Immune restoration affects 10‐year survival in people living with HIV/AIDS

Abstract

Introduction In recent years, a reduction in the life expectancy gap between people living with HIV (PLWH) and the general population has been observed, irrespective of CD4 lymphocyte count, due to widespread access to antiretroviral treatment. The increase in the life expectancy of PLWH has increased awareness of both the ageing process and gender discrepancies in immune restoration and survival. Materials and Methods Longitudinal data were collected for 2240 patients followed up at the Hospital for Infectious Diseases in Warsaw, Poland (n = 1482), and the Department of Acquired Immunodeficiency, Pomeranian Medical University, Szczecin, Poland (n = 758). Immune restoration was measured from the time of starting combination antiretroviral therapy until achieving 500 CD4 lymphocytes/μL, 800 CD4 lymphocytes/μL, and CD4/CD8 lymphocyte ratios of > 0.8 and > 1.0. Full recovery was achieved when the patient was restored to both 800 CD4 lymphocytes/μL and a CD4/CD8 lymphocyte ratio > 1.0. Results For all endpoints, immune restoration had a protective effect by reducing mortality. Patients who achieved immune restoration had a greater chance of reduced mortality than those who did not achieve immune restoration: for CD4 count > 500 cells/μL, HR = 5.4 (interquartile range: 3.09–9.41), p < 0.001; for CD4 > 800 cells/μL, HR = 5.37 (2.52–11.43), p < 0.001; for CD4/CD8 ratio > 0.8, HR = 3.16 (1.81–5.51), p < 0.001; for CD4/CD8 ratio > 1.0, HR = 2.67 (1.49–5.24), p = 0.001, and for full immune recovery, HR = 3.62 (1.63–8.04), p = 0.002. Conclusions Immune restoration remains a powerful factor in improving the survival of PLWH, regardless of the speed of recovery.

Altered plasma metabolites and inflammatory networks in HIV-1 infected patients with different immunological responses after long-term antiretroviral therapy

“…Although the introduction of antiretroviral therapy (ART) has achieved viral suppression and subsequent immune reconstitution in most people living with HIV-1 (PLWH), increased risks of chronic AIDS-related illnesses associated with aging are still challenging in this population ( 1 ). Nevertheless, 10-30% of PLWH suffer from poor immune recovery despite prolonged successful suppressive ART, which further speeds up the disease progression and contributes to increased mortality, referred to as “immunological non-responders” (INRs) ( 1 , 2 ). Though there was no unified standard for INRs, the CD4+T cell count could not reach 350 cells/μl or 500 cells/μl after years of ART was used in some reports ( 3 , 4 ).…”

CD4/CD8 ratio and CD8+ T-cell count as prognostic markers for non-AIDS mortality in people living with HIV. A systematic review and meta-analysis

“…Items assessing study attrition showed the highest risk of bias. The overall risk of bias in the included studies was high (n=7; 35%) ( 28 , 30 , 31 , 36 , 37 , 40 , 43 ), moderate (n=11: 55%) ( 9 , 18 , 19 , 21 , 29 , 32 , 33 , 35 , 38 , 39 , 41 ), or low (n=2; 10%) ( 20 , 42 ). Nearly all included studies (n=18; 90%) ( 9 , 18 , 19 , 21 , 28 – 33 , 35 – 41 , 43 ) lacked a description of the lost and censored participants, their characteristics, and the methodology for statistical imputation of the missing values.…”

Long-term safety and impact of immune recovery in heavily treatment-experienced adults receiving fostemsavir for up to 5 years in the phase 3 BRIGHTE study

“…Low CD4+/CD8+ ratio (<0.3) correlates with higher risk of non–AIDS-defining events and mortality ( 15 – 17 ). Restoration of immunologic function, measured by increases in absolute CD4+ T-cell count to >200 cells/mm 3 and CD4+/CD8+ ratio to >0.45, is an important treatment goal for all people living with HIV, particularly those with low CD4+ T-cell count ( 16 – 20 ).…”