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Study identifies rare cases of immune system failure in virally suppressed HIV patients
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Patients with HIV can experience a significant decline in CD4+ T cell levels despite years of viral suppressions, a rare response to ART that researchers are calling extreme immune decline, or EXID, according to a study published in JCI Insight.
“Over the years, we had patients who experienced [a] decline in CD4 cell count despite suppressed plasma viremia who were referred to NIH to investigate possible causes of such a paradoxical immunological outcome of ART,” Andrea Lisco, MD, PhD, assistant clinical investigator at the National Institute of Allergy and Infectious Diseases, told Infectious Disease News. “Therefore, a simple but quite perplexing clinical question prompted [our] study and a more articulate workup on these patients.”
According to the study, the researchers examined the clinical and immunological characteristics of five patients with EXID, comparing them with immunological responders (IRs), immunological nonresponders (INRs), healthy controls and patients with idiopathic CD4+ lymphopenia (ICL). They also evaluated T cell immunophenotyping and assembly and activation of inflammasomes.
Results showed that patients with EXID were infected with HIV-1 non-B subtypes, and despite 192 weeks of consistent ART-mediated viral suppression, they had a median CD4+ decrease of 157 cells/L, compared with CD4+ increases of 193 cells/L and 427 cells/L in INRs and IRs, respectively. Additionally, the researchers found that patients with EXID had reduced naive CD4+ T cells but similar proportions of cycling CD4+ T cells and HLA-DR+CD38+CD8+ T cells compared with IRs and INRs, according to the study.
“Since combination antiretroviral therapies had been adopted in the 90s, we had not seen decline in CD4 counts despite HIV-1 suppressed viremia. It was surprising to observe such immunological outcome and connect it with particular host and viral factors,” Lisco said. “Even more surprising was to observe reconstitution of CD4 cell counts after treatment with [tumor necrosis factor (TNF)] blockade of one of these patients [who was] diagnosed with idiopathic orbital inflammation, confirming the role of a peculiar inflammatory signature in the immunopathogenesis of poor CD4 reconstitution for this particular patient.”
According to Lisco, patients with EXID require an extensive workup to rule out possible causes of CD4-T cells lymphopenia, such as lymphoproliferative disorders, primary immunodeficiencies, inflammatory or infectious diseases. If a diagnosis of EXID is confirmed, patients require close clinical follow-up, Lisco said.
Of the patients in the study, Lisco said two are still severely lymphopenic and three recovered CD4 T cell counts. In one case, the recovery came by TNF blockade treatment prompted by a new diagnosis of granulomatous inflammatory disease, and in the other two cases, CD4 T cell decline was attributed to anti CD4-T cells autoantibodies, which were eventually lost after several years, Lisco explained.
“Importantly, the CD4 T cells recovery observed in one of these two patients was associated with severe clinical manifestations with mental status decline and radiological evidence of basilar arteritis and cerebral ischemic lesions, concerning for an inflammatory immunoreconstitution event,” Lisco said.
“Decline in CD4 T cell counts after suppression of HIV-1 plasma viremia is a rare event which requires a specialized and articulate clinical, immunological and genetic workup. It is possible that the particular virological and host factors leading to such [a] paradoxical immunological outcome are more common in the context of non-B HIV subtypes as seen in all the patients described in the study and for this reason have not been previously reported.” – by Caitlyn Stulpin
Disclosures: Lisco reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
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