Alcohol consumption leads to injury in various tissues/organs, and impairs immune functions. The effects of alcohol consumption on HIV-1 infection and acceleration of disease progression remain controversial. It is also not well-known if alcohol abuse leads to reactivation of HIV-1 replication from latency and causes virologic failure. Using susceptible U1 cells chronically infected with HIV-1, we examined the effects of alcohol on latency in macrophages. We found that low levels (0.05~0.2 g/ml) of ethanol treatments increased HIV-1 replication with upregulating expression of AP-1 and NFAT and activation of NF?Bp65 through inducing TCR-related pathways, P-TEFb pathway and MAPK-signaling pathways, regulating expression of epigenetic factors with enhanced expression of histone acetylation, inhibition of HDAC and controlling histone methylation. Ethanol treatments increased p47phox expression and decreased cell viabilities in a dose-dependent manner with inducing both apoptotic pathways and autophagy pathways. High levels (0.4 g/ml) of ethanol treatment caused significantly lower cell viability with no detectable changes in reactivation of HIV-1 replication through inhibited expression/activation of CD3, CD28, PKC? and ZAP-70 in TCR-related pathways. These results indicate that low levels of ethanol enhance HIV-1 replication without significant loss of cells while ethanol at high levels reduces cell counts with no detectable changes of HIV-1 replication.