Anatomical compartments (e.g., the reproductive tract) are reservoirs of hu
man immunodeficiency virus type-1 (HIV-1) and potential sites of residual i
nfection in patients receiving anti-retroviral therapy (ART). Viral hyper-e
xcretion relative to blood is a hallmark of reservoirs. To determine whethe
r hyper-excretion can occur in the oral cavity, we compared viral loads in
blood plasma and saliva of 67 adults. Salivary viral hyper-excretion was de
fined as a four-fold or higher viral load in saliva than in plasma. HIV-1 R
NA was detected in 79% of plasma samples, in 44% of unfiltered saliva sampl
es, in 16% of filtered saliva samples, and in 59% of saliva-derived cell pe
llets. Compared with non-hyper-excretors (n = 62), hyper-excretors (n = 5)
had elevated levels of viral RNA in unfiltered saliva and saliva-derived ce
lls, HIV-associated periodontal disease, gingival inflammation, and no comb
ination ART. Morphological characterization of cell pellets identified lymp
hocytes as a likely HIV-1 source. These collective findings are consistent
with an oral HIV-1 reservoir in selected individuals.