Lancet Hiv最新文献

{"title":"Magnitude and characteristics of unsuppressed HIV viral load in children and adolescents on antiretroviral therapy in sub-Saharan Africa: a systematic review and meta-analysis.","authors":"Olivier Mukuku, Kaymarlin Govender, Stanislas Okitotsho Wembonyama, Yannick Nkiambi Kiakuvue","doi":"10.1016/S2352-3018(25)00039-6","DOIUrl":"10.1016/S2352-3018(25)00039-6","url":null,"abstract":"<p><strong>Background: </strong>HIV/AIDS remains a major health issue in sub-Saharan Africa, especially among children and adolescents, with a substantial proportion of people with HIV having unsuppressed viral loads despite the availability of antiretroviral therapy (ART), complicating efforts to manage and control the epidemic. We aimed to estimate the prevalence of unsuppressed viral load and identify the factors contributing to this issue among children and adolescents living with HIV on ART in sub-Saharan Africa.</p><p><strong>Methods: </strong>In this systematic review and meta-analysis, we assessed data from Web of Science, Google Scholar, Scopus, PsycINFO, Embase, PubMed (MEDLINE), EBSCOhost Research Databases, and Wiley Online Library, as well as grey literature searches. We included studies published between Jan 1, 2010, and Nov 30, 2024 that focused on children and adolescents (aged <20 years) on ART in sub-Saharan Africa and reported on factors related to viral load suppression, defined by a viral load of less than 1000 copies per mL. Eligible studies included observational and interventional designs. Data appraisal and extraction were conducted by two independent reviewers from the author group, with summary data extracted from published reports. The primary outcome assessed was the prevalence of unsuppressed viral loads, with meta-analysis performed using STATA software to calculate prevalence and associated factors. The study is registered with PROSPERO (CRD42023451212).</p><p><strong>Findings: </strong>From an initial 13 121 identified articles, 52 studies involving 169 949 children and adolescents on ART met the inclusion criteria. Prevalence of unsuppressed viral load among children and adolescents in sub-Saharan Africa was 26·47% (95% CI 23·06-29·87); specifically, 26·01% (20·51-31·52) for studies in children (<15 years), 24·76% (17·36-32·16) for studies in adolescents (10-19 years), and 28·52% (23·33-33·72) for studies in a combined group of children and adolescents. Factors associated with unsuppressed viral load included younger age (<5 years), male sex, rural residence, orphan status, attendance at a level 1 or 2 health-care facility, HIV status not disclosed, poor ART adherence, advanced WHO clinical stage of HIV, low CD4 cell counts, history of opportunistic infections, nevirapine-based treatment regimen, drug substitution history, and not receiving co-trimoxazole prophylaxis. This meta-analysis showed a significant heterogeneity across the included studies, as evidenced by I²=99·66% and p<0·0001.</p><p><strong>Interpretation: </strong>Unsuppressed viral load among children and adolescents is a key concern in sub-Saharan Africa, and is influenced by sociodemographic, clinical, immunological, and treatment-related factors. Addressing these issues through targeted interventions and improved ART adherence strategies is crucial for better health outcomes.</p><p><strong>Funding: </strong>HEARD PhD Scholarship, Swedi","PeriodicalId":48725,"journal":{"name":"Lancet Hiv","volume":" ","pages":"e506-e521"},"PeriodicalIF":12.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144235648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging landscape for long-acting HIV prevention","authors":"Thiago S Torres, Brenda Hoagland","doi":"10.1016/s2352-3018(25)00159-6","DOIUrl":"https://doi.org/10.1016/s2352-3018(25)00159-6","url":null,"abstract":"","PeriodicalId":48725,"journal":{"name":"Lancet Hiv","volume":"18 1","pages":""},"PeriodicalIF":16.1,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144515343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety, tolerability, and pharmacokinetics of an annual tenofovir alafenamide silicone subdermal implant in South African women: a two-part, randomised, placebo-controlled, double-blind, first-in-human, phase 1 trial","authors":"Tanuja N Gengiah PhD, Lara Lewis MS, Ishana Harkoo MBChB, Leila E Mansoor PhD, Johara Khan MBChB, Zainab Kharva MBChB, Razia Hassan-Moosa MBChB, Natasha Samsunder PhD, Prof Catherine Hankins PhD, Prof Bruno Pozzetto PhD, James F Rooney MD, Jaideep Gogtay MBBS, John A Moss PhD, Marc M Baum PhD, Prof Salim S Abdool Karim PhD, Prof Quarraisha Abdool Karim PhD","doi":"10.1016/s2352-3018(25)00079-7","DOIUrl":"https://doi.org/10.1016/s2352-3018(25)00079-7","url":null,"abstract":"Women in sub-Saharan Africa are at high risk for HIV acquisition. To overcome adherence challenges with daily oral pre-exposure prophylaxis we developed and tested the safety, tolerability, and pharmacokinetics of a novel long-acting tenofovir alafenamide implant.","PeriodicalId":48725,"journal":{"name":"Lancet Hiv","volume":"46 1","pages":""},"PeriodicalIF":16.1,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144515344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oral antiretroviral adherence interventions in the era of U=U","authors":"Claire M Keene PhD, Lora L Sabin PhD, Lauren Jennings MPH, Chantel Schreuder MBChB, Carl-Oscar Källström-Ståhlgren MSc, Ingrid T Katz MD, Yashna Singh MPH, Catherine Orrell PhD, K Rivet Amico PhD","doi":"10.1016/s2352-3018(25)00096-7","DOIUrl":"https://doi.org/10.1016/s2352-3018(25)00096-7","url":null,"abstract":"Antiretroviral therapy (ART) is a keystone of the public health response to HIV, making the support of adherence a point of focus in research and service delivery. Over the past decade, measurements of viral suppression have increasingly been used to evaluate interventions, with more robust study designs gaining traction. Effective approaches include adherence counselling beyond ART education (including mental health and wellbeing approaches), reducing burden of care, tackling structural and societal determinants of health, and using mHealth platforms to deliver interventions. Increasingly, single-strategy interventions are giving way to multicomponent approaches to respond to nuances in adherence behaviour. However, determining which effective strategy to offer and to whom, when, and how remain pressing questions if professionals in the field (eg, researchers, clinicians, and community health workers) are to reach the UNAIDS 95-95-95 goals in the recent context of decreased funding. As new long-acting treatments enter global formularies, interventions showing success with oral ART will probably remain relevant to inform service delivery in most contexts.","PeriodicalId":48725,"journal":{"name":"Lancet Hiv","volume":"1 1","pages":""},"PeriodicalIF":16.1,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144515346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predictors of treatment-emergent resistance to dolutegravir","authors":"Suzanne M McCluskey MD, Prof Monica Gandhi MD","doi":"10.1016/s2352-3018(25)00127-4","DOIUrl":"https://doi.org/10.1016/s2352-3018(25)00127-4","url":null,"abstract":"Integrase strand transfer inhibitor (INSTI)-based regimens became a first-line treatment for HIV worldwide in 2018, with 93% of people with HIV who are on antiretroviral therapy (ART) estimated to be taking dolutegravir-based regimens as of 2023. Since the genetic barrier to resistance of dolutegravir is not impenetrable, rising rates of dolutegravir resistance among those with virological failure on this drug regimen have been reported. Risk factors for dolutegravir resistance include treatment experience, having background resistance to the nucleoside reverse transcriptase inhibitors in the regimen, switching to tenofovir, lamivudine, and dolutegravir when viraemic on a former regimen, previous experience with first-generation INSTIs, and being on dolutegravir monotherapy or dual therapy, with rates higher in children than in adults. HIV drug resistance does not emerge if selective drug pressure is not present, so some exposure to the ART regimen with virological failure is associated with higher rates of resistance than complete non-adherence. Detectable objective metrics of adherence (eg, ART drug concentrations in urine, plasma, dried blood spots, and hair) have been associated with high levels of viral resistance and can be used to triage who needs resistance testing the most.","PeriodicalId":48725,"journal":{"name":"Lancet Hiv","volume":"70 1","pages":""},"PeriodicalIF":16.1,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144341085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"UNAIDS cuts leave enormous gap in global HIV response.","authors":"Talha Burki","doi":"10.1016/s2352-3018(25)00183-3","DOIUrl":"https://doi.org/10.1016/s2352-3018(25)00183-3","url":null,"abstract":"","PeriodicalId":48725,"journal":{"name":"Lancet Hiv","volume":"32 1","pages":""},"PeriodicalIF":16.1,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lenacapavir-associated drug resistance: implications for scaling up long-acting HIV pre-exposure prophylaxis.","authors":"Gert van Zyl,Mateo Prochazka,Heather-Marie Ann Schmidt,Catherine Orrell,Jonathan M Schapiro,Suzanne M McCluskey,Marco Vitoria,Rami Kantor,Urvi M Parikh,Michelle Rodolph,Michael R Jordan,Robert W Shafer","doi":"10.1016/s2352-3018(25)00128-6","DOIUrl":"https://doi.org/10.1016/s2352-3018(25)00128-6","url":null,"abstract":"Although drug resistance could emerge if lenacapavir is initiated during undiagnosed acute infection or if infection occurs during the drug's pharmacokinetic tail, these cases will not compromise the effectiveness of WHO-recommended therapies, as there is no cross-resistance between lenacapavir and other licensed antiretroviral drugs. Lenacapavir pre-exposure prophylaxis (PrEP) is also unlikely to drive population-level lenacapavir resistance given the rarity of breakthrough infections and the reduced replication capacity of most lenacapavir-resistant variants, which most likely reduces their transmission potential. Conversely, the risk of acquiring lenacapavir-resistant HIV-1 while receiving lenacapavir PrEP is likely to remain extremely low, as lenacapavir-associated drug-resistance mutations are rare among individuals without previous lenacapavir exposure, and widespread use of lenacapavir-based regimens remains years away. Nonetheless, as the number of lenacapavir PrEP programmes increase, surveillance for emerging lenacapavir resistance should also be implemented.","PeriodicalId":48725,"journal":{"name":"Lancet Hiv","volume":"628 1","pages":""},"PeriodicalIF":16.1,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to Lancet HIV 2025; published online April 3. https://doi.org/10.1016/S2352-3018(25)00097-9.","authors":"","doi":"10.1016/s2352-3018(25)00170-5","DOIUrl":"https://doi.org/10.1016/s2352-3018(25)00170-5","url":null,"abstract":"","PeriodicalId":48725,"journal":{"name":"Lancet Hiv","volume":"38 1","pages":""},"PeriodicalIF":16.1,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144335325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Do we need routine integrase resistance testing before starting antiretroviral therapy?","authors":"Rami Kantor,Alice K Pau,Michael J Kozal,Emily P Hyle","doi":"10.1016/s2352-3018(25)00108-0","DOIUrl":"https://doi.org/10.1016/s2352-3018(25)00108-0","url":null,"abstract":"Oral second-generation integrase strand transfer inhibitors are now anchor drugs of antiretroviral therapy (ART) globally due to their high resistance barriers. In high-income settings, guidelines recommend routine protease and reverse transcriptase resistance testing before ART initiation but suggest routine integrase resistance testing only for individuals at elevated risk of integrase resistance. Improved characterisation of transmitted integrase resistance, its detection, and its clinical impact will guide future recommendations for clinical decision making. Balancing the need to protect this important drug class against concerns about resource allocation and care complexity presents a substantial challenge. Shifting the responsibility to providers to decide whether and when to test for integrase resistance before ART initiation can be problematic, particularly given the uncertainty around the need to reassess related available recommendations. As our understanding of integrase resistance evolves, prioritising this discussion is essential, and providers, researchers, and policy makers should engage in addressing this important issue.","PeriodicalId":48725,"journal":{"name":"Lancet Hiv","volume":"9 1","pages":""},"PeriodicalIF":16.1,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144335346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety, pharmacokinetics, and neutralisation activity of PGDM1400LS, a V2 specific HIV-1 broadly neutralising antibody, infused intravenously or subcutaneously in people without HIV-1 in the USA (HVTN 140/HPTN 101 part A): a first-in-human, phase 1 randomised trial.","authors":"Kelly E Seaton, Carmen A Paez, Chenchen Yu, Shelly T Karuna, Theresa Gamble, Maurine D Miner, Jack Heptinstall, Lu Zhang, Fei Gao, Margaret Yacovone, Hans Spiegel, Julie B Dumond, Maija Anderson, Estelle Piwowar-Manning, Bonnie Dye, India Tindale, Lori Proulx-Burns, Meg Trahey, Simbarashe Takuva, Azwidihwi Takalani, Veronique C Bailey, Spyros A Kalams, Hyman Scott, Nonhlanhla N Mkhize, Joshua A Weiner, Margaret E Ackerman, M Juliana McElrath, Michael Pensiero, Dan H Barouch, David Montefiori, Georgia D Tomaras, Lawrence Corey, Myron S Cohen, Yunda Huang, Sharana Mahomed, Marc Siegel, Colleen F Kelley","doi":"10.1016/S2352-3018(25)00012-8","DOIUrl":"10.1016/S2352-3018(25)00012-8","url":null,"abstract":"<p><strong>Background: </strong>PGDM1400LS is a human monoclonal antibody targeting the HIV envelope V2 apex with a lysine-serine modification intended to enhance serum and tissue half-lives and is being considered for use in combination monoclonal antibody trials. We sought to test whether PGDM1400LS was safe and had favourable serum concentration, pharmacokinetics, and neutralising ability in healthy adults.</p><p><strong>Methods: </strong>HVTN 140/HPTN 101 part A is an open-label, dose escalation, first-in-human phase 1 trial of PGDM1400LS given intravenously or subcutaneously to healthy adults aged 18-50 years without HIV-1. The study enrolled participants at four sites in the USA, across five groups, each receiving one dose of PGDM1400-LS intravenously (group 1: 5 mg/kg; group 2: 20 mg/kg; and group 4: 40 mg/kg) or subcutaneously (group 3: 20 mg/kg; and group 5: 40 mg/kg). Participants in group 1 were enrolled sequentially without random assignment. Participants in groups 2 and 3 were block randomised and enrolled simultaneously after group 1 safety review. Groups 4 and 5 followed the same process, contingent on groups 2 and 3 safety review. The primary endpoints were safety and tolerability of PGDM1400LS, serum concentration of PGDM1400LS, and serum neutralising activity after single administration of PGDM1400LS. Serum PGDM1400LS concentrations collected at seven timepoints (day 0, day 3, day 6, day 28, day 56, day 112, and day 168) were assessed via an anti-idiotype binding assay and characterised via non-compartmental pharmacokinetic analysis. Serum neutralisation activity (ID₈₀) was assessed by a TZM-bl assay. The study is registered with ClinicalTrials.gov, NCT05184452.</p><p><strong>Findings: </strong>Between Nov 15, 2021, and March 4, 2022, 15 participants were enrolled into the five study groups (three participants per group) with 6 months of follow-up. Ten of 15 participants were female, 14 of 15 participants were non-Hispanic, and 11 of 15 participants were White, with a median age of 27 years (range 24-47). PGDM1400LS was safe and well tolerated, with mild to moderate solicited symptoms. Serum concentrations showed dose proportionality by administration route, with peak concentrations observed immediately after intravenous infusion (range 95·7-727·4 μg/mL) or on day 6 after subcutaneous infusion (205·6-547·1 μg/mL). The median elimination half-life was 55 days (range 48-59), representing a 2-to-3-times increase versus parental PDGM1400. Estimated subcutaneous (vs intravenous) bioavailability was 50-60%. ID₈₀ titres showed agreement with concentration-predicted ID₈₀ titres, indicating maintenance of neutralisation activity in vivo.</p><p><strong>Interpretation: </strong>PGDM1400LS is a promising candidate for combination monoclonal antibody efficacy trials going forward.</p><p><strong>Funding: </strong>National Institute of Allergy and Infectious Diseases-National Institutes of Health.</p>","PeriodicalId":48725,"journal":{"name":"Lancet Hiv","volume":"12 6","pages":"e405-e415"},"PeriodicalIF":13.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12266790/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144182870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}