Background:  HIV invades the central nervous system early after viral infection and eventually induces cognitive and motor abnormalities referred to as HIV-1-associated dementia. In the era of HAART, HIV-infected individuals with advanced disease show a mild form of the disease, termed cognitive impairment. Neuroinvasion of HIV-1 occurs through the trafficking of infected monocytes and lymphocytes across the blood–brain barrier and a release of neurotoxins into the brain. Additionally, there is late emergence of viral variants that affect disease neuropathogenesis. The hypothesis of this study is that HIV-1 variants from patients with dementia will influence macrophage secretory function.

Methods:  A cohort of HIV-positive Hispanic women have been followed for several years for the development of HIV-associated dementia using a Memorial Sloan Kettering Scale (MSK) ≥1.Virus isolated from peripheral blood of HIV-positive women with cognitive impairment (n = 5) were compared with those isolated from patients without cognitive impairment (n = 5) by testing the tropism on monocyte-derived-macrophages (MDM) and on MT2 lymphocyte cell line. Monocytes from normal donors were cultured for 7 days and inoculated with 10 viral isolates containing 25 ng of p24 antigen per well. Supernatants were tested by p24 antigen ELISA at various times post-infection. The MT2 cell line was inoculated with the viral isolates (n = 10) and monitored for syncytia formation on days 3, 6, 9, 12, and 14 post-infection. MDM at days 7 and 14 post-infection were left with DMEM plain for 24 hours and monocyte lysates were collected at 8 days post-infection and tested by SELDI-TOF for differences in protein profiles.

Results:  Of the 10 isolates, 7 were found to be dual tropic on macrophages and lymphocytes. Protein profiles of uninfected and HIV-1-infected monocyte lysates showed intensity differences at 11313.08, 13799.41, 15375.45 M/Z values. The peak of 11313.08 M/Z was found significantly decreased in the lysates from monocytes infected with HIV-1 from demented as compared with non-demented patients and negative controls (p < 0.05).

Conclusions:  The viral tropism of the blood HIV-1 isolates did not correlate with dementia in these patients. The down-regulation of the 11313.08 M/Z peak in MDM infected with HIV-1 isolates from demented patients may play a role in the development of HIV-associated dementia.

Keywords: Neuropathogenesis; Monocytes; Tropism