinic acid on the brain. HIV-infected patients in general and ADC patients in particular are now living longer. The number of patients over the age of 60 years is increasing.
Given that the risk of ADC increases as the CD4 cell count falls, especially when it is below 200 cells, and that such a CD4 cell count may allow or facilitate autonomous brain infection by HIV, it seems that the nadir CD4 cell count may be a new important risk factor for ADC.....HAART has thus raised the CD4 cell count which is commonly seen in patients with ADC, and has introduced two potentially new risk factors: nadir CD4 cell count and disease duration......The 'natural history' of ADC has also changed..... Hepatitis C, testosterone deficiency and the effects of aging are now becoming important confounders......part from the potentially increased importance of confounding factors, the actual cognitive deficit in ADC may be changing....standard CSF markers of ADC, such as beta-2 microglobulin and the HIV viral load in the CSF, are no longer sensitive to the presence or severity of ADC. Of the six patients who developed ADC, four did so despite CSF suppression. This is in marked contrast to the pre-HAART era in which such markers were strongly correlated with the severity of ADC.....patients had an inactive or 'burnt out' form of ADC.....[patients] responded maximally to HAART before starting the trial, and may have been left with a fixed deficit, perhaps as a result of neuronal loss.....HAART may also be associated with a chronic form of ADC. The above-mentioned prospective PET-CSF study contained patients who developed ADC over several years in the face of undetectable CSF and plasma HIV viral loads at least at the time points studied. Moreover, there is indirect evidence. A recent study by Abdulle et al. found that neuroasyptomatic HIV-infected patients who had been treated with HAART for 2 years still had mildly elevated CSF concentrations of neopterin in the presence of normal concentrations of beta-2 microglobulin and HIV RNA in both compartments. This suggests that HAART cannot return all CSF parameters to normal. The elevated neopterin concentration implies that there is activation within the central nervous system of monocytes, microglia or both. Such immune activation may be secondary to productive brain infection, which is below the detection limits in the CSF, or it may be related to local unchecked immune activation from past damage. Whether this leads in the long term to brain damage and a chronic form of ADC is, however, speculative at present. Nonetheless, the lack of awareness of this possibility may also confound efforts aimed at understanding ADC pathogenesis. There is also indirect evidence from systemic HIV infection for the presence of a chronic form of ADC. It is well known that HIV can be cultured from lymph nodes in patients with plasma HIV viral loads below 20 copies/ml. It seems likely that this could also be true for the brain.
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