Tobacco smoking is highly prevalent in patients with psychosis, who also often experience negative affect (NA) and stress. The relationship between these factors remains unclear in this population. We aimed to investigate everyday life associations in 158 patients with psychosis, 136 unaffected siblings, and 117 controls from the Genetic Risk and Outcome of Psychosis (GROUP) study with Experience Sampling Method measurements.

Generalized linear mixed models were used to evaluate across time and within-subject associations. Across time analyses investigated the relationship between smoking status and overall NA and stress. Within-subject analyses assessed whether smoking between two measurements (t−1 and t0) was associated with changes in NA and stress at the measurement after smoking a cigarette (t0) and at the subsequent measurement (t+1).

Across assessments, smoking status was initially associated with NA in patients (B=0.26, p=0.036), but this association disappeared after controlling for psychotic symptoms and cannabis use. Within-subject analyses in smokers showed a decrease in NA in patients after smoking (t0: −0.23, p=0.016), which remained significant after correcting for confounders (t0: −0.20, p=0.015). Siblings showed a decrease in NA (t0: −0.22, p=0.009), also after controlling for confounders (t0: −0.14, p=0.018). No time-lagged effect was found at t+1 after correction for subsequent smoking.

Overall smoking behavior was not associated with NA in patients with psychosis. In the short term, smoking in the daily life context is associated with a reduction in NA in people vulnerable to psychosis, possibly due to alleviation of withdrawal symptoms, which may complicate smoking cessation.

The objective of this assessment was to determine the benefit of using a next-generation sequencing gene panel for the clinical management of patients with non-small cell lung cancer. The aim was to assess the diagnostic performance, identify the molecular alterations of interest, and define the role of this technology in the therapeutic care of these patients.

The method used for this assessment were based on: (i) a critical analysis of systematic reviews and meta-analyses and clinical practice guidelines identified by a systematic search based on PICO criteria (Population, Intervention, Comparator, Outcome); (ii) the identification of the level of evidence of the clinical actionability of molecular targets, as set out by the European Society for Medical Oncology scale, and targeted therapies included on the list of reimbursable drugs, or drugs that have compassionate use authorizations; and (iii) stakeholder consultations, as well as public health institutions.

Assessment of the evidence and data demonstrated that next-generation sequencing gene panel testing (EGFR, ALK, ROS1, BRAF, RET, and KRAS): (i) is highly concordant with the comparators (Kappa coefficient of 0.884); (ii) can detect additional targetable molecular alterations (marginal increase in the detection capacity of 2%); (iii) makes better use of the tumor tissue; and (iv) has clinical utility, demonstrated by the benefits provided by targeted therapies.

The next-generation sequencing gene panel (EGFR, ALK, ROS1, BRAF, RET, KRAS) was recommended for patients with locally advanced or metastatic non-small cell lung cancer, following diagnosis or in cases of progression, excluding any emergency situations. The composition of the gene panel may be subject to change, in accordance with favorable assessments of new gene alterations.

Social media listening studies (SMLS) analyze online dialogue from patients, caregivers, and clinicians to gain insights into the lived experience of disease including treatment efficacy and safety, and unmet needs. This analysis aims to understand whether SMLS is a feasible method for generating real-world data that can shape pivotal trial design or supplement trial data for health technology assessment (HTA).

A targeted literature search was conducted on PubMed to identify articles published in English that describe and report the findings of SMLS specifically investigating health conditions and diseases. No limits were placed on date of publication or geographical scope. Information was extracted from these papers and used to map concepts and themes covered in SMLS to key domains of HTA submission dossiers in the UK, France, and Germany, as well as the upcoming joint clinical assessments (JCA). This analysis was used to determine the extent to which SMLS can be used to generate payer-relevant data.

A total of 19 papers were included in this analysis. All studies used a retrospective approach, and the majority (84%) analyzed data from more than one market. The most common markets included were the UK (74%), USA (58%), France, and Germany (53%). Thirty-two percent included only patient conversations; 47 percent included conversations from patients, caregivers, family, and friends; and 21 percent included physicians. The most common themes covered were quality of life (89%), burden of disease or symptomology (79%), and treatment patterns (79%), which align closest to the dossier templates for HAS (French National Authority for Health) and the JCA.

All studies in this analysis included data that would be relevant for HTA submission, and the majority provided data that would speak to multiple payer concerns. While there are no published guidelines for leveraging SMLS for HTA, this analysis indicated that this methodology could potentially be used alongside trial data to highlight the patient experience within reimbursement submissions.

Patient and citizen perspectives are a cornerstone of health technology assessments (HTA), ensuring transparency and alignment with societal needs. This study examined the role of public opinion on the evaluation of button feeding tubes for recommendation in Brazil’s Unified Health System (SUS). The objective was to assess how public opinion shaped the final recommendation ensuring equitable access to this technology.

This was a qualitative review of the contributions received by the Brazilian Ministry of Health during the public consultation process about button feeding tubes in 2021. Data sources included contributions from various stakeholders, which were analyzed for their alignment with the preliminary recommendation and their impact on the final deliberation.

A total of 425 contributions from patients, caregivers, healthcare professionals, and industry representatives were analyzed. All of them supported the recommendation of button feeding tubes for pediatric patients in need of long-term enteral nutrition. Overall, they highlighted the advantages of the technology compared to long gastrostomy tubes such as reduced complications, cost effectiveness, ease of use, and improved quality of life. Their impact on patient dignity and social inclusion was also mentioned. Transparent communication throughout the process fostered trust and encouraged meaningful participation. Stakeholder input significantly influenced decision-making, particularly in prioritizing equitable access and designing implementation strategies.

Patient and citizen involvement proved crucial to the unanimous agreement to recommend the inclusion of button feeding tubes in the SUS. Their perspective on the technology’s potential to improve patient care and resource allocation was an important component to decision-making. This case highlighted the value of public engagement in fostering transparent and equitable HTA processes.

The development and implementation of the health technology assessment process by the Superintendence of Health and Labor Risks (SISALRIL) optimizes the inclusion of technologies in the Basic Health Plan, based on scientific evidence. This process (known as EVTESA) strengthens the social security system in the Dominican Republic by promoting informed decision-making, transparency, and spending efficiency; ensuring access to safe and effective technologies; and addressing historical challenges in the analysis and incorporation of technologies into the healthcare system.

SISALRIL, an autonomous entity created by Law 87-01, evaluates and updates the impact of the Basic Health Plan. Since 2020, it has been part of RedETSA, the Health Technology Assessment Network of the Americas, and leads EVTESA, which was institutionalized in 2022 through Resolution No. 0010-2022. EVTESA ensures evidence-based decisions for including technologies in the Dominican Family Health Insurance, promoting transparency, participation, and financial sustainability, while optimizing resources and improving healthcare quality. EVTESA represents a key methodological framework for evaluating and prioritizing healthcare technologies in the Dominican Republic, transforming the evaluation of technology inclusion and exclusion, and modernizing the historical approach to analyzing benefits for the population.

The implementation of EVTESA has established a structured framework with key documents, such as Resolution No. 0010-2022, which institutionalizes the process, and the methodological manuals for prioritizing and evaluating health technologies. The process includes the reception and verification of requests, evaluation using standardized methodologies, report approval after consensus with medical societies and patients, and decision-making by the National Health Insurance Council regarding the inclusion of technologies in the Dominican Social Security System. The prior analysis for the inclusion of coverage in the plan has strengthened coverage policies, resulting in the allocation of benefits to populations where the greatest clinical impact is achieved and healthcare spending is used more efficiently.

EVTESA marks a pivotal advancement in the Dominican Republic’s social security system by optimizing resources and ensuring access to effective health technologies. This evidence-based, equitable model enhances healthcare quality while promoting sustainability, transparency, and public trust. It also serves as a benchmark for other developing countries, demonstrating how systematic, transparent decision-making can strengthen health systems.

Geriatric assessment and management (GAM) is a guideline-recommended strategy for optimizing cancer management among older adults. In a recent cost-utility analysis of the Canadian 5C randomized controlled trial (RCT), GAM appeared cost effective only in selective patients. We assessed the cost-utility of GAM plus usual care (UC) versus UC alone in older adults with cancer using a decision model and best available evidence from four international RCTs: GAIN, GAP70, INTEGERATE, and 5C.

We conducted a model-based economic evaluation using pooled data from four international RCTs (GAIN, GAP70, INTEGERATE, and 5C), supplemented by additional evidence from the literature. Deterministic and probabilistic analyses were performed from the healthcare payer perspective, applying a six-month time horizon. The base case and main analyses used Canadian cost data. Sensitivity analyses included per-trial scenario analyses, one-year time horizon, and the use of USA costs. We reported healthcare costs per quality-adjusted life year (QALY) and the incremental net monetary benefit (INMB) using a CAD50,000(USD36,277) per QALY threshold.

The base case analysis using Canadian costs indicated that GAM was cost effective with an INMB of CAD1,117 (USD819) (95% credibility interval [CrI]: −CAD2,450 [−USD1,796], CAD5,035 [USD3,692]) and 70.7 percent probability of GAM being cost effective at a cost-effectiveness threshold of CAD50,000 (USD36,666) per QALY. Trial-specific results varied, with the GAP70 and INTEGERATE trials yielding positive INMB values (CAD2,635 [USD1932] and CAD2,886 [USD2,116], respectively), while 5C and GAIN resulted in negative INMB values (−CAD642 [−USD471] and −CAD268 [−USD196], respectively). Sensitivity analyses revealed that chemotherapy costs were the main driver of costs in both GAM and UC strategies.

Evidence showed that GAM is generally cost effective. However, GAM’s cost effectiveness varied across trial scenarios, driven primarily by differences in chemotherapy costs. Future research should focus on identifying key GAM components that most effectively reduce severe toxicity, hospitalizations, and chemotherapy-related costs to optimize overall cost effectiveness.

Although randomized controlled trials (RCTs) are the gold standard for evaluating health interventions, their methodology is challenging for arthroplasties. An international network of arthroplasty registries (AR) provides real-world data to generate evidence. However, the extent to which AR data contribute to scientific evidence remains unclear. This scoping review aimed to analyze the use of AR data in scientific publications.

All methodological stages of a scoping review were conducted in accordance with the Joanna Briggs Institute manual. The database search utilized official Medical Subject Heading and Health Science Descriptors terms, retrieving 25,846 studies. Study selection was performed in two stages by pairs of reviewers to ensure accuracy and reliability. The report followed the PRISMA Extension for Scoping Reviews. The analysis of the results was carried out using descriptive categories to classify and interpret the data comprehensively. No funding was provided for this study.

After selection, 140 studies were included. Studies on national AR were most prevalent in Australia and the UK, followed by studies on institutional and regional AR in the USA. Retrospective cohort designs dominated, involving large and heterogeneous populations. Total and unicompartmental arthroplasties were the primary subjects, with surgical revision being the most reported outcome. Authors identified limitations related to AR data application and observational study methodologies, impacting evidence reliability.

When properly implemented, AR are crucial data repositories that enable the generation of scientific evidence on arthroplasty technologies, predictive failure models, and post-sale prosthesis monitoring. This demands institutional efforts, collaborations, and researcher training for the proper use of observational studies, alongside paradigm shifts in confidence toward the evidence produced to support decision-making.

To design healthcare system strategies to inform policy decisions in prevention and early diagnosis of melanoma in children, adolescents, and young adults (CAYA) in Europe, a patient perspective is needed. The MELCAYA project addresses this issue, since this disease lacks preventive and diagnostic strategies. A focus session was conducted to identify challenges and potential improvements in current policies on rare cancers.

The focus session involved 15 participants, including patients, caregivers, patient advocates, and healthcare professionals from seven European countries. This session explored, through open discussions, challenges in melanoma prevention and early diagnosis as well as the role of patient advocates in policy development and implementation. Furthermore, a group dynamic was carried out to collect patients’ insights on 20 policy strategies from National Cancer Control Plans (NCCP), which were categorized into three areas: (i) early diagnosis and symptom awareness; (ii) health promotion and ultraviolet radiation prevention; and (iii) precision medicine and genetic counseling. Participants provided insights by identifying lacking policies and proposing actions for their implementation.

Key challenges in melanoma prevention and early diagnosis include: (i) low awareness and education among the general population and a misconception about its severity; (ii) fragmented care in the patient journey from diagnosis to treatment; (iii) ineffective communication with younger generations; and (iv) difficulties on how to navigate through the healthcare systems. Participants proposed 18 additional potential strategies to the NCCP and 22 actions for policy integration into healthcare systems. The current ad hoc approach fails to fully leverage contributions from advocates and healthcare professionals, often resulting in policies misaligned with clinical realities and patient needs.

This focus session provided patient ideas for policy initiatives, identified gaps in current policies from the NCPP, and emphasized the need for improved awareness, education, and communication strategies. Patient involvement in policy development, in a more structured way, is crucial for creating effective strategies, and its integration into healthcare systems could enhance melanoma prevention and early diagnosis in CAYA populations.

Spina bifida (myelomeningocele [MMC]) is the most common congenital anomaly with permanent disability. Traditional treatment consists of repairing the defect itself and correcting hydrocephalus (via shunt surgery), when present, within the first 48 hours after birth. Since 2011, fetal surgery to correct MMC has become an impactful treatment alternative, with better short-term results, both neurological and cognitive. However, cost remains a limiting factor for guidelines and health policy changes.

Fetal surgery (the alternative) was compared with neonatal surgery (the comparator) in a cost-utility analysis. The perspective of the study was from supplementary health, with direct cost data extracted from the public database of the National Supplementary Health Agency (Agência Nacional de Saúde Suplementar). The time horizon considered was 10 years, with a discount rate of five percent. The effectiveness measure was quality-adjusted life years (QALYs). Eligibility, utility, and outcome data were obtained from medical literature. The model used was Markov, with coupled decision tree. Subsequently, probabilistic and deterministic sensitivity analyses were carried out, and the cost-effectiveness acceptability curve (CEAC) was calculated.

The results indicated that the incremental cost-effectiveness ratio (ICER) of fetal surgery for MMC was dominant, with savings of BRL162,956 (USD26,972.80) per QALY gained. Probabilistic sensitivity analysis showed uncertainty, with 87.3 percent of points agreeing with base case results, but with some dispersion. CEAC showed that fetal surgery is more likely to be cost effective, regardless of the willingness-to-pay threshold. Through deterministic univariate sensitivity analysis, the variation in the cost of the shunt and complications due to prematurity by ±20 percent presented the greatest variations in the ICER, showing the possibility of an increase in cost.

This study demonstrated that prenatal repair generated cost savings, being cost effective, with an ICER of minus BRL162,956 (USD26,972.80) per QALY gained. This is the first study conducted at national level comparing fetal and neonatal myelomeningocele surgery. Although this new approach has been associated with higher costs, these additional costs translate into better long-term results, which could justify changes in health policies.

Integrating large language models (LLMs) into horizon scanning workflows requires understanding of baseline features, like the ability to extract data and handle noisy data, and contextual understanding to inform considerations for LLM use. We evaluated 25 LLMs to assess their applicability for horizon scanning methods in general and to inform the design and integration strategy of our unit’s advanced horizon scanning system.

We developed a comprehensive framework detailing 32 features across 10 categories for 25 LLMs. To build this framework, we used ChatGPT-4 to generate a preliminary list of categories, features, and LLMs relevant to HS. We supplemented this with parameters from the 2024 LeewayHertz assessment and finalized it through team consensus. Next, we employed a human-in-the-loop approach utilizing a recursive prover-verifier-chain: Microsoft Copilot>Claude 3.5>ChatGPT-4. Each LLM was assessed for variations in baseline features impacting their applicability in horizon scanning methods and potential integration into our horizon scanning system.

We identified six variable features (19%) across five categories. Nineteen of the LLMs support on-premises or self-hosted deployment. Regarding integration flexibility, only seven LLMs were open source and four lacked strong vendor support. Eighteen models offered a usage-based pricing system, allowing budget tailoring. Five LLMs excelled in handling noisy data, beneficial for horizon scanning methods dealing with diverse information sources. Seventeen models had multimodal capabilities.

Variations in key features among the 25 candidate LLMs affected their suitability for integration into horizon scanning workflows. Units must consider the trade-offs between deployment options, open-source availability, vendor support, pricing models, data handling capabilities, and multimodal features. This extensive framework supports assessment and selection of appropriate LLMs for horizon scanning workflows by filtering models according to these key features.

Differentiated thyroid cancer (DTC) treatment involves thyroidectomy and radioiodine ablation. Some patients have contraindications to induced endogenous hypothyroidism or cannot produce endogenous thyroid-stimulating hormone (TSH), preventing ablation unless recombinant TSH is used. This study aimed to evaluate the cost effectiveness of recombinant TSH followed by ablation in patients with DTC from the Brazilian Unified Health System perspective.

An economic evaluation was conducted to estimate the incremental cost-effectiveness ratio of radioiodine ablation (with prior recombinant TSH), compared with the absence of these procedures in patients who, after thyroidectomy, are unable to induce endogenous hypothyroidism. A Markov model was built with three health states: no recurrence, recurrence, and death. The outcomes evaluated were quality-adjusted life years (QALYs) and life years (LYs) gained. Direct medical costs were included over a 30-year time horizon, with a five percent discount rate applied to both costs and outcomes. A deterministic and probabilistic sensitivity analysis was also performed.

In general, the combination of recombinant TSH with radioiodine ablation proved to be dominant compared with not performing ablation, resulting in lower costs (BRL25,062 versus BRL26,941 [USD10,271 versus USD11,041]) and better clinical outcomes (QALYs 9.69 versus 9.55 and LYs 10.82 versus 10.57). This result was mainly due to a statistically significant difference in recurrence rates. In the probabilistic sensitivity analysis, most simulations showed greater clinical benefit with recombinant TSH and ablation than no ablation. Additionally, the deterministic analysis indicated that the correction factor applied to costs and recurrence risk were the most impactful parameters in the economic model.

The combination of recombinant TSH with radioiodine ablation was considered dominant in terms of QALYs and LYs gained, compared with no ablation, meaning the evaluated technology resulted in greater clinical benefit and lower cost.

The Epidemiology and Health Services: Journal of the Brazilian National Health System (RESS; Epidemiologia e Serviços de Saúde: revista do SUS) is a journal edited by the Brazilian Ministry of Health focused on disseminating scientific evidence relevant to the Brazilian Unified Health System. We aimed to assess the patterns of publication relevant to health technology assessment (HTA) and appraise the journal’s contribution to advancing knowledge and decision-making in the field.

We performed a cluster analysis of RESS publications from 2016 to 2024. Abstracts were imported from PubMed to EndNote and exported to Excel. Text preprocessing (tokenization, removal of punctuation, numbers, stop words, and stemming) was performed. Abstracts with terms related to diseases and technologies were regarded as HTA relevant. Corpuses were converted into term frequency–inverse document frequency, and dimensionality was reduced using principal component analysis. K-means clustering with silhouette coefficient for consistency were calculated. Thematic groups were analyzed based on frequent terms, document distribution, and intra-cluster similarity and compared to HTA Core Model®. Python 3.13 was used for analyses.

From 674 abstracts, 409 were deemed relevant for HTA. Six clusters were identified: risk factors (22.2% of abstracts; cohesion 95.5%), health services (33.5%; cohesion 0.8%), infections and clinical services (18.8%; cohesion 86.4%), mortality trends (14.2%; cohesion 95.6%), causes of death (8.8%; cohesion 86.9%), and congenital syphilis (2.4%; cohesion 94.2%). The silhouette coefficient was 0.4, indicating moderate clustering quality. Most clusters displayed high internal cohesion, except for health services, and were related to HTA domains of current use, safety, organization, and patient and social. No clusterization of technical, clinical effectiveness, cost and economic, ethical analysis, or legal domains was observed.

Main patterns of HTA relevant research were identified, with thematic clusters such as risk factors, mortality, health services, and infections. Other HTA relevant domains—like economic evaluations and patient-reported outcomes—were not detected in the clusters, suggesting a gap in RESS focus. To improve its relevance for the Brazilian HTA field, RESS should prioritize less represented HTA domains.

Cutaneous leishmaniasis (CL) is a neglected infectious disease with a known negative impact on health-related quality of life (HRQoL). However, no studies were found that quantitatively defined the health utility of CL. Our aim was to evaluate the impact of CL on HRQoL in patients attending a Brazilian reference center using the EQ-5D-3L visual analogue scale questionnaire to generate utility measures for CL.

This cross-sectional study included patients with CL from a referral center for the disease in Minas Gerais, Brazil between 2020 and 2023. Patients were interviewed during active disease and retrospectively before the onset of disease symptoms. Each patient’s health status was assessed using the EQ-5D-3L questionnaire. The losses in HRQoL were estimated by comparing the proportion of responses before CL onset with those during its active phase. Socioeconomic data were collected using a standardized questionnaire, and sociodemographic and clinical data were collected directly from the medical records. This study was approved by the Fiocruz Minas ethics committee.

A total of 143 patients with a mean age of 52 years (standard deviation 17) were included, 73 percent of whom were male. The mean utility score before the onset of CL symptoms was 0.858. A comparison of the responses related to health status before and after the illness revealed significant losses (p<0.05) in all dimensions of the EQ-5D, especially those related to pain, malaise, and usual activities, which were reduced to 50 percent and 27 percent, respectively. CL also affected the median visual analogue scale score and utility scores, which were 87 and 70 and 0.858 and 0.716, respectively.

These results confirmed the negative impact of CL on all dimensions assessed by the EQ-5D-3L visual analogue scale questionnaire, revealing another mechanism perpetuating the cycle of suffering and poverty surrounding neglected tropical diseases. These findings are essential for conducting future cost-utility studies, enabling comparisons of different treatments for this disease.

Implementation of the Health Technology Assessment (HTA) Regulation (HTAR) marks a shift in the assessment of high-risk medical devices (MDs) and in vitro diagnostics (IVDs) across the European Union (EU) and European Economic Area (EEA). Understanding current decision-making pathways for reimbursement of these technologies is crucial to inform HTAR integration within national frameworks. This review aimed to understand how comparative safety and effectiveness evidence is used in reimbursement decisions.

A scoping review was conducted in accordance with a registered protocol (osf.io/65bdk). Relevant documents were identified through searches of websites of HTA bodies and national health authorities across the EU, EEA, and UK. Relevant publications were identified from key databases (MEDLINE Complete, Embase, and the Cochrane Library) and supplemented by a comprehensive gray literature search. Data were extracted and checked by a second reviewer. National health officials further validated the extracted data.

The searches of official websites resulted in the retrieval of 369 relevant records. Database and gray literature searches resulted in the retrieval of 953 records, with 134 of these being included after full-text screening. The results revealed diverse reimbursement pathways and HTA processes across the EU, EEA, and UK for high-risk devices. Findings highlighted the variability in reimbursement processes. Some countries rely on centralized decision-making bodies, while others rely on regional or hospital-specific approaches. The findings also emphasized the limited integration of comparative safety and effectiveness data in the reimbursement frameworks of some countries and underscored the complexity of reimbursement processes across the European region.

This review identified key variations in reimbursement pathways for high-risk MDs and IVDs across the EU, EEA, and UK. The review of the European reimbursement decision-making landscape and the role of HTA underscores the importance of sharing experiences to facilitate the efficient use of HTAR-generated evidence in decision-making and to support unified patient access to safe and effective technologies.

The HI-PRIX European project aims to accelerate access to high value, affordable health innovations. This Delphi exercise aimed to build a consensus on new payment schemes that could facilitate the adoption or uptake of innovative medical devices, including digital health technologies, in an integrated care (IC) context.

A two-round Delphi exercise was performed, which included 29 statements distributed into four sections: (i) principles for innovation to qualify for a new payment scheme; (ii) payment schemes to support the adoption of innovative technologies by healthcare providers in an IC context; (iii) additional payment schemes for digital health technologies; and (iv) targeted funding sources. The Delphi was sent to 180 thematic-knowledgeable professionals. A six-point Likert scale was used to quantify agreement and consensus rules were established. Round two focused only on statements with moderate consensus.

Round one received 92 responses, with around 65 percent of the statements achieving moderate consensus, 28 percent high consensus, and seven percent low consensus. High consensus statements emphasized the importance of incorporating health technology assessment processes to inform pricing negotiations, establishing clear criteria for qualifying innovations into an innovative payment scheme, and incorporating performance-based payments to incentivize their adoption. The findings also highlighted the need to align payment schemes with broader healthcare objectives, such as improving patient pathways and ensuring equitable access, while addressing implementation barriers. Participants stressed the importance of tailoring payment schemes to specific healthcare contexts and ensuring financial sustainability.

The Delphi exercise highlighted both the need and the feasibility of implementing new payment schemes to support the adoption of innovative technologies, specifically in IC contexts. Combining different payment schemes is advisable to leverage the benefits of innovative technologies, while minimizing potential perverse incentives and ensuring alignment with broader healthcare objectives.

Most treatment regimens for people living with HIV (PLHIV) require the intake of multiple daily pills, which can pose challenges to adherence. As an alternative, long-acting (LA) dual regimens have gained attention for their potential to simplify treatment. Given the importance of evaluating the long-term effects of LA regimens, this study aimed to synthesize evidence on their effectiveness and safety.

A systematic review was performed following the Cochrane Collaboration recommendations and the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines, with searches in PubMed, Scopus, and Web of Science (July 2024) (PROSPERO-CRD42024570754). Longitudinal studies evaluating any dual-therapy antiretroviral regimen with LA agents (islatravir, cabotegravir, lenacapavir, rilpivirine, albuvirtide) for PLHIV were included. For each outcome of interest, data were pooled using bivariate meta-analysis (discontinuations due to adverse events) and network meta-analysis (NMA) (virologic failure [VF]), with results presented as risk ratios (RR) with 95 percent credibility intervals (CrIs); heterogeneity was assessed using the I-squared statistic. The surface under the cumulative rating curve analysis (SUCRA) was also conducted for the NMA.

Thirty-two studies (2016 to 2024) evaluating 11 treatments were included. Four cohorts (n=2,570) were assessed in the NMA of VF, where the rilpivirine/dolutegravir (RPV/DTG) regimen was superior to non-LA regimens dolutegravir/lamivudine (RR −1.60, 95% CrI: −4.08, 0.91) and dolutegravir/doravirine (RR −0.42, 95% CrI: −1.68, 0.68), with SUCRA probabilities of 9.6 percent, 31 percent, and 59.5 percent, respectively. The triplet regimens dolutegravir plus tenofovir/emtricitabine and dolutegravir plus abacavir/lamivudine had the highest probabilities of leading to CD4+ count increases at six to 24 months (65.6 to 85.7% and 65.8 to 84.4%, respectively), followed by RPV/DTG (59 to 60%) and dolutegravir/lamivudine (46 to 53%). However, RPV/DTG regimens were considered safer than dolutegravir/lamivudine (RR 0.53, 95% CrI: 0.32, 0.89) regarding discontinuation due to adverse events.

This updated synthetized evidence suggested that the RPV/DTG regimen is a promising alternative for simplifying the treatment of PLHIV, demonstrating comparable effectiveness to the dolutegravir/lamivudine and dolutegravir/doravirine regimens, while offering better tolerability. However, considerations of drug accessibility and cost must be carefully weighed in the decision-making process in different settings.