The effect of chronic binge ethanol consumption on the primary stage of SIV infection in rhesus macaques

Abstract

Background: Alcohol abuse and infection with HIV individually compromise immune function, but the consequence of both conditions together is poorly understood owing to the difficulties of performing appropriate studies in human subjects. Simian immunodeficiency virus (SIV) infection of rhesus macaques is considered to closely model HIV disease in that the virus infects CD4+ cells and this infection leads to a similar AIDS state. This study was initiated to study the combined effects of chronic binge alcohol consumption on the primary stage of SIV infection.

Methods: Rhesus macaques were administered alcohol or isocaloric sucrose via a permanently indwelling intragastric catheter 4 consecutive days per week for the duration of the study. Doses were individualized to achieve plasma alcohol concentrations of 50-60 mM over a 5-hr period. After 3 months, animals were inoculated intravenously with 10,000 times the ID(50) (50% infective dose) of SIV(DeltaB670) at the conclusion of an alcohol session and followed for 2 months postinoculation.

Results: At 1 week, plasma SIV RNA was greater than 60-fold higher in alcohol-consuming animals compared with sucrose controls. Likewise, alcohol consumption enhanced the SIV-induced increase in cell cycling T lymphocytes (i.e., cells expressing Ki67 protein) in blood. These differences between alcohol- and sucrose-treated animals were not sustained during the observation period. Peak viral load occurred 2 weeks post-SIV inoculation at 7.6 +/- 4.2 and 5.2 +/- 3.1 x 106 copies/ml in alcohol- versus sucrose-consuming animals, respectively. Blood CD4+ lymphocyte numbers were decreased 1 and 2 months after SIV inoculation to a similar degree in both sucrose-control and alcohol-treated animals.

Conclusions: The consequence of the early rise in viral load and increase in lymphocyte turnover seen with excess alcohol consumption is unknown. We hypothesize that alcohol intoxication may increase the susceptibility of the host to HIV/SIV infection. This possibility needs to be explored further.