Cytokine Storm Syndrome as a Manifestation of Primary HIV Infection.

HIV infection triggers an inflammatory response that manifests as acute retroviral syndrome (ARS) in most individuals infected by HIV. While this syndrome is usually self-limited, primary HIV infection sometimes triggers a fulminant inflammatory process consistent with cytokine storm syndrome (CSS). Many of the key findings of CSS including fever, splenomegaly, and cytopenias are routinely observed in ARS, suggesting CSS may be under recognized in the setting of acute HIV infection. Unlike other CSS scenarios, ARS-associated CSS generally responds well to HIV-targeted therapies. Advanced HIV infection is also associated with CSS, although typically this involves additional infectious insults. Occasionally, HIV therapy results in rapid recovery of the immune response that evolves into CSS.

Association of Integrase Strand Transfer Inhibitor-Based Antiretroviral Therapy with Blood Pressure and Sustained Hypertension in People with HIV.

BACKGROUND: Integrase strand transfer inhibitors (INSTI) are a commonly used antiretroviral therapy (ART) class in people with human immunodeficiency virus (HIV) and associated with weight gain. We studied the association of INSTI-based ART with systolic and diastolic blood pressure (SBP and DBP). METHODS: We recruited 50 people taking INSTI-based ART and 40 people taking non-INSTI-based ART with HIV and hypertension from the University of Alabama at Birmingham HIV clinic. Office BP was measured unattended using an automated (AOBP) device. Awake, asleep and 24-hour BP were measured through ambulatory BP monitoring. Among participants with SBP ≥130 mmHg or DBP≥80 mmHg on AOBP, sustained hypertension was defined as awake SBP≥130 mmHg or DBP≥80 mmHg. RESULTS: Mean SBP and DBP was higher among participants taking INSTI-based versus non-INSTI-based ART (AOBP-SBP/DBP: 144.7/83.8 versus 135.3/79.3 mmHg; awake-SBP/DBP: 143.2/80.9 versus 133.4/76.3 mmHg; asleep-SBP/DBP: 133.3/72.9 versus 120.3/65.4 mmHg; 24-hour-SBP/DBP: 140.4/78.7 versus 130.0/73.7 mmHg). After multivariable adjustment, AOBP, awake, asleep and 24-hour SBP was 12.5 (95%CI 5.0-20.1), 9.8 (95%CI 3.6-16.0), 10.4 (95%CI 2.0-18.9), and 9.8 (95%CI 4.2-15.4) mmHg higher among those taking INSTI-based versus non-INSTI-based ART, respectively. AOBP, awake, asleep and 24-hour DBP was 7.5 (95%CI 0.3-14.6), 6.1 (95%CI 0.3-11.8), 7.5 (95%CI 1.4-13.6), and 6.1 (95%CI 0.9-11.3) mmHg higher among those taking INSTI-based versus non-INSTI-based ART after multivariable adjustment. All participants had SBP ≥130 mmHg or DBP≥80 mmHg on AOBP and 97.9% and 65.7% of participants taking INSTI-based and non-INSTI-based ART had sustained hypertension, respectively. CONCLUSION: INSTI-based ART was associated with higher SBP and DBP than non-INSTI-based ART.

Outpatient COVID-19 convalescent plasma recipient antibody thresholds correlated to reduced hospitalizations within a randomized trial.

BACKGROUNDCOVID-19 convalescent plasma (CCP) virus-specific antibody levels that translate into recipient posttransfusion antibody levels sufficient to prevent disease progression are not defined.METHODSThis secondary analysis correlated donor and recipient antibody levels to hospitalization risk among unvaccinated, seronegative CCP recipients within the outpatient, double-blind, randomized clinical trial that compared CCP to control plasma. The majority of COVID-19 CCP arm hospitalizations (15/17, 88%) occurred in this unvaccinated, seronegative subgroup. A functional cutoff to delineate recipient high versus low posttransfusion antibody levels was established by 2 methods: (i) analyzing virus neutralization-equivalent anti-Spike receptor-binding domain immunoglobulin G (anti-S-RBD IgG) responses in donors or (ii) receiver operating characteristic (ROC) curve analysis.RESULTSSARS-CoV-2 anti-S-RBD IgG antibody was volume diluted 21.3-fold into posttransfusion seronegative recipients from matched donor units. Virus-specific antibody delivered was approximately 1.2 mg. The high-antibody recipients transfused early (symptom onset within 5 days) had no hospitalizations. A CCP-recipient analysis for antibody thresholds correlated to reduced hospitalizations found a statistical significant association between early transfusion and high antibodies versus all other CCP recipients (or control plasma), with antibody cutoffs established by both methods-donor-based virus neutralization cutoffs in posttransfusion recipients (0/85 [0%] versus 15/276 [5.6%]; P = 0.03) or ROC-based cutoff (0/94 [0%] versus 15/267 [5.4%]; P = 0.01).CONCLUSIONIn unvaccinated, seronegative CCP recipients, early transfusion of plasma units in the upper 30% of study donors' antibody levels reduced outpatient hospitalizations. High antibody level plasma units, given early, should be reserved for therapeutic use.TRIAL REGISTRATIONClinicalTrials.gov NCT04373460.FUNDINGDepartment of Defense (W911QY2090012); Defense Health Agency; Bloomberg Philanthropies; the State of Maryland; NIH (3R01AI152078-01S1, U24TR001609-S3, 1K23HL151826NIH); the Mental Wellness Foundation; the Moriah Fund; Octapharma; the Healthnetwork Foundation; the Shear Family Foundation; the NorthShore Research Institute; and the Rice Foundation.

Impact of antiretroviral therapy during acute or early HIV infection on virologic and immunologic outcomes: results from a multinational clinical trial.

OBJECTIVE: To assess how antiretroviral therapy (ART) initiation during acute or early HIV infection (AEHI) affects the viral reservoir and host immune responses. DESIGN: Single-arm trial of ART initiation during AEHI at 30 sites in the Americas, Africa, and Asia. METHODS: HIV DNA was measured at week 48 of ART in 5 million CD4 + T cells by sensitive qPCR assays targeting HIV gag and pol . Peripheral blood mononuclear cells were stimulated with potential HIV T cell epitope peptide pools consisting of env , gag , nef, and pol peptides and stained for expression of CD3, CD4, CD8, and intracellular cytokines/chemokines. RESULTS: From 2017 to 2019, 188 participants initiated ART during Fiebig stages I ( n  = 6), II ( n  = 43), III ( n  = 56), IV ( n  = 23), and V ( n  = 60). Median age was 27 years (interquartile range 23-38), 27 (14%) participants were female, and 180 (97%) cisgender. Among 154 virally suppressed participants at week 48, 100% had detectable HIV gag or pol DNA. Participants treated during Fiebig I had the lowest HIV DNA levels ( P  < 0.001). Week 48 HIV DNA mostly did not correlate with concurrent CD4 + or CD8 + T cell HIV-specific immune responses (rho range -0.11 to +0.19, all P  > 0.025). At week 48, the magnitude, but not polyfunctionality, of HIV-specific T cell responses was moderately reduced among participants who initiated ART earliest. CONCLUSION: Earlier ART initiation during AEHI reduced but did not eliminate the persistence of HIV-infected cells in blood. These findings explain the rapid viral rebound observed after ART cessation in early-treated individuals with undetectable HIV DNA by less sensitive methods.