Outcomes of immunomodulatory and biologic therapy in people living with HIV

Abstract

Objectives: Immunomodulatory drugs (IMDs) are crucial for treating autoimmune, inflammatory, and oncologic conditions. Data regarding the safety of IMDs in people living with HIV (PLWH) are limited. We describe outcomes in all PLWH prescribed these agents from 2000--2019 at two academic medical centers. Design: Retrospective cohort study. Methods: We systematically identified and reviewed charts of all PLWH receiving IMDs. We defined a treatment episode as an uninterrupted period on an IMD regimen. We quantified infections, blips (detectable plasma HIV RNA following an undetectable result), and virologic failure (progression from plasma HIV RNA <200 copies/ml to two consecutive values >200 copies/ml despite ART). Results: Seventy-seven patients contributed 110 treatment episodes. Rheumatologic comorbidities were the most frequent indication. The most common IMD classes were TNF inhibitors, antimetabolites, and checkpoint inhibitors. Ninety percent of treatment episodes involved concomitant ART. Median pretreatment CD4+ T-cell count was 609 cells/μl (IQR 375--861). Among 51 treatment episodes on ART with undetectable pretreatment plasma HIV RNA, HIV became detectable within 1 year in 21 of 51 cases (41.2%); there were no instances of virologic failure. Compared with other agents, treatment episodes involving checkpoint inhibitors were more likely to involve a blip (77.8 vs. 33.3%, P = 0.015). Thirteen treatment episodes (11.8%) were associated with concomitant infection; none was attributed to IMDs by the treating clinician. Conclusion: PLWH treated with IMDs should be monitored carefully for virologic blips and incident infections. Checkpoint inhibitors may be associated with a higher rate of viral blips, although the clinical significance is unclear.

Post-Acute Sequelae and Adaptive Immune Responses in People Living With Hiv Recovering From Sars-Cov-2 Infection

“…If a higher prevalence of PASC among PWH recovering from COVID-19 is confirmed in larger epidemiologic studies, one possible explanation could be that this is driven in part by immune dysregulation from SARS-CoV-2 infection compounded upon higher baseline inflammation from HIV infection, which in turn could drive organ system dysfunction and the experience of somatic symptoms. In addition to elevated inflammatory responses, additional factors that could potentially predispose PWH to PASC include an increased frequency of autoimmune phenomena [57][58][59], localized tissue inflammation related to mucosal and endothelial injury [31,32], and other syndemic comorbidities including substance use [60,61] and metabolic disorders [62][63][64]. Furthermore, reactivation of latent human herpes viruses, such as Epstein Barr Virus or Cytomegalovirus (CMV) during acute SARS-CoV-2 infection may further perturb immune dysregulation and promote inflammation.…”

HIV and COVID-19 Coinfection: A Synergism That Results in More Severe Forms of Reactive Arthritis

“…Additionally, 11.8% of the patients presented an additional severe infection not directly associated with the drug, even with a median CD4+ T cell count of 609 cells/μL. Given these findings, careful monitoring is required to detect signs of virologic relapse and incident infections [ 19 ]. Highly effective antiretroviral therapies (HAARTs) have managed to increase the lymphocyte count, improve survival, have changes in the profile of immune responses, and direct cellular metabolic changes, which is why their early initiation is of vital importance [ 20 ].…”

TNF-α inhibition in the setting of undiagnosed HIV infection: a call for enhanced screening guidelines

“…We identified these cases during a search of the electronic medical record for all PWH prescribed immunomodulatory therapy from 1 January 2000 to 31 December 2019 [18]. A clinician completed a detailed case review and abstraction of clinical details.…”