Antiretroviral Therapy Reduces T-cell Activation and Immune Exhaustion Markers in Human Immunodeficiency Virus Controllers

Abstract

Background Despite low plasma human immunodeficiency virus (HIV) RNA, HIV controllers have evidence of viral replication and elevated inflammation. We assessed the effect of antiretroviral therapy (ART) on HIV suppression, immune activation, and quality of life (QoL). Methods A5308 was a prospective, open-label study of rilpivirine/emtricitabine/tenofovir disoproxil fumarate in ART-naive HIV controllers (N = 35), defined as having HIV RNA <500 copies/mL for ≥12 months. The primary outcome measured change in %CD38+HLA-DR+ CD8+ T cells. Residual plasma viremia was measured using the integrase single-copy assay. QoL was measured using the EQ-5D questionnaire. Outcomes were evaluated using repeated measures general estimating equations models. Results Before ART, HIV controllers with undetectable residual viremia <0.6 HIV-1 RNA copies/mL had higher CD4+ counts and lower levels of T-cell activation than those with detectable residual viremia. ART use was effective in further increasing the proportion of individuals with undetectable residual viremia (pre-ART vs after 24–48 weeks of ART: 19% vs 94%, P < .001). Significant declines were observed in the %CD38+HLA-DR+CD8+ T cells at 24–48 (−4.0%, P = .001) and 72–96 (−7.2%, P < .001) weeks after ART initiation. ART use resulted in decreases of several cellular markers of immune exhaustion and in a modest but significant improvement in self-reported QoL. There were no significant changes in CD4+ counts or HIV DNA. Conclusions ART in HIV controllers reduces T-cell activation and improves markers of immune exhaustion. These results support the possible clinical benefits of ART in this population.

Incomplete immune reconstitution in HIV/AIDS patients on antiretroviral therapy: Challenges of immunological non-responders

“…During HIV-1 infection, persistent immune activation and inflammation are driven by multiple factors, including residual virus replication, inflammatory lipids, gut microbial translocation, and coinfection [92][93][94]. Although long-term effective ART substantially reduces the level of immune activation and inflammation in HIV-1-infected individuals, it fails to normalize the activation and inflammation [95][96][97][98][99]. It was reported that persistent T-cell activation was associated with decreased CD4 + T-cell gains in HIV-1-infected individuals during ART 53.…”

HIV controllers: to treat or not to treat? Is that the right question?

“…"at [their] study sites, even those who had actively participated in research studies for years, were reluctant to begin ART, mostly due to concerns about drug toxicity" (52). Indeed, ARTtoxicities exist and, even these therapies are nowadays mostly well tolerated, the potential sideeffects might be taken into account in the discussion about the risk-reward ratio to start ART.…”

Persistent HIV‐controllers are more prone to spontaneously clear HCV: a retrospective cohort study

“…It is a key to detect these patients before the loss of control takes place and differentiate them of the persistent HIV‐controllers. This will enable a correct treatment in transient HIV‐controllers to avoid non AIDS events, as cardiovascular diseases [16,20,21] and, on the other hand, the persistent control phenotype will become a good model of persistent HIV‐remission in order to design immunotherapeutic strategies [7]. In this manuscript we describe a new characteristic of persistent HIV‐controllers as is a higher ability to spontaneously clear HCV unlike transient controllers.…”