Cognitive performance related to HIV-1-infected monocytes

Abstract

The effect that HIV type 1 (HIV) has on neurocognition is a dynamic process whereby peripheral events are likely involved in setting the stage for clinical findings. In spite of antiretroviral therapy (ART), patients continue to be at risk for HIV-associated neurocognitive disorders (HAND), which might be related to persistence of inflammation. In a yearly assessment of HIV DNA levels in activated monocytes, increased HIV DNA copies were found in patients with persistent HAND. Furthermore, activated monocytes from patients with high HIV DNA copies secreted more inflammatory cytokines. Since these activated monocytes traffic to the CNS and enter the brain, they may contribute to an inflammatory environment in the CNS that leads to HAND.

FIGURE 1. NPZ8 Scores and HIV DNA Copy

Activated monocyte (A), PBMC (B), non-activated monocyte (C), and lymphocyte (D) HIV DNA (log) from Years 1–5 and NPZ8 score, using a mixed-effects model to adjust for repeated measurements. For both activated monocytes and PBMC, HIV DNA copies per million cells were strongly associated with NPZ8 scores (p <0.001) independent of baseline/nadir CD4 cell counts, gender, or education. A one-unit increase in log HIV DNA copy in activated monocytes and PBMC resulted in 0.34 and 0.32 decrease in NPZ8 score, respectively. The estimated lines assumed that HIV RNA level was 50 at baseline. No linear relationships with HIV DNA copies were found in lymphocytes (CD14⁻; NS) or non-activated monocytes (CD14⁺CD16⁻; NS).

FIGURE 2. Longitudinal NPZ8 Scores for High- Versus Low-Activated Monocytes (A) and PBMC (B) HIV DNA Copy Groups

Patients were divided into High (≥400 HIV DNA copies/10⁶ cells; N=32) and Low (<400 HIV DNA copies/10⁶ cells; N=32) and NPZ8 scores averaged over Years 1–5.

FIGURE 3. In-Vitro and Ex-Vivo Monocyte Cytokines

In-vivo cytokines from activated and non-activated monocytes isolated from patients diagnosed with HIV-associated dementia (HAD; N=5), normal cognition (NC; N=6), and HIV-seronegative controls (NEG; N=4); TNFα (A) and IL6 (B). Supernatants from activated monocytes from patients with HAD contained higher TNFα and IL6 than supernatants from non-activated monocytes isolated from those with NC and HIV-1-seronegative controls. In-vitro monocyte cytokine secretions showing TNFα and IL6 levels from activated and non-activated monocytes infected with R5 viruses, BaL (C) and JR-CSF (D); and X4 virus, LAI (E), on Days 11, 15, and 19. For BaL and JR-CSF infections, high cytokine levels from activated monocytes were associated with high HIV DNA copies (N=3), as compared with LAI infection (N=3). Results were descriptive because the number of specimen analyzed was small.