Indirect Treatment Comparisons of Lenacapavir Plus Optimized Background Regimen Versus Other Treatments for Multidrug-Resistant Human Immunodeficiency Virus.

BACKGROUND/AIMS: Heavily treatment-experienced (HTE) people with human immunodeficiency virus (HIV) (PWH) may not achieve virologic suppression (VS) with combination antiretroviral therapy due to multidrug resistance (MDR), intolerance, and safety concerns. These PWH often receive highly individualized treatment regimens, but these regimens may not enable PWH to achieve VS, thereby halting disease progression. Novel medications are required for treating individuals with MDR HIV. Lenacapavir (LEN), a first-in-class HIV capsid inhibitor, is under investigation for the treatment of HTE individuals with MDR HIV in the phase 2/3 CAPELLA study. This study aimed to compare LEN plus optimized background regimen (OBR) with fostemsavir (FTR) + OBR, ibalizumab (IBA) + OBR, and OBR alone in terms of VS, CD4 cell count change from baseline, immunologic recovery, and discontinuation due to adverse events, using indirect treatment comparisons. METHODS: A systematic review identified clinical evidence on HIV-1 treatments in HTE PWH. A feasibility assessment evaluated the identified studies for indirect treatment comparison analyses based on population characteristics, interventions, comparators, and outcomes of interest. Unanchored simulated treatment comparisons of LEN + OBR versus comparators were conducted. RESULTS: LEN + OBR had 6.57 times higher odds of VS at weeks 24 to 28 than FTR + OBR (95% confidence interval [CI] 1.34-32.28), 8.93 times higher odds of VS than IBA + OBR (95% CI 2.07-38.46), and 12.74 times higher odds of VS than OBR alone (95% CI 1.70-95.37). Change from baseline in CD4 cell count was similar across LEN + OBR, FTR + OBR, and IBA + OBR. CONCLUSION: LEN + OBR has statistically significantly greater odds of VS at weeks 24 to 28 than its comparators and represents a novel treatment for people with MDR HIV.

Interventions to improve obstetric emergency referral decision making, communication and feedback between health facilities in sub-Saharan Africa: A systematic review.

OBJECTIVE: The objective of the study was to review the evidence on interventions to improve obstetric emergency referral decision making, communication and feedback between health facilities in sub-Saharan Africa (SSA). METHODS: A systematic search of PubMed, Embase, Cochrane Register and CINAHL Plus was conducted to identify studies on obstetric emergency referral in SSA. Studies were included based on pre-defined eligibility criteria. Details of reported referral interventions were extracted and categorised. The Joanna Biggs Institute Critical Appraisal checklists were used for quality assessment of included studies. A formal narrative synthesis approach was used to summarise findings guided by the WHO's referral system flow. RESULTS: A total of 14 studies were included, with seven deemed high quality. Overall, 7 studies reported referral decision-making interventions including training programmes for health facility and community health workers, use of a triage checklist and focused obstetric ultrasound, which resulted in improved knowledge and practice of recognising danger signs for referral. 9 studies reported on referral communication using mobile phones and referral letters/notes, resulting in increased communication between facilities despite telecommunication network failures. Referral decision making and communication interventions achieved a perceived reduction in maternal mortality. 2 studies focused on referral feedback, which improved collaboration between health facilities. CONCLUSION: There is limited evidence on how well referral interventions work in sub-Saharan Africa, and limited consensus regarding the framework underpinning the expected change. This review has led to the proposition of a logic model that can serve as the base for future evaluations which robustly expose the (in)efficiency of referral interventions.

Burden of respiratory syncytial virus in adults in the United Kingdom: A systematic literature review and gap analysis.

Despite the growing recognition of a potentially significant respiratory syncytial virus (RSV) disease burden in adults, relevant evidence in the United Kingdom (UK) is limited. This systematic literature review (SLR) aimed to identify the disease burden of RSV in UK adults, including certain high-risk subgroups and existing evidence gaps. Published studies (2011 onwards) reporting epidemiological, economic and clinical burden outcomes in UK adults (≥15 years) with RSV were identified from indexed databases, including MEDLINE, Embase and the Cochrane library. High-risk groups included elderly (≥65 years), immunocompromised, co-morbid and co-infected patients. Outcomes included RSV incidence/prevalence, mortality, clinical presentation and direct/indirect resource use/costs. Twenty-eight publications on 28 unique studies were identified, mostly in general/respiratory indicator (n = 17), elderly (n = 10) and immunocompromised (n = 6) cohorts. Main outcomes reported in the general/respiratory indicator cohort were RSV infection incidence (seasonal/annual: 0.09-17.9%/6.6-15.1%), mortality (8,482 deaths/season) and direct resource use (including mean general practitioner [GP] episodes/season: 487,247). Seasonal/annual incidence was 14.6-26.5%/0.7-16% in high-risk cohorts. Attributed to RSV in the elderly were 7,915 deaths/season and 175,070 mean GP episodes/season. Only two studies reported on co-morbid cohorts. Clinical burden outcomes were only reported in general and immunocompromised patients, and no evidence was found in any cohort on indirect economic burden or RSV complications. Evidence captured suggests that RSV may have a substantial burden in UK adults. However, available data were limited and highly heterogenous, with further studies needed to characterise the burden of RSV in adults and to validate our findings.