Absence of peripapillary retinal nerve-fiber-layer thinning in combined antiretroviral therapy-treated, well-sustained aviremic persons living with HIV

Abstract

Purpose: To compare peripapillary retinal nerve-fiber-layer (pRNFL) thickness, total retina macular volume, and ganglion-cell-layer (GCL) macular volume and thickness between persons living with HIV (PLHIVs) with well-controlled infections and good immune recovery, and sex- and age-matched HIV-uninfected controls (HUCs).

Methods: This prospective cross-sectional study (www.clinicaltrials.gov identifier: NCT02003989) included 56 PLHIVs, infected for ≥10 [median 20.2] years and with sustained plasma HIV-load suppression on combined antiretroviral therapy (cART) for ≥5 years, and 56 matched HUCs. Participants underwent spectral-domain optical coherence tomography (SD-OCT) with thorough ophthalmological examinations and brain magnetic resonance imaging (MRI). Their overall and quadrant pRNFL thicknesses, total macular volumes, and GCL macular volumes and thicknesses were compared. Cerebral small-vessel diseases (CSVD) complied with STRIVE criteria.

Results: Median [interquartile range, IQR] ages of PLHIVs and HUCs, respectively, were 52 [46-60] and 52 [44-60] years. Median [IQR] PLHIVs' nadir CD4+ T-cell count and current CD4/CD8 T-cell ratio were 249/μL [158-350] and 0.95 [0.67-1.10], respectively; HIV-seropositivity duration was 20.2 [15.9-24.5] years; cART duration was 16.8 [12.6-18.6] years; and aviremia duration was 11.4 [7.8-13.6] years. No significant between-group pRNFL thickness, total macular volume, macular GCL-volume and -thickness differences were found. MRI-detected CSVD in 21 (38%) PLHIVs and 14 (25%) HUCs was associated with overall thinner pRNFLs, and smaller total retina and GCL macular volumes, independently of HIV status.

Conclusions: SD-OCT could not detect pRNFL thinning or macular GCL-volume reduction in well-sustained, aviremic, cART-treated PLHIVs who achieved good immune recovery. However, CSVD was associated with thinner pRNFLs and GCLs, independently of HIV status.

Fig 1. Association between overall peripapillary retinal nerve-fiber–layer (pRNFL) thickness (top) or ganglion-cell–layer (GCL) volume (bottom) and age of PLHIVs and HUCs.

Significant linear correlations were found between the overall pRNFL or macular GCL volume and the ages of the persons living with human immunodeficiency virus (PLHIVs) or the HIV-uninfected controls (HUCs). The HIV status had no significant effect on this association. The linear-regression equation is given.

Fig 2. No association between PLHIVs’ overall peripapillary retinal nerve-fiber–layer (pRNFL) thickness (top) or ganglion-cell–layer (GCL) volume (bottom) and CD4+ T-cell count nadirs of the persons living with human immunodeficiency virus (PLHIVs).

The vertical line represents the CD4+ T-cell count nadir of 100 cells/μL, because previous studies found that only PLHIVs with nadirs <100 cells/μL were more likely to have thinner pRNFLs. In our study only nine PLHIVs had a nadir <100 cells/μL but their pRNFL thicknesses and macular GCL volumes did not differ from those of the other PLHIVs.

Fig 3. Effect of cerebral small-vessel disease (CSVD) on overall peripapillary retinal nerve-fiber–layer (pRNFL) thickness (top) and ganglion-cell–layer (GCL) volume (bottom) in all participants.

The mean overall pRNFL thickness (top) and the mean macular GCL volume (bottom) are reported for all participants, persons living with human immunodeficiency virus (PLHIVs) and for HIV-uninfected controls (HUCs). Error bars represent the standard deviation. Participants with MRI-defined CSVD had significantly thinner pRNFL (p = 0.04; ANOVA) and smaller macular GCL volume (p<0.01; ANOVA) compared to the participants with no CSVD. HIV status had no significant effect on pRNFL and no significant interaction with the effect of CSVD on pRNFL (S2 Table).