Salivary protein profile of PLHIV on long-term antiretroviral therapy suggests latent reservoir and immune exhaustion.

OBJECTIVE

To compare salivary protein profiles in people living with HIV (PLHIV) undergoing antiretroviral therapy (ART) for different durations. This cross-sectional study examined how long-term ART affects the salivary proteome in PLHIV.

DESIGN

Unstimulated saliva was collected from 23 adult men: those on ART for more than 7 years (group HIV.UP7, n = 11) and for up to 7 years (group HIV.DOWN7, n = 12). Samples were analyzed by nano-LC-ESI-MS/MS, followed by label-free quantification and bioinformatic analysis using the UNIPROT database. Differential protein expression was assessed using Student's t-test (p < 0.05).

RESULTS

Mean age was 48.36 (±14.94) years in HIV.UP7 and 32.08 (±5.75) in HIV.DOWN7. ART duration averaged 13 (±4.92) and 3 (±1.62) years, respectively. A total of 187 proteins were identified. Compared to HIV.DOWN7, HIV.UP7 showed 34 up-regulated and 22 down-regulated proteins. Up-regulated proteins included Hemoglobin subunit alpha, Histones H2B, Albumin, Actin aortic smooth muscle, Actin alpha cardiac muscle 1, and POTE ankyrin domain family member E. Down-regulated proteins included Leukocyte elastase inhibitor and Immunoglobulin heavy variable (IGHV3).

CONCLUSIONS

Long-term ART in PLHIV is linked to proteomic alterations that may contribute to sustaining the latent HIV reservoir. Reduced expression of immune-related proteins suggests immune exhaustion, potentially weakening immune responsiveness over time.