Peripheral blood lymphocyte HIV DNA levels correlate with HIV associated neurocognitive disorders in Nigeria

Abstract

Mononuclear cells play key roles in the pathogenic mechanisms leading to HIV associated neurocognitive disorders (HAND). We examined the association between HIV DNA within peripheral blood mononuclear cell (PBMC) subsets and HAND in Nigeria. PBMCs were collected at baseline from 36 antiretroviral naïve participants. CD14+ cells and T&B lymphocyte fractions were isolated by, respectively, positive and negative magnetic bead separation. Total HIV DNA within CD14+ and T&B cells were separately quantified using real-time PCR assay targeting HIV LTR-gag and cell input numbers determined by CCR5 copies/sample. Utilizing demographically adjusted T scores obtained from a 7-domain neuropsychological test battery, cognitive status was determined by the global deficit score (GDS) approach, with a GDS of ≥0.5 indicating cognitive impairment. In a linear regression adjusting for plasma HIV RNA, CD4 and lymphocyte count, Beck’s depression score, and years of education, there was 0.04 lower log10 HIV DNA copies within T&B lymphocytes per unit increase in global T score (p= 0.02). Adjusting for the same variables in a logistic regression, the odds of cognitive impairment were 6.2 times greater per log10 increase in HIV DNA within T&B lymphocytes (p= 0.048). The association between cognitive impairment and HIV DNA within CD14+ monocytes did not reach statistical significance. In this pretreatment cohort with mild cognitive dysfunction we found a strong association between levels of HIV DNA within the lymphocyte subset and HAND independent of plasma HIV RNA. These findings likely reflect the neurologic impact of a larger HIV reservoir and active viral replication.

Plasma HIV RNA level is associated with neurocognitive function among HIV-1-infected patients in Nigeria

“…Details of these are described in our other reports (Akolo et al 2014; Royal et al 2016; Jumare et al 2017). Participants were screened for effort using the Hiscock Digit Memory Test, and for depression with the Beck Depression Inventory (Beck et al 1996).…”

HIV-1 CRF01_AE subtype and HIV-1 DNA level among patients with chronic HIV-1 infection: a correlation study

“…To date, the HIV-1 DNA reservoir and recovery of replication-competent HIV in antiretroviral therapy (ART) treated patients with undetectable HIV-1 RNA remains the major obstacle in identifying a cure for HIV [9]. The HIV reservoir is influenced by multiple factors, including the clinical stage of HIV infection, CD4 + T cell count, CD4/ CD8 ratio, degree of immune activation/inflammation, treatment duration, and HIV-associated neurocognitive disorders [10][11][12][13][14][15]. As a biomarker, HIV-1 DNA level is usually used to evaluate the persistence and dynamics of the HIV reservoir [14].…”

Clinical Relevance of Total HIV DNA in Peripheral Blood Mononuclear Cell Compartments as a Biomarker of HIV-Associated Neurocognitive Disorders (HAND)

“…An appropriate clinical specimen gives information which reflects on the condition of the disease by correlating with findings from clinical assessments [ 41 ]. The choice of the sample should consider the stage of HIV disease as it is known that there are differences between early HIV disease and advanced stages of infection with regard to shift in tropism [ 42 ]. Advanced stages of HIV diseases shows depletion of CD4+ T lymphocytes, while there is both expansion and increased turnover of peripheral monocytes, including CD14+/CD16+ subsets known to be associated with increased susceptibility to HIV infection [ 43 ].…”

“…The quantity of infected memory cells in this study also correlated with plasma viral load, which is a virological marker for monitoring and predicting HIV infection. However, with regard to HAND, there are limited data on correlation studies linking peripheral lymphocyte HIV DNA levels and severity of neurocognitive impairment [ 42 , 51 ]. Investigations using ART naïve participants with mild to moderate neurocognitive impairment, lymphocyte HIV DNA levels were shown to be significantly associated with HAND independent of plasma viral load and CD4+ count [ 42 , 54 ].…”

“…However, with regard to HAND, there are limited data on correlation studies linking peripheral lymphocyte HIV DNA levels and severity of neurocognitive impairment [ 42 , 51 ]. Investigations using ART naïve participants with mild to moderate neurocognitive impairment, lymphocyte HIV DNA levels were shown to be significantly associated with HAND independent of plasma viral load and CD4+ count [ 42 , 54 ]. There is need for more data on association studies between peripheral lymphocyte HIV DNA reservoirs and HAND, since this is the preferential target of HIV infection [ 57 ].…”