Ex vivo sensitivity to broadly neutralizing antibodies and anti-CD4 antibody UB-421 of infectious viral isolates from people living with multidrug-resistant HIV.

BACKGROUND: People living with HIV (PLWH) with multidrug-resistant (MDR) viruses have limited therapeutic options and present challenges regarding clinical management. Recent studies have shown that passive transfer of combination broadly neutralizing antibodies (bNAbs) against HIV and anti-domain 1 CD4 antibody UB-421 can sustain virologic suppression in PLWH in the absence of antiretroviral therapy (ART). Yet studies addressing the therapeutic potential of these antibodies and/or detailed characterization of immunologic and virologic parameters in PLWH with MDR HIV are lacking. METHODS: We examined levels of immune activation and exhaustion markers on CD8+ T cells and the intact HIV proviral DNA burden in 11 PLWH with MDR viruses. For comparison purposes, we included a control group consisting of 27 ART-naïve viremic PLWH. In addition, we determined the sensitivity of infectious viral isolates obtained from the participants against eight bNAbs (3BNC117, 10-1074, VRC01, VRC07, N6, 10E8, PGDM1400, and PGT121) and two anti-CD4 antibodies (ibalizumab and UB-421) using a TZM-bl-based neutralization/suppression assay. FINDINGS: The level of intact HIV proviral DNA was comparable between the two groups (P = 0.29). The levels of activation and exhaustion markers PD-1 (P = 0.0019), TIGIT (P = 0.0222), 2B4 (P = 0.0015), CD160 (P = 0.0015), and CD38+/HLA-DR+ (P = 0.0138) were significantly lower in the MDR group. The infectious viral isolates from each study participant with MDR HIV were resistant to at least 2 bNAbs; however, they were sensitive to at least one of the CD4-binding and non-CD4-binding site antibodies. The majority of participants had ibalizumab-sensitive viruses although the isolates from some participants showed reduced sensitivity to ibalizumab. Notably, none of the 93 viral isolates obtained from the participants were resistant to UB-421. INTERPRETATION: Our data suggest that combination therapy with HIV-specific bNAbs and/or UB-421 in the presence of optimized background therapy could potentially provide sustained virologic suppression in PLWH with MDR HIV. However, this therapeutic strategy needs to be evaluated in human clinical trials. FUNDING: Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health.

Pandemic-Related Post-traumatic Stress Symptomatology in COVID-19 Patients with and without Post-COVID Conditions.

Trauma and stressor-related symptoms have been frequently reported during the COVID-19 pandemic. Few studies compare post-traumatic stress symptoms (PTSS) between patients and non-infected controls. Using data from an ongoing natural history study of COVID-19, this study compared PTSS between patients infected with SARS-CoV-2 during the first year of the pandemic and controls. Within the COVID-19 patient cohort, we also compared PTSS between patients with and without post-COVID conditions, also known as post-acute sequelae of SARS-CoV-2 infection (PASC). This study also examined the association of PTSS with trait resilience and prior trauma exposure. PTSS were assessed using the Impact of Event Scaled-Revised (IES-R), which has a validated probable PTSD cutoff (score ≥33). The results showed that patients (n=131) reported significantly higher IES-R scores than controls (n=82) and had significantly higher odds of having scores indicative of PTSD [AOR: 4.17 p: 0.029]. IES-R scores among PASC patients (n=68) were significantly elevated compared to patients without PASC (n=63) and PASC patients did not have higher odds for probable PTSD [AOR: 2.60; p: 0.14]. Trait resilience was associated with lower PTSS. These findings help characterize the mental health impact of the COVID-19 illness experience and highlight elevated PTSS in patients with persistent post-COVID conditions.