Conclusion
These results demonstrate that monocytes/macrophages significantly affect HIV/SIV pathogenesis outcomes. Monocyte turnover analyses are not currently feasible in humans, so there is a need to identify surrogate biomarkers reflecting tissue macrophage damage that predict HIV infection disease progression.
Methods
Rhesus macaques were infected with various strains of SIV/SHIV and evaluated longitudinally for monocyte turnover, CD4+ T-cell loss, plasma viral load, and SIV/SHIV strain. Correlation analyses and machine learning algorithm modeling were applied to compare relative contributions of each of the co-variates to survival time.
Results
All animals with AIDS-related clinical signs requiring euthanasia exhibited increased monocyte turnover regardless of CD4+ T-cell level, viral strain, or plasma viral load. Regression analyses and machine learning algorithms indicated a stronger correlation and contribution between increased monocyte turnover and reduced survival time than between CD4+ T-cell decline, plasma viral load, or virus strain and reduced survival time. Decision tree modeling categorized monocyte turnover of 13.2% as the initial significant threshold that best predicted decreased survival time.