Pub Date : 2024-12-30eCollection Date: 2024-12-01DOI: 10.1016/j.jve.2024.100581
Daniele Focosi, Pietro Giorgio Spezia, Fabrizio Maggi
{"title":"Fixation and reversion of mutations in the receptor-binding domain of the SARS-CoV-2 spike protein: A 2020-2024 analysis.","authors":"Daniele Focosi, Pietro Giorgio Spezia, Fabrizio Maggi","doi":"10.1016/j.jve.2024.100581","DOIUrl":"10.1016/j.jve.2024.100581","url":null,"abstract":"","PeriodicalId":17552,"journal":{"name":"Journal of Virus Eradication","volume":"10 4","pages":"100581"},"PeriodicalIF":3.5,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11755027/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-27eCollection Date: 2024-12-01DOI: 10.1016/j.jve.2024.100580
Maximillian Kolbe Domapielle, Sadat Zakari Abugbila, Marshall Kala
The uptake of antiretroviral therapy (ART) is critical to meeting the global HIV treatment goal of 95-95-95 by 2025. Although a few Sub-Saharan African countries have already achieved this target, the prevalence of bypassing primary ART centres in many countries in the subregion has negative implications for ART uptake and use. This study used the access to health services framework to analyse the evidence and factors contributing to bypassing primary ART centres by individuals in the sub-region seeking HIV care and support. We found compelling evidence of the prevalence of ART clients bypassing their primary ART centres in search of specialised care in higher-tiered health facilities. Others use bypassing to conceal their HIV-positive status to avoid social stigma. We argue that introducing specialised and differentiated ART at the primary level of care can address this phenomenon. While we anticipate that this measure will satisfy clients' desire for specialised care, we recommend enhancing public awareness about the effectiveness of ART to reduce stigma towards ART clients. Legislation and strict enforcement of anti-HIV stigma laws, which outlaw and criminalise stigmatising people living with HIV (PLHIV), could potentially be an effective stigma-deterring measure. To complement this effort, PLHIV should be empowered to understand legislative instruments and steps to take when confidentiality and discriminatory issues arise. We recommend further research in Sub-Saharan Africa to investigate the relationship between bypassing primary ART centres and client adherence. The findings will help design appropriate strategies to increase ART uptake at primary ART centres.
{"title":"Bypassing primary antiretroviral therapy centres in Sub-Saharan Africa: An integrative review of the theoretical and empirical literature.","authors":"Maximillian Kolbe Domapielle, Sadat Zakari Abugbila, Marshall Kala","doi":"10.1016/j.jve.2024.100580","DOIUrl":"10.1016/j.jve.2024.100580","url":null,"abstract":"<p><p>The uptake of antiretroviral therapy (ART) is critical to meeting the global HIV treatment goal of 95-95-95 by 2025. Although a few Sub-Saharan African countries have already achieved this target, the prevalence of bypassing primary ART centres in many countries in the subregion has negative implications for ART uptake and use. This study used the access to health services framework to analyse the evidence and factors contributing to bypassing primary ART centres by individuals in the sub-region seeking HIV care and support. We found compelling evidence of the prevalence of ART clients bypassing their primary ART centres in search of specialised care in higher-tiered health facilities. Others use bypassing to conceal their HIV-positive status to avoid social stigma. We argue that introducing specialised and differentiated ART at the primary level of care can address this phenomenon. While we anticipate that this measure will satisfy clients' desire for specialised care, we recommend enhancing public awareness about the effectiveness of ART to reduce stigma towards ART clients. Legislation and strict enforcement of anti-HIV stigma laws, which outlaw and criminalise stigmatising people living with HIV (PLHIV), could potentially be an effective stigma-deterring measure. To complement this effort, PLHIV should be empowered to understand legislative instruments and steps to take when confidentiality and discriminatory issues arise. We recommend further research in Sub-Saharan Africa to investigate the relationship between bypassing primary ART centres and client adherence. The findings will help design appropriate strategies to increase ART uptake at primary ART centres.</p>","PeriodicalId":17552,"journal":{"name":"Journal of Virus Eradication","volume":"10 4","pages":"100580"},"PeriodicalIF":3.5,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11751520/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-13eCollection Date: 2024-12-01DOI: 10.1016/j.jve.2024.100575
Shreyal Maikoo, Robert-Jan Palstra, Krista L Dong, Tokameh Mahmoudi, Thumbi Ndung'u, Paradise Madlala
Sub-Saharan Africa accounts for almost 70 % of people living with HIV (PLWH) worldwide, with the greatest numbers centred in South Africa where 98 % of infections are caused by subtype C (HIV-1C). However, HIV-1 subtype B (HIV-1B), prevalent in Europe and North America, has been the focus of most cure research and testing despite making up only 12 % of HIV-1 infections globally. Development of latency models for non-subtype B viruses is a necessary step to address this disproportionate focus. Furthermore, the impact of genetic variation between viral subtypes, specifically within the long terminal repeat (LTR) element of the viral transcriptional promoter on latency reversal, remains unclear. To address this scientific gap, we constructed a minimal genome retroviral vector expressing HIV-1C consensus transactivator of transcription protein (Tat) and green fluorescent protein (GFP) under the control of either HIV-1C consensus LTR (C731CC) or the transmitted/founder (T/F) LTRs derived from PLWH (CT/F731CC), produced corresponding LTR pseudotyped viruses using a vesicular stomatitis virus (VSV-G) pseudotyped Envelope vector and the pCMVΔR8.91 packaging vector containing HIV-1 accessory and rev genes. Viruses produced in this way were used to infect Jurkat E6 and primary CD4+ T cells in vitro. By enriching for latently infected cells, and treating them with different latency reversing agents, we developed an HIV-1C latency model that demonstrated that the HIV-1C consensus LTR has lower reactivation potential compared to its HIV-1B counterpart. Furthermore, HIV-1C T/F LTR pseudotyped proviral genetic variants exhibited a heterogenous reactivation response which was modulated by host cell (genetic) variation. Our data suggests that genetic variation both within and between HIV-1 subtypes influences latency reversal. Future studies should investigate the specific role of variation in host cellular environment on reactivation differences.
{"title":"Development of a latency model for HIV-1 subtype C and the impact of long terminal repeat element genetic variation on latency reversal.","authors":"Shreyal Maikoo, Robert-Jan Palstra, Krista L Dong, Tokameh Mahmoudi, Thumbi Ndung'u, Paradise Madlala","doi":"10.1016/j.jve.2024.100575","DOIUrl":"10.1016/j.jve.2024.100575","url":null,"abstract":"<p><p>Sub-Saharan Africa accounts for almost 70 % of people living with HIV (PLWH) worldwide, with the greatest numbers centred in South Africa where 98 % of infections are caused by subtype C (HIV-1C). However, HIV-1 subtype B (HIV-1B), prevalent in Europe and North America, has been the focus of most cure research and testing despite making up only 12 % of HIV-1 infections globally. Development of latency models for non-subtype B viruses is a necessary step to address this disproportionate focus. Furthermore, the impact of genetic variation between viral subtypes, specifically within the long terminal repeat (LTR) element of the viral transcriptional promoter on latency reversal, remains unclear. To address this scientific gap, we constructed a minimal genome retroviral vector expressing HIV-1C consensus transactivator of transcription protein (Tat) and green fluorescent protein (GFP) under the control of either HIV-1C consensus LTR (C731CC) or the transmitted/founder (T/F) LTRs derived from PLWH (C<sub>T/F</sub>731CC), produced corresponding LTR pseudotyped viruses using a vesicular stomatitis virus (VSV-G) pseudotyped Envelope vector and the pCMVΔR8.91 packaging vector containing HIV-1 accessory and <i>rev</i> genes. Viruses produced in this way were used to infect Jurkat E6 and primary CD4<sup>+</sup> T cells <i>in vitro</i>. By enriching for latently infected cells, and treating them with different latency reversing agents, we developed an HIV-1C latency model that demonstrated that the HIV-1C consensus LTR has lower reactivation potential compared to its HIV-1B counterpart. Furthermore, HIV-1C T/F LTR pseudotyped proviral genetic variants exhibited a heterogenous reactivation response which was modulated by host cell (genetic) variation. Our data suggests that genetic variation both within and between HIV-1 subtypes influences latency reversal. Future studies should investigate the specific role of variation in host cellular environment on reactivation differences.</p>","PeriodicalId":17552,"journal":{"name":"Journal of Virus Eradication","volume":"10 4","pages":"100575"},"PeriodicalIF":3.5,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11730875/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142983723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: While certain studies have demonstrated that antiviral treatment administered to index patients with influenza can mitigate the transmission within households, the efficacy of anti-SARS-CoV-2 agents in curtailing household transmission remains to be conclusively established.
Methods: A retrospective study conducted from April 2021 to May 2022 across multiple centers in Thailand compared 892 individuals treated with favipiravir to 84 who received standard treatment among mild to moderate COVID-19 index patients. The study focused on the impact of favipiravir treatment in reducing household SARS-CoV-2 transmission by examining the secondary attack rate.
Results: Favipiravir significantly reduced household SARS-CoV-2 transmission, comparing 1836 household contacts with favipiravir-treated index cases to 170 contacts whose index cases received standard care. Favipiravir led to a 58 % secondary attack rate, substantially lower than the 71.8 % observed with standard treatment, representing a 54 % reduction in transmission likelihood, with an odds ratio of 0.46 (95 % confidence interval [CI] [0.23-0.89]). Index cases treated with favipiravir also demonstrated a relative risk reduction of 0.19 in transmission (95 % CI [0.11-0.27]). Remarkably, favipiravir effectiveness was most notable in unvaccinated index cases, those with symptomatic infections, individuals living in shared spaces like dormitories, flats, or apartments, and those not adhering to mask-wearing within their households.
Conclusions: Favipiravir has demonstrated in this study an indirect role in reducing household SARS-CoV-2 transmission, showing notable efficacy in symptomatic and unvaccinated index cases. This breakthrough highlights its potential in broader public health strategies. Exploring the roles and challenges of other anti-SARS-CoV-2 agents remains a vital goal in ongoing research.
{"title":"Assessing favipiravir impact on SARS-CoV-2 transmission within households: Insights from a multi-center study (FaviPrev).","authors":"Taweegrit Siripongboonsitti, Marisa Muadchimkaew, Kriangkrai Tawinprai, Ornisa Issaranon, Wichuda Meepholkij, Pureepat Arttawejkul, Apiradee Vararungzarit, Onwalee Dhissayakamol, Wilaiporn Preeyachit, Kamonwan Soonklang, Nithi Mahanonda","doi":"10.1016/j.jve.2024.100576","DOIUrl":"10.1016/j.jve.2024.100576","url":null,"abstract":"<p><strong>Background: </strong>While certain studies have demonstrated that antiviral treatment administered to index patients with influenza can mitigate the transmission within households, the efficacy of anti-SARS-CoV-2 agents in curtailing household transmission remains to be conclusively established.</p><p><strong>Methods: </strong>A retrospective study conducted from April 2021 to May 2022 across multiple centers in Thailand compared 892 individuals treated with favipiravir to 84 who received standard treatment among mild to moderate COVID-19 index patients. The study focused on the impact of favipiravir treatment in reducing household SARS-CoV-2 transmission by examining the secondary attack rate.</p><p><strong>Results: </strong>Favipiravir significantly reduced household SARS-CoV-2 transmission, comparing 1836 household contacts with favipiravir-treated index cases to 170 contacts whose index cases received standard care. Favipiravir led to a 58 % secondary attack rate, substantially lower than the 71.8 % observed with standard treatment, representing a 54 % reduction in transmission likelihood, with an odds ratio of 0.46 (95 % confidence interval [CI] [0.23-0.89]). Index cases treated with favipiravir also demonstrated a relative risk reduction of 0.19 in transmission (95 % CI [0.11-0.27]). Remarkably, favipiravir effectiveness was most notable in unvaccinated index cases, those with symptomatic infections, individuals living in shared spaces like dormitories, flats, or apartments, and those not adhering to mask-wearing within their households.</p><p><strong>Conclusions: </strong>Favipiravir has demonstrated in this study an indirect role in reducing household SARS-CoV-2 transmission, showing notable efficacy in symptomatic and unvaccinated index cases. This breakthrough highlights its potential in broader public health strategies. Exploring the roles and challenges of other anti-SARS-CoV-2 agents remains a vital goal in ongoing research.</p>","PeriodicalId":17552,"journal":{"name":"Journal of Virus Eradication","volume":"10 4","pages":"100576"},"PeriodicalIF":3.5,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11721425/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chronic hepatitis B (HBV) and C (HCV) are major health challenges in Thailand, with Phetchabun province, a known HCV-endemic area, being a key target for elimination efforts. This study aimed to assess HBV prevalence and identify associated risk factors in this province. Data was collected from three cross-sectional population studies: (1) adults in 2015 (n = 1,667, age 30-64 years), (2) young adults in 2017 (n = 1,453, age 18-30 years), both from high HCV-endemic districts, and (3) a province-wide study in 2018 (n = 4,769, age 35-64 years). Plasma samples were tested for HBsAg using the ARCHITECT assay. Results showed HBsAg seropositivity in 3.1 % of young adults in high-endemic districts, with significant associations with age, education, injecting drug use, and MSM behavior. Among adults, HBsAg prevalence was 5.9 %, linked to age and family liver disease history. Province-wide, 6.3 % of adults tested positive, with factors like gender and history of blood donation playing significant roles. Notably, age and blood donation were protective factors against HBV in adults. Analysis revealed a moderate HBV prevalence in those born before Thailand Expanded Program on Immunization (EPI) program, while those born after had rates below 1 %. The findings emphasize distinct HBV transmission patterns in different age groups, influenced by social and behavioral shifts. This knowledge is crucial for effective hepatitis elimination strategies in the Phetchabun province and nationwide.
{"title":"Hepatitis B prevalence in an endemic area of hepatitis C virus: A population-based study implicated in hepatitis elimination in Thailand.","authors":"Nawarat Posuwan, Rujipat Wasitthankasem, Napaporn Pimsing, Wijittra Phaengkha, Saranya Ngamnimit, Preeyaporn Vichaiwattana, Sirapa Klinfueng, Maneerat Raksayod, Yong Poovorawan","doi":"10.1016/j.jve.2024.100577","DOIUrl":"https://doi.org/10.1016/j.jve.2024.100577","url":null,"abstract":"<p><p>Chronic hepatitis B (HBV) and C (HCV) are major health challenges in Thailand, with Phetchabun province, a known HCV-endemic area, being a key target for elimination efforts. This study aimed to assess HBV prevalence and identify associated risk factors in this province. Data was collected from three cross-sectional population studies: (1) adults in 2015 (n = 1,667, age 30-64 years), (2) young adults in 2017 (n = 1,453, age 18-30 years), both from high HCV-endemic districts, and (3) a province-wide study in 2018 (n = 4,769, age 35-64 years). Plasma samples were tested for HBsAg using the ARCHITECT assay. Results showed HBsAg seropositivity in 3.1 % of young adults in high-endemic districts, with significant associations with age, education, injecting drug use, and MSM behavior. Among adults, HBsAg prevalence was 5.9 %, linked to age and family liver disease history. Province-wide, 6.3 % of adults tested positive, with factors like gender and history of blood donation playing significant roles. Notably, age and blood donation were protective factors against HBV in adults. Analysis revealed a moderate HBV prevalence in those born before Thailand Expanded Program on Immunization (EPI) program, while those born after had rates below 1 %. The findings emphasize distinct HBV transmission patterns in different age groups, influenced by social and behavioral shifts. This knowledge is crucial for effective hepatitis elimination strategies in the Phetchabun province and nationwide.</p>","PeriodicalId":17552,"journal":{"name":"Journal of Virus Eradication","volume":"10 4","pages":"100577"},"PeriodicalIF":3.5,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11699449/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-09eCollection Date: 2024-12-01DOI: 10.1016/j.jve.2024.100570
Maaike A J Noorman, John B F de Wit, Tamika A Marcos, Sarah E Stutterheim, Thijs Albers, Kai J Jonas, Chantal den Daas
Background: Community engagement is important for inclusive HIV cure development. This study evaluates current engagement in HIV cure research among affected communities in the Netherlands by analyzing awareness, interest, and information-seeking behavior. It also identifies participant characteristics and HIV-related illness perceptions linked to each engagement stage.
Methods: A cross-sectional survey was conducted from July 2023 to March 2024, involving 499 people with HIV and 578 individuals without HIV, including partners and gay, bisexual, and other men who have sex with men. Multivariate regression analyses examined the relationships between participant characteristics, HIV-related illness perceptions, and three outcomes: awareness, interest, and information-seeking.
Results: The mean awareness was 3.08 (SD = 0.99) interest was higher at 3.67 (SD = 0.85), while the information-seeking frequency was lower at 2.33 (SD = 0.97). Higher awareness was seen in older participants, non-cisgender men, and those with increased perceived control and comprehensibility of HIV. Interest in cure research was higher among people with HIV, those with a migration background, individuals with steady partner(s), and those experiencing greater HIV-related concerns, negative HIV-related emotions, and better HIV comprehension. Information-seeking frequency was greater among people with HIV, those with a bachelor's degree, individuals from a migration background, those with steady partner(s), and those perceiving more severe HIV-related symptoms, and heightened concerns and negative emotions about HIV.
Conclusion: While moderate awareness exists, engagement remains passive with limited information-seeking; however, significant interest in a cure underscores the need for enhanced communication efforts to foster inclusive HIV cure development.
{"title":"Relatively high interest but limited active engagement in HIV cure research: Awareness, interest, and information-seeking among affected communities in the Netherlands.","authors":"Maaike A J Noorman, John B F de Wit, Tamika A Marcos, Sarah E Stutterheim, Thijs Albers, Kai J Jonas, Chantal den Daas","doi":"10.1016/j.jve.2024.100570","DOIUrl":"https://doi.org/10.1016/j.jve.2024.100570","url":null,"abstract":"<p><strong>Background: </strong>Community engagement is important for inclusive HIV cure development. This study evaluates current engagement in HIV cure research among affected communities in the Netherlands by analyzing awareness, interest, and information-seeking behavior. It also identifies participant characteristics and HIV-related illness perceptions linked to each engagement stage.</p><p><strong>Methods: </strong>A cross-sectional survey was conducted from July 2023 to March 2024, involving 499 people with HIV and 578 individuals without HIV, including partners and gay, bisexual, and other men who have sex with men. Multivariate regression analyses examined the relationships between participant characteristics, HIV-related illness perceptions, and three outcomes: awareness, interest, and information-seeking.</p><p><strong>Results: </strong>The mean awareness was 3.08 (SD = 0.99) interest was higher at 3.67 (SD = 0.85), while the information-seeking frequency was lower at 2.33 (SD = 0.97). Higher awareness was seen in older participants, non-cisgender men, and those with increased perceived control and comprehensibility of HIV. Interest in cure research was higher among people with HIV, those with a migration background, individuals with steady partner(s), and those experiencing greater HIV-related concerns, negative HIV-related emotions, and better HIV comprehension. Information-seeking frequency was greater among people with HIV, those with a bachelor's degree, individuals from a migration background, those with steady partner(s), and those perceiving more severe HIV-related symptoms, and heightened concerns and negative emotions about HIV.</p><p><strong>Conclusion: </strong>While moderate awareness exists, engagement remains passive with limited information-seeking; however, significant interest in a cure underscores the need for enhanced communication efforts to foster inclusive HIV cure development.</p>","PeriodicalId":17552,"journal":{"name":"Journal of Virus Eradication","volume":"10 4","pages":"100570"},"PeriodicalIF":3.5,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11697764/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-03eCollection Date: 2024-12-01DOI: 10.1016/j.jve.2024.100569
Shana Yi, David Truong, Brian Conway
<p><strong>Background: </strong>Several clinical trials, including the recently published the GRAND PLAN study from Vancouver Infectious Diseases Center (VIDC), have demonstrated the efficacy of hepatitis C (HCV) therapy among active drug users, including those facing significant addiction-related and social challenges. In the GRAND PLAN, we documented sustained virological response post-treatment Week12 (SVR12) in 108/117 (92.3 %) individuals (108/111 (mITT) or 97.3 % of those reaching the SVR12 timepoint) receiving an 8-week course of glecaprevir/pibrentasvir (G/P), with almost all using fentanyl and over half being unstably housed. Data on the maintenance of this favorable outcome in the long-term in such a population with a significant risk of reinfection is limited. We hypothesized that the offer of ongoing multidisciplinary care (including addiction care) after SVR12 was achieved would reduce the likelihood of loss to follow up, HCV reinfection or death and consolidate the gains achieved by initial engagement in care to diagnose and treat HCV infection.</p><p><strong>Methods: </strong>The inception cohort for this analysis was the 108 individuals achieving a cure of HCV infection within the GRAND PLAN study. All were offered the opportunity to continue to receive care at the VIDC. This is a multidisciplinary model of care to address medical, mental health, social and addiction-related concerns on an ongoing basis. This included, if necessary, opiate agonist and safer supply therapy, usually provided by the pharmacy adjacent to our inner-city campus. Among those choosing to be retained in care, the endpoint of this analysis was loss to follow up, mortality and HCV reinfection and their correlates. Reinfection was ascertained by repeat HCV RNA testing every 6 months, more frequently if clinically indicated.</p><p><strong>Results: </strong>Of the 108 individuals making up the inception cohort for this analysis, all chose to remain in care at the VIDC. We note a median age of 47 (22-75) years, 28 % female, 21.3 % identifying as indigenous, the majority with mild fibrosis (90.8 % F0-F2), slightly more than half with unstable housing. It is of note that we recorded a 20 % decrease in fentanyl users among those who were cured compared to the baseline evaluation of the overall study cohort (73.5 % vs 94.9 %, p < 0.000001). Among the cured individuals, 104 (96.3 %) remained alive, while 4 individuals died of opioid overdoses. Out of the 104 , 99 (95.2 %) remained HCV-free, while 5 (4.8 %) were re-infected. All five have recently initiated repeat HCV therapy at VIDC, 2 of whom are already documented to be cured.</p><p><strong>Conclusion: </strong>Among a population of vulnerable inner-city residents cured of HCV infection within a multidisciplinary program of care at the VIDC, all individuals accepted the offer to remain in long-term follow up, with a statistically significant reduction in fentanyl use over time. In the setting of an ongoing opioid c
{"title":"Long-term outcome in people who use drugs successfully treated for hepatitis C infection with glecaprevir/pibrentasvir.","authors":"Shana Yi, David Truong, Brian Conway","doi":"10.1016/j.jve.2024.100569","DOIUrl":"10.1016/j.jve.2024.100569","url":null,"abstract":"<p><strong>Background: </strong>Several clinical trials, including the recently published the GRAND PLAN study from Vancouver Infectious Diseases Center (VIDC), have demonstrated the efficacy of hepatitis C (HCV) therapy among active drug users, including those facing significant addiction-related and social challenges. In the GRAND PLAN, we documented sustained virological response post-treatment Week12 (SVR12) in 108/117 (92.3 %) individuals (108/111 (mITT) or 97.3 % of those reaching the SVR12 timepoint) receiving an 8-week course of glecaprevir/pibrentasvir (G/P), with almost all using fentanyl and over half being unstably housed. Data on the maintenance of this favorable outcome in the long-term in such a population with a significant risk of reinfection is limited. We hypothesized that the offer of ongoing multidisciplinary care (including addiction care) after SVR12 was achieved would reduce the likelihood of loss to follow up, HCV reinfection or death and consolidate the gains achieved by initial engagement in care to diagnose and treat HCV infection.</p><p><strong>Methods: </strong>The inception cohort for this analysis was the 108 individuals achieving a cure of HCV infection within the GRAND PLAN study. All were offered the opportunity to continue to receive care at the VIDC. This is a multidisciplinary model of care to address medical, mental health, social and addiction-related concerns on an ongoing basis. This included, if necessary, opiate agonist and safer supply therapy, usually provided by the pharmacy adjacent to our inner-city campus. Among those choosing to be retained in care, the endpoint of this analysis was loss to follow up, mortality and HCV reinfection and their correlates. Reinfection was ascertained by repeat HCV RNA testing every 6 months, more frequently if clinically indicated.</p><p><strong>Results: </strong>Of the 108 individuals making up the inception cohort for this analysis, all chose to remain in care at the VIDC. We note a median age of 47 (22-75) years, 28 % female, 21.3 % identifying as indigenous, the majority with mild fibrosis (90.8 % F0-F2), slightly more than half with unstable housing. It is of note that we recorded a 20 % decrease in fentanyl users among those who were cured compared to the baseline evaluation of the overall study cohort (73.5 % vs 94.9 %, p < 0.000001). Among the cured individuals, 104 (96.3 %) remained alive, while 4 individuals died of opioid overdoses. Out of the 104 , 99 (95.2 %) remained HCV-free, while 5 (4.8 %) were re-infected. All five have recently initiated repeat HCV therapy at VIDC, 2 of whom are already documented to be cured.</p><p><strong>Conclusion: </strong>Among a population of vulnerable inner-city residents cured of HCV infection within a multidisciplinary program of care at the VIDC, all individuals accepted the offer to remain in long-term follow up, with a statistically significant reduction in fentanyl use over time. In the setting of an ongoing opioid c","PeriodicalId":17552,"journal":{"name":"Journal of Virus Eradication","volume":"10 4","pages":"100569"},"PeriodicalIF":3.5,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11728950/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142979063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-03eCollection Date: 2024-12-01DOI: 10.1016/j.jve.2024.100571
Jiayi Wang, Lingyao Du, Dongmei Zhang, Chen Zhou, Yilan Zeng, Miao Liu, Xing Cheng, Xiaona Song, Han Chen, Ning Han, Enqiang Chen, Hong Tang
Background: Hepatitis C virus (HCV) eradication with sofosbuvir/velpatasvir (SOF/VEL) represents a significant advancement, offering hope for eliminating the virus in diverse patient populations. But real-world data on its effectiveness and safety remains scarce for patients with chronic hepatitis C (CHC) in China, especially those with HCV GT3b, cirrhosis, hepato-cellular carcinoma (HCC), or HCV/hepatitis B (HBV), HCV/HIV, or HCV/HBV/HIV coinfection.
Methods: In this real-world prospective observational study, we recruited patients from the West China Hospital and Public Health Clinical Center of Chengdu in China. Patients included adults with with CHC and any genotype (GT), with or without cirrhosis, hepatocellular carcinoma (HCC), HCV/HBV, HCV/HIV, or HCV/HBV/HIV coinfection. Patients were administered SOF/VEL (400/100 mg) ± ribavirin (RBV) once daily for 12 weeks. The primary efficacy endpoint was sustained virological response at post-treatment week 12 (SVR12). Adverse events (AEs) were evaluated during treatment.
Results: The study included 483 patients with HCV genotypes 1, 2, 3, 6 and uncertain ones. Among them, 35.4 % (171/483, ITT) and 36.7 % (166/452, mITT) received SOF/VEL + RBV. At the end of treatment , 99.2 % (ITT, 479/483) and 99.1 % (mITT, 448/452) of patients had undetectable HCV RNA. SVR12 rates were 92.8 % [intention to treat (ITT), 448/483] and 99.1 % [modified ITT (mITT), 448/452]. In the mITT analysis, SVR12 for patients with HCV GT3b, those with cirrhosis or HCC, and those coinfected with HBV/HIV was 99.2 % (130/131), 99.4 % (168/169), and 97.6 % (40/41), respectively. The albumin-bilirubin (ALBI) (-3.01 vs. -3.18 P < 0.001), Fibrosis-4 (FIB4) Index (2.53 vs. 1.88, P = 0.004) and AST to Platelet Ratio Index (APRI) (0.99 vs. 0.44, P < 0.001) scores showed a significant decrease from baseline to SVR12. No patients experienced grade 3-5 AEs.
Conclusions: Although a high proportion of patients included in this study had HCV GT3b, cirrhosis, HCC, or HCV/HBV, HCV/HIV, or HCV/HBV/HIV coinfection, SOF/VEL ± RBV was highly effective and well tolerated in Chinese patients with CHC.
背景:索非布韦/维帕他韦(SOF/VEL)根除丙型肝炎病毒(HCV)是一项重大进展,为在不同患者群体中消除病毒提供了希望。但在中国慢性丙型肝炎(CHC)患者,特别是HCV GT3b、肝硬化、肝细胞癌(HCC)、HCV/乙型肝炎(HBV)、HCV/HIV或HCV/HBV/HIV合并感染的患者,其有效性和安全性的真实数据仍然很少。方法:在这项现实世界的前瞻性观察研究中,我们从中国成都华西医院和公共卫生临床中心招募了患者。患者包括患有CHC和任何基因型(GT)的成年人,伴有或不伴有肝硬化、肝细胞癌(HCC)、HCV/HBV、HCV/HIV或HCV/HBV/HIV合并感染。患者给予SOF/VEL (400/100 mg)±利巴韦林(RBV),每日1次,连续12周。主要疗效终点是治疗后第12周的持续病毒学应答(SVR12)。在治疗期间评估不良事件(ae)。结果:纳入HCV基因型1、2、3、6及不确定型患者483例。其中,35.4% (171/483,ITT)和36.7% (166/452,mITT)接受了SOF/VEL + RBV治疗。在治疗结束时,99.2% (ITT, 479/483)和99.1% (mITT, 448/452)的患者无法检测到HCV RNA。SVR12率为92.8%[意向治疗(ITT), 448/483]和99.1%[改良ITT (mITT), 448/452]。在mITT分析中,HCV GT3b患者、肝硬化或HCC患者和HBV/HIV合并感染患者的SVR12分别为99.2%(130/131)、99.4%(168/169)和97.6%(40/41)。白蛋白-胆红素(ALBI) (-3.01 vs. -3.18 P vs. 1.88, P = 0.004)和AST /血小板比值指数(APRI) (0.99 vs. 0.44, P)结论:尽管本研究中有很高比例的患者患有HCV GT3b、肝硬化、HCC或HCV/HBV、HCV/HIV或HCV/HBV/HIV合并感染,SOF/VEL±RBV对中国CHC患者非常有效且耐受性良好。
{"title":"Real-life study on the effectiveness and safety of sofosbuvir/velpatasvir-based antiviral agents for hepatitis C eradication in Chinese patients.","authors":"Jiayi Wang, Lingyao Du, Dongmei Zhang, Chen Zhou, Yilan Zeng, Miao Liu, Xing Cheng, Xiaona Song, Han Chen, Ning Han, Enqiang Chen, Hong Tang","doi":"10.1016/j.jve.2024.100571","DOIUrl":"10.1016/j.jve.2024.100571","url":null,"abstract":"<p><strong>Background: </strong>Hepatitis C virus (HCV) eradication with sofosbuvir/velpatasvir (SOF/VEL) represents a significant advancement, offering hope for eliminating the virus in diverse patient populations. But real-world data on its effectiveness and safety remains scarce for patients with chronic hepatitis C (CHC) in China, especially those with HCV GT3b, cirrhosis, hepato-cellular carcinoma (HCC), or HCV/hepatitis B (HBV), HCV/HIV, or HCV/HBV/HIV coinfection.</p><p><strong>Methods: </strong>In this real-world prospective observational study, we recruited patients from the West China Hospital and Public Health Clinical Center of Chengdu in China. Patients included adults with with CHC and any genotype (GT), with or without cirrhosis, hepatocellular carcinoma (HCC), HCV/HBV, HCV/HIV, or HCV/HBV/HIV coinfection. Patients were administered SOF/VEL (400/100 mg) ± ribavirin (RBV) once daily for 12 weeks. The primary efficacy endpoint was sustained virological response at post-treatment week 12 (SVR12). Adverse events (AEs) were evaluated during treatment.</p><p><strong>Results: </strong>The study included 483 patients with HCV genotypes 1, 2, 3, 6 and uncertain ones. Among them, 35.4 % (171/483, ITT) and 36.7 % (166/452, mITT) received SOF/VEL + RBV. At the end of treatment , 99.2 % (ITT, 479/483) and 99.1 % (mITT, 448/452) of patients had undetectable HCV RNA. SVR12 rates were 92.8 % [intention to treat (ITT), 448/483] and 99.1 % [modified ITT (mITT), 448/452]. In the mITT analysis, SVR12 for patients with HCV GT3b, those with cirrhosis or HCC, and those coinfected with HBV/HIV was 99.2 % (130/131), 99.4 % (168/169), and 97.6 % (40/41), respectively. The albumin-bilirubin (ALBI) (-3.01 <i>vs.</i> -3.18 <i>P</i> < 0.001), Fibrosis-4 (FIB4) Index (2.53 <i>vs.</i> 1.88, <i>P</i> = 0.004) and AST to Platelet Ratio Index (APRI) (0.99 <i>vs.</i> 0.44, <i>P</i> < 0.001) scores showed a significant decrease from baseline to SVR12. No patients experienced grade 3-5 AEs.</p><p><strong>Conclusions: </strong>Although a high proportion of patients included in this study had HCV GT3b, cirrhosis, HCC, or HCV/HBV, HCV/HIV, or HCV/HBV/HIV coinfection, SOF/VEL ± RBV was highly effective and well tolerated in Chinese patients with CHC.</p>","PeriodicalId":17552,"journal":{"name":"Journal of Virus Eradication","volume":"10 4","pages":"100571"},"PeriodicalIF":3.5,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11681871/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142903305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01DOI: 10.1016/j.jve.2024.100392
Jozefien De Clercq , Marie-Angélique De Scheerder , Sophie Vanherrewege , Els Caluwé , Nathalie Moreels , Danny Delooze , Annemieke Dhondt , Marc Coppens , Stefaan J. Vandecasteele , Sabine D. Allard , Coca Necsoi , Stéphane De Wit , Sarah Gerlo , Linos Vandekerckhove
Background
The events during acute HIV infection (AHI) set the stage for the subsequent course of the disease. Early initiation of antiretroviral therapy (ART) has been associated with favorable immunovirological outcomes, yet the precise impact of ART timing during AHI remains unclear, particularly on lymphoid tissues.
Materials and methods
The ACS cohort is a prospective cohort study in Belgium, collecting longitudinal clinical data and human bodily material (HBM) from people diagnosed and treated during AHI. The aim of the cohort is to study the impact of ART initiation during AHI on HIV reservoir and immune dysfunction in peripheral blood and anatomical sanctuary sites, as well as its effect on the gut microbiome. The cohort consists of two HBM sampling trajectories: one limited (blood, stool and leukapheresis) and a more extensive one (blood, stool, leukapheresis, colonoscopy, inguinal lymph node excision and lumbar puncture). Here we describe the baseline characteristics, immunovirological outcomes, safety and tolerability of HBM sampling.
Results
Between March 2016 and April 2024, 47 participants were enrolled, predominantly men who have sex with men (MSM), with a median age of 36 years [IQR 30–43.5]. Almost 90 % of participants initiated ART within 72 h after study inclusion, irrespective of HBM sampling trajectory. The timing of ART initiation according to the Fiebig stage did not significantly impact immune recovery (CD4/CD8 ratio ≥1) or the time to viral suppression. Approximately 40 % of participants opted for the extensive HBM sampling trajectory during AHI. However, the participation rate for the extensive trajectory decreased by nearly half at the longitudinal follow-up timepoint. In general, study-related procedures were safe and well-tolerated, with limited procedure-related adverse events (AEs). Inguinal lymph node excision was associated with the highest AE rate, in line with previous reports.
Conclusions
Our findings reaffirm the beneficial effect of ART initiation during AHI on long term immunovirological outcomes, regardless of Fiebig stage at treatment initiation. Additionally, we demonstrate that the collection of HBM during and longitudinally after AHI is safe and feasible, without compromising time to ART initiation. Cohorts that integrate comprehensive clinical data with high-quality HBM samples are essential to longitudinally study the impact of early ART on reservoir dynamics and immune responses across various anatomical sites after AHI.
{"title":"Staging of immuno-virological dynamics during acute HIV infection in a Belgian prospective cohort study","authors":"Jozefien De Clercq , Marie-Angélique De Scheerder , Sophie Vanherrewege , Els Caluwé , Nathalie Moreels , Danny Delooze , Annemieke Dhondt , Marc Coppens , Stefaan J. Vandecasteele , Sabine D. Allard , Coca Necsoi , Stéphane De Wit , Sarah Gerlo , Linos Vandekerckhove","doi":"10.1016/j.jve.2024.100392","DOIUrl":"10.1016/j.jve.2024.100392","url":null,"abstract":"<div><h3>Background</h3><div>The events during acute HIV infection (AHI) set the stage for the subsequent course of the disease. Early initiation of antiretroviral therapy (ART) has been associated with favorable immunovirological outcomes, yet the precise impact of ART timing during AHI remains unclear, particularly on lymphoid tissues.</div></div><div><h3>Materials and methods</h3><div>The ACS cohort is a prospective cohort study in Belgium, collecting longitudinal clinical data and human bodily material (HBM) from people diagnosed and treated during AHI. The aim of the cohort is to study the impact of ART initiation during AHI on HIV reservoir and immune dysfunction in peripheral blood and anatomical sanctuary sites, as well as its effect on the gut microbiome. The cohort consists of two HBM sampling trajectories: one limited (blood, stool and leukapheresis) and a more extensive one (blood, stool, leukapheresis, colonoscopy, inguinal lymph node excision and lumbar puncture). Here we describe the baseline characteristics, immunovirological outcomes, safety and tolerability of HBM sampling.</div></div><div><h3>Results</h3><div>Between March 2016 and April 2024, 47 participants were enrolled, predominantly men who have sex with men (MSM), with a median age of 36 years [IQR 30–43.5]. Almost 90 % of participants initiated ART within 72 h after study inclusion, irrespective of HBM sampling trajectory. The timing of ART initiation according to the Fiebig stage did not significantly impact immune recovery (CD4/CD8 ratio ≥1) or the time to viral suppression. Approximately 40 % of participants opted for the extensive HBM sampling trajectory during AHI. However, the participation rate for the extensive trajectory decreased by nearly half at the longitudinal follow-up timepoint. In general, study-related procedures were safe and well-tolerated, with limited procedure-related adverse events (AEs). Inguinal lymph node excision was associated with the highest AE rate, in line with previous reports.</div></div><div><h3>Conclusions</h3><div>Our findings reaffirm the beneficial effect of ART initiation during AHI on long term immunovirological outcomes, regardless of Fiebig stage at treatment initiation. Additionally, we demonstrate that the collection of HBM during and longitudinally after AHI is safe and feasible, without compromising time to ART initiation. Cohorts that integrate comprehensive clinical data with high-quality HBM samples are essential to longitudinally study the impact of early ART on reservoir dynamics and immune responses across various anatomical sites after AHI.</div></div>","PeriodicalId":17552,"journal":{"name":"Journal of Virus Eradication","volume":"10 3","pages":"Article 100392"},"PeriodicalIF":3.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142358110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01DOI: 10.1016/j.jve.2024.100386
Karine Dubé , Thomas J. Villa , William Freshwater , Brittney Mauk , Annette Rid , Michael J. Peluso
Analytical treatment interruptions (ATIs) are widely used to evaluate HIV cure-related research interventions. However, sex partners of cure-related trial participants might be at risk of acquiring HIV during ATIs. Addressing this risk is key to ensuring the continued success of trials involving ATIs and offer greater acceptability across multiple trials sites. In 2022, the Advancing Clinical Therapeutics Globally (ACTG) Network convened a Partner Protections Working Group (PPWG) to update the 2020 HIV transmission risk toolkit developed by Peluso and colleagues. In our review of the original toolkit, we identified new challenges and needs at the participant, partner and study levels, as well as new evidence on measures to address these needs and more advanced ethical thinking on partner protections in HIV cure-related trials with ATIs. Based on these findings, we developed an updated toolkit that will provide trial participants and their partners with better support to address new and unfamiliar situations and protect partners from undue harm. We present this toolkit, make it available as a resource for cure-related trials with ATIs and discuss possible future directions.
分析性治疗中断(ATI)被广泛用于评估与艾滋病治愈相关的研究干预措施。然而,与治愈相关的试验参与者的性伴侣可能有在 ATI 期间感染 HIV 的风险。解决这一风险是确保涉及 ATIs 的试验持续成功的关键,并能为多个试验点提供更高的可接受性。2022 年,全球推进临床治疗(ACTG)网络召集了合作伙伴保护工作组(PPWG),以更新 Peluso 及其同事开发的 2020 年 HIV 传播风险工具包。在对原始工具包的审查中,我们发现了参与者、伴侣和研究层面的新挑战和新需求,以及解决这些需求的措施的新证据和在使用 ATIs 的 HIV 治愈相关试验中伴侣保护方面更先进的伦理思想。基于这些发现,我们开发了一个更新的工具包,为试验参与者及其伴侣提供更好的支持,以应对新的和陌生的情况,并保护伴侣免受不必要的伤害。我们将介绍该工具包,将其作为ATIs治愈相关试验的资源,并讨论未来可能的发展方向。
{"title":"Partner protections in HIV cure-related trials involving analytical treatment interruption: Updated toolkit to mitigate HIV transmission risk","authors":"Karine Dubé , Thomas J. Villa , William Freshwater , Brittney Mauk , Annette Rid , Michael J. Peluso","doi":"10.1016/j.jve.2024.100386","DOIUrl":"10.1016/j.jve.2024.100386","url":null,"abstract":"<div><div>Analytical treatment interruptions (ATIs) are widely used to evaluate HIV cure-related research interventions. However, sex partners of cure-related trial participants might be at risk of acquiring HIV during ATIs. Addressing this risk is key to ensuring the continued success of trials involving ATIs and offer greater acceptability across multiple trials sites. In 2022, the Advancing Clinical Therapeutics Globally (ACTG) Network convened a Partner Protections Working Group (PPWG) to update the 2020 HIV transmission risk toolkit developed by Peluso and colleagues. In our review of the original toolkit, we identified new challenges and needs at the participant, partner and study levels, as well as new evidence on measures to address these needs and more advanced ethical thinking on partner protections in HIV cure-related trials with ATIs. Based on these findings, we developed an updated toolkit that will provide trial participants and their partners with better support to address new and unfamiliar situations and protect partners from undue harm. We present this toolkit, make it available as a resource for cure-related trials with ATIs and discuss possible future directions.</div></div>","PeriodicalId":17552,"journal":{"name":"Journal of Virus Eradication","volume":"10 3","pages":"Article 100386"},"PeriodicalIF":3.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2055664024000232/pdfft?md5=4998fea798603048df3d77fc61673ab9&pid=1-s2.0-S2055664024000232-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142312731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}