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There are limited data for the clinical efficacy of bebtelovimab in preventing severe coronavirus disease 2019. Among outpatients unable to take nirmatrelvir-ritonavir at a large health system, 10 of 377 (2.7%) patients who received bebtelovimab and 17 of 377 (4.5%) matched untreated patients were hospitalized or died. The 43% observed risk reduction with bebtelovimab was not statistically significant (P = 0.14). [ABSTRACT FROM AUTHOR]

Background Unbiased assessment of the risks associated with acquisition of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical to informing mitigation efforts during pandemics. The objective of our study was to understand the risk factors for acquiring coronavirus disease 2019 (COVID-19) in a large prospective cohort of adult residents in a large US metropolitan area. Methods We designed a fully remote longitudinal cohort study involving monthly at-home SARS-CoV-2 polymerase chain reaction (PCR) and serology self-testing and monthly surveys. Results Between October 2020 and January 2021, we enrolled 10 289 adults reflective of the Boston metropolitan area census data. At study entry, 567 (5.5%) participants had evidence of current or prior SARS-CoV-2 infection. This increased to 13.4% by June 15, 2021. Compared with Whites, Black non-Hispanic participants had a 2.2-fold greater risk of acquiring COVID-19 (hazard ratio [HR], 2.19; 95% CI, 1.91–2.50; P <.001), and Hispanics had a 1.5-fold greater risk (HR, 1.52; 95% CI, 1.32–1.71; P <.016). Individuals aged 18–29, those who worked outside the home, and those living with other adults and children were at an increased risk. Individuals in the second and third lowest disadvantaged neighborhood communities were associated with an increased risk of acquiring COVID-19. Individuals with medical risk factors for severe disease were at a decreased risk of SARS-CoV-2 acquisition. Conclusions These results demonstrate that race/ethnicity and socioeconomic status are the biggest determinants of acquisition of infection. This disparity is significantly underestimated if based on PCR data alone, as noted by the discrepancy in serology vs PCR detection for non-White participants, and points to persistent disparity in access to testing. Medical conditions and advanced age, which increase the risk for severity of SARS-CoV-2 disease, were associated with a lower risk of COVID-19 acquisition, suggesting the importance of behavior modifications. These findings highlight the need for mitigation programs that overcome challenges of structural racism in current and future pandemics. [ABSTRACT FROM AUTHOR]

Background Human immunodeficiency virus (HIV) infection leads to blood–brain barrier (BBB) dysfunction that does not resolve despite viral suppression on antiretroviral therapy (ART) and is associated with adverse clinical outcomes. In preclinical models, cannabis restores BBB integrity. Methods We studied persons with HIV (PWH) and HIV-negative (HIV−) individuals who had used cannabis recently. We assessed 2 biomarkers of BBB permeability: the cerebrospinal fluid (CSF) to serum albumin ratio (CSAR) and CSF levels of soluble urokinase plasminogen activator receptor (suPAR), a receptor for uPA, a matrix-degrading proteolytic enzyme that disrupts the BBB. A composite index of the BBB markers was created using principal components analysis. Neural injury was assessed using neurofilament light (NFL) in CSF by immunoassay. Results Participants were 45 PWH and 30 HIV− individuals of similar age and ethnicity. Among PWH, higher CSF suPAR levels correlated with higher CSAR values (r  = 0.47, P  < .001). PWH had higher (more abnormal) BBB index values than HIV− individuals (mean ± SD, 0.361 ± 1.20 vs −0.501 ± 1.11; P  = .0214). HIV serostatus interacted with cannabis use frequency, such that more frequent use of cannabis was associated with lower BBB index values in PWH but not in HIV− individuals. Worse BBB index values were associated with higher NFL in CSF (r  = 0.380, P  = .0169). Conclusions Cannabis may have a beneficial impact on HIV-associated BBB injury. Since BBB disruption may permit increased entry of toxins such as microbial antigens and inflammatory mediators, with consequent CNS injury, these results support a potential therapeutic role of cannabis among PWH and may have important treatment implications for ART effectiveness and toxicity. [ABSTRACT FROM AUTHOR]

Distance to care is a common exposure and proposed instrumental variable in health research, but it is vulnerable to violations of fundamental identifiability conditions for causal inference. We used data collected from the Botswana Birth Outcomes Surveillance study between 2014 and 2016 to outline 4 challenges and potential biases when using distance to care as an exposure and as a proposed instrument: selection bias, unmeasured confounding, lack of sufficiently well-defined interventions, and measurement error. We describe how these issues can arise, and we propose sensitivity analyses for estimating the degree of bias. [ABSTRACT FROM AUTHOR]

Background. It is unknown whether adverse birth outcomes are associated with maternal highly active antiretroviral therapy (HAART) in pregnancy, particularly in resource-limited settings.Methods. We abstracted obstetrical records at 6 sites in Botswana for 24 months. Outcomes included stillbirths (SBs), preterm delivery (PTD), small for gestational age (SGA), and neonatal death (NND). Among human immunodeficiency virus (HIV)–infected women, comparisons were limited to HAART exposure status at conception, and those with similar opportunities for outcomes. Comparisons were adjusted for CD4+ lymphocyte cell count.Results. Of 33 148 women, 32 113 (97%) were tested for HIV, of whom 9504 (30%) were HIV infected. Maternal HIV was significantly associated with SB, PTD, SGA, and NND. Compared with all other HIV-infected women, those continuing HAART from before pregnancy had higher odds of PTD (adjusted odds ratio [AOR], 1.2; 95% confidence interval [CI], 1.1, 1.4), SGA (AOR, 1.8; 95% CI, 1.6, 2.1) and SB (AOR, 1.5; 95% CI, 1.2, 1.8). Among women initiating antiretroviral therapy in pregnancy, HAART use (vs zidovudine) was associated with higher odds of PTD (AOR, 1.4; 95% CI, 1.2, 1.8), SGA (AOR, 1.5; 95% CI, 1.2, 1.9), and SB (AOR, 2.5; 95% CI, 1.6, 3.9). Low CD4+ was independently associated with SB and SGA, and maternal hypertension during pregnancy with PTD, SGA, and SB.Conclusions. HAART receipt during pregnancy was associated with increased PTD, SGA, and SB. [ABSTRACT FROM AUTHOR]

Background Despite population antiretroviral treatment (ART) utilization exceeding UNAIDS 90-90-90 targets, Kaposi sarcoma (KS) remains one of the most prevalent malignancies in Botswana. We sought to examine the characteristics and outcomes of KS in the context of high ART utilization. Methods Consenting patients at one of four oncology centers for KS treatment were enrolled prospectively (October 2010 to March 2019) and followed quarterly for 5 years. Survival was estimated using Kaplan–Meier estimator and predictors assessed with Cox proportional hazards modeling. Results A total of 408 KS patients were enrolled and of those, 396 (97%) were HIV-positive and included in analyses. Median age at diagnosis was 40 years (IQR: 34.1, 46.7) and 247 patients (62%) were male. The median CD4 cell count at the time of KS diagnosis was 253 cells/mL (IQR: 134, 364) and 279 (73%) were receiving ART at the time of KS diagnosis. Among those on ART, the median duration of ART prior to KS diagnosis was 11.9 months (IQR: 2.7, 46.7). The proportion receiving ART prior to KS increased during the surveillance period from 58% to 80% (P < 0.001). Of the 248 (62.6%) patients with recent measurement, 91% had HIV-1 RNA < 1000 copies/mL. Five-year overall survival was 73% (95% CI 68–78%). In multivariable analysis, Female sex and higher income were associated with improved survival, but not age or CD4 cell count. The duration of ART was significantly associated with survival (P = 0.02), with improved survival for individuals on ART < 6 months compared with longer ART (HR 0.54; 95% CI 0.29–0.98). The incidence of KS cases declined by nearly 50%, but has remained relatively stable since 2015. Conclusion Survival rates in this cohort were comparable to other KS cohorts. While KS treatment initially declined with ART expansion, KS remains a significant disease burden in Botswana with 80% of cases occurring among individuals receiving ART. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

During the first hour after a sublethal dose of ionizing radiation, 72 genes were upregulated threefold or higher in D. radiodurans R1. Thirty-three of these loci were also among a set of 73 genes expressed ill R1 cultures recovering from desiccation. The five transcripts most highly induced in response to each stress are the same and encode proteins of unknown function. The genes (ddrA, ddrB, ddrC, ddrD, and pprA) corresponding to these transcripts were deleted, both alone and in all possible two-way combinations. Characterization of the mutant strains defines three epistasis groups that reflect different cellular responses to ionizing radiation-induced damage. The ddrA and ddrB gene products have complementary activities and inactivating both loci generates a strain that is more sensitive to ionizing radiation than strains in which either single gene has been deleted. These proteins appear to mediate efficient RecA-independent processes connected to ionizing radiation resistance. The pprA gene product is not necessary for homologous recombination during natural transformation, but nevertheless may participate in a RecA-dependent process during recovery from radiation damage. These characterizations clearly demonstrate that novel mechanisms significantly contribute to the ionizing radiation resistance in D. radiodurans. [ABSTRACT FROM AUTHOR]

Background Cancer is now the leading cause of mortality for persons living with HIV (PLWH) in the United States, but it is uncertain whether PLWH access cancer screening that could lower this burden. We sought to assess cancer screening for breast, cervical, and colon cancer among PLWH compared with the HIV-uninfected population at a multicenter healthcare system over the past two decades. Methods Data were obtained from a prospective, observational HIV clinical care cohort comprised of PLWH engaged in care in the Partners Healthcare System. Patients eligible for cancer screening between the years 2002 and 2016 were included. Patients were matched in a maximum of 1:4 ratio with HIV-uninfected patients from the Massachusetts General Primary Care Practice-Based Research Network based on age, sex, race, year of study entry, and length of follow-up. The mean proportion of time in which eligible patients were guideline concordant for cervical, breast, and colon cancer screening was assessed. Non-parametric tests were used to compared screening rates between PLWH and HIV-infected and on the basis of multiple clinical and sociodemographic factors. Results During the observation period, a total of 495 PLWH were eligible for breast cancer screening, 1011 for cervical cancer screening, and 1965 for colon cancer screening. For each screening group, the majority of PLWH were on antiretroviral therapy (ART) and had relatively high CD4 cell counts (Table 1). Screening rates for PLWH compared with controls were 67.3% vs. 82.8% (P < 0.0001) for breast cancer, 49.0% vs. 73.3% (P < 0.0001) for cervical cancer, and 92.7% vs. 91.2% (P = 0.96) for colon cancer (Figure 1). Among PLWH, factors significantly associated with lower rates of screening guideline concordance were older age, lower CD4 count, HIV-1 RNA >1000 copies/mL, and HIV duration < 5 years for breast cancer, and older age, white race, English language, and lack of ART use for cervical cancer. Conclusion Among patients engaged in longitudinal care, PLWH had significantly lower rates of screening for breast and cervical cancer than HIV-uninfected. Disparity is not explained by racial or primary language differences. Further work to improve access to cancer screening for PLWH is needed. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]