More than one quarter of people with advanced HIV who had never taken antiretroviral therapy (ART) harbored antibodies that target the body’s own immune cells, and the presence of those antibodies was associated with slower immune system recovery once they initiated ART, according to an analysis of NIAID-sponsored studies. The antibodies, called anti-CD4 autoantibodies, target CD4+ T cells—a type of white blood cell essential for maintaining the body’s immune system—which are also the target of HIV. Typically, initiating ART helps to restore the body’s CD4+ T-cell count to a typical range. However, the analysis found that people with advanced HIV and anti-CD4 autoantibodies experienced limited CD4+ T-cell reconstitution through up to four years of observation after ART initiation, highlighting a potential immune effect of long-term unsuppressed HIV. The findings were published in Clinical Infectious Diseases.
The analysis included 210 people with advanced HIV—defined as having CD4+ T-cell counts of less than or equal to 100 cells per microliter (μL) of blood—who had never taken ART and were enrolled in one of two clinical studies examining the effects of HIV and ART on the immune system between December 2006 and June 2019. Study participants initiated ART and were clinically assessed for a median of 192 weeks after ART initiation at the NIH Clinical Center.
Anti-CD4 autoantibodies were identified in the blood samples of 29% of participants with advanced HIV. The prevalence of anti-CD4 autoantibodies was four times higher in female participants compared to male participants. After initiating ART, the pace and extent of CD4+ T-cell recovery was lower in participants with anti-CD4 autoantibodies, who had a median CD4+ T cell count of 268 cells/µL after 192 weeks after ART, compared to 355 cells/µL in those without anti-CD4 autoantibodies. In a sub analysis, the investigators found that participants with anti-CD4 autoantibodies who were also incidentally taking clinically indicated immunosuppressive therapy such as corticosteroids experienced a significantly higher rate of CD4+ T-cell recovery and higher median CD4+ T-cell counts at week 192 than participants with autoantibodies and no immunosuppressive therapy.
Researchers also examined blood samples from other study populations without advanced HIV, such as people with untreated HIV and CD4+ T-cell counts above 200 cells/μL, people who met criteria for designation as long-term non-progressors, people with autoimmune lymphoproliferative disease, people with idiopathic CD4 lymphocytopenia and healthy controls without HIV. Anti-CD4 autoantibodies were found in 9% of long-term non-progressors and 26% of people with untreated HIV and CD4+ T-cell counts above 200 cells/μL. Yet, the autoantibodies were absent in the other study groups, showing the strength of association between untreated HIV and the development of anti-CD4 autoantibodies.
Overall, the findings show that untreated HIV is associated with the presence of anti-CD4 autoantibodies that could negatively impact CD4+ T-cell recovery in advanced disease. According to the authors, larger cohort studies are necessary to validate these findings, and further studies are needed to support the potential association seen with improved CD4+ T cell recovery in those with anti-CD4 autoantibodies who received immunosuppressive therapy. Authors also suggest large cohort studies can support the investigation of how sex disparities in anti-CD4 autoantibody prevalence relate to other sex-specific immunological mechanisms that predispose women to autoimmunity.
Reference:
B Epling et al. Impact of Anti-CD4 Autoantibodies on Immune Reconstitution in People With Advanced Human Immunodeficiency Virus. Clinical Infectious Diseases DOI: 10.1093/cid/ciae562 (2024)