Despite antiretroviral therapy (ART), people living with HIV (PLWH) are at increased risk of developing cardiovascular disease (CVD) and HIV-associated neurocognitive disorder (HAND), among other comorbidities. Studies from ART-treated individuals identified galectin-3 (gal-3) and IL-18 as CVD biomarkers, galectin-9 (gal-9) as a HAND biomarker, and sCD163, a marker of monocyte/macrophage activation, as a biomarker of both. We asked if plasma gal-3, gal-9, and IL-18 are associated with an individual comorbidity or increase in both with animals that develop AIDS with both pathologies vs. (CVD-path) alone or SIV encephalitis (SIVE) alone. We found that no biomarkers were selective between individual pathologies and all biomarkers increased with co-development of CVD-path and SIVE (gal-3, p=0.11; gal-9, p=0.001; IL-18, p=0.007; sCD163, p<0.001; %BrdU p=0.02. While gal-3, gal-9, and IL-18 did not distinguish between pathologies, they correlate strongly with one another, with sCD163, a marker of monocyte/macrophage activation, and the %BrdU monocytes, a markerof monocyte turnover. Compared to animals with CVD-path or SIVE alone, animals that co-developed both pathologies had consistently elevated IL-18 throughout infection (p = 0.02) and increased sCD163 in late infection (p = 0.01). These data indicate that gal-3, gal-9, and IL-18 are associated with monocyte/macrophage activation by sCD163 and monocyte turnover by the %BrdU+ monocytes more so than CVD-path or SIVE.