Pub Date : 2025-09-20DOI: 10.1016/j.jve.2025.100609
Kazuo Suzuki , Lucy Gold , Angelique Levert , Shannen Butterly , Emma Yoo , Takaomi Ishida , John Zaunders 1 , Lucette A. Cysique , Bruce J. Brew
Integrase strand transfer inhibitors (INSTIs) are the cornerstone of modern antiretroviral therapy (ART), achieving durable plasma HIV-1 suppression in most people living with HIV (PLWH). Previous comparisons of INSTI- and non-INSTI-based regimens have largely focused on HIV reservoir proviral assessments— typically total HIV DNA —without assessing reservoir activity. In this first functional comparison, we measured cell-associated (CA) short HIV-1 RNA transcripts, a marker of active transcription, alongside HIV-1 DNA in white blood cells from 92 virally suppressed individuals on INSTI-based (n = 73) or non-INSTI-based (n = 19) ART. CA short RNA transcripts were detected in all participants and HIV-1 DNA in 99 %, despite undetectable plasma viremia in >93 %. Individuals with prior “blips” — defined as a maximum of two episodes with 20–200 copies/mL plasma HIV-1 RNA over more than two years — had significantly higher CA RNA and HIV DNA than non-blip participants, confirming our previous findings. However, reservoir size and transcriptional activity did not differ significantly between INSTI and non-INSTI groups. These findings indicate that while INSTIs effectively block new integration events, they do not suppress ongoing transcription from the latent reservoir. Therapeutic strategies directly targeting HIV transcription should therefore be prioritized in cure-oriented research for PLWH on long-term suppressive ART.
{"title":"Persistent cell-associated HIV-1 RNA in virally suppressed individuals on INSTI-based ART","authors":"Kazuo Suzuki , Lucy Gold , Angelique Levert , Shannen Butterly , Emma Yoo , Takaomi Ishida , John Zaunders 1 , Lucette A. Cysique , Bruce J. Brew","doi":"10.1016/j.jve.2025.100609","DOIUrl":"10.1016/j.jve.2025.100609","url":null,"abstract":"<div><div>Integrase strand transfer inhibitors (INSTIs) are the cornerstone of modern antiretroviral therapy (ART), achieving durable plasma HIV-1 suppression in most people living with HIV (PLWH). Previous comparisons of INSTI- and non-INSTI-based regimens have largely focused on HIV reservoir proviral assessments— typically total HIV DNA —without assessing reservoir activity. In this first functional comparison, we measured cell-associated (CA) short HIV-1 RNA transcripts, a marker of active transcription, alongside HIV-1 DNA in white blood cells from 92 virally suppressed individuals on INSTI-based (n = 73) or non-INSTI-based (n = 19) ART. CA short RNA transcripts were detected in all participants and HIV-1 DNA in 99 %, despite undetectable plasma viremia in >93 %. Individuals with prior “blips” — defined as a maximum of two episodes with 20–200 copies/mL plasma HIV-1 RNA over more than two years — had significantly higher CA RNA and HIV DNA than non-blip participants, confirming our previous findings. However, reservoir size and transcriptional activity did not differ significantly between INSTI and non-INSTI groups. These findings indicate that while INSTIs effectively block new integration events, they do not suppress ongoing transcription from the latent reservoir. Therapeutic strategies directly targeting HIV transcription should therefore be prioritized in cure-oriented research for PLWH on long-term suppressive ART.</div></div>","PeriodicalId":17552,"journal":{"name":"Journal of Virus Eradication","volume":"11 4","pages":"Article 100609"},"PeriodicalIF":2.0,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145268402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-15DOI: 10.1016/j.jve.2025.100608
P. Ferrer , V. Ramos , M. Durán , D. Maureira , C. Beltrán , A. Afani
Background
Integrase strand transfer inhibitors (INSTIs) are widely used in HIV treatment, yet few large-scale studies have examined acquired resistance (AR) at the population level. This study assessed the prevalence, patterns, and clinical implications of AR to INSTIs in Chile over a 12-year period.
Methods
We analyzed 5266 genotypic sequences from ART-experienced individuals with confirmed virological failure and INSTI-based regimens between 2012 and 2023. Resistance-associated mutations were classified using the Stanford HIVdb algorithm. Resistance trends were compared between pre-pandemic (2012–2019) and post-pandemic (2020–2023) periods.
Results
High AR rates were observed for first-generation INSTIs: raltegravir (28 %) and elvitegravir (27.7 %). Lower resistance levels were found for dolutegravir (8.3 %), bictegravir (8.3 %), and cabotegravir (18.7 %). Major resistance mutations included N155H (25.2 %), Q148 H/K/R (17.2 %), and Y143R (14.3 %). Notably, Q148 H/K/R mutations were always found in combination with other major mutations. Subtype-specific differences were observed, with higher first-generation INSTI resistance in subtype F (55.6 %) than in subtype B (23.9 %). Post-pandemic resistance increased significantly for first-generation INSTIs (25 % vs. 31 %, p < 0.05). The mutation N155H, while not impacting DTG or BIC significantly, conferred intermediate resistance to CAB. CAB resistance was detected despite its absence in treatment protocols, likely due to cross-resistance pathways.
Conclusions
Acquired INSTIs resistance in Chile is high, especially for first-generation drugs. These findings highlight the need for nationwide molecular surveillance and pre-treatment genotyping, particularly before initiating long-acting regimens such as CAB-LA. Strategic monitoring will be critical to maintaining the efficacy of current and next-generation INSTIs.
{"title":"Prevalence of acquired resistance to HIV integrase strand transfer inhibitors (INSTIs) in clinical samples from treatment-experienced patients in Chile, 2012–2023","authors":"P. Ferrer , V. Ramos , M. Durán , D. Maureira , C. Beltrán , A. Afani","doi":"10.1016/j.jve.2025.100608","DOIUrl":"10.1016/j.jve.2025.100608","url":null,"abstract":"<div><h3>Background</h3><div>Integrase strand transfer inhibitors (INSTIs) are widely used in HIV treatment, yet few large-scale studies have examined acquired resistance (AR) at the population level. This study assessed the prevalence, patterns, and clinical implications of AR to INSTIs in Chile over a 12-year period.</div></div><div><h3>Methods</h3><div>We analyzed 5266 genotypic sequences from ART-experienced individuals with confirmed virological failure and INSTI-based regimens between 2012 and 2023. Resistance-associated mutations were classified using the Stanford HIVdb algorithm. Resistance trends were compared between pre-pandemic (2012–2019) and post-pandemic (2020–2023) periods.</div></div><div><h3>Results</h3><div>High AR rates were observed for first-generation INSTIs: raltegravir (28 %) and elvitegravir (27.7 %). Lower resistance levels were found for dolutegravir (8.3 %), bictegravir (8.3 %), and cabotegravir (18.7 %). Major resistance mutations included N155H (25.2 %), Q148 H/K/R (17.2 %), and Y143R (14.3 %). Notably, Q148 H/K/R mutations were always found in combination with other major mutations. Subtype-specific differences were observed, with higher first-generation INSTI resistance in subtype F (55.6 %) than in subtype B (23.9 %). Post-pandemic resistance increased significantly for first-generation INSTIs (25 % vs. 31 %, p < 0.05). The mutation N155H, while not impacting DTG or BIC significantly, conferred intermediate resistance to CAB. CAB resistance was detected despite its absence in treatment protocols, likely due to cross-resistance pathways.</div></div><div><h3>Conclusions</h3><div>Acquired INSTIs resistance in Chile is high, especially for first-generation drugs. These findings highlight the need for nationwide molecular surveillance and pre-treatment genotyping, particularly before initiating long-acting regimens such as CAB-LA. Strategic monitoring will be critical to maintaining the efficacy of current and next-generation INSTIs.</div></div>","PeriodicalId":17552,"journal":{"name":"Journal of Virus Eradication","volume":"11 4","pages":"Article 100608"},"PeriodicalIF":2.0,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145097797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-08DOI: 10.1016/j.jve.2025.100606
Yu Liu , Miao Fang , Hongying Guo , Xin Zhang , Xue Mei , Longshan Ji , Wei Yuan , Yating Gao , Jiefei Wang , Zhiping Qian , Man Li , Yueqiu Gao
Background
Multiple analyses have suggested that osteopontin (OPN) is involved in acute and chronic liver disease. We aimed to investigate the value of serum OPN in predicting the short-term prognosis of patients with hepatitis B-related acute-on-chronic liver failure (HBV-ACLF).
Methods
A total of 205 patients with HBV-ACLF were enrolled in a retrospective study and stratified into survivors and non-survivors according to their 90-day prognosis. Multivariate Cox regression and receiver operating characteristic curves were used to evaluate the predictive value of serum OPN levels for the 90-day prognosis of patients with HBV-ACLF.The prevalence of different OPN levels (<36.8 ng/ml; ≥36.8 ng/ml) and their relationship with 90-day prognosis were investigated.
Results
Patients with HBV-ACLF had significantly higher serum OPN levels than patients with HBV-LC, patients with CHB, and healthy subjects. Patients were assigned to low- and high-level OPN groups according to the cut-off value of OPN (36.8 ng/ml). Survival curves revealed that patients with high OPN levels had significantly poorer survival than those with low OPN levels, as determined using Kaplan-Meier analysis. Importantly, Multivariate Cox regression analysis revealed that OPN levels were an independent risk factor for 90-day adverse outcomes in patients with HBV-ACLF according to the fully adjusted Model IV.
Conclusions
Our results demonstrated that plasma OPN level is a clinically meaningful biomarker for predicting the short-term prognosis of patients with HBV-ACLF.
{"title":"Serum osteopontin levels predict short-term outcomes in patients with hepatitis B-related acute-on-chronic liver failure","authors":"Yu Liu , Miao Fang , Hongying Guo , Xin Zhang , Xue Mei , Longshan Ji , Wei Yuan , Yating Gao , Jiefei Wang , Zhiping Qian , Man Li , Yueqiu Gao","doi":"10.1016/j.jve.2025.100606","DOIUrl":"10.1016/j.jve.2025.100606","url":null,"abstract":"<div><h3>Background</h3><div>Multiple analyses have suggested that osteopontin (OPN) is involved in acute and chronic liver disease. We aimed to investigate the value of serum OPN in predicting the short-term prognosis of patients with hepatitis B-related acute-on-chronic liver failure (HBV-ACLF).</div></div><div><h3>Methods</h3><div>A total of 205 patients with HBV-ACLF were enrolled in a retrospective study and stratified into survivors and non-survivors according to their 90-day prognosis. Multivariate Cox regression and receiver operating characteristic curves were used to evaluate the predictive value of serum OPN levels for the 90-day prognosis of patients with HBV-ACLF.The prevalence of different OPN levels (<36.8 ng/ml; ≥36.8 ng/ml) and their relationship with 90-day prognosis were investigated.</div></div><div><h3>Results</h3><div>Patients with HBV-ACLF had significantly higher serum OPN levels than patients with HBV-LC, patients with CHB, and healthy subjects. Patients were assigned to low- and high-level OPN groups according to the cut-off value of OPN (36.8 ng/ml). Survival curves revealed that patients with high OPN levels had significantly poorer survival than those with low OPN levels, as determined using Kaplan-Meier analysis. Importantly, Multivariate Cox regression analysis revealed that OPN levels were an independent risk factor for 90-day adverse outcomes in patients with HBV-ACLF according to the fully adjusted Model IV.</div></div><div><h3>Conclusions</h3><div>Our results demonstrated that plasma OPN level is a clinically meaningful biomarker for predicting the short-term prognosis of patients with HBV-ACLF.</div></div>","PeriodicalId":17552,"journal":{"name":"Journal of Virus Eradication","volume":"11 4","pages":"Article 100606"},"PeriodicalIF":2.0,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145048518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-07DOI: 10.1016/j.jve.2025.100605
Jaeden Pyburn , Juan Zhao , Ling Wang , Madison Schank , Addison C. Hill , Puja Banik , Yi Zhang , Xiao Y. Wu , Janet W. Lightner , Holly K. Orfield , Tabitha O. Leshaodo , Mohamed El Gazzar , Shunbin Ning , Jonathan P. Moorman , Zhi Q. Yao
Evaluation of CD4 T cell status in early HIV infection is critical for developing strategies targeting HIV replication. In this study, we infected CD4 T cells with HIV-1 and investigated the cell survival mechanisms in HIV-infected versus uninfected cells during early HIV infection. Notably, HIV-infected CD4 T cells exhibited elevated levels of phosphorylated eukaryotic translation initiation factor 2-alpha (p-eIF2α) compared to uninfected cells. Importantly, inhibition of protein kinase R (PKR) in HIV-infected cells significantly suppressed HIV p24 protein expression by disrupting HIV reverse transcription and integration. These results suggest that targeting PKR could be a promising therapeutic approach against HIV infection.
{"title":"Inhibition of protein kinase R suppresses HIV replication and integration in CD4 T cells","authors":"Jaeden Pyburn , Juan Zhao , Ling Wang , Madison Schank , Addison C. Hill , Puja Banik , Yi Zhang , Xiao Y. Wu , Janet W. Lightner , Holly K. Orfield , Tabitha O. Leshaodo , Mohamed El Gazzar , Shunbin Ning , Jonathan P. Moorman , Zhi Q. Yao","doi":"10.1016/j.jve.2025.100605","DOIUrl":"10.1016/j.jve.2025.100605","url":null,"abstract":"<div><div>Evaluation of CD4 T cell status in early HIV infection is critical for developing strategies targeting HIV replication. In this study, we infected CD4 T cells with HIV-1 and investigated the cell survival mechanisms in HIV-infected versus uninfected cells during early HIV infection. Notably, HIV-infected CD4 T cells exhibited elevated levels of phosphorylated eukaryotic translation initiation factor 2-alpha (p-eIF2α) compared to uninfected cells. Importantly, inhibition of protein kinase R (PKR) in HIV-infected cells significantly suppressed HIV p24 protein expression by disrupting HIV reverse transcription and integration. These results suggest that targeting PKR could be a promising therapeutic approach against HIV infection.</div></div>","PeriodicalId":17552,"journal":{"name":"Journal of Virus Eradication","volume":"11 3","pages":"Article 100605"},"PeriodicalIF":2.0,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144842098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-27DOI: 10.1016/j.jve.2025.100604
Vibeke Klastrup , Jesper Damsgaard Gunst , Ole Schmeltz Søgaard
Objective
Analytical treatment interruption (ATI) is crucial for assessing the efficacy of HIV-1 cure strategies. Recent cure studies have implemented more flexible ART restart criteria, permitting higher plasma viral loads (pVLs) for longer periods, which could potentially impair CD4+ T cell recovery even following ART resumption.
Design
We conducted a pooled analysis of six clinical HIV cure trials that included an ATI to evaluate the impact of magnitude and duration of plasma viremia during ATI on CD4+ T cell dynamics.
Methods
Wilcoxon signed-rank or rank-sum test was used to analyze differences in CD4+ T cell counts from 3 time points: 1) pre-ATI, 2) ART resumption, and 3) ART-induced viral re-suppression, with analyses stratified by peak pVL (≤10,000 or >10,000 copies/mL) or by duration of viremia (0–14, 15–28, or >28 days).
Results
Among 114 participants, we found no change in CD4+ T cell counts from pre-ATI to post-ATI (at viral re-suppression, P = 0.80). We also found no impact of low (≤10,000 copies/mL) versus high (>10,000 copies/mL) peak viremia on CD4+ T cell counts at the time of ART resumption or viral re-suppression (P = 0.48, P = 0.88, respectively). Similarly, the change in CD4+ T cell count from pre-ATI to viral re-suppression did not differ significantly between individuals with viremia lasting 0–14 days versus those with >28 days.
Conclusion
In our pooled analysis, high peak rebound pVLs and longer duration of viremia did not impair CD4+ T cell recovery following the resumption of ART, supporting the safety of more flexible ATIs in HIV-1 cure trials.
{"title":"The impact of magnitude and duration of plasma viremia during analytical treatment interruptions on CD4+ T cell recovery after ART resumption","authors":"Vibeke Klastrup , Jesper Damsgaard Gunst , Ole Schmeltz Søgaard","doi":"10.1016/j.jve.2025.100604","DOIUrl":"10.1016/j.jve.2025.100604","url":null,"abstract":"<div><h3>Objective</h3><div>Analytical treatment interruption (ATI) is crucial for assessing the efficacy of HIV-1 cure strategies. Recent cure studies have implemented more flexible ART restart criteria, permitting higher plasma viral loads (pVLs) for longer periods, which could potentially impair CD4<sup>+</sup> T cell recovery even following ART resumption.</div></div><div><h3>Design</h3><div>We conducted a pooled analysis of six clinical HIV cure trials that included an ATI to evaluate the impact of magnitude and duration of plasma viremia during ATI on CD4<sup>+</sup> T cell dynamics.</div></div><div><h3>Methods</h3><div>Wilcoxon signed-rank or rank-sum test was used to analyze differences in CD4<sup>+</sup> T cell counts from 3 time points: 1) pre-ATI, 2) ART resumption, and 3) ART-induced viral re-suppression, with analyses stratified by peak pVL (≤10,000 or >10,000 copies/mL) or by duration of viremia (0–14, 15–28, or >28 days).</div></div><div><h3>Results</h3><div>Among 114 participants, we found no change in CD4<sup>+</sup> T cell counts from pre-ATI to post-ATI (at viral re-suppression, <em>P</em> = 0.80). We also found no impact of low (≤10,000 copies/mL) versus high (>10,000 copies/mL) peak viremia on CD4<sup>+</sup> T cell counts at the time of ART resumption or viral re-suppression (<em>P</em> = 0.48, <em>P</em> = 0.88, respectively). Similarly, the change in CD4<sup>+</sup> T cell count from pre-ATI to viral re-suppression did not differ significantly between individuals with viremia lasting 0–14 days versus those with >28 days.</div></div><div><h3>Conclusion</h3><div>In our pooled analysis, high peak rebound pVLs and longer duration of viremia did not impair CD4<sup>+</sup> T cell recovery following the resumption of ART, supporting the safety of more flexible ATIs in HIV-1 cure trials.</div></div>","PeriodicalId":17552,"journal":{"name":"Journal of Virus Eradication","volume":"11 3","pages":"Article 100604"},"PeriodicalIF":3.5,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144518137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-27DOI: 10.1016/j.jve.2025.100603
Aude Christelle Ka'e , Collins Ambe Chenwi , Livo Esemu , Hillary Tene , Romeo Djounda , Bouba Yagai , Aubin Nanfack , Alex Durand Nka , Naomi-Karell Etame , Ezechiel Ngoufack Jagni Semengue , Celestin Godwe , Honore Awanakan , Fon Abongwa Acho , Caroline Mofor , Mambo Musi Beryle , Benoit Bissohong , Jang Joanes T , Lum Forgwei , Rogers Ajeh Awoh , Gregory Edie Halle Ekane , Joseph Fokam
<div><div>Despite global efforts to eliminate HIV as a public health threat, sub-Saharan Africa (SSA) still harbours about the highest burden of the pandemic, home to around 70 % of people living with HIV with limited contribution in the field of HIV cure research, especially in West and Central Africa (WCA). This gap is mainly due to challenges that researchers of this region are facing in initiating and advancing HIV cure research locally, with lesser commitment from the French-speaking countries. Furthermore, capacity-building of early career scientists on HIV cure research remains constrained due to limited awareness and language barriers to existing opportunities. Even though HIV non-B subtypes represent 89 % of circulating subtypes worldwide, cure research has been extensively focused on subtype B (prevalent in America and Europe). Interestingly, WCA (known as HIV pandemic epicentre with a broad genetic diversity) offers a unique landscape for cure research with a likelihood of generalisability across various HIV subtypes. This viewpoint discusses the importance of establishing an HIV Cure Academy for WCA to support scientists, policymakers and community stakeholders from French-speaking countries in contributing to the global efforts towards HIV cure.</div><div>Building on discussions, the establishment of an "HIV Cure Academy" emerges as a hallmark to: (i) raise awareness, (ii) build capacity, (iii) address scientific gaps, (iv) develop networks, and (v) foster advocacy and policy-briefing on integrating HIV cure research into national HIV agenda. The Academy is envisioned as a hub, facilitating relationships between community-based organizations, people living with HIV (PLHIV), research institutions and decision makers. This hub will also champion the "Advocacy for Cure" agenda in the sub-region, enhance multidisciplinary approach to identify local HIV cure research priorities that address the global problem. Of prime importance, research priorities in WCA include: (i) the measurement and characterization of viral reservoirs; (ii) investigation in immune responses including bNAbs, T-cell function, cytokines profiles and hosts genetic factors; (iii) identification of elite and post-treatment controllers; (iv) development of accessible technologies for point-of-care HIV DNA testing, biomarker detection, and latency-modifying agents to support functional cure strategies; (v) innovation in cost-effective and scalable therapeutic interventions suitable for low-resource settings; (vi) the strengthen of community involvement through citizen science, address ethical considerations, and engage PLHIV in the co-design of cure research initiatives; (vii) the establishment of regional training platforms, such as a Research-for-Cure Academy, to enhance scientific capacity and collaboration in West and Central Africa.</div><div>Following the model of the International AIDS Society (IAS) Research-for-cure academy, the WCA HIV Cure Academy represents a k
{"title":"Achieving the global agenda toward HIV cure calls for establishing a research-for-cure academy in West and Central Africa","authors":"Aude Christelle Ka'e , Collins Ambe Chenwi , Livo Esemu , Hillary Tene , Romeo Djounda , Bouba Yagai , Aubin Nanfack , Alex Durand Nka , Naomi-Karell Etame , Ezechiel Ngoufack Jagni Semengue , Celestin Godwe , Honore Awanakan , Fon Abongwa Acho , Caroline Mofor , Mambo Musi Beryle , Benoit Bissohong , Jang Joanes T , Lum Forgwei , Rogers Ajeh Awoh , Gregory Edie Halle Ekane , Joseph Fokam","doi":"10.1016/j.jve.2025.100603","DOIUrl":"10.1016/j.jve.2025.100603","url":null,"abstract":"<div><div>Despite global efforts to eliminate HIV as a public health threat, sub-Saharan Africa (SSA) still harbours about the highest burden of the pandemic, home to around 70 % of people living with HIV with limited contribution in the field of HIV cure research, especially in West and Central Africa (WCA). This gap is mainly due to challenges that researchers of this region are facing in initiating and advancing HIV cure research locally, with lesser commitment from the French-speaking countries. Furthermore, capacity-building of early career scientists on HIV cure research remains constrained due to limited awareness and language barriers to existing opportunities. Even though HIV non-B subtypes represent 89 % of circulating subtypes worldwide, cure research has been extensively focused on subtype B (prevalent in America and Europe). Interestingly, WCA (known as HIV pandemic epicentre with a broad genetic diversity) offers a unique landscape for cure research with a likelihood of generalisability across various HIV subtypes. This viewpoint discusses the importance of establishing an HIV Cure Academy for WCA to support scientists, policymakers and community stakeholders from French-speaking countries in contributing to the global efforts towards HIV cure.</div><div>Building on discussions, the establishment of an \"HIV Cure Academy\" emerges as a hallmark to: (i) raise awareness, (ii) build capacity, (iii) address scientific gaps, (iv) develop networks, and (v) foster advocacy and policy-briefing on integrating HIV cure research into national HIV agenda. The Academy is envisioned as a hub, facilitating relationships between community-based organizations, people living with HIV (PLHIV), research institutions and decision makers. This hub will also champion the \"Advocacy for Cure\" agenda in the sub-region, enhance multidisciplinary approach to identify local HIV cure research priorities that address the global problem. Of prime importance, research priorities in WCA include: (i) the measurement and characterization of viral reservoirs; (ii) investigation in immune responses including bNAbs, T-cell function, cytokines profiles and hosts genetic factors; (iii) identification of elite and post-treatment controllers; (iv) development of accessible technologies for point-of-care HIV DNA testing, biomarker detection, and latency-modifying agents to support functional cure strategies; (v) innovation in cost-effective and scalable therapeutic interventions suitable for low-resource settings; (vi) the strengthen of community involvement through citizen science, address ethical considerations, and engage PLHIV in the co-design of cure research initiatives; (vii) the establishment of regional training platforms, such as a Research-for-Cure Academy, to enhance scientific capacity and collaboration in West and Central Africa.</div><div>Following the model of the International AIDS Society (IAS) Research-for-cure academy, the WCA HIV Cure Academy represents a k","PeriodicalId":17552,"journal":{"name":"Journal of Virus Eradication","volume":"11 3","pages":"Article 100603"},"PeriodicalIF":3.5,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144534501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-06DOI: 10.1016/j.jve.2025.100600
Gloria Sukali , Jacob Busang , Jaco Dreyer , Thandeka Khoza , Marion Delphin , Nonhlanhla Okesola , Carina Herbst , Elizabeth Waddilove , Janine Upton , Janet Seeley , Collins Iwuji , Motswedi Anderson , Philippa C. Matthews , Maryam Shahmanesh
Background
Guidelines for Hepatitis B treatment released by the World Health Organization in 2024 include the potential for use of dual therapy, combining tenofovir with either emtricitabine or lamivudine. These fixed-dose combinations are also used for Pre-Exposure Prophylaxis (PrEP) in people at risk of Human Immunodeficiency Virus (HIV). We hypothesize that pre-existing HIV PrEP programmes can support access to HBV testing and treatment.
Methods
At the Africa Health Research Institute (AHRI) in KwaZulu Natal, South Africa, we evaluated PrEP uptake and retention amongst adolescents and young adults aged 15–30 years. We reviewed HBV status, acceptance of PrEP and retention in follow-up between June 2022–Sept 2024.
Results
15847 adolescents and young adults received an assessment in the community, of whom 3481/15847 (21.9 %) were eligible for sexual health prevention interventions. 3431/3481 (98.6 %) accepted HBV screening, of whom 21/3431 (0.6 %) tested positive for HBsAg. These 21 individuals had not previously been aware of their HBV status, but one was already on antiretroviral therapy for HIV infection. Amongst the others, 16/20 (80 %) were considered eligible for PrEP, and 15/16 started PrEP. When investigating retention in care, among 15 individuals due for a refill, 8/15 (53.3 %) returned at least once.
Conclusion
Sexual reproductive health and PrEP programmes provide an opportunity for HBV testing and treatment. However, attrition from the care cascade at each step highlights the pressing need for interventions that address barriers to sustainable delivery of long-term care.
{"title":"HIV PrEP programmes as a framework for diagnosing and treating HBV infection in adolescents and young adults in KwaZulu-Natal, South Africa","authors":"Gloria Sukali , Jacob Busang , Jaco Dreyer , Thandeka Khoza , Marion Delphin , Nonhlanhla Okesola , Carina Herbst , Elizabeth Waddilove , Janine Upton , Janet Seeley , Collins Iwuji , Motswedi Anderson , Philippa C. Matthews , Maryam Shahmanesh","doi":"10.1016/j.jve.2025.100600","DOIUrl":"10.1016/j.jve.2025.100600","url":null,"abstract":"<div><h3>Background</h3><div>Guidelines for Hepatitis B treatment released by the World Health Organization in 2024 include the potential for use of dual therapy, combining tenofovir with either emtricitabine or lamivudine. These fixed-dose combinations are also used for Pre-Exposure Prophylaxis (PrEP) in people at risk of Human Immunodeficiency Virus (HIV). We hypothesize that pre-existing HIV PrEP programmes can support access to HBV testing and treatment.</div></div><div><h3>Methods</h3><div>At the Africa Health Research Institute (AHRI) in KwaZulu Natal, South Africa, we evaluated PrEP uptake and retention amongst adolescents and young adults aged 15–30 years. We reviewed HBV status, acceptance of PrEP and retention in follow-up between June 2022–Sept 2024.</div></div><div><h3>Results</h3><div>15847 adolescents and young adults received an assessment in the community, of whom 3481/15847 (21.9 %) were eligible for sexual health prevention interventions. 3431/3481 (98.6 %) accepted HBV screening, of whom 21/3431 (0.6 %) tested positive for HBsAg. These 21 individuals had not previously been aware of their HBV status, but one was already on antiretroviral therapy for HIV infection. Amongst the others, 16/20 (80 %) were considered eligible for PrEP, and 15/16 started PrEP. When investigating retention in care, among 15 individuals due for a refill, 8/15 (53.3 %) returned at least once.</div></div><div><h3>Conclusion</h3><div>Sexual reproductive health and PrEP programmes provide an opportunity for HBV testing and treatment. However, attrition from the care cascade at each step highlights the pressing need for interventions that address barriers to sustainable delivery of long-term care.</div></div>","PeriodicalId":17552,"journal":{"name":"Journal of Virus Eradication","volume":"11 3","pages":"Article 100600"},"PeriodicalIF":3.5,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144306987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Innate, cellular and humoral immunity in acute HIV infection (AHI) play crucial roles in dictating immunological and pathological outcomes. However, understanding immune cell dynamics in different compartments during AHI is limited. In this study, we characterized immune cells from matched blood and lymph node samples in the RV254 Thai AHI cohort, the RV304 Thai chronic HIV infection cohort, and HIV-negative individuals, using flow cytometry. Our results showed a significant loss of the CD4:CD8 ratio in both PBMCs and LNMCs during AHI. Similarly, we observed increased immune activation of CD4+ and CD8+ T cells in both blood and lymph node compartments during AHI. In contrast, we found no increase in T follicular helper cells (Tfh) and a lack of association between circulating Tfh and lymph node Tfh during AHI. Furthermore, early B cell depletion, particularly in resting memory B cells, was observed in blood but not in lymph nodes during AHI. Additionally, during AHI, plasmacytoid dendritic cell activation was increased in lymph nodes but not in blood. These findings suggest that certain immune cell phenotypes and dynamics are unique in lymph nodes compared to blood during AHI. Understanding the immune cell alteration in these compartments during AHI may help define the mechanisms leading to lack of immune control in natural HIV infection.
{"title":"Dynamic changes in immune cell subsets in blood and lymph node over the course of acute HIV infection","authors":"Supranee Buranapraditkun , Julie L. Mitchell , Hiroshi Takata , Eugene Kroon , Suteeraporn Pinyakorn , Nicha Tulmethakaan , Sopark Manasnayakorn , Suthat Chottanapund , Pattarawat Thantiworasit , Peeriya Prueksakaew , Nisakorn Ratnaratorn , Khunthalee Benjapornpong , Bessara Nuntapinit , Praphan Phanuphak , Carlo P. Sacdalan , Nittaya Phanuphak , Kiat Ruxrungtham , Jintanat Ananworanich , Sandhya Vasan , Lydie Trautmann","doi":"10.1016/j.jve.2025.100598","DOIUrl":"10.1016/j.jve.2025.100598","url":null,"abstract":"<div><div>Innate, cellular and humoral immunity in acute HIV infection (AHI) play crucial roles in dictating immunological and pathological outcomes. However, understanding immune cell dynamics in different compartments during AHI is limited. In this study, we characterized immune cells from matched blood and lymph node samples in the RV254 Thai AHI cohort, the RV304 Thai chronic HIV infection cohort, and HIV-negative individuals, using flow cytometry. Our results showed a significant loss of the CD4:CD8 ratio in both PBMCs and LNMCs during AHI. Similarly, we observed increased immune activation of CD4<sup>+</sup> and CD8<sup>+</sup> T cells in both blood and lymph node compartments during AHI. In contrast, we found no increase in T follicular helper cells (Tfh) and a lack of association between circulating Tfh and lymph node Tfh during AHI. Furthermore, early B cell depletion, particularly in resting memory B cells, was observed in blood but not in lymph nodes during AHI. Additionally, during AHI, plasmacytoid dendritic cell activation was increased in lymph nodes but not in blood. These findings suggest that certain immune cell phenotypes and dynamics are unique in lymph nodes compared to blood during AHI. Understanding the immune cell alteration in these compartments during AHI may help define the mechanisms leading to lack of immune control in natural HIV infection.</div></div>","PeriodicalId":17552,"journal":{"name":"Journal of Virus Eradication","volume":"11 2","pages":"Article 100598"},"PeriodicalIF":3.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144185653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-01DOI: 10.1016/j.jve.2025.100599
Shari Margolese , Robert Reinhard , Renee Masching , Nazanin Mohammadzadeh , Petronela Ancuta , Jonathan B. Angel , Jean-Pierre Routy , Sharon Walmsley , Nicolas Chomont , Cecilia T. Costiniuk
{"title":"Reflections upon a life well-lived: A tribute to Ron Rosenes","authors":"Shari Margolese , Robert Reinhard , Renee Masching , Nazanin Mohammadzadeh , Petronela Ancuta , Jonathan B. Angel , Jean-Pierre Routy , Sharon Walmsley , Nicolas Chomont , Cecilia T. Costiniuk","doi":"10.1016/j.jve.2025.100599","DOIUrl":"10.1016/j.jve.2025.100599","url":null,"abstract":"","PeriodicalId":17552,"journal":{"name":"Journal of Virus Eradication","volume":"11 2","pages":"Article 100599"},"PeriodicalIF":3.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144240739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-05-20DOI: 10.1016/j.jve.2025.100597
Chenbo Yang , Ling Tong , Jing Xue
Antiretroviral therapy (ART) has transformed HIV from a fatal disease into manageable circumstance. However, the HIV reservoirs remain a main barrier to complete cure. This review emphasized when, where and how the latency is established, with focus on various host factors and viral proteins. We highlight the importance of Tat and Rev in facilitating the export and stability of HIV latency. We discuss how transcription factors such as NFκB, NFAT, and Sp1 regulate HIV gene expression during T cell activation, while other factors like MRTFB, BACH2, FOXO1, HMGB1, SAMHD1, APOBEC3, TRIM5, Wnt/β-catenin and LEDGF/p75 also contribute to the persistence of reservoirs. Recent studies have also identified novel restriction and immune regulatory factors such as, LAPTM5, KRT72, and CARD8, directly or indirectly influencing HIV 1 latency. The advancements in CRISPR screening technology have also identified novel host factors, such as FBXO34, FTSJ3, TMEM178A, NICN1, PEBP1, ZNF304 and ORC1, that are associated with HIV-1 latency. These findings underscore the multifaceted nature of viral latency and ongoing need for research to develop effective strategies for viral eradication.
{"title":"HIV-1 latency: From acquaintance to confidant","authors":"Chenbo Yang , Ling Tong , Jing Xue","doi":"10.1016/j.jve.2025.100597","DOIUrl":"10.1016/j.jve.2025.100597","url":null,"abstract":"<div><div>Antiretroviral therapy (ART) has transformed HIV from a fatal disease into manageable circumstance. However, the HIV reservoirs remain a main barrier to complete cure. This review emphasized when, where and how the latency is established, with focus on various host factors and viral proteins. We highlight the importance of Tat and Rev in facilitating the export and stability of HIV latency. We discuss how transcription factors such as NFκB, NFAT, and Sp1 regulate HIV gene expression during T cell activation, while other factors like MRTFB, BACH2, FOXO1, HMGB1, SAMHD1, APOBEC3, TRIM5, Wnt/β-catenin and LEDGF/p75 also contribute to the persistence of reservoirs. Recent studies have also identified novel restriction and immune regulatory factors such as, LAPTM5, KRT72, and CARD8, directly or indirectly influencing HIV 1 latency. The advancements in CRISPR screening technology have also identified novel host factors, such as FBXO34, FTSJ3, TMEM178A, NICN1, PEBP1, ZNF304 and ORC1, that are associated with HIV-1 latency. These findings underscore the multifaceted nature of viral latency and ongoing need for research to develop effective strategies for viral eradication.</div></div>","PeriodicalId":17552,"journal":{"name":"Journal of Virus Eradication","volume":"11 2","pages":"Article 100597"},"PeriodicalIF":3.5,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144115769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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