Naïve CD4+ cell counts significantly decay and high HIV RNA levels contribute to immunological progression in long-term non-progressors infected with HIV by blood products: a cohort study

Abstract

Background: Some long-term non-progressors (LTNPs) have decreasing CD4⁺ T cell counts and progress to AIDS. Exploring which subsets of CD4⁺ T cell decreasing and the determinants associated with the decay in these patients will improve disease progression surveillance and provide further understanding of HIV pathogenesis.

Methods: Twenty-five LTNPs infected with HIV by blood products were classified as decreased (DG) if their CD4⁺ cell count dropped to < 400 cells/μL during follow-up or as non-decreased (non-DG) if their CD4⁺ cell count was ≥400 cells/μL. Laboratory and clinical assessments were conducted at 6 consecutive visits to identify DG characteristics.

Results: The LTNPs were infected with HIV for 12 (IQR: 11.5-14) years, and 23 were classified as the B' subtype. Six individuals lost LTNP status 14.5 (IQR: 12.5-17.5) years after infection (DG), and the CD4⁺ T cell count decreased to 237 (IQR: 213-320) cells/μL at the latest visit. The naïve CD4⁺ T cell count decrease was greater than that of memory CD4⁺ T cells [- 128 (IQR: - 196, - 107) vs - 64 (IQR: - 182, - 25) cells/μL)]. Nineteen individuals retained LTNP status (non-DG). At enrolment, the viral load (VL) level (p = 0.03) and CD8⁺CD38⁺ percentage (p = 0.03) were higher in DG than non-DG individuals. During follow-up, viral load and CD8⁺CD38⁺ percentage were significantly increased and negatively associated with CD4⁺ cell count [(r = - 0.529, p = 0.008), (r = - 0.476, p = 0.019), respectively]. However, the CD8⁺CD28⁺ percentage and B cell count dropped in DG and were positively correlated with CD4⁺ T cell count [(r = 0.448, p = 0.028), (r = 0.785, p < 0.001)].

Conclusion: Immunological progression was mainly characterized by the decrease of naïve CD4⁺ T cell in LTNPs infected with HIV by blood products and it may be associated with high HIV RNA levels.

Keywords: Blood products; High HIV RNA levels; Immune activation; LTNPs; naïve CD4+ T cell count diminishing.

Fig. 1

The dynamics of CD4⁺ T cell subsets during follow-up between DG and non-DG. The CD4⁺ T cell percentage decreased gradually in the DG(a). The CD4⁺ T cell count dropped significantly in the DG while it maintained the similar level with that at enrolment in the non-DG(b). The naïve CD4⁺ T cell percentage experienced a down trend(c) while memory CD4⁺ T cell percentage was comparable to that at enrolment (e). The naïve CD4⁺ T cell counts decreased significantly(d) while memory CD4⁺ T cell counts decayed slightly(f) in the DG

Fig. 2

The fluctuations of lymphocyte subsets in the different visits. The CD8⁺ T cell percentage (a), CD8⁺ T cell counts (b), CD4⁺/CD8⁺ ratio (c) and NK cell counts (d) did not differ significantly between the two groups

Fig. 3

The activation subset of CD8⁺ T cell and its correlation with CD4⁺ T cell count. The dynamics of CD8⁺CD38⁺/CD8⁺ percentage during follow-up period was shown (a) and the percentage of the CD8⁺CD38⁺ subset was negatively associated with the CD4⁺ T cell count (b)

Fig. 4

The plasma HIV RNA level and its correlation with CD4⁺ T cell count. The plasma HIV RNA level at enrollment and the latest visit between DG and non-DG was shown (a). Negative association was found between the plasma HIV RNA level and CD4 cell counts in LTNPs in the latest visit (b)