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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]

Background: Sub‐Saharan Africa is simultaneously facing a rising incidence of cancer and a dearth of medical professionals because of insufficient training numbers and emigration, creating a growing shortage of cancer care. To combat this, Massachusetts General Hospital and Beth Israel Deaconess Medical Center partnered with institutions in South Africa, Tanzania, and Rwanda to develop a fellowship exchange program to supplement the training of African oncologists practicing in their home countries. Methods: In its initial year, 2018, the Program for Enhanced Training in Cancer (POETIC) hosted a pilot cohort of seven fellows for 3‐week observerships in their areas of interest. Researchers distributed questionnaires for program evaluation to participants prior to arrival and upon departure; additionally, three participated in semistructured interviews. Results: Five themes emerged from the qualitative data: expectations of POETIC, differences between oncology in the U.S. and in sub‐Saharan Africa, positive elements of the program, areas for improvement, and potential impact. Fellows identified several elements of Western health care that will inform their practice: patient‐centered care; clinical trials; and collaboration among medical, radiation, and surgical oncologists. From the quantitative data, feedback was primarily around logistical areas for improvement. Conclusion: POETIC was found to be feasible and valuable. The results from the pilot year justify the program's continuation in hopes of strengthening global health partnerships to support oncology training in Africa. One weakness is the small number of fellows, which will limit the impact of the study and the relevance of its conclusions. Future research will report on the expansion of the program and follow‐up with former participants. Implications for Practice: This work presents a novel model for fellowship exchange between lower‐ and higher‐resourced areas. The program is a short‐term observership with tumor boards and didactic teaching sessions incorporated. By attracting oncologists who aim to practice in their home countries, it facilitates international collaboration without contributing to the preexisting lack of medical professionals in low‐ and middle‐income countries. This brief communication presents case reports for two patients with metastatic melanoma treated with empiric BRAF and MEK inhibitors. [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: Cancer incidence is increasing in Africa, and the majority of patients are diagnosed with advanced disease, limiting treatment options and survival. We sought to understand care patterns and factors contributing to delayed diagnosis and treatment initiation among patients with cancer in Botswana. Patients and Methods: We recruited 20 patients who were enrolled in a prospective cancer cohort in Botswana to a qualitative substudy that explored cancer care pathways and factors affecting cancer care access and quality. We conducted an in‐depth interview with each participant between October 2014 and January 2015, using a a structured interview guide with questions about initial cancer symptoms, previous consultations, diagnosis, and care pathways. Medical records were used to confirm dates or treatment details when needed. Results: Individual and interpersonal factors such as cancer awareness and social support facilitated care‐seeking behaviors. However, patients experienced multiple delays in diagnosis and treatment because of provider and health system barriers. Health system factors, such as misdiagnosis, understaffed facilities, poor referral communication and scheduling, and inadequate laboratory reporting systems, affected access to and quality of cancer care. Conclusion: These findings highlight the need for interventions at the patient, provider, and health system levels to improve cancer care quality and outcomes in Botswana. Results also suggest that widespread cancer education has potential to promote early diagnosis through family and community networks. Identified barriers and facilitators suggest that interventions to improve community education and access to diagnostic technologies could help improve cancer outcomes in this setting. Implications for Practice: The majority (54%) of patients with cancer in Botswana present with advanced‐stage cancer despite universal access to free health care, limiting the options for treatment and decreasing the likelihood of positive treatment outcomes. To reduce time from symptom onset to cancer treatment initiation, causes of delay in cancer care trajectories must be identified. The narratives of the patients interviewed for this study give insight into psychosocial factors, outlooks on disease, lower‐level provider delays, and health system barriers that contribute to substantial delays for patients with cancer in Botswana. Identification of problems and barriers is essential for development of effective interventions to mitigate these factors, in order to improve cancer outcomes in this population. The cancer burden in low‐and middle‐income countries (LMIC) is significant and is increasing. The objective of this qualitative study was to explore care‐seeking patterns and identify factors contributing to delayed cancer diagnosis and treatment among cancer patients in Botswana. [ABSTRACT FROM AUTHOR]

Background. Three-quarters of cancer deaths occur in resource-limited countries, and delayed presentation contributes to poor outcome. In Botswana, where more than half of cancers arise in HIV-infected individuals, we sought to explore predictors of timely oncology care and evaluate the hypothesis that engagement in longitudinal HIV care improves access. Methods. Consenting patients presenting for oncology care from October 2010 to September 2014 were interviewed and their records were reviewed. Cox and logistic models were used to examine the effect of HIV and other predictors on time to oncology care and presentation with advanced cancer (stage III or IV). Results. Of the 1,146 patients analyzed, 584 (51%) had HIV and 615 (54%) had advanced cancer. The initial clinic visit occurred a mean of 144 days (median 29, interquartile range 0-185) after symptom onset, but subsequent mean time to oncology care was 406 days (median 160, interquartile range 59-653). HIV status was not significantly associated with time to oncology care (adjusted hazard ratio [aHR] 0.91, 95% confidence interval [CI] 0.79-1.06). However, patients who reported using traditional medicine/healers engaged in oncology care significantly faster (aHR 1.23, 95% CI 1.09-1.40) and those with advanced cancer entered care earlier (aHR 1.48,95% CI 1.30-1.70). Factors significantly associated with advanced cancer included income,<$50 per month (adjusted odds ratio [aOR] 1.35, 95% CI 1.05-1.75), male sex (aOR 1.45, 95% CI 1.12-1.87), and pain as the presenting symptom (aOR 1.39, 95% CI 1.03-1.88). Conclusion. Longitudinal HIV care did not reduce the substantial delay to cancer treatment. Research focused on reducing health system delay through coordination and navigation is needed. [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]

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]

The article reflects on the delivery of cancer care in Botswana which reveals the complexity of cancer. It highlights the medical drawbacks of Botswana including lack of oncologists, radiologists and pathologists, over-crowded and under-staffed hospitals, and confined public access to generic cytotoxic drugs. It states that efforts are made for oncology research after the successful programs for AIDS disease prevention and treatment.

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]