CROI 2024 Abstract eBook

Abstract eBook

Poster Abstracts

419

Early Tecovirimat Treatment for Mpox Disease Among People With HIV: A Matched Cohort Analysis Bruce Aldred , Robert H. Lyles, Jane Y. Scott, Daniel J. Gromer, Amalia Aldredge, Kimberly Workowski, Boghuma K. Titanji, Minh Nguyen, Vincent Marconi, Colleen Kelley, Jesse T. Jacob, Jonathan Colasanti, Emily J. Cartwright, Valeria D. Cantos, for the Emory Mpox Analysis Patient Series (MAPS) Study Group Emory University, Atlanta, GA, USA Background: Despite a lack of efficacy data in humans, tecovirimat was widely prescribed to people with HIV (PWH) with mpox during the 2022 mpox epidemic, particularly among those with low CD4+ T-cell counts or severe mpox clinical manifestations. Methods: This is a matched cohort study of PWH diagnosed with mpox at four hospitals in Atlanta, Georgia between 6/1/2022 and 10/7/2022. The exposure cohort ("early tecovirimat") included PWH with mpox who were treated with tecovirimat within 7 days of symptom onset. The unexposed cohort ("late/ no tecovirimat") included PWH diagnosed with mpox who did not receive tecovirimat or who received tecovirimat >7 days after symptom onset. Multivariate logistic regression models were used to identify factors associated with progression of mpox disease, defined as development of at least one severe mpox criteria after symptom day 7. The 2 cohorts were matched 1:1 using propensity scores based on the identified predictors. Results: Each cohort included 56 matched individuals. Predictors selected for inclusion in the final propensity score estimation model included age, race, HIV viral load suppression, involvement of any mucosal site(s), and hospitalization at day 7. Mpox progression occurred in 3 (5.4%) individuals in the early tecovirimat cohort and in 13 (23.2%) individuals in the late/no tecovirimat cohort (paired odds ratio 11.0 (95% CI 1.4, 85.1), exact binomial test p = 0.006). Conclusion: PWH with mpox who were prescribed tecovirimat within 7 days of symptom onset were less likely to have mpox progression compared with matched PWH who didn't receive early tecovirimat. While awaiting the completion of randomized controlled trials of tecovirimat efficacy for mpox, these results favor starting tecovirimat in all PWH as soon as a mpox diagnosis is suspected.

days, is currently recommended as pre- and post-exposure prophylaxis in the high-risk populations. However, orthopoxvirus-specific (OPXV) IgG remains less investigated in people with HIV (PWH), especially for those born after 1979. Methods: Men who have sex with men (MSM) planning to receive two doses of MVA-BN vaccine were enrolled. Blood samples were collected on D0, 28±7, and 96±7 for all individuals after each dose. All serum specimens were tested for the presence of OPXV-specific IgG. Those testing positive for OPXV-specific IgG and being infected with Mpox were excluded from subsequent analysis. Results: A total of 299 participants, including 188 PWH and 111 people without HIV (PWoH), were included. The median age of the participants for PWH and PWoH 38 and 31 years, respectively; 51 PWH and 3 PWoH were born before 1979. Most of the included PWH (97.9%) were virologically suppressed with antiretroviral therapy and had a median CD4 count of 648 cells/mm 3 . Overall, 16 (8.5%) of 188 PWH and 8 (7.2%) of 111 PWoH had seroconversion of OPXV-specific IgG 28 days after the first dose, while 31 (24.8%) of 125 PWH and 12 (19.4%) of 62 PWoH had a seroconversion 28 days after the second dose of Mpox vaccination. The median titer of OPXV-specific IgG for PWH and PWoH was 3.8 and 6.4 ng/mL. respectively. Those born before 1979 were more likely to seroconvert after Mpox vaccination than those born after 1979 (51.3% vs 16%; adjusted odds ratio [aOR], 5.54; 95% CI, 2.54-12.07). After excluding PWH born before 1979, PWH tended to have a lower seroconversion rate than PWoH (14.6% vs 18.0%; aOR, 0.78; 95% CI, 0.32-1.87). Conclusion: The median OPXV-specific IgG titer among individuals who received two doses of Mpox vaccine was higher in those who had had prior smallpox vaccination. For those born after 1979, OPXV-specific IgG was higher in PWoH compared to virologically-suppressed PWH, though the differences between the two groups did not reach statistical significance, probably related to a relatively small case number. MPXV Replication Induces an IFN Response and Is Suppressed by IFN-γ Alessandra D'Auria 1 , Federica Frasca 1 , Licia Bordi 2 , Eleonora Lalle 2 , Matteo Fracella 1 , Leonardo Sorrentino 1 , Gabriella D'Ettorre 1 , Claudio Maria Mastroianni 1 , Mauro Pistello 3 , Guido Antonelli 1 , Carolina Scagnolari 1 1 Sapienza University of Rome, Rome, Italy, 2 Lazzaro Spallanzani National Institute for Infectious Diseases, Rome, Italy, 3 University of Pisa, Pisa, Italy Background: Poxviruses have developed strategies to evade host antiviral immunity, particularly the Interferon (IFN) response, but limited data are available for Monkeypox virus (MPXV). To better understand how MPXV affects the IFN response, we analyzed type I, II and III IFNs and IFN stimulated genes (ISGs) expression in different MPXV-infected anatomical sites from male patients. Also, we investigate MPXV in vitro sensitivity to different type of IFNs. Methods: Eighteen samples from different anatomical sites [Skin lesions (SL), anal canal brushing (ACB) and nasopharyngeal swabs (NSP)] were collected from MPXV-infected male patients. Gene expression of type I (IFN-α/β/ω), type II (IFN-γ), type III IFNs (IFN-λ1/2/3) and ISGs (ISG15, ISG56 and PKR) was measured by quantitative RT-PCR assays. MPXV-DNA levels were evaluated by Bioperfectus Monkeypox Virus Real Time PCR kit. Antiviral assays were performed to evaluate MPXV (MOI=0.1) sensitivity to different types of IFNs (IFN-α, IFN-α natural, IFN‐β, IFN-ω and IFN-γ) on different cell lines (human lung adenocarcinoma epithelial A549 cells, cervival carcinoma HeLa cells and african green monkey kidney VeroE6 cells). Viral yield after IFN treatment was quantified in VeroE6 cells. Results: Examination of IFN-related genes across anatomical sites revealed that IFN-α, IFN-λ1, and PKR were significantly upregulated in ACB compared to other clinical samples. Conversely, levels of IFN-β and IFN-ω increased in SL (p<0.05). IFN-I/III and ISGs showed higher expression in samples with low MPXV-DNA Ct values, while the opposite trend was observed for IFN-γ production (p<0.05 for all the genes). Pre-treatment of A549, HeLa, and VeroE6 cells with high concentrations of IFN-α, IFN-αn, and IFN-ω (greater than or equal to 300,000 IU/mL) did not significantly inhibit MPXV replication, while MPXV exhibited moderate sensitivity to the antiviral action of IFN-β. In contrast, IFN-γ strongly inhibited MPXV replication in all the cell lines used. Conclusion: This study provides evidence that MPXV infection triggers the production of various types of IFNs and ISGs, with IFN-γ being particularly effective in inhibiting MPXV replication in vitro. These findings contribute to a better understanding of how MPXV evades the host immune response and may inform potential therapeutic strategies for MPXV infections.

Poster Abstracts

418

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Combination of Extended Antivirals With Antiretrovirals for Severe Mpox in Advanced HIV Infection Michael T. Duong, Pablo Tebas, Bhavya Ancha, Jillian Baron, Stuart N. Isaacs, Zsofia Szep University of Pennsylvania, Philadelphia, PA, USA Background: Appropriate therapeutic management of mpox in people with advanced HIV remains challenging given an absence of clinical trial evidence. This case series aims to provide our experience during the 2022 outbreak for patients with severe mpox treated aggressively with a combination of extended tecovirimat and cidofovir with antiretrovirals (ART). Methods: This is a retrospective review of cases at the University of Pennsylania during the 2022 mpox outbreak collecting clinical data and evaluating effectiveness and safety of combination antivirals in people with advanced HIV and disseminated mpox. Results: We identified four male patients with mpox and advanced HIV (CD4 count 0-53 cells/mm 3 , viral load 2,104-217,000 copies/ml, age range 30s-50s). They exhibited necrotic skin lesions across the face, trunk, groin and extremities, with one developing keratitis and conjunctival ulcers. Three cases were associated with super- and co-infections: HSV1/2, severe COVID-19 and MRSA. All patients started/resumed ART and began daily oral tecovirimat and cidofovir infusions with probenecid/fluids every 2 weeks. While one patient exhibited full recovery after a single 6-week course of tecovirimat, 6 doses of cidofovir and ART, the other three had a more complicated course including two with

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