High Monocyte Turnover Predicts Progression to AIDS in SIV Infected Aging Rhesus Macaques

Abstract

Abstract Incidence of newly-acquired HIV infections in persons over age 50 is increasing, from 13% in 2006 to 21% in 2013. Advanced age corresponds with lower 12-month survival and ART is contraindicated with the simultaneous use of many chronic disease medications. To address the need for age-specific interventions, we are studying aged rhesus macaques (RM) infected with SIV. In a pilot study, four young (6.27–7.37 years) and six older (17.71–23.82 years) RM were injected i.v. with SIVmac239. The older RM exhibited lower survival times compared to younger macaques (112.5 ± 76.8 days v. 353 ± 74.9 days, respectively). In young adult RM with SIV, we reported that increasing monocyte turnover (via BrdU uptake) as well as declining CD4+ cell counts, predicted disease progression. Among the aged RM, we observed that 3 animals developed increased or high monocyte turnover (HMT) after the first month of infection (35.2% ± 2.36) while the other 3 maintained steady state or low monocyte turnover (LMT) (5.74% ± 4.92) similar to that in the young animals (9.97% ± 2.34). Older RM with LMT survived longer (151 ± 85.6 days) than those with HMT (74 ± 54.5 days). The young adult and aged RM with LMT exhibited a dramatic decline of CD4+ T cells during peak viral load (−46% and −41%) 2 wks post infection compared to only a 22% decrease in aged RM with HMT. Also, the numbers of naïve T cells (CD4 and CD8) were lower in the HMT aged animals than in the LMT and young adults, at baseline and 2 wks post infection. These results suggest that there may be an additional or alternative preferential host cell target of SIV early in infection of older susceptible RM that we speculate to be macrophages. Work is continuing to examine the role of macrophages in pathogenesis of HIV infection in the elderly.