Serum Immune Activation Markers Are Persistently Increased in Patients with HIV Infection after 6 Years of Antiretroviral Therapy despite Suppression of Viral Replication and Reconstitution of CD4⁺T Cells

Abstract

The effect of long-term antiretroviral therapy on serum immune activation markers was assessed in a cohort of 63 patients before and after 6 years of boosted lopinavir-based antiretroviral therapy. High levels of most markers were associated with lower CD4(+) T cell counts at baseline and at year 6, with the exception of soluble cytotoxic T lymphocyte antigen-4 (sCTLA-4); high levels of sCTLA-4 were associated with higher CD4(+) T cell counts at year 6. Abnormalities of serum immune activation markers persisted after 6 years of ART but probably had different causes. Further investigation of the clinical usefulness of assaying immunoglobulin A, neopterin, and sCTLA-4 levels to assess the effectiveness of treatments for human immunodeficiency virus (HIV) disease are warranted.

Impact of HIV infection and smoking on lung immunity and related disorders

“…While HAART remains the cornerstone of treatment of HIV infection, persistent immune activation/chronic inflammation extending several years beyond the implementation of virally suppressive therapy [163], apparently exacerbated by smoking [54,61], underscores the necessity for effective adjunctive/ anti-inflammatory strategies in this setting. Notwithstanding aggressive implementation of smoking cessation strategies, various therapies targeting chronic immune activation and inflammation which may ameliorate the long-term complications of HIV infection, especially in those who smoke, have been, or are currently being investigated (table 2) [164][165][166].…”

Immunovirological parameters and cytokines in HIV infection

“…According to many authors such Hunt et al 28 , French et al 51 , Nixon et al 52 and Kamat et al 54 persistent chronic inflammation and immune activation are factors potentially determinant of morbidity and mortality not associated with AIDS, even during effective cART. Thus, it is necessary that these parameters be minimized to augment the patient survival.…”

The role of SNPs in the α-chain of the IL-7R gene in CD4+ T-cell recovery in HIV-infected African patients receiving suppressive cART

“…14,15 Various clinical factors have been associated with impaired CD4 T-cell reconstitution following cART, including lower CD4 T-cell counts at initiation of cART, [16][17][18][19] being older at cART initiation 1,17,19,20 and higher levels of immune activation both before and while on cART as measured by T-cell activation markers (such as human leukocyte antigen (HLA)-DR þ CD38 þ expression). [21][22][23][24] Multiple host genetic factors have also been found to influence CD4 T-cell recovery. [25][26][27][28][29][30][31] We recently demonstrated by using a multivariable model that IL-7Ra haplotype-2 was a significant predictor of more rapid CD4 T-cell recovery following suppressive cART in an Australian-based largely Caucasian HIVinfected cohort.…”