Research Appraisals
Evidence-based critical appraisals of the latest medical research, systematically evaluated using Oxford CEBM methodology.
Showing 18 appraisals
Journal of medical Internet research
Advancing Human-Centered AI in Clinical Decision Support: Sociocognitive Human-in-the-Loop Study in HIV Care
BACKGROUND: AI-powered clinical decision support systems (CDSS) have shown promise in improving prediction, monitoring, and treatment optimization across clinical domains, including HIV care. However, translating AI outputs derived from electronic health records into clinically meaningful, trustworthy, and actionable decision support remains challenging, underscoring the need for more human-centered and socioecologically grounded CDSS design. OBJECTIVE: This study aimed to explore how we can effectively translate the outputs of machine learning models based on HIV electronic health records into a real AI-powered CDSS for HIV care. Using the human-in-the-loop method, we engaged a set of stakeholders, including HIV physicians, nurse practitioners, infectious disease pharmacists, social workers, and case managers. Stakeholders interacted with an AI-powered CDSS prototype to identify barriers and challenges to adoption, as well as to inform a more holistic and context-aware AI-powered CDSS design. METHODS: We conducted a field study at Prisma Health in South Carolina that included pre- and postsurveys, interactive usability testing sessions, think-alouds, and in-depth interviews with 16 clinicians providing HIV care between March and September 2025. We analyzed survey responses using descriptive statistics, and then transcribed and analyzed think-aloud and interview data using an etic and emic approach. RESULTS: Clinicians identified multiple challenges and design considerations for AI-powered HIV CDSS, demonstrating that clinician-AI interaction is inherently sociotechnical and embedded across multiple socioecological levels. While clinicians relied on familiar clinical indicators as cognitive anchors for interpreting AI predictions, they emphasized that social determinants of health were central to their own risk assessment and clinical decision-making. Additionally, clinicians' trust in AI is conditional and develops over time, with explainability and actionability emerging as critical factors for translating predictions into meaningful clinical interventions. CONCLUSIONS: Findings highlight the need to move beyond technically accurate predictions toward AI-powered CDSS designs that align with clinicians' cognitive practices and socioecological realities of HIV care. By extending a sociocognitive framework through empirical grounding in HIV clinical practice, this study offers design insights for developing AI-powered CDSS that are trustworthy, context-aware, and capable of supporting actionable decision-making in HIV care settings and beyond.
2 Aug 2026
Read appraisal →Infectious diseases of poverty
Broadly neutralizing antibodies for HIV therapy in clinical trials: a systematic review
BACKGROUND: Lifelong daily antiretroviral therapy (ART) effectively suppresses human immunodeficiency virus type 1 (HIV-1) replication but does not eradicate the virus, underscoring the urgent need for long-acting antivirals and functional cure strategies. Broadly neutralizing antibodies (bNAbs) have emerged as a promising approach for achieving durable HIV-1 remission. In this systematic review, we summarize recent advances in the development of bNAbs for HIV-1 treatment. METHODS: We searched PubMed, Embase, and Web of Science for clinical trials published up to March 22, 2026. We included data evaluating intravenously administered bNAbs, with or without concomitant conventional ART, and comparing them with placebo, ART or no intervention. These data were used to evaluate the pharmacokinetics, antiviral efficacy, resistance profiles, immunologic effects, and safety of intravenously administered bNAbs. RESULTS: LS-modified bNAbs extended half-life by 2- to 5-fold relative to their parental counterparts (e.g., VRC01LS: 71 vs 15 days), although viremia reduced half-life by 20-40%. In viremic participants harboring bNAb-sensitive virus, monotherapy achieved viral load (VL) reductions of 0.93-1.8 log₁₀ copies/ml, with rebound occurring within approximately 4-8 weeks, whereas combinations regimens achieved declines of up to 2.04 log₁₀ copies/ml and delayed rebound to 15-33 weeks. No consistent reduction in total reservoir size was observed, although early intervention and baseline viral sensitivity appeared to limit reservoir expansion. Resistance emerged through epitope-proximal mutations, with cross-resistance observed mainly among antibodies targeting shared epitope classes. Overall, bNAbs were well tolerated, with rare discontinuations (0.4%) and low immunogenicity. CONCLUSIONS: LS-engineered bNAbs exhibit a longer half-life than their parental antibodies. Combination regimens achieve greater VL reductions and a longer delayed rebound compared with monotherapy, indicating that LS-modified multi-epitope bNAb cocktails are promising for long-acting HIV-1 remission. To become clinically competitive, larger resistance-guided trials are needed to extend dosing intervals, improve resistance mitigation, and define optimal integration with other long-acting therapies.
4 July 2026
Read appraisal →Scientific reports
Prevalence and Risk Factors for Cytomegalovirus Retinitis Among People Living with HIV in Sub-Saharan Africa in the Antiretroviral Therapy Era: A Systematic Review and Meta-Analysis
Cytomegalovirus retinitis has remained an alarming and potentially vision-threatening opportunistic disease in the population living with HIV, especially in cases of extreme immunosuppression. Although the introduction of antiretroviral therapy has led to a drastic decline in the number of cytomegalovirus retinitis cases reported in most parts of the world, the current epidemiology of cytomegalovirus retinitis in sub-Saharan Africa has seemed unusual in early reports, unexpectedly portraying low disease prevalence rates despite the high number of HIV cases in the concerned region. This systematic review and meta-analysis aimed to estimate the pooled prevalence of cytomegalovirus retinitis among people living with HIV in sub-Saharan Africa in the antiretroviral therapy era, and to identify associated risk factors. The search of databases included Medline using the search engine PubMed, Google Scholar, and the African Journals Online database named AJOL. For inclusion, studies must have included an eye examination to verify the presence of cytomegalovirus retinitis. The data was combined using the logit transformation model. Heterogeneity was tested using the I-squared test and the Cochran Q test. A total of ten studies involving 1,931 participants from nine sub-Saharan Africa countries were found eligible. The proportion of cytomegalovirus retinitis varied from 0.34% to 15.8%. Pooled prevalence was found to be 3% (95% CI: 1.6-5.4%) with low to moderate inter-study variation (I² = 17.8%). Substantial variation in the proportion was found in different sub-Saharan Africa regions; it was found to be less than 1% in West Africa, 3-4% in Southern Africa, 7% in East Africa and 6% in Central Africa. Across all studies, the strongest and most consistent risk factors for cytomegalovirus retinitis were profound immunosuppression, particularly CD4 < 50 cells/µL. Antiretroviral therapy-naïve status, poor adherence, and presence of advanced AIDS-defining illnesses were additional contextual risk markers. Cytomegalovirus retinitis is an under-recognized but important source of preventable blindness among people living with HIV. Prevalence in sub-Saharan Africa differed from that in Asian early antiretroviral therapy era cohorts but is relevant in settings where late HIV presentation occurs. Systematic retinal screening in people living with HIV with low CD4 counts < 50 cells/µL and expanded HIV care and treatment services are important to prevent blindness due to cytomegalovirus retinitis.
31 May 2026
Read appraisal →PloS one
Views, barriers, and facilitators of people living with human immunodeficiency virus and healthcare professionals regarding the use of a mobile health application to improve HIV self-care in Malaysia
AIM: The views, barriers, and facilitators of people living with HIV (PLWH) and healthcare professionals (HCPs), regarding the use of a mobile health application (m-HA) to improve HIV self-care were explored. SUBJECT AND METHODS: Seventeen PLWH, nine doctors and two nurses who owned a smartphone and understood English or Malay were recruited from the infectious disease clinic of a tertiary hospital in Malaysia. Semi-structured in-depth interviews were conducted face-to-face using a topic guide, audio-recorded and transcribed verbatim. Data was analysed using reflexive thematic analysis. Two researchers independently coded transcripts and met to resolve discrepancies and develop themes. Data collection continued until thematic saturation was achieved. RESULTS: Three themes emerged: (1) Perceived benefits and concerns regarding m-HA usage: participants perceived m-HA could improve knowledge, but expressed concerns regarding information overload. Participants viewed m-HA as a means to enhance access to hospital services like clinic visits, medication refills, communication with HCPs, and medical records documentation. However, concerns regarding misuse, data confidentiality and security remained. (2) Perceived motivators of m-HA: participants perceived that high utilitarian and hedonic motivators increase m-HA usage. (3) Perceived influences to use m-HA: participants believed PLWH would use m-HA if introduced by their peers or HCPs. CONCLUSION: These findings provided information for developing a patient-centred m-HA to improve HIV self-care in Malaysia.
24 May 2026
Read appraisal →Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Dolutegravir Reduces Human T-Cell Lymphotropic Virus Type 1 Proviral Load and Improves Neurological Outcomes in a Phase 2 Controlled Trial
BACKGROUND: No specific therapy is approved for human T-cell lymphotropic virus type 1 (HTLV-1) infection. We tested the effect of dolutegravir (DTG) on clinical outcomes and on HTLV-1 proviral load (PVL) in adults with HTLV-1 infection. METHODS: We conducted an open-label, randomized controlled phase 2 trial in Salvador, Brazil. Symptomatic adults with HTLV-1 infection were randomized 1:1 to DTG 50 mg once daily or vitamin C (VTC) 500 mg once daily for 48 weeks. We evaluated changes in gait performance (timed 10-meter walk test [T10MWT]). Key secondary endpoints included change in PVL and prespecified neurofunctional and urinary outcomes. Primary analyses emphasized intragroup and between-group comparisons; exploratory per-protocol analyses were performed for neurofunctional measures. Asymptomatic participants were included for PVL and immunological evaluations. RESULTS: Eighty-three participants (53 symptomatic) were randomized (DTG, n = 43; VTC, n = 40). At week 48, there was no between-group difference in T10MWT. However, DTG use significantly reduced PVL over 48 weeks compared with VTC (P < .001). Exploratory per-protocol analyses found significant improvements associated with DTG use in lower limb spasticity (P < .001), sensory function (light touch, P = .035; pinprick, P = .001), and median nocturia frequency (P = .012). Network analysis of cytokine expression showed a change in the DTG group from baseline to week 48, with loss of negative correlations and a more balanced pattern. DTG was well tolerated, with no unexpected safety signals. CONCLUSIONS: In this pilot randomized trial, DTG use was associated with significantly reduced PVL and improvement in neurofunctional and immunological characteristics of participants in exploratory analyses. These findings provide evidence supporting the use of integrase inhibitors for HTLV-1 infection. Clinical Trials Registration. Brazilian Clinical Trial Register (ReBEC), code RBR-5x7ccxp.
22 May 2026
Read appraisal →Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Effects of Semaglutide on Cognitive Function in People With HIV: A Randomized, Controlled Trial
BACKGROUND: People with human immunodeficiency virus (HIV, PWH) are at higher risk for visceral adiposity, enhanced inflammation, and cognitive decline than controls who do not have HIV. We previously demonstrated that PWH with lipohypertrophy had a decrease in weight, visceral adipose tissue, and several inflammatory markers after receiving semaglutide, a glucagon-like peptide-1 receptor agonist. Our aim was to investigate the effect of semaglutide on cognitive function in PWH and the possible mediation of this effect by changes in adiposity or inflammation. METHODS: In this randomized, double-blind, placebo-controlled phase 2b clinical trial, PWH on antiretroviral therapy were randomized 1:1 to receive 32 weeks of subcutaneous semaglutide or placebo. The primary outcome was the change in cognitive function at 32 weeks. Secondary measures included changes in body composition and inflammatory markers. Causal mediation analysis assessed semaglutide's direct and indirect effects on Cognivue scores through changes in adiposity and inflammation. RESULTS: 108 participants were included (54 per arm); 65% were non-White, 40% were female, and median age was 53 years. Compared with placebo, PWH on semaglutide significantly increased visuospatial, naming/language, and delayed recall scores at 32 weeks (P = .01, .05, and .04, respectively). After adjusting for sex and absolute CD4 count, only visuospatial score remained statistically significant (P = .05). Semaglutide's total natural direct effect maintained a positive effect on the visuospatial score while accounting for potential changes in high-sensitivity C-reactive protein and soluble CD163 levels (P = .04). CONCLUSIONS: Semaglutide may have a beneficial impact on visuospatial cognitive function in PWH through its effect on inflammation. Clinical Trials Registration . NCT04019197.
22 May 2026
Read appraisal →Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Pharmacokinetics of Dexamethasone in Tuberculous Meningitis
BACKGROUND: Dexamethasone is recommended as adjunctive therapy for tuberculous meningitis (TBM). Co-administration with rifampicin is expected to reduce dexamethasone exposure in TBM, an effect that may be more pronounced with the higher rifampicin doses currently being evaluated in clinical trials. METHODS: This pharmacokinetic study was nested in a randomized controlled trial comparing the safety of high-dose rifampicin (oral, 35 mg/kg; intravenous, 20 mg/kg) plus linezolid, with or without aspirin, versus standard-dose rifampicin (10 mg/kg) for adults with HIV-associated TBM. All participants received adjunctive oral dexamethasone every 12 hours starting at a dose of 0.4 mg/kg/day. Dexamethasone concentrations were measured on intensively sampled plasma on day 3 after study enrollment and analysed using nonlinear mixed-effects modeling. RESULTS: In total, 261 dexamethasone concentrations from 43 participants were available for model development. Eight (18%) participants were on efavirenz-based ART and five (11%) were on a lopinavir/ritonavir-based regimen. The median duration of rifampicin therapy at the time of pharmacokinetic sampling was 4 days (range: 0-7). Dexamethasone pharmacokinetics was best described by a one-compartment disposition model with first-order absorption and elimination. Typical oral clearance (CL/F) was 131 L/h, reduced to 11.5 L/h with concomitant lopinavir/ritonavir. High-dose rifampicin had no significant additional effect on dexamethasone pharmacokinetic parameters compared with the standard-dose. CONCLUSIONS: In adults with HIV-associated TBM, there was high dexamethasone clearance, likely related to a drug-drug interaction with rifampicin. High-dose rifampicin had no additional effect on dexamethasone exposure.
22 May 2026
Read appraisal →Journal of virology
Is the molecular microenvironment of the latent HIV reservoir predictable using deep learning approaches?
Although current antiretroviral therapy effectively suppresses viral replication in infected individuals, infections remain incurable. One of the main reasons for this is the uncertainty of the molecular microenvironment of the latent HIV reservoir. If this microenvironment can be precisely targeted, the effectiveness of current antiretroviral therapy can be leveraged. To better depict the potent microenvironments of the latent HIV reservoir, it is crucial to first understand the mechanisms that make some viruses transcriptionally active and others silent in the first place. It is currently feasible to predict gene activity from DNA sequence, coupled with epigenetics, using deep learning approaches. Substantial progress has been made in creating multidimensional data sets related to the HIV latent reservoir. The implementation of deep learning to mine potent attributes, enabling the characterization and prediction of the microenvironment of the latent HIV reservoir, is thus imperative. This minireview discusses potent features that can be integrated into deep learning methodologies to predict the likelihood of the potential microenvironment from different tiered levels of the latent HIV reservoir organization, and proposes the principal workflow to tackle this question using deep learning approaches.
20 May 2026
Read appraisal →Antiviral therapy
Factors associated with immunological non-response in HIV patients receiving antiretroviral therapy in Southeast Asia: A systematic review
ObjectiveThis systematic review summarizes factors associated with immunological non-response (INR) among people with HIV on antiretroviral therapy (ART) in Southeast Asia.MethodsWe conducted a systematic search of PubMed, ScienceDirect, DOAJ, and Lens.org for studies published between 2010 and 2025. Observational studies examining immunological outcomes following ART initiation and related factors were included. Study quality was assessed using the Newcastle-Ottawa Scale, and results were synthesized using a harvest plot.ResultTen eligible studies were included in the synthesis, comprising a total of 6,988 participants with substantial heterogeneity observed across studies. Factors associated with INR included age, sex, baseline CD4 cell count, HIV RNA levels, and co-infections. Among these factors, baseline CD4 cell count at the initiation of ART emerged as the most consistently associated determinant; lower baseline CD4 levels were linked to a higher risk of INR even with virological suppression.ConclusionThis review highlights baseline immunological status at ART initiation as a key predictor of immunological non-response in Southeast Asia. These findings underscore the critical importance of early HIV diagnosis and timely initiation of ART to prevent advanced immune damage and optimize immunological recovery.
12 May 2026
Read appraisal →Journal of medical Internet research
Rapid Deployment of Telemedicine in HIV Care: Mixed Methods Study of Providers' Attitudes and Perceptions
BACKGROUND: The COVID-19 pandemic prompted an abrupt transition to telemedicine for HIV care, necessitating the exploration of provider attitudes and experiences to understand its ongoing viability and impact. OBJECTIVE: This study aimed to assess providers' attitudes toward and experiences with telemedicine at HIV clinics in the Chicago area during the COVID-19 pandemic at 2 time points and at 2 clinical sites. METHODS: We conducted a convergent mixed methods study to evaluate and explore providers' attitudes toward and experiences with telemedicine at HIV clinics in the Chicago area during the COVID-19 pandemic, applying the RE-AIM (reach, effectiveness, adoption, implementation, and maintenance) framework and the updated Consolidated Framework for Implementation Research. This study assessed HIV providers via surveys at 2 time points, capturing responses on the acceptability, appropriateness, feasibility, and maintenance of telemedicine. Semistructured key informant interviews were conducted on a random selection of 10 participants to explore perceived experiences with telemedicine. RESULTS: Among emailed providers, 43 of 83 (51.8%) and 27 of 82 (32.9%) responded to survey 1 and survey 2, respectively. The first survey recorded telemedicine usage at 75%, which decreased to 58% by the second survey. Overall, the majority of respondents agreed with statements that assessed telemedicine as appropriate, acceptable, and feasible. There were overall few statistical differences in responses between sites, although more providers at the community site indicated at least some potential value in telemedicine when compared to providers at the university hospital (100% agree or strongly agree vs 82.3%; P=.04) in survey 1. In survey 1, providers with more than 10 years of experience were less likely to report telemedicine helped them see more patients (31.6% agree or strongly agree vs 70.6% for providers with ≤10 y of experience; P=.008). Fewer experienced providers felt they could talk about private issues with their patients during telemedicine (57.9% of more experienced vs 88.3% of less experienced providers; P=.03). Key informant interviews provided qualitative insights into telemedicine integration, revealing mixed sentiments; providers appreciated the flexibility and accessibility that telemedicine offered but preferred in-person visits for their thoroughness, especially for physical examinations and laboratory tests. Despite initial barriers such as technical challenges and patient preferences for in-person visits, telemedicine was deemed feasible for maintaining communication and care quality. Providers highlighted the need for better technological support and ongoing training to optimize telemedicine usage. CONCLUSIONS: Our study underscores telemedicine as a sustainable adjunct to traditional HIV care, emphasizing the importance of addressing technological and training barriers to enhance its efficacy.
3 May 2026
Read appraisal →Journal of Korean medical science
Association Between Changes in Socioeconomic Status Before and After Human Immunodeficiency Virus Infection Diagnosis and Mortality Rates in Korea
BACKGROUND: This study investigated changes in medical insurance status as a surrogate marker of socioeconomic status after human immunodeficiency virus (HIV) infection, and their association with mortality among people living with HIV in Korea. METHODS: This study included 13,112 individuals newly diagnosed with HIV between 2004 and 2018, identified from the claims data of the National Health Insurance System-National Health Information Database. Participants' medical insurance status was categorized into National Health Insurance (NHI) and medical aid (MA). Using the Cox proportional hazards model, the association between mortality and changes in medical insurance status before and after HIV infection diagnosis was assessed using hazard ratios (HRs) and confidence intervals (CIs). RESULTS: The insurance coverage rates before HIV diagnosis were 95.1% and 4.9% for NHI and MA recipients, respectively. After diagnosis, the insurance coverage rates were 13.4% and 86.6% for MA and NHI recipients, respectively, demonstrating a threefold increase in the proportion of MA recipients. The conversion rate from NHI to MA was highest in the 35-44 and 45-54-year age groups at HIV infection diagnosis (32.9% and 29.4%, respectively). Compared with NHI recipients, the HR was significantly higher among individuals that transitioned from NHI to MA (HR, 1.66; 95% CI, 1.39-1.97) and individuals that remained on MA (HR, 1.74; 95% CI, 1.40-2.18), suggesting a higher mortality rate in these groups. CONCLUSION: In Korea, where highly active antiretroviral therapy is essentially free of charge, a significant association was observed between a decline in medical insurance status following HIV diagnosis and increased mortality.
23 Apr 2026
Read appraisal →JMIR formative research
A Survey of Primary Care Clinician Experiences With Electronic Health Record-Based Clinical Decision Support to Improve HIV Pre-Exposure Prophylaxis Prescribing
A survey of primary care clinicians suggests that a clinical decision support tool to support sexual risk assessment and prescribing of HIV pre-exposure prophylaxis was appropriate and useful for identifying at-risk patients, but uptake was hindered by workflow and usability barriers, which underscores the importance of postimplementation clinician feedback to improve the use of clinical decision support tools.
17 Apr 2026
Read appraisal →Journal of medical Internet research
Digital Monitoring of Pre-Exposure Prophylaxis Users Through Electronic Patient-Reported Outcome Measures and Electronic Patient-Reported Experience Measures: Multicenter Prospective Study on Feasibility, Safety, and Predictive Modeling of Digital Engagement
BACKGROUND: Digital health tools integrating electronic patient-reported outcome and experience measures (ePROMs/ePREMs) enable longitudinal monitoring of health-related quality of life (HRQoL), psychological well-being, and treatment satisfaction in pre-exposure prophylaxis (PrEP) users. However, determinants of sustained engagement with digital follow-up platforms remain insufficiently characterized. OBJECTIVE: To describe the feasibility of the Naveta-Phemium digital platform for longitudinal monitoring of safety, HRQoL, and treatment satisfaction among PrEP users, and to develop and internally validate a machine learning framework to characterize and predict engagement with digital follow-up. METHODS: A prospective observational study was conducted using the Naveta digital follow-up platform. HIV-negative adults at high risk of HIV infection received tenofovir disoproxil fumarate (245 mg) plus emtricitabine (200 mg). Clinical safety, HRQoL, and satisfaction were assessed using laboratory parameters and validated ePROMs/ePREMs (Hospital Anxiety and Depression Scale, Patient-Reported Outcome Measurement Information System Profile-29, Treatment Satisfaction Questionnaire for Medication, and Person-Centered Coordinated Care Experience Questionnaire). Engagement was defined at the questionnaire level and analyzed using the ALGOPROMIA-Classification framework with repeated stratified cross-validation. Model explainability was assessed using permutation-based Shapley Additive Explanations. RESULTS: A total of 81 participants contributed repeated questionnaire-level observations (mean PrEP duration 689 d). PrEP was well tolerated, with no moderate or severe adverse events; mild transient symptoms were mainly gastrointestinal (31/45, 68.9%) and neurological (26/45, 57.8%). Renal function remained stable (creatinine: 0.86 [SD 0.13] mg/dL; estimated glomerular filtration rate: P=.498). Psychological well-being and HRQoL remained stable (Hospital Anxiety and Depression Scale<7; Patient-Reported Outcome Measurement Information System Profile-29 near population norms). Treatment satisfaction was consistently high (Treatment Satisfaction Questionnaire for Medication≈85-87), and satisfaction with the NAVETA telemedicine model remained stable (8/10). Engagement showed clear sociodemographic and behavioral gradients. Ensemble-based machine learning models achieved good discrimination in predicting engagement (area under the curve≈0.82) across ≈12,300 questionnaire-level observations. Random forest was retained for robustness and consistency. Shapley Additive Explanations analysis highlighted lifestyle-related variables as the most influential predictors, with heterogeneous individual-level effects. CONCLUSIONS: Naveta enabled feasible telemedicine-based PrEP follow-up with preserved HRQoL, high satisfaction, and stable safety. Combining longitudinal ePROMs/ePREMs with explainable machine learning allowed detailed characterization of digital engagement, supporting digitally supported PrEP care optimization and informing future comparative and cost-effectiveness studies.
15 Apr 2026
Read appraisal →PloS one
Virologic suppression among HIV-positive pregnant and lactating women receiving antiretroviral therapy in Africa: A systematic review and meta-analysis
BACKGROUND: The elimination of mother-to-child transmission of human immunodeficiency virus (HIV) is a key global public health priority. In Africa, virologic failure among people living with HIV continues to pose a significant public health challenge, affecting both individual well-being and community health. Maintaining viral load suppression is crucial to prevent vertical transmission of HIV and to minimize maternal morbidity and mortality. To stop the vertical transmission of HIV and lower the risk of maternal morbidity and mortality, it is important to achieve viral load suppression. Although many African countries have adopted the global 95-95-95 targets, comprehensive data on virologic suppression among pregnant and lactating mothers across the continent remains limited. The objective of this systematic review and meta-analysis was to determine the pooled estimate of virologic suppression and to examine the factors associated with it among HIV-positive pregnant and lactating women on antiretroviral therapy in Africa. METHODS: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The study protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD420251186121). We carried out a thorough systematic review by examining PubMed, ScienceDirect, Hinari, and Google Scholar for relevant studies. Data from the studies were retrieved using an Excel sheet and analyzed with STATA version 17. The Joanna Briggs Institute appraisal tool was used to evaluate the methodological quality of studies. A random-effects model with restricted maximum likelihood (REML) was applied to determine the pooled prevalence of virologic suppression (viral load threshold ≤1000 copies/ml) among pregnant and lactating mothers in Africa. A funnel plot and the Egger's test were used to investigate publication bias. Statistical heterogeneity was assessed using the I2 statistic and Cochrane's Q test. RESULTS: A total of 55 eligible studies, comprising 304,883 participants, were included in the quantitative meta-analysis. Accordingly, the overall prevalence of virologic suppression among HIV-positive pregnant and breastfeeding women in Africa was 80.86% (95% CI: 77.63%, 84.09%, I2 = 99.84%). In contrast, the pooled estimate for achieving an undetectable viral load was substantially lower, at 60.92% (95% CI: 52.46%, 69.39%; I2 = 99.91%). Virologic suppression was significantly associated with women's age (15-24 years) (AOR = 0.49; 95% CI: 0.32-0.77), disclosure of HIV status to a partner (AOR = 1.66; 95% CI: 1.31-2.11), first-line antiretroviral therapy regimen (AOR = 6.53; 95% CI: 1.93-22.06), and good antiretroviral drug adherence (AOR = 3.61; 95% CI: 1.18-11.02). In addition, other socio-demographic variables, higher educational level, being married/cohabitant, urban residency, healthcare utilization (time of ANC booking, time of ART initiation, duration of ART), fear of stigma, distance to health facility, shortage of health professionals, ART drug stock-out, and lack of HIV care commodities were significantly associated with virologic suppression among HIV-positive pregnant and lactating women in Africa. CONCLUSION: The pooled estimate of virologic suppression among HIV-positive pregnant and breastfeeding women in Africa was approximately 81%, below the global target of 95% virological suppression. This emphasizes the necessity of targeted strategies for younger HIV-positive women, disclosing HIV status, initiating first-line antiretroviral regimens, and promoting antiretroviral treatment adherence. Upgrading health care systems to enable regular viral load monitoring, as well as addressing socio-demographic and antiretroviral therapy-related variables, are vital steps towards attaining and sustaining VS in these groups of population, ultimately assisting in achieving elimination of MTCT of HIV.
14 Apr 2026
Read appraisal →Medicine
Comparative evaluation of human T lymphocytes in HIV patients treated with lamivudine + zidovudine combined with nevirapine versus efavirenz
This study aimed to explore the efficacy of lamivudine + zidovudine plus nevirapine and efavirenz in the treatment hf human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS). A total of 100 patients with HIV/AIDS admitted to our hospital from June 2021 to September 2024 were selected and randomly assigned into nevirapine and efavirenz groups (n = 50 per group). The nevirapine group was treated with lamidudine plus zidovudine combined with nevirapine, and the efavirenz group was treated with lamidudine plus zidovudine plus efavirenz. The primary outcomes measured were the changes of lymphocyte count and adverse effects after 3 months of treatment. There was no statistical difference in baseline information between the 2 groups. After treatment, CD3 + and CD4 + levels were higher in the nevirapine group than in the efavirenz group (P <.05, 95% CI: 45.2-98.7 for CD3 + and 32.8-76.4 for CD4+), and CD8 + levels were lower in the nevirapine group than in the efavirenz group (P <.05); the overall incidence of adverse effects in the nevavirapine group was significantly lower than that in the efavirenz group (P <.05). In HIV/AIDS patients, treatment with lamivudine + zidovudine combined with nevirapine resulted in significantly improved CD4 + T cell counts, enhanced immune function, and fewer adverse reactions compared to treatment with lamivudine + zidovudine plus efavirenz, suggesting superior clinical value of the nevirapine-containing regimen.
12 Apr 2026
Read appraisal →Vaccine
Adenovirus type 5 vector-based COVID-19 vaccine does not increase the likelihood of HIV infection
BACKGROUND: There is a concern about the potential increased risk of acquiring HIV infection after vaccination with adenovirus type 5 (Ad5) vector-based vaccines. We aimed to investigate whether Ad5-nCoV increases the risk of HIV infection. METHODS: Between September 2020 and March 2021, a Phase 3 clinical trial was executed to evaluate the efficacy of Ad5-nCoV. This trial, employing a double-blind, randomized, and placebo-controlled design, enrolled 44,247 participants from 66 clinical sites spanning Argentina, Chile, Mexico, Russia, and Pakistan. Participants were allocated randomly in a 1:1 ratio to receive either Ad5-nCoV or a placebo, and their HIV-negative status was assessed by self-report and confirmed by HIV testing on a baseline blood sample at the end of the study. Consequently, individuals initially administered a placebo received one dose of Ad5-nCoV, while those initially given Ad5-nCoV finally received two doses, with an interval of approximately 6-10 months between administrations. The trial design and primary outcomes have been previously reported. This analysis involves a comprehensive assessment of the associations between pre-existing Ad5 neutralizing antibodies, HIV prevalence and incidence before and after vaccination while accounting for demographic variables. RESULTS: A total of 43,780 participants who had valid HIV baseline testing results were included in this study. Prior to vaccination, there was no discernible difference in HIV prevalence between the placebo group (0·39% of 21,877 participants) and the Ad5-nCoV group (0·38% of 21,893 participants). This similarity persisted when the data were stratified by country, gender, age, and race. Paired analyses assessing HIV incidence were conducted on participants who tested negative for HIV before vaccination, with data collected over a 6-month period post-vaccination. The results revealed notable similarity in HIV incidence across all groups: 0·29% for Group A (Ad5-nCoV group), 0·21% for Group B (Placebo group), 0·27% for group A + D (Ad5-nCoV group and 1 × Placebo+1 × Ad5-nCoV group), 0·1% for Group C (2 × Ad5-nCoV group), and 0·25% for Group A + C + D (participants who received at least one dose of Ad5-nCoV). Testing approximately 100 randomly chosen participants in each country revealed a similar distribution of pre-existing Ad5 neutralizing antibodies (Nab), with the ratio above a titer of 200 ranged from 65·42% to 67·71%. Notably, the heightened presence of pre-existing Ad5 Nab did not result in an increased risk of HIV infection. CONCLUSION: The Ad5-nCoV did not increase the short-term risk of HIV infection in this large and diverse sample of the general population, regardless of the presence of pre-existing Ad5 Nab providing valuable insights into the safety of Ad5 vector-based vaccines. CLINICALTRIALS: gov, NCT04526990.
12 Apr 2026
Read appraisal →Journal of medicinal chemistry
Rational Design of Broad-Spectrum Non-Nucleoside Reverse Transcriptase Inhibitors via Pharmacophore-Oriented Generative Artificial Intelligence
Guided by the pharmacophore-oriented molecular generation platform PhoreGen, we employed rilpivirine (RPV) as a lead compound to generate 300 structurally diverse analogs that preserve key pharmacophoric features. Subsequent drug-likeness evaluation, molecular docking score, and synthetic feasibility led to the identification of compound No.102 (A19), which displayed potent inhibition activity against WT HIV-1 (EC50 = 3.15 nM) and low cytotoxicity (CC50 > 335 μM). Subsequent structure-activity relationship optimization identified A24, which demonstrated robust activity against clinically relevant drug-resistant HIV-1 mutants (EC50 = 2.07-28.8 nM). Notably, compared to RPV, A24 exhibited significantly reduced cytotoxicity (CC50 = 82.3 μM vs. 3.98 μM) and enhanced potency against the Y188L (EC50 = 28.8 nM vs. 79.4 nM) and F227L + V106A (EC50 = 19.0 nM vs. 81.6 nM) mutants. Pharmacokinetic evaluations revealed that A24 exhibited attenuated CYP enzyme inhibition (IC50 ≥ 1.88 μM), reduced hERG-related toxicity (IC50 = 2.633 μM), and improved metabolic stability (human t1/2 = 39.1 min). Collectively, these favorable properties position A24 as a promising NNRTI for further development.
10 Apr 2026
Read appraisal →Sexual health
Co-creation and evaluation of people-centered mobile health messages to promote PrEP adherence among GBMSM in China: a feasibility study
BACKGROUND: Co-creation has the potential to generate people-centered mobile health (mHealth) interventions to improve PrEP adherence. This study generated people-centered mHealth messages with Chinese gay, bisexual and other men who have sex with men (GBMSM) via a structured co-creation approach, and evaluated the messages quality, and assessed the feasibility of the co-creation approach. METHODS: A three-step co-creation framework was implemented with 19 GBMSM PrEP users and six HIV researchers between 2021 and 2023. Messages were assessed via 10-point scales, and the degree of usefulness by co-creators and 783 participants from a PrEP demonstration trial. Thematic analysis identified PrEP adherence barriers and participants' reflections from meeting notes and materials, with descriptive statistics summarizing evaluation results. RESULTS: Four levels of PrEP adherence barriers were identified (insufficient education, efficacy concerns, inadequate behavioral skills, PrEP stigma). Based on these barriers, 25 mHealth messages (19 posters, three videos, three text messages) were co-created, covering nine themes (e.g. missed dose coping, side-effect management). Seventeen high-quality messages were selected, with mean scores of 8.25 (relevance), 7.86 (appropriateness) and 7.25 (elaboration). Among GBMSM PrEP users who received the messages, 90.4% (708/783) valued the co-created messages as helpful. Reflections from the co-creators highlighted the value of the participatory process, confirming that co-creation effectively engages GBMSM PrEP users. CONCLUSIONS: Co-creation groups are feasible for Chinese GBMSM to identify context-specific PrEP adherence barriers and develop people-centered mHealth messages, supporting the value of co-creation for PrEP adherence intervention development in this population.
9 Apr 2026
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