Seronegative MSM at high risk of HIV-1 acquisition show an immune quiescent profile with a normal immune response against common antigens

Human immunodeficiency virus (HIV) infection still represents a major public health problem worldwide, and its vaccine remains elusive. The study of HIV-exposed seronegative individuals (HESN) brings important information about the natural resistance to HIV, allows a better understanding of the infection, and opens doors for new preventive and therapeutic strategies. Among HESN groups, there are some men who have sex with men (MSM) with high-risk sexual behaviors, who represent an adequate cohort for HESN study because of their major HIV exposure without infection. This study aimed to compare the immunological profile of Colombian seronegative MSM with different risk sexual behaviors. This study included 60 MSM at high-risk (n = 16) and low-risk (n = 44) of HIV-1 acquisition. No sex worker nor homozygous delta 32 mutation subjects were included. All participants were negative for anti-HIV-1/2 antibodies and HIV-1 proviral DNA. A higher frequency of sexual partners in the last 3 months before the study participation (median, 30 vs. 2), lifetime sexual partners (median, 1,708 vs. 26), and unprotected anal intercourse (median 12.5 vs. 2) was determined in high-risk MSM than low-risk MSM. High-risk MSM also showed a quiescent profile of T cells and natural killer (NK) cells, with a significantly lower percentage of CD4+CD38+, CD4+HLADR−CD38+, CD4+Ki67+ T cells, and NKG2D+ NK cells (CD3−CD16+CD56+), a significantly higher percentage of CD4+HLADR−CD38−, and a tendency to show a higher percentage of CD8+HLADR+CD38− T cells than the low-risk group. Likewise, they showed higher mRNA levels of Serpin A1 from PBMCs. The results suggest that this MSM cohort could be HESN individuals and their resistance would be explained by a quiescent profile of T cells and NK cells and an increased Serpin A1 expression. Further study on MSM at high risk of exposure to HIV-1 is necessary to better understand the natural resistance to HIV.