Lenacapavir and the novel HIV-1 capsid inhibitors: an emerging therapy in the management of multidrug-resistant HIV-1 virus.

PURPOSE OF REVIEW: The aim of this study was to summarize current evidence regarding lenacapavir, a first in class HIV-1 capsid inhibitor, and its role as an emergent therapy for the treatment of HIV-1 infection. RECENT FINDINGS: HIV-1 capsid inhibitors (of which lenacapavir is the first in class) has been postulated to have activity against multidrug resistant HIV-1 viral isolates. Initial results from the phase 3 trial CAPELLA (combining oral and subcutaneous lenacapavir alongside failing drug therapies) suggest that there may be a role for these novel agents in a cohort of patients living with HIV-1 infection (PLWH) for whom multidrug resistance has previously been a barrier to effective therapy. Despite emergent lenacapavir resistance mutations detected in some study participants, virological suppression was still potentially attainable, offering some hope to PLWH with limited antiviral regimens available. Initial results from the CALIBRATE trial show promise for the role of lenacapavir-containing regimens in a treatment-naive cohort as well. SUMMARY: Lenacapavir may prove to be an adjunctive agent in the management of PLWH with significant HIV-1 drug resistance.

Oral versus Intravenous Antibiotics for Bone and Joint Infection.

BACKGROUND: The management of complex orthopedic infections usually includes a prolonged course of intravenous antibiotic agents. We investigated whether oral antibiotic therapy is noninferior to intravenous antibiotic therapy for this indication. METHODS: We enrolled adults who were being treated for bone or joint infection at 26 U.K. centers. Within 7 days after surgery (or, if the infection was being managed without surgery, within 7 days after the start of antibiotic treatment), participants were randomly assigned to receive either intravenous or oral antibiotics to complete the first 6 weeks of therapy. Follow-on oral antibiotics were permitted in both groups. The primary end point was definitive treatment failure within 1 year after randomization. In the analysis of the risk of the primary end point, the noninferiority margin was 7.5 percentage points. RESULTS: Among the 1054 participants (527 in each group), end-point data were available for 1015 (96.3%). Treatment failure occurred in 74 of 506 participants (14.6%) in the intravenous group and 67 of 509 participants (13.2%) in the oral group. Missing end-point data (39 participants, 3.7%) were imputed. The intention-to-treat analysis showed a difference in the risk of definitive treatment failure (oral group vs. intravenous group) of -1.4 percentage points (90% confidence interval [CI], -4.9 to 2.2; 95% CI, -5.6 to 2.9), indicating noninferiority. Complete-case, per-protocol, and sensitivity analyses supported this result. The between-group difference in the incidence of serious adverse events was not significant (146 of 527 participants [27.7%] in the intravenous group and 138 of 527 [26.2%] in the oral group; P=0.58). Catheter complications, analyzed as a secondary end point, were more common in the intravenous group (9.4% vs. 1.0%). CONCLUSIONS: Oral antibiotic therapy was noninferior to intravenous antibiotic therapy when used during the first 6 weeks for complex orthopedic infection, as assessed by treatment failure at 1 year. (Funded by the National Institute for Health Research; OVIVA Current Controlled Trials number, ISRCTN91566927 .).

A Survey of Orthopedic Surgical Management of Pressure Ulcer-Related Pelvic Osteomyelitis.

Pressure-ulcer related pelvic osteomyelitis is managed with little high-quality evidence. We undertook an international survey of orthopedic surgical management, covering diagnostic parameters, multidisciplinary input, and surgical approaches (indications, timing, wound closure, and adjunctive therapies). This identified areas of consensus and disagreement, representing a starting point for future discussion and research.

The index case of SARS-CoV-2 in Scotland.

Since its identification in December 2019, SARS-CoV-2 has infected 125,048 persons globally with cases identified in 118 countries across all continents. We report on the Scottish index case of SARS-CoV-2 infection, the virus causing COVID-19.

Outcomes, Microbiology and Antimicrobial Usage in Pressure Ulcer-Related Pelvic Osteomyelitis: Messages for Clinical Practice.

Introduction: Pressure ulcer-related pelvic osteomyelitis is a relatively under-studied entity in the field of bone infection. We sought to add to the limited evidence base for managing this challenging syndrome. Methods: Cases were identified retrospectively from a surgical database and hospital discharge codes at a U.K. tertiary centre (2009-2018). Risk factors associated with outcomes were analysed by logistic regression. Results: We identified 35 patients (mean age 57.4 years), 69% managed with a combined medical and surgical approach, with mean follow-up of 3.7 years from index admission. Treatment failure (requiring further surgery or intravenous antimicrobials) occurred in 71% and eventual ulcer healing in 36%. One-year mortality was 23%. Lack of formal care support on discharge, post-traumatic (asensate) neurological deficit and index CRP (>184mg/L) were associated with treatment failure (p=0.001). Age (>59.5 years), lack of attempted soft tissue coverage, haemoglobin (<111g/L) and albumin (<25g/L) were associated with non-healing ulcers (p=0.003). Superficial wound swabs had low sensitivity and specificity compared to deep bone microbiology. Infection (based on deep bone microbiology from 46 infection episodes) was usually polymicrobial (87%), commonly involving S. aureus, Enterococci, GNB and anaerobes. Antimicrobial duration ranged from 0-103 days (mean 54) and was not associated with subsequent treatment failure. Conclusions: Attempted soft tissue coverage after surgical debridement, ensuring appropriate support for personal care after discharge and nutritional optimisation could improve outcomes. Superficial wound swabs are uninformative and deep bone sampling should be pursued. Long antimicrobial courses do not improve outcomes. Clinicians should engage patients in anticipatory care planning.