OBJECTIVE
To analyze and compare human immunodeficiency virus type-1 (HIV) env sequences from the eye to those from the blood of individuals with uveitis attributed to HIV with the goal of gaining insight into the pathogenesis of HIV-associated eye disease.
DESIGN
A prospective case series of five HIV-infected antiretroviral (ARV)-naïve individuals with uveitis negative for other pathogens.
METHODS
RNA from blood plasma and ocular aqueous humor was reverse transcribed using random hexamers. HIV env C2–V5 (HXB2: 6990–7668) sequences were generated by single-genome-amplification (SGA) using nested polymerase-chain-reaction (PCR) followed by bi-directional Sanger sequencing. Sequence analyses by Geneious, Geno2Pheno, N-GLYCOSITE, DIVEIN, and HyPhy evaluated relationships between HIV in plasma and aqueous humor.
RESULTS
A median of 20 (range: 13–22) plasma and 15 (range: 9–18) aqueous humor sequences were generated from each individual. The frequencies of sequences with predicted-N-linked-glycosylation-sites (PNLGS) and C-X-C chemokine receptor type 4 (CXCR4) were comparable in aqueous humor and plasma of all five subjects. Aqueous humor sequences had lower median genetic diversity compared to plasma across all subjects, but similar divergence, in 4 of 5 subjects. Aqueous humor HIV sequences were compartmentalized from plasma across subjects by Critchlow correlation coefficient, Slatkin and Maddison, nearest-neighbor statistic, and Fixation index.
CONCLUSIONS
Among ARV-naïve individuals with uveitis attributed to HIV, the universal compartmentalization and decreased diversity of eye compared to blood sequences suggests time-limited passage of a small subset of variants from each subject’s viral population into the eye tissues, followed by limited immune selection despite the inflammatory uveitis.