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Background: Sargramostim (recombinant human glycosylated GM-CSF derived from fungi) enhances innate and adaptive immune responses and accelerates hematopoietic recovery during chemotherapy-induced neutropenia. However, few data are available on its efficacy as an adjuvant immunotherapy for invasive fungal infections.

Method: The clinical course of 15 patients with pediatric cancer and invasive fungal infection treated with sargramostim was analyzed retrospectively at a single center. In addition, a systematic review of published cases involving the use of recombinant human GM-CSF in invasive fungal infections was also conducted.

Results: Of 65 cases, 15 were newly reported pediatric patients, and 50 were previously published cases of invasive fungal infections treated with recombinant human GM-CSF. Among the new cases, the invasive fungal infections were caused by Candida spp., Trichosporon sp., and filamentous fungi (Aspergillus spp., Rhizopus sp., Lichtheimia sp., and Scedosporium sp.). Among the 15 children, 12 (80%) were neutropenic on Day 0, and 12 (80%) were refractory to antifungal therapy. Among the 12 evaluable patients, the overall clinical response rate was 92% (8 (67%) with a complete response, 3 (25%) with a partial response, and 1 (8%) stable). Treatment is still ongoing in 3 patients. Among the 54 published cases (15 Candida spp., 13 Mucorales, 11 Aspergillus spp., 11 other fungi), 20 (40%) were neutropenic on Day 0, and 36 (72%) were refractory to standard antifungal therapy prior to administration of recombinant human GM-CSF. Similar to the response observed in the 15 new patients, the overall response rate in the literature review was 82% (40 [80%] with complete response, 1 [2%] with partial response, and 9 [18%] with no response).

Conclusion: Sargramostim may be a promising potential immunomodulatory treatment for selected patients with hematologic malignancies and refractory invasive fungal infections.

Objectives: In difficult-to-treat infections, such as nosocomial ventriculitis, the distribution of meropenem in infected compartments is often unknown but critical for antibacterial efficacy. The aim of this study was to investigate the penetration of meropenem into cerebrospinal fluid (CSF) in patients with nosocomial ventriculitis and to develop a nomogram to predict effective meropenem doses based on clinical parameters.

Methods: Retrospective patient data, including serum and CSF concentrations of meropenem and inflammatory markers in the CSF, were analyzed using NONMEM to evaluate pharmacokinetic data and penetration into the CSF. Monte Carlo simulations were used to evaluate different meropenem dosages. The probability of achieving the target CSF concentration (POC) was assessed, and a nomogram was developed to achieve a meropenem concentration twice the MIC during the dosing interval.

Results: A one-compartment model with meropenem clearance dependent on glomerular filtration rate (GFR) estimated using the CKD-EPI formula (CKD-EPI GFR; p < 0.001) best predicted meropenem pharmacokinetics in 51 patients with severe ventriculitis. Penetration into the CSF correlated with proteinuria (p < 0.001), with higher proteinuria associated with higher penetration rates. Normal renal function (CKD-EPI eGFR > 50 mL/min/1.73 m²) and a low cerebrospinal fluid protein level (< 0.5 g/L) resulted in an 80% probability of maintaining concentrations > 2 times the MIC throughout the dosing interval for a meropenem dosage of 6 g/24 h.

Discussion: Significant interindividual variability in meropenem concentrations in CSF was observed in patients with nosocomial ventriculitis. A nomogram predicting the meropenem dosage required to achieve the target CSF concentration, based on eGFR and CSF protein levels, was developed.

Objective: To demonstrate that a 7-day course of antibiotic therapy for Enterobacteriaceae bacteremia reduces patients’ exposure to antibiotics while ensuring clinical efficacy comparable to that of a 14-day course of treatment.

Methods: A randomized clinical trial was conducted. Adult patients with Enterobacteriaceae bacteremia and a confirmed source of infection were randomized to receive either 7 or 14 days of treatment and were followed up for up to 28 days after the end of treatment. If necessary, antibiotic therapy was resumed. The primary endpoint was the number of days of treatment at the end of follow-up. Clinical endpoints included clinical cure, recurrence of bacteremia, and recurrence of fever. The superiority threshold for the primary endpoint was set at 3 days, and a 10% non-inferiority margin was used for the clinical endpoints. A post-hoc sensitivity analysis evaluating the benefit of the shortened treatment and the risk of reduced efficacy was performed using a DOOR/RADAR analysis (desirability of response level adjusted for duration of antibiotic therapy).

Results: 248 patients were randomized to a 7-day treatment duration (n = 119) or a 14-day treatment duration (n = 129). In the ITT analysis, the median number of days of antibiotic treatment at the end of follow-up was 7 and 14 days (difference: 7 days, 95% CI: 7 to –7). Non-inferiority was also demonstrated for the clinical endpoints, except for recurrence of fever (–0.2%, 95% CI: –10.4 to 10.1). The DOOR/RADAR analysis showed that a 7-day course of antibiotic therapy had a 77.7% probability of yielding better outcomes than a 14-day course of antibiotic therapy.

Conclusion: A 7-day course of antibiotic therapy reduced antibiotic exposure in patients with Enterobacteriaceae bacteremia while ensuring a cure rate similar to that of a 14-day course of antibiotic therapy. The possibility of a febrile relapse in a limited number of patients — which had no impact on clinical outcomes at day 28— should not be overlooked, but this was offset by the benefit of a shorter treatment duration.

Introduction: SARS-CoV-2 viral RNA (vRNA) is detectable in the blood of some patients with COVID-19. The question remains as to whether this detection of vRNA corresponds to viremia (the presence of viral particles), as well as its relationship to the host’s immune response and disease progression.

Methods: SARS-CoV-2 RNA was detected and quantified in the plasma of 51 patients with COVID-19, including 9 outpatients, 19 patients hospitalized in general wards, and 23 in the ICU. vRNA levels were compared with the severity of COVID-19 and clinical course. Virions in plasma were visualized using several imaging

methods:

Results: Viral RNA was detected in the plasma of 100% of ICU patients, 52 ± 6% of patients hospitalized in general wards, and 11.1% of outpatients. Virions were detected in plasma pellets by electron microscopy and immunolabeling. vRNA levels were significantly higher in ICU patients than in patients in conventional hospital wards, who in turn had higher levels than outpatients (p < 0.0001); for hospitalized patients, plasma vRNA levels were strongly associated with a higher score on the WHO ordinal scale at admission (p = 0.01), the maximum WHO score reached during hospitalization (p = 0.002), and outcome (p = 0.004). A viral RNA level > 6,000 copies/mL was strongly associated with death (hazard ratio = 10.7). Viral RNA levels were significantly associated with several inflammatory biomarkers (p < 0.01), but not with plasma neutralizing antibody titers (p = 0.8).

Conclusion: The detection of viral particles in plasma indicates that the presence of SARS-CoV-2 viral RNA is due, in part, to viremia. Viral RNA levels are strongly correlated with disease severity, patient outcomes, and specific inflammatory markers, but not with neutralizing antibody titers.

Introduction: Clostridium difficile toxin concentrations in stool may influence the severity of the infection and its course. We correlated C. difficile toxin concentrations in stool, measured using a highly sensitive quantitative method, with initial severity, disease course, and recurrence of C. difficile infection (CDI).

Methods: We included 615 adults (≥ 18 years) hospitalized for C. difficile infection (acute diarrhea, positive stool PCR, decision to treat). Baseline concentrations of toxins A and B were measured using a highly sensitive assay. Participants were classified according to the initial severity of C. difficile infection (using 4 different scores) and their clinical course up to day 40 (death, transfer to the intensive care unit, colectomy, recurrence).

Results: Among the 615 patients (median age 68 years), across the four scores used, individuals with severe initial presentation had higher stool concentrations of toxin A + B (p < 0.01). Nineteen individuals (3.1%) had an adverse outcome, primarily attributable to DIC (Group 1). This group had higher median concentrations of toxin A + B (14,303 pg/mL [IQR 416 to 141,967]) than patients with an unfavorable outcome in which ICD was a contributing factor (Group 2 (n = 43), 163.2 pg/mL [0 to 8,423.3]), those with an unfavorable outcome not attributable to ICD (Group 3 (n = 69), 158.6 pg/mL [0 to 1,759.2]) or those without an adverse outcome (Group 4 (n = 484), 209.5 pg/mL [0 to 8,566.3]); p = 0.003). Group 1 was more likely to have detectable toxin (94.7%) than groups 2 through 4 (60.5% to 66.1%); p = 0.02. Individuals with recurrence (n = 42) had a higher baseline level of toxin A + B than those without recurrence (2,266.8 pg/mL [188.8 to 29,411] vs. 154.0 pg/mL [0 to 5,684.3]); p < 0.001 and a higher frequency of toxin detection (85.7% vs. 64.0%; p = 0.004).

Conclusion: In patients with ICD, the detection and quantification of toxins using an ultrasensitive method is correlated with initial severity, adverse clinical outcomes attributable to ICD, and recurrence. This confirms the role of the amount of toxins present in stool on the clinical presentation and course of the disease.

Staphylococcus aureus bacteremia is complicated by infective endocarditis in 10 to 20% of cases. Clinical risk scores can identify patients with Staphylococcus aureus bacteremia who are at high risk for endocarditis, thereby improving diagnostic performance. The authors compared the performance of three scores for assessing the risk of endocarditis in patients with POSITIVE Staphylococcus aureus bacteremia (Prediction Of Staphylococcus aureus Infective Endocarditis: Time to Positivity, IV Drug Use, Vascular Phenomena, Pre-existing Heart Condition), PREDICT (Predicting Risk of Endocarditis Using a Clinical Tool), and VIRSTA. Between August 2017 and September 2019, all consecutive adult patients with Staphylococcus aureus bacteremia were included in a prospective cohort across 7 hospitals in the Netherlands. Using the modified Duke criteria as the gold standard for the diagnosis of definite endocarditis, the sensitivity, specificity, negative predictive value, and positive predictive value were determined for the three risk scores. A negative predictive value of 98% was considered sufficient to rule out the diagnosis of endocarditis. Among the 447 cases of Staphylococcus aureus bacteremia included in the study, 33% were community-acquired; 8% of patients had a prosthetic valve; and 11 % had an implanted cardiac electrical device. An echocardiogram was performed in 87% of patients, and a transesophageal echocardiogram (TEE) in 42%. Definite endocarditis was diagnosed in 87 patients (18.2%). The sensitivity was 77.6% (65.8% –86.9%) for POSITIVE (n = 362), 85.1% (75.8% – 91.8% %) for PREDICT, and 98.9% (95.7% –100%) for VIRSTA. The negative predictive value was 92.5% (87.9% –95.8%) for POSITIVE, 94.5 % (90.7% –97%) for PREDICT, and 99.3% (94.9% –100%) for VIRSTA. The classification of patients as being at high risk for endocarditis was 44.5% for POSITIVE, 50.7% for PREDICT, and 70.9% for VIRSTA. Only the VIRSTA score had a negative predictive value greater than 98%, but at the cost of a high number of patients classified as being at high risk for endocarditis who required transesophageal echocardiography.

LEMP has been reported only rarely in patients living with HIV who have sustained immunovirological control. The authors described the clinical and biological characteristics of patients with confirmed LEMP (clinical signs and MRI findings plus positive JC virus PCR in CSF and/or brain tissue), with a CD4 count > 200/mm³ and an undetectable viral load, and who had received more than 6 months of antiretroviral therapy at the time of LEMP diagnosis. This study is based on the Dat’AIDS cohort. Of the 571 cases of PMP diagnosed in the Dat’AIDS cohort between 2000 and 2019, 10 (1.75%) occurred in patients with a CD4 count > 200/mm³, an undetectable viral load, and antiretroviral therapy (ART) initiated more than 6 months prior. The median CD4 count at the time of PLEM diagnosis was 395/mm³ (IQR: 310–477). The median time from the last detectable viral load to the diagnosis of PLL was 41.1 months (IQR: 8.2–67.4). Only 1 out of 10 patients had a risk factor for PLS: large B-cell lymphoma treated with rituximab and chemotherapy. Among the other 9 patients, who showed no evidence of severe immunosuppression, numerous factors impairing immunity may have played a role in the development of PLS: HCV coinfection (n = 6), cirrhosis (n = 4), HHV-8 coinfection (n = 3)— including 2 with Kaposi’s sarcoma, associated with Castleman’s disease in 1 case and indolent IgA myeloma in 1 case. This study highlights that factors other than a low CD4 count and a high viral load may be associated with the development of PEMS. Further studies are needed to more precisely explore the immunological characteristics of HIV-positive patients who are immunovirologically controlled and who develop PEMS.

Rilpivirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) approved for the treatment of Human Immunodeficiency Virus (HIV) infection in combination with other antiretrovirals (ARVs). This review provides an update on the development of the extended-release formulation of rilpivirine (RPV-LP) and its use in clinical practice In 2017, the results of the Phase IIb LATTE-2 trial were published. This study showed that the combination of RPV-LP with another extended-release medication (cabotegravir), administered intramuscularly every 4 or 8 weeks, was equivalent to standard antiretroviral therapy in terms of plasma viral load suppression rates. RPV-LP is an injectable nanoparticle suspension for intramuscular use. Phase I trials in healthy volunteers showed that RPV-LP, administered at doses of 600 and 1,200 mg, was well tolerated and effective in maintaining satisfactory drug concentrations in plasma, vaginal secretions, and rectal tissue compartments for at least 4 weeks. The efficacy of RPV-LP was also observed in Phase II clinical trials, and Phase III trials are currently underway. Most trial participants indicated that they would use or continue to use an injectable treatment, both for the treatment of HIV infection and for prophylaxis. LP-CPR has the potential to improve the comfort of HIV treatments.

Pre-exposure prophylaxis (PrEP) is an effective tool for preventing Human Immunodeficiency Virus (HIV) infection among men who have sex with men (MSM), a key population whose engagement is crucial for achieving effective public health goals. An optimal service model could be important for planning the implementation of PrEP centers where such services have not yet been established. A qualitative study was therefore conducted to determine the characteristics of a model PrEP service for MSM in Hong Kong, a city where no formal PrEP program currently exists. A group of 20 MSM enrolled in two PrEP pilot projects participated in semi-structured interviews designed to encourage open-ended responses. The coded data were analyzed thematically using the Grounded Theory approach, focusing on identifying the essential characteristics of an optimal PrEP model and the reasons behind specific preferences. The participating MSM were of Chinese descent and ranged in age from 26 to 52. All received PrEP as part of pilot projects that included periodic screening for sexually transmitted infections (STIs), HIV serology, and serum creatinine levels. Four major themes emerged as the characteristics of an ideal PrEP service: Monitoring for both STIs and HIV, as well as monitoring of drug tolerance A practical, integrated service No stigma associated with accessing PrEP and strict confidentiality Affordable pricing While regular access to PrEP was acceptable to MSM, high costs and stigma were the challenges potential PrEP service providers needed to anticipate The qualitative assessment of MSM preferences for a PrEP dispensing service yielded important insights into the various aspects of a desirable ideal service.

The SARS-CoV-2 pandemic responsible for COVID-19 has claimed the lives of more than 800,000 people in the United States, and it is estimated that it will incur a social cost of $16 trillion over the next decade. The availability of COVID-19 vaccines has had a significant impact on the course of the pandemic, yielding a wide range of benefits. The objective of this study is to estimate the total societal economic value generated in the United States by COVID-19 vaccines. An economic population model was therefore developed, informed by existing data and data from the literature, to assess the total societal value generated by COVID-19 vaccines by preventing SARS-CoV-2 infections and also enabling a faster resumption of social and economic activity. To do so, the value generated by life years saved, avoided healthcare costs, gains in quality of life, and the increase in Gross Domestic Product (GDP) in the United States were separated based on various plausible assumptions. The results of the base-case scenario suggest that since their launch in December 2020, COVID-19 vaccines are estimated to have generated $5 trillion in societal economic value by preventing infections and enabling a faster return to unrestricted economic and social activity. The scenario analysis suggests that the value could range from $1.8 trillion to $9.9 trillion. The model indicates that the most substantial sources of value come from the reduction in the prevalence of depression ($1.9 trillion), GDP gains ($1.4 trillion), and lives saved due to fewer infections ($1.0 trillion). The limitations of this analysis include the emergence of new variants, such as the Delta variant or future variants, as well as improvements in the therapeutic management of COVID-19. The magnitude of the economic benefit from vaccination underscores the need for coordinated policy decisions to support widespread vaccination in the United States.

Remdesivir is currently the only antiviral drug approved by the FDA (Food and Drug Administration ) for the treatment of SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) infection, which causes COVID-19 (Coronavirus Disease 2019). The drug is approved for use in adults and children 12 years of age and older who are hospitalized for COVID-19, based on its ability to accelerate clinical recovery in patients hospitalized for this condition. Unfortunately, the drug must be administered intravenously, which limits its use to patients requiring hospitalization for a relatively advanced stage of the disease. Remdesivir is also unstable in plasma and has a complex activation pathway that may contribute to the wide variability in antiviral efficacy in cells infected with SARS-CoV-2. Potent antiviral drugs with oral bioavailability for the early treatment of SARS-CoV-2 infection are now urgently needed, and some are currently in clinical development, such as molnupiravir and PF-07321332 (Paxlovid). Currently, particular attention is therefore being paid to the simple production of an orally bioavailable lipid analog of the nucleoside remdesivir (RVn, GS- 441524), which is converted into RVn monophosphate — a precursor to the active form, RVn triphosphate — through a single-step intracellular cleavage. In addition to high oral bioavailability, plasma stability, and simpler metabolic activation, the new oral lipid prodrug of RVn exhibits sub-micromolar activity against SARS-CoV-2 in various cell types, such as Vero E6, Calu-3, Caco-2, human pluripotent stem cells (PSCs) derived from lung cells, and Huh7.5 cells. In Syrian hamsters, oral treatment with ODBG-P-RVn was well tolerated and resulted in therapeutic plasma levels above the EC90 for SARS-CoV-2 These results warrant further evaluation as an early oral treatment for SARS-CoV-2 infection to limit severe disease and reduce hospitalizations.

The objective of this study is to assess the incidence of extrahepatic cancers among people co-infected with the Human Immunodeficiency Virus (HIV) and the Hepatitis C Virus (HCV) and the potential impact of Direct-Acting Antivirals (DAAs) on the risk of extrahepatic cancer in this patient population. This study included adult patients who began HIV care at a CNICS center in the United States between 1995 and 2017, excluding those with a history of cancer and those who had not been screened for HCV. A total of 18,422 adults were included; 1,775 (10%) were HCV-positive, and 10,899 (59%) were on antiretroviral therapy (ART) at enrollment. The incidence rates of all extrahepatic cancers among patients • with HIV/HCV coinfection were 1,027 per 100,000 person-years • and 771 per 100,000 person-years among patients with HIV monoinfection Based on the weight-standardized morbidity ratio, the risk of extrahepatic cancer among patients with coinfection whose HCV was untreated at enrollment was identical to that of those who had been successfully treated. Patients with coinfection whose HCV was untreated at enrollment had a higher incidence of kidney, lung, and inflammation-related cancers than if their HCV infection had been successfully treated, but these associations were not statistically significant. In conclusion, this study did not demonstrate that treating HCV infection in HIV-coinfected patients receiving AIDs medications could reduce the incidence of extrahepatic cancers in patients receiving ARVs.

The objective of this study is to assess the incidence of anal cancer across ethnic groups in a clinical cohort of men who have sex with men (MSM). This is a clinical cohort study. The study included MSM from the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) who began antiretroviral (ARV) therapy to manage their HIV infection. The incidence of anal cancer was compared between Black and non-Black men, and the hazard ratio (HR) was calculated based on demographic characteristics (age, CNICS site, year of ARV treatment initiation), indicators of HIV infection (CD4 nadir CD4 count, peak plasma viral load), and co-infections/behavioral factors including hepatitis B virus (HBV), hepatitis C virus (HCV), smoking, and heavy alcohol consumption. A total of 7,473 HIV-infected MSM, representing 41,810 patient-years of follow-up, were studied after initiation of antiretroviral therapy between 1996 and 2004 in the CNICS. An incident diagnosis of anal cancer was made in 41 patients. The crude incidence rate of anal cancer among Black men was 204 per 100,000 patient-years, compared with 61 per 100,000 among non-Black men. For Black MSM, the hazard ratio (HR) for anal cancer (after adjusting for demographic characteristics, HIV-related factors, and co-infections/behavioral factors) was 2.37 (95% CI: 1.17, 4.82) compared with non-Black MSM. In this large, multicenter cohort, Black MSM had a significantly increased risk of anal cancer compared with non-Black MSM. Further detailed studies evaluating the factors influencing the incidence of anal cancer and its progression among Black men living with HIV are needed.

The GEMINI-1 and GEMINI-2 studies are two randomized, double-blind, multicenter trials that demonstrated the non-inferiority of once-daily dolutegravir plus lamivudine compared with dolutegravir plus tenofovir disoproxil fumarate/emtricitabine in achieving a plasma HIV viral load < 50 copies/mL at 48, 96, and 144 weeks in adult patients infected with HIV-1 who were antiretroviral-naive (ARV). The objective of this post-hoc study is to analyze the impact of treatment adherence on the virologic response at week 48 of treatment. Treatment adherence was estimated using tablet counts and classified as • ≥ 90% • < 90% The unadjusted differences observed between the two treatment groups (with 95% CI) were due to the proportions of patients with HIV-1 RNA < 50 copies/mL in each adherence group. In each treatment group, 5% of patients had treatment adherence < 90%: • 35/716 in the dolutegravir + lamivudine group • 34/717 in the dolutegravir + tenofovir disoproxil fumarate/emtricitabine group The proportion of patients with a plasma HIV viral load < 50 copies/mL (Snapshot) at week 48 in the < 90% treatment adherence group was 69% in the dolutegravir + lamivudine group 65% in the dolutegravir + tenofovir disoproxil fumarate/emtricitabine group Using the “last viral load while on treatment” analysis: 91% in the dolutegravir + lamivudine group 85% in the dolutegravir + tenofovir disoproxil fumarate/emtricitabine group The proportion of patients with a plasma HIV viral load < 50 copies/mL (Snapshot) at Week 48 in the group with treatment adherence ≥ 90% was 93% in the dolutegravir + lamivudine group 96% in the dolutegravir + tenofovir disoproxil fumarate/emtricitabine group Using the “last viral load while on treatment” analysis: • 97% in the dolutegravir + lamivudine group • 99% in the dolutegravir + tenofovir disoproxil fumarate/emtricitabine group Reduced treatment adherence led to lower virologic efficacy at week 48, which was comparable between the two treatment groups. These results indicate that the good antiviral activity and “tolerability” of the dolutegravir + lamivudine regimen are comparable to triple therapy with dolutegravir.

The NVX-CoV2373 vaccine is a recombinant spike protein nanoparticle vaccine with an adjuvant that has demonstrated clinical efficacy in preventing COVID-19 (Coronavirus Disease 2019) in Phase 2b-3 trials in the United Kingdom and South Africa, but its efficacy has not been tested in North America. To this end, a Phase 3, a randomized, double-blind, placebo-controlled trial was conducted in the United States and Mexico during the first half of 2021 to evaluate the efficacy and safety of NVX-CoV2373 in adults (aged 18 years and older) who had not previously been infected with SARS-CoV- 2 (Severe Acute Respiratory Syndrome Coronavirus 2) Participants were randomized (2:1) to receive, 21 days apart, Two doses of NVX-CoV2373 Placebo The primary endpoint was efficacy against the onset of PCR-confirmed COVID-19 at least 7 days after the second dose. Vaccine efficacy against moderate-to-severe disease and against various variants was also evaluated. Of the 29,949 participants randomized between December 27, 2020, and February 18, 2021, a total of 29,582 people (median age 47 years, with 65% aged 65 or older) received at least one dose of NVX-CoV2373, and 9,868 received the placebo. Over a 3-month period, 77 cases of COVID-19 were recorded: 14 in the vaccinated group and 63 in the placebo group. The vaccine’s efficacy is therefore 90.4% (95% CI: 82.9–94.6; p < 0.001). There were 10 cases of moderate COVID-19 and 4 cases of severe COVID-19, all in participants in the placebo group, resulting in a vaccine efficacy of 100% against moderate and severe forms of the disease (95% CI: 87.0–100). Most of the sequenced viral genomes (48 out of 61, or 79%) were variants of concern or interest — predominantly Alpha (31 out of 35 variants of interest, or 89%). The vaccine’s efficacy against variants of concern or interest was 92.6% (95% CI: 83.6–96.7). Reactogenicity was mainly mild to moderate and transient but was more common among those who received NVX-CoV2373 than among those who received the placebo, and was more common after the second dose than after the first. The NVX-CoV2373 vaccine was therefore safe and effective in preventing COVID-19. Most cases were caused by current viral strains.

At this time, there is no effective antiviral treatment against SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2), the virus responsible for the COVID-19 (Coronavirus Disease 2019) pandemic, but numerous drugs have been evaluated since the start of the pandemic, and some of them + Read this article SHORT-TERM TREATMENT FOR SEPTIC ARTHRITIS OF THE FINGERS Published on June 15, 2022 - By Philippe CASTIEL, Infectious Disease Specialist (Paris) Diama Ndiaye et al. Spray-Dried Septic arthritis of the fingers: is short-term oral antibiotic therapy appropriate?. Hand Surg Rehabil. 2022 Jan 14;S2468-1229(22)00003-2. Filter by category : Antibiotics (?addFilter=Ab) The management of septic arthritis of the hand has been poorly documented, and there is no consensus on the subject. It is based on the management of septic arthritis of large joints, despite certain specific characteristics of the hand, typically involving hospitalized patients receiving intravenous antibiotic therapy. The primary objective of this study was to evaluate the postoperative management protocol for septic arthritis of the hand using a short course of antibiotic therapy. The secondary objective was to identify risk factors for treatment failure. This was a retrospective, descriptive, single-center study in which the medical records of patients treated for septic arthritis of the fingers were analyzed over a one-year period from January to December 2018. Demographic data and pre-, intra-, and postoperative data were collected. A total of 128 patients were included, with a mean age of 52.4 years (range 41–66). An exogenous source of contamination was reported in 98% of cases (animal bite, plant prick, injury, etc.). The most frequently isolated microorganism was Staphylococcus aureus (45%), followed by Streptococcus spp. (22%) and Pasteurella spp. (18%). The majority of patients (79%) were treated with oral amoxicillin/clavulanic acid. Treatment was continued in 91% of patients after microbiology results were obtained for a median duration of 8 days (7–15). Treatment failure was observed in 9% of patients. The identified risk factors were: • Crush injury (p = 0.04) • Initial radiographic abnormalities (chondrolysis and/or osteolysis) (p = 0.016) • Infection with Pasteurella spp. (p = 0.015) This study suggests that a simplified antibiotic regimen is feasible for the management of septic arthritis of the hand, involving a short course of treatment with broad-spectrum antibiotics in the absence of identified risk factors.

Multidrug-resistant tuberculosis (MDR-TB) is a major public health problem. Treating this form of tuberculosis requires prolonged multi-drug therapy involving second-line antituberculosis antibiotics that cause severe side effects. Capreomycin, a polypeptide antibiotic, is the first-choice second-line antituberculosis drug for treating MDR-TB. It requires repeated intramuscular or intravenous administration five times a week. Pulmonary drug delivery is noninvasive and offers the advantages of local targeting and a reduced risk of systemic toxicity. In this study, a lung-targeted capreomycin inhalation powder-spray formulation was developed using the dry powder spray technique. Among the 16 formulations designed, the one containing 25% capreomycin and a drying spray with an inlet temperature of 90°C had a median mass aerodynamic diameter (MMAD) of 3.38 µm and a fine particle fraction of approximately 65%. In pharmacokinetic studies in mice, pulmonary concentrations were approximately 8 times higher than the Minimum Inhibitory Concentration (MIC) (1.25 to 2.5 µg/mL) for at least 24 hours following intratracheal administration (20 mg/kg). Compared with intravenous injection, inhaled capreomycin exhibited a significantly higher area under the curve, a shorter clearance time, and a longer mean residence time in both lungs and in plasma.

Liver fibrosis is common in patients co-infected with the Human Immunodeficiency Virus (HIV) and the Hepatitis B Virus (HBV), but it is unclear whether antiretroviral (ARV) therapy can reduce fibrosis. This retrospective observational study was therefore conducted. A primary logistic regression analysis was used to assess predictors of fibrosis in patients coinfected with HIV and HBV. Comparisons of FIB-4 scores before and after ARV treatment were performed using the chi-square test and t-test. A total of 458 patients co-infected with HIV and HBV were included in this study. The results show that antiretroviral (ARV) therapy was a protective factor against liver fibrosis (HR = 0.016; 95% CI: 0.009–0.136; p < 0.001). Patients with normal AST, ALT, and platelet counts throughout the course of their illness (40 patients) were stratified into different groups based on their FIB-4 score prior to starting ARV therapy: FIB-4 < 1.45 (n = 14) 1.45 ≤ FIB-4 ≤ 3.25 (n = 19) FIB-4 > 3.25 (n = 7) In the group of patients treated with ARVs, a shift was observed: from the 1.45 ≤ FIB-4 ≤ 3.25 group to the FIB-4 < 1.45 group for 11 out of 19 patients (57.9%) from the FIB-4 > 3.25 group to the 1.45 ≤ FIB-4 ≤ 3.25 group for 1 out of 7 patients (14.3%) In the group of ARV-naive patients, the FIB-4 scores were: • After 1 year of ARV treatment: 4.29 ± 0.43 • After 2–5 years of ARV treatment: 3.63 ± 0.38 After 5–10 years of ARV treatment: 2.52 ± 0.38 p = 0.034 ARV therapy is therefore associated with a decrease in the FIB-4 score, and the benefit of ARVs in reversing fibrosis can be maintained for about ten years in patients coinfected with HIV and HBV.

Patients with hematologic and oncologic conditions are among those at high risk for severe COVID-19 (Coronavirus Disease 2019) due to infection with SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2). Furthermore, vaccination results in significantly lower response rates in patients with hematologic cancer and lower antibody levels in patients with solid tumors. This study evaluates the efficacy and tolerability of a heterologous booster vaccination with Ad26.COV2.S (Janssen vaccine) — a recombinant adenovirus type 26 vector vaccine — in patients with hematologic cancer who did not develop an antibody response after a two-dose vaccination series with BNT162b2 (Pfizer), a messenger RNA vaccine against COVID-19. A total of 32 patients with hematologic cancer who did not respond to a two-dose vaccination regimen with BNT162b2 received a heterologous booster dose of the Ad26.COV2.S vaccine. Blood samples were analyzed: • immediately before vaccination (T0) • 4 weeks later (T1) Tolerability was assessed using a standard questionnaire. The overall response rate was 31%, with a mean antibody titer of 693.79 (± 1,096.99) BAU/mL. Patients with chronic lymphocytic leukemia or lymphoma had a significantly lower response rate (p = 0.048). Adverse events were reported in 29.6% of patients, 7.1% of which were severe, including Grade III and IV events according to the Common Terminology Criteria for Adverse Events (CTCAE). Heterologous booster vaccination with Ad26.COV2.S resulted in a serological response in 9 out of 29 patients who had not responded after a two-dose vaccination regimen with BNT162b2. Furthermore, vaccination was safe in this cohort, leading primarily to mild local and systemic reactions. Overall, this vaccination strategy should be further evaluated to increase the response rate in highly vulnerable populations of onco-hematologic patients.

A number of repurposed drugs, such as hydroxychloroquine (HCQ), have been evaluated for the treatment of COVID-19 (Coronavirus Disease 2019), but none have demonstrated efficacy. While in vitro studies have shown antiviral activity of HCQ, data from clinical trials have been more ambiguous regarding its benefit for treating COVID. Drugs that limit viral replication may be beneficial in the early stages of the disease by reducing progression to severe or critical illness. An open-label, randomized Phase II trial was therefore conducted between October and December 2020. In practice, patients with a COVID-19 diagnosis confirmed by RT-PCR were included in the study if they were over 18 years of age and had received a COVID diagnosis within the past 3 days. Patients were randomized in blocks to receive • HCQ 400 mg twice daily on day 1, followed by 200 mg twice daily for 4 days + standard of care (SOC) • SOC alone The SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) viral load was measured by PCR using nasal/oropharyngeal swabs on Day 0, Day 2, Day 4, Day 6, Day 8, and Day 10. The primary endpoint was the median time from randomization to viral clearance on Day 6. Of the 105 patients enrolled, 55 were randomized to the intervention group (HCQ + SOC) and 50 to the control group (SOC alone). Baseline characteristics were identical between the groups. Viral clearance did not differ between the groups; the median number of days to viral clearance between the two groups was 4 (3–4) vs. 4 (2–4); p = 0.457. There were no significant differences in the secondary endpoints (resolution of symptoms and adverse events) between the intervention group and the control group. There were also no differences in specific adverse events, such as elevated alkaline phosphatase levels or QT prolongation, between the two groups. These results show that HCQ (at the trial dosage) is well tolerated but is not associated with a reduction in viral clearance or symptom resolution in adults with COVID-19 in Uganda.

Levofloxacin has been widely used for pre-transplant prophylaxis in patients undergoing hematopoietic stem cell transplantation (HSCT), but the evidence supporting this practice is inconsistent. Furthermore, this practice could increase rates of Clostridioidium difficile (C. diff) infection, the incidence of multidrug resistance, or graft-versus-host disease (GVHD). The objective of this study is to evaluate the tolerability and efficacy of levofloxacin for prophylaxis in pediatric patients and young adults scheduled to undergo allogeneic or autologous stem cell transplantation. This is a retrospective analysis evaluating patients aged 6 months or older who underwent an allogeneic or autologous stem cell transplant between January 1, 2016, and July 31, 2020. Patients who underwent transplantation before March 2018 did not receive levofloxacin, whereas patients who underwent transplantation since April 2018 received prophylaxis. Each transplantation was included as a separate episode if patients underwent more than one transplantation during the inclusion period. The primary endpoint of this study was the proportion of patients with at least one bacteremia (BSI) within the first 100 days post-transplant. Secondary endpoints: • The number of days of non-levofloxacin antibiotics post-transplant • The incidence of aGvHD • The number of C. diff infections • The emergence of multidrug-resistant bacteria A total of 370 patients who had undergone a hematopoietic stem cell transplant (HSCT), with a median age of 6.7 years (0.5–39), were included in the study. Seventy-two of these patients had more than one transplant, resulting in 443 transplants analyzed. Of these 443 transplants, 216 did not receive levofloxacin prophylaxis (227 did). There were no differences between the two groups in baseline characteristics except for age: patients in the non-levofloxacin prophylaxis group were younger (8.1 years vs. 9.6; p = 0.05). There were no differences between the two groups in 100-day mortality rates, antibiotic use, fungal infections, or infections caused by multidrug-resistant organisms. Patients in the group without prophylaxis developed more bacteremia within the first 100 days after HSCT (27% vs. 17%; p = 0.004) and more C. diff infections than patients who received levofloxacin prophylaxis (20% vs. 9%; p = 0.003). In addition, there were more cases of GVHD among patients without prophylaxis than among those who received levofloxacin (p = 0.014). Levofloxacin prophylaxis administered starting on day 2 of the HSCT was significantly associated with a reduction in bacteremia during the first 100 days post-transplant. Furthermore, this prophylaxis was not associated with an increased risk of C. diff. infections, GVHD, or the emergence of multidrug-resistant pathogens. This study therefore supports the use of levofloxacin prophylaxis during the peri-transplant period.

People living with HIV (PLHIV) are more likely to smoke (tobacco) than the general population. Previous research has shown that PLHIV have a faster nicotine metabolism than people not infected with HIV, which could explain this disparity, but the cause remains unknown. This study investigates whether a higher ratio of the nicotine metabolite (NMR; 3-hydroxycotinine:cotinine) — a validated biomarker of nicotine metabolism via CYP2A6 — is associated with antiretroviral (ARV) use among HIV-infected smokers. This study is a retrospective cohort study of HIV-infected smokers from the University of Pennsylvania Center for AIDS Research cohort The NMR (nicotine metabolite ratio) was compared before plasma viral load control (>10,000 copies/mL) and after control (plasma HIV RNA <200 copies/mL). A total of 89 individuals were included in the study. Changes in the NMR were observed based on the use of efavirenz. • Among patients on efavirenz-free regimens, the mean increase in NMR was 0.14 (95% CI: 0.05–0.23, p = 0.002). • Among patients on treatment regimens containing efavirenz, the mean increase in MNR was 0.53 (95% CI: 0.39–0.66, p < 0.001). There is therefore a clinically and statistically significant increase in MNR after adjusting for viral load among HIV-infected smokers, which is more than doubled in patients on regimens containing efavirenz A higher MNR among HIV-positive smokers on antiretroviral therapy (ART) could explain the higher rates of tobacco use and lower rates of smoking cessation among people living with HIV (PLHIV) on treatment. These data suggest that the choice of antiretroviral therapy and other modifiable factors could be targets for efforts to increase the success rate of smoking cessation among people living with HIV.

Adherence to antiretroviral (ARV) therapy is critical for reducing morbidity and mortality and improving survival among patients infected with the Human Immunodeficiency Virus (HIV). ARV therapy is a lifelong commitment, and various factors can influence treatment adherence. This study examines the factors influencing treatment adherence in the private and public outpatient sectors in Ahmedabad, India. The primary objective of this study is to compare adherence levels and the factors influencing adherence among patients enrolled in the government’s free ARV access program and those in the private sector. This is an 8-week cross-sectional study of HIV-infected patients receiving ARVs at a private or public facility from July to September 2019. All consecutive patients over the age of 18 who were under follow-up were included. Logistic regression was used to identify factors independently associated with ARV treatment adherence. A total of 306 patients were included in the study: 151 patients (49.34%) were treated at a private hospital, and 155 patients (50.65%) were treated in the public sector. Patients receiving care in the private sector were more likely to have been diagnosed with HIV ≥ 10 years prior compared to patients receiving care at free antiretroviral (ARV) centers. Higher rates of opportunistic infections were found in free ARV centers (64.51%), and treatment adherence was significantly lower among patients treated at these centers (p = 0.004). Patients taking concomitant treatment for a comorbidity (≥ 4 tablets/day) were more likely to have inadequate adherence (OR = 1.216; 95% CI: 1.171–1.454). Univariate analysis showed that age, education, alcohol use, smoking, the number of tablets, and duration of illness played a role in predicting ARV adherence (p < 0.05). Patients treated in private facilities have higher survival rates after an HIV diagnosis, experience fewer opportunistic infections, and demonstrate better treatment adherence compared to those treated in public facilities.

Pre-Exposure Prophylaxis (PrEP) for Human Immunodeficiency Virus (HIV) is the standard antiretroviral treatment for people who are not infected with HIV to prevent seroconversion. Israel approved PrEP for continuous use in 2017, and Israeli Health Maintenance Organizations (HMOs) offered PrEP with cost-sharing to eligible individuals. This is a retrospective cohort study including all individuals who received PrEP between September 2017 and June 2019 at Israel’s two largest HMOs. Statistical analysis, including a Kaplan-Meier analysis, was conducted to assess PrEP adherence, adherence to medical follow-up, and clinical outcomes. In total, a cohort of 757 PrEP users was followed for 657.8 person-years. With the exception of one female user, all others were men, with a median age of 35 years. At enrollment, recent sexually transmitted infections (STIs) were as follows: • Gonorrhea: 0.8% • Chlamydia: 1.5% • Syphilis: 4.4% PrEP use was: Continuous (without interruption or discontinuation): 29.9% Intermittent: 39.9% Discontinued: 30.3% The median time to the first interruption or discontinuation was 4.0 months. At 6–12 months after starting PrEP, the documented tests were: HIV testing for 79.8% of participants Chlamydia and gonorrhea testing for 77.3% of participants Serum creatinine testing for 78.9% of participants There was only one new case of HIV infection in the cohort, 5 months after stopping PrEP. The estimated STI infection rates for the first year are: Gonorrhea: 5.0% Chlamydia: 8.6% Syphilis (first infection): 6.8% This study highlights the heterogeneity of PrEP purchasing patterns and underscores the need for medical follow-up, as well as an increase in STIs among PrEP users. Improving adherence during medical follow-up visits is essential for integrating PrEP into Israel’s national HIV prevention strategy.

Of all new sexually transmitted infections (STIs) in the United States, 50% occur among young people aged 15–24. Previous studies conducted among young people infected with the Human Immunodeficiency Virus (HIV) did not distinguish between those infected with HIV perinatally (YPHIV) and those not infected perinatally (YNPHIV). In three studies involving adolescents (Adolescent Medicine Trials Network for HIV/AIDS Interventions [ATN] Studies ) conducted between 2009 and 2015, the incidence of sexually transmitted infections (STIs) was estimated, stratified • by sex, • mode of HIV transmission (perinatal and non-perinatal) • age group (13–17 and 18–24 years) • CD4 count (< 200, 200–499, and ≥ 500/mm³) • viral load level (< and ≥ 400 copies/mL). Among 3,131 HIV-infected young people across the three studies, the mean age was 20.6 (2.6) years; 28% were female; 80% were not infected at birth; and 73% were African Americans. The average follow-up period for these patients was 0.9 (0.3) years. Compared to YPHIV, YNPHIV spent less person-time with a viral load < 400/mL (47% vs. 53%), spent more time without antiretroviral therapy (49% vs. 15%), and had higher rates of STIs: • men: 65.9 vs. 8.5 per 100 patient-years • women: 54.7 vs. 17.2 per 100 patient-years Among PLHIV, bacterial STIs were more common for person-years spent with a viral load ≥ vs. < 400 copies/mL: • men: 10.9 vs. 0.6 per 100 patient-years • Women: 11.2 vs. 2.9 per 100 patient-years No difference was observed among YNPHIV, which may be due to the concurrent acquisition of HIV and other STIs and limited follow-up. Compared to young people living with HIV (YPHIV), young people newly diagnosed with HIV (YNPHIV) spend less time on antiretroviral therapy (ART) and with a controlled plasma viral load; YNPHIV also have higher rates of STI diagnoses. Very high rates of STI diagnoses among young people living with HIV, including those with a controlled plasma viral load, underscore the importance of focusing efforts on maintaining a controlled viral load and on screening for and treating STIs.

Antiretroviral (ARV) therapy restores immune function and reduces the consequences of Human Immunodeficiency Virus (HIV) infection. Despite its well- documented benefits, ARV therapy is not without adverse effects. Protease inhibitors (PIs) and, to a lesser extent, nucleoside and non-nucleoside reverse transcriptase inhibitors (NRTIs/NNRTIs) are known to disrupt carbohydrate and lipid metabolism. Furthermore, insulin resistance is exacerbated by immune activation and chronic inflammation associated with HIV infection. Recent data have reported disturbances in carbohydrate metabolism associated with the use of integrase inhibitors (INIs), with studies showing that the incidence of moderate hyperglycemia (126–250 mg/dl) was 6–9% and that of severe hyperglycemia (>250 mg/dl) was 1–2 %. The series reported here presents the first cases of diabetes following the use of dolutegravir in Ethiopia. For patients who had been treated with a regimen including a non-nucleoside reverse transcriptase inhibitor for more than 10 years, the treatment was switched to an integrase inhibitor-based regimen (dolutegravir) as recommended by the National Comprehensive HIV Care Guidelines The diagnosis of diabetes (with or without ketoacidosis) was made based on polyuria, polydipsia, and severe hyperglycemia (>250 mg/dl) with or without ketonuria (3+) after 1–12 months of treatment including dolutegravir. Two of the patients who presented with ketonuria were treated with intravenous fluids and insulin. NPH insulin was initiated after recovery from diabetic ketoacidosis and was subsequently replaced with metformin therapy. One of the patients who presented with severe hyperglycemia without diabetic ketoacidosis began treatment with NPH insulin, which was subsequently replaced by metformin. Effective blood glucose control was achieved with metformin, while treatment with dolutegravir was continued. Hyperglycemia is a potential and known side effect of dolutegravir-based treatment. Regular monitoring of blood glucose levels may therefore be essential with this type of treatment.

Effective vaccines are essential for controlling the Coronavirus Disease 2019 (COVID-19) pandemic caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). CoronaVac, an inactivated virus vaccine, was the first COVID-19 vaccine imported into Thailand. To evaluate the safety and immunogenicity of CoronaVac in the Thai population, a prospective study was conducted among healthcare workers (HCWs) aged 18 to 59 years who received two doses of CoronaVac 21 days apart between March and April 2021 at a hospital in Samut Sakhon, Thailand. A total of 185 participants with a mean age of 32 years were included. Total antibodies against the spike protein region, the receptor-binding domain (RBD), and IgG antibodies against the nucleocapsid (N) protein of SARS- CoV-2 were tested. Total antibodies against RBD were negative prior to immunization. One volunteer tested positive for anti-N antibodies but negative for anti-RBD antibodies. The seroconversion rate for total antibodies against RBD after the first dose of CoronaVac was 67%, with a geometric mean concentration of 1.98 U/ml. After the second dose, the seroconversion rate increased to 100%, with a geometric mean concentration of 92.9 U/mL. Regarding the N protein, seroconversion rates were 1% after the first dose and 62.8% after the second. The overall incidence of adverse reactions was 59.9%. The most common local reaction was pain at the injection site (52.4%), while myalgia was the most frequent systemic reaction (31.9%). No serious adverse events were observed. Two doses of CoronaVac administered 21 days apart therefore appear to be safe and induce a satisfactory immune response compared to convalescent serum obtained 4 to 6 weeks after natural infection. Antibody responses after two doses of CoronaVac were comparable to those in “convalescent” plasma but declined rapidly after three months. ? This is why the recommendation is based on administering two doses of CoronaVac with a possible booster dose.

Molnupiravir is a new oral antiviral drug that has recently been tested against SARS-CoV-2, the virus responsible for the COVID-19 pandemic. The objective of this study is to conduct a systematic review of the literature to assess the efficacy and safety data for molnupiravir in patients with COVID- 19. A systematic review was conducted in the electronic databases PubMed, MedRxiv, and Google Scholar from their inception through October 15, 2021, using MeSH keywords. In addition, ongoing clinical trials of molnupiravir for COVID-19 were also searched for on ClinicalTrials.gov and ctri.nic.in/Clinicaltrials. All details of Phase 1 through 3 trials of molnupiravir for COVID-19 were retrieved. Two randomized, double-blind, placebo-controlled (DBPRC) Phase 1 trials of molnupiravir showed that 1,600 mg/day is a that is safe and well-tolerated without serious adverse events for up to 5.5 days. A Phase 2 DBPRC trial showed a significantly shorter time to clearance (RNA negativity) with molnupiravir 800 mg twice daily compared to placebo (log- rank p = 0.013) in patients with mild to moderate COVID-19. An interim analysis of a Phase 3 DBPRC trial in non-hospitalized patients found a significant 50% reduction in the risk of hospitalization or death (p = 0.0012). However, no significant benefit was observed with molnupiravir in later stages of moderate-to-severe COVID-19. Molnupiravir is the first oral antiviral to demonstrate a significant benefit in reducing hospitalizations or deaths in mild cases of COVID-19 and may be an important weapon in the fight against SARS-CoV-2. However, its role in moderate-to-severe forms of COVID-19 remains unclear, and further studies are needed.

Pancreatic tumors are often associated with obstruction requiring intraoperative biliary drainage (IBD) prior to pancreatoduodenectomy (PD), exposing patients to infectious complications. The objectives of this study are to compare postoperative complications following PD with or without PBD and to analyze biliary bacteriology and antibiotic susceptibility. All patients who underwent PD between 2014 and 2019 were retrospectively evaluated, and postoperative outcomes were compared based on the use of PBD. Narrow-spectrum antibiotic prophylaxis was administered for 24 hours and then adjusted according to the bacteriological profile. Intraoperative bile cultures and antibiotic susceptibility tests were then collected. Among 164 patients with intraoperative bile cultures during PD (75 PBD+, 89 PBD-), a biliary infection was observed in 95% of cases in the PBD group and in 70% of cases in the non-PBD group (p < 0.001). Postoperative mortality and severe morbidity, including infectious complications, were identical between the two groups (5% and 15%). The median duration of antibiotic therapy was longer in the group with PBD compared with the group without (9 vs. 2 days, p = 0.009). Malignant indications and PBD were associated with bile contamination in univariate analysis, and PBD was significantly associated in multivariate analysis. The most common pathogens identified in bile cultures were: • Escherichia coli • Klebsiella spp. • Enterobacter spp. Overall susceptibility to commonly used antibiotics was reduced, including those recommended in local guidelines. PBD exposes nearly 100% of patients with PD to biliary infection and an increase in the duration of postoperative antibiotic therapy, without an increase in infectious complications in this study. Adjustments to antibiotic prophylaxis should be further studied based on local epidemiology to avoid antibiotic overuse.

Antiretroviral (ARV) therapy generally consists of three drugs, whereas two-drug therapy (2DR)— historically rarely used but recently validated as non- inferior to triple therapy — is emerging as a potential option and is currently recommended as an initial treatment in certain guidelines. The objective of this study is to define the indications and clinical efficacy of 2DR use in real-world settings through a national survey. This is a cross-sectional study of Israeli patients treated with 2DR through July, analyzing data demographic, immunological, virological, and biochemical/metabolic data. The following parameters were analyzed: At the start of ARV therapy At the time of switching to 2DR and then to S24 S48 , S96 ◦ S144 A total of 176 patients were included in the study. Compared to historical data, which cited ARV resistance and adverse effects as the main reasons for switching to a 2DR regimen, treatment simplification was the primary reason for switching to 2DR in 2019. The 2DR regimen with an INSTI and an IP was more commonly used in cases of resistance mutations, whereas the INSTI and INNTI combination was used for all other indications for 2DR. Switching to a 2DR regimen resulted in an average increase in CD4 count from 599/mm³ at treatment initiation to 680/mm³ at week 96 (p < 0.001) and an improvement in viral suppression from 73.9% at initiation to 87.0% at week 48 (p = 0.004). The 2DR regimen with IP and INSTI was less effective at controlling viral load compared to other 2DR strategies, but this combination was used for patients in more complex situations. The large-scale 2DR strategy in a national real-world study demonstrates that it is safe and effective. Most 2DR combinations, other than PI and NRTIs, were also effective in controlling plasma viral load and increasing CD4 counts.

Treatments for the eradication of Helicobacter pylori are widely used to • alleviate inflammation of the gastric mucosa, promote the healing of gastric ulcers, and reduce the incidence of gastric cancers. However, questions remain regarding the treatment for Helicobacter pylori eradication. First, various therapeutic strategies are used worldwide, and the standard of care varies by region and country. Second, bacterial resistance to Helicobacter pylori is on the rise due to the indiscriminate use of antibiotics. Finally, treatment for Helicobacter pylori may potentially disrupt the gut microbiota. Based on international guidelines and meta-analyses comparing the effects of different treatment strategies, a 10- to 14-day bismuth-free quadruple therapy and a 7-day triple therapy based on vonoprazan are currently the recommended strategies for treating Helicobacter pylori. These strategies have good eradication rates of around 90%, even in areas where resistant strains are highly prevalent. However, these treatments have drawbacks that can lead to antibiotic resistance and induce dysbiosis of the gut microbiota due to the empirical use of multiple antibiotics. The ideal approach to Helicobacter pylori eradication involves a simple, cost-effective strategy that promotes treatment adherence without negatively impacting the microbiota or contributing to the future development of antibiotic resistance. One possible option that aligns with this principle is a dual-drug regimen combining vonoprazan and amoxicillin. This is the simplest treatment that offers acceptable eradication rates, improves tolerability, and minimizes the risk of antibiotic resistance or alterations in the gut microbiota.

The objective of this study is to investigate the SARS-CoV-2 infection rate among healthcare workers at a hospital following the first wave of the COVID- 19 pandemic and to provide further insight into the relationship between infection, symptoms, and the source of infection. + Read this article HESITANCY TOWARD COVID VACCINATION AMONG AMERICANS WITH DISABILITIES Published on January 18, 2022 - By Philippe CASTIEL, Infectious Disease Specialist (Paris) Andrew Myers et al. “COVID-19 Vaccination Hesitancy Among Americans with Disabilities Aged 18–65: An Exploratory Analysis.” Disabil Health J. 2021 Oct 9;101223. doi: 10.1016/j.dhjo.2021.101223. Filter by category Vaccine (?addFilter=vacc) It is important for people with disabilities to be vaccinated against COVID-19 because, as a group, they are at increased risk of severe illness. While several vaccines are available to prevent COVID-19, a significant proportion of Americans report hesitancy toward vaccination, including among people with disabilities. The objective of this study is to explore the factors that may contribute to vaccine hesitancy in this specific population. To conduct this survey of 439 people with disabilities (aged 18 and older), Amazon Mechanical Turk was used to track their concerns regarding COVID-19, vaccines, and their reluctance to get vaccinated in order to better understand the factors influencing their hesitancy. Vaccine-related concerns were analyzed as composite variables representing different dimensions, such as adverse effects, the vaccines being too new, their development being too rapid, political influence, and efficacy. The results of the logistic regression indicate that vaccine-related concerns were the most significant predictors of hesitancy, even after accounting for demographic, economic, and geographic factors. Concerns about COVID-19 infection, testing, trust in expert opinions, education level, and being a Democrat were negatively associated with hesitancy. In conclusion, these results suggest that certain groups of people may be more hesitant about vaccination because they are more concerned about vaccine safety than about COVID-19 infection. Public health messages that focus on the risks of the vaccine relative to the risks of COVID-19 may be a strategy to reduce hesitancy and increase vaccination rates. Messages should also be tailored to specific disabilities (i.e., physical, mental, sensory), written in plain language, and disseminated in accessible formats.

Temsavir (TMR), the active ingredient in Fostemsavir (FTR), is a gp120-targeted attachment inhibitor, Ibalizumab (IBA), a CD4-targeted attachment inhibitor, and maraviroc (MVC), a CCR5 antagonist, are antiretrovirals (ARVs) that target the entry of the Human Immunodeficiency Virus (HIV) Although the mechanisms of inhibition for these three drugs are different, it is important to understand whether there is potential cross-resistance among them, given that they all involve interactions with gp120. In practice, plasma envelope derivatives from participants in the BRIGHTE study who experienced virologic failure as defined by the protocol (PDVF) and who were receiving FTR and either IBA or MVC were analyzed for their susceptibility to these molecules. In addition, MVC-resistant strains from the MOTIVATE trial were generated, and studies were conducted to determine whether there was a relationship between the susceptibilities to the different molecules. The cloned envelopes exhibited reduced susceptibility to TMR and resistance to the co-administered agents. At the PDVF, emerging or pre-existing amino acid substitutions were present at positions of interest in TMR. When the amino acid substitutions at these positions were reverted to the consensus sequence, full susceptibility to TMR was restored without altering resistance to the co-administered agents. Furthermore, only one strain exhibited reduced susceptibility to TMR and had an M426L polymorphism. After reversion to 426M, susceptibility to TMR was restored, but resistance to MVC persisted. These data confirm that reduced susceptibility to TMR and resistance to IBA or MVC are not linked and that there is no cross-resistance between these two molecules and FTR.

There is a growing body of evidence showing that people living with HIV (PLHIV) experience significant morbidity related to alcohol, recreational drugs, and smoking. The objective of this study was to report the associations between these factors and nonadherence to antiretroviral (ARV) therapy, lack of viral suppression, and, consequently, viral rebound. The ASTRA (Antiretroviral Sexual Transmission Risk and Attitudes ) study recruited PLHIV receiving care at 8 clinics in England between February 2011 and December 2012. The data included • a self-report of heavy drinking (estimated consumption > 20 units of alcohol per week) • alcohol dependence (CAGE score ≥ 2 with current alcohol use) • recreational drug use (including injection drug use in the past 3 months) • tobacco use status. Of 3,258 people living with HIV (PLHIV), 2,248 (69%) were men who have sex with men (MSM), 373 (11.4%) were heterosexual men, and 367 (19.6%) were women. A CAGE score of ≥ 2 was found in 568 patients (17.6%), 325 (10.1%) drank more than 20 units of alcohol per week, 1,011 (31.5%) were current smokers, 1,242 (38.1%) used recreational drugs, and 74 (2.3%) reported having ever used drugs intravenously. In each case, the prevalence was much higher among men than among women. Among 2,459 people on ARVs who had started treatment at least 6 months earlier, the following were associated with treatment nonadherence • a CAGE score of ≥ 2 • drinking > 20 units of alcohol per week • current smoking • recreational drug use (injectable or non-injectable) After adjusting for demographic and socioeconomic factors, the following were associated with an uncontrolled viral load: • a CAGE score ≥ 2 (aOR = 1.52; 95% CI: 1.09–2.13) • current smoking (aOR = 1.58; 95% CI: 1.10–2.17) • Injectable drug use (aOR = 2.11; 95% CI: 1.00–4.47) During follow-up of a subgroup of 592 patients with a controlled plasma viral load at the time of enrollment, the following were associated with virologic rebound: • a CAGE score ≥ 2 (aHR = 1.66, 95% CI: 1.03–2.74) • use of three or more non-injectable drugs (aHR = 1.82, 95% CI: 1.12–3.57) • injection drug use (aHR = 2.73, 95% CI: 1.08–6.89) Screening for and managing alcohol, tobacco, and drug use should be integrated into the follow-up care of HIV-infected patients in outpatient settings, and clinicians should be made aware of the potential for reduced control of plasma viral load.

The self-test for Human Immunodeficiency Virus (HIV) infection is an effective tool for improving diagnostic coverage among key populations, creating a link to care and access to antiretroviral (ARV) treatment. Its implementation requires a better understanding of patients’ perspectives on this new strategy. The objective of this study was to assess the perceptions of men who have sex with men (MSM) regarding saliva-based self-testing in São Paulo, Brazil, and to analyze the demographic characteristics and strategy preferences of individuals who registered to take a self-test. Prior to the implementation of self-testing as public policy in 2019, MSM living in São Paulo were recruited to take a self-test using a digital platform, and their sociodemographic profiles, testing experiences, and testing preferences were studied. The results were then compared based on the tests they had taken throughout their lives. A total of 6,477 MSM (median age: 28.7 years) were recruited between April 9 and December 31, 2018. Previous testing was reported by 78% of them. The main barriers to testing were: • The operating hours of healthcare centers (53%) • Concerns about sharing intimate and personal information with healthcare providers (34%) • Fear of stigma (21%) The following factors were associated with previous testing (p < 0.001) Being older Higher level of education • Illegal drug use • Self-identification as gay Most participants (67%) were unaware that self-tests were available before being enrolled in the study. Preference for self-tests over other screening methods was higher among those who had never been tested (71%) compared to those who had been tested previously (61%, p < 0.001) In conclusion, self-testing was identified as an effective tool for improving screening among MSM, particularly among those who had never been tested before. Characterizing the MSM most likely to use self-tests will help inform implementation and improve this screening method within the Brazilian healthcare system.