Abstract
BackgroundSome 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.MethodsTwenty-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.ResultsThe 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)].ConclusionImmunological 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.
Highlights
There were 38 million people living with Human immunodeficiency virus (HIV)-1 worldwide in 2019
We found that 24.0% of long-term non-progressors (LTNPs) experienced CD4+ T cell count decay at 14.5 (IQR: 12.4–17.5) years following HIV infection
These results extend our understanding of the association between the clinical outcomes and HIV RNA loads levels as well as dynamics of immune cell profiles in LTNPs infected with HIV by blood products from China by longterm follow-up
Summary
There were 38 million people living with HIV-1 worldwide in 2019 (https://www.unaids.org). HIV-infected individuals are characterized by continuous HIV RNA replication and CD4+ T cell count decline, and most of them progress to AIDS in an average of 10 years [1]. Approximately 5–15% of HIV-infected patients can naturally maintain high CD4+ T cell counts and remain asymptomatic for several years without cART (combined antiretroviral therapy). These individuals are considered as long-term non-progressors (LTNPs), including elite controllers (ECs), who only account for 1%. 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
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