Pub Date : 2022-02-01DOI: 10.1177/13596535211072673
Antoine Troger, S. Burrel, M. Pineton de Chambrun, M. Schmidt, N. Brechot, Olivier Bomme, G. Hékimian, A. Combes, D. Boutolleau, C. Luyt
Background To evaluate the impact of preemptive acyclovir treatment on herpes simplex virus (HSV) bronchopneumonitis in mechanically ventilated patients with HSV oropharyngeal reactivation. Methods Ancillary study of the Preemptive Treatment for Herpesviridae (PTH) clinical trial. Patients included in that trial from one centre (Pitié-Salpêtrière Hospital) and in whom at least one bronchoalveolar lavage (BAL) was performed for ventilator-associated pneumonia suspicion were included in the present study. Rate of HSV bronchopneumonitis, defined as clinical symptoms suggesting of pneumonia and presence of HSV in BAL fluid ≥105 copies of HSV/106 cells, were compared in patients who received either acyclovir or placebo. Results Eighty-three patients were included; 40 having received preemptive acyclovir and 43 having received a placebo, without differences between groups at admission or at randomization. The number of patients who developed HSV bronchopneumonitis was lower among acyclovir-treated patients than among placebo-treated patients (40% vs. 72%, respectively, p = .003). Results were similar when restricted to patients without HSV detected in the lower respiratory tract at randomization (31% vs. 61%, respectively, p = .03). Conclusions Preemptive acyclovir treatment in mechanically ventilated patients with HSV oropharyngeal reactivation reduces HSV bronchopneumonitis rate.
{"title":"Preemptive acyclovir to prevent herpes simplex virus bronchopneumonitis in mechanically ventilated patients with herpes simplex virus oropharyngeal reactivation: An ancillary study of the preemptive treatment for herpesviridae trial","authors":"Antoine Troger, S. Burrel, M. Pineton de Chambrun, M. Schmidt, N. Brechot, Olivier Bomme, G. Hékimian, A. Combes, D. Boutolleau, C. Luyt","doi":"10.1177/13596535211072673","DOIUrl":"https://doi.org/10.1177/13596535211072673","url":null,"abstract":"Background To evaluate the impact of preemptive acyclovir treatment on herpes simplex virus (HSV) bronchopneumonitis in mechanically ventilated patients with HSV oropharyngeal reactivation. Methods Ancillary study of the Preemptive Treatment for Herpesviridae (PTH) clinical trial. Patients included in that trial from one centre (Pitié-Salpêtrière Hospital) and in whom at least one bronchoalveolar lavage (BAL) was performed for ventilator-associated pneumonia suspicion were included in the present study. Rate of HSV bronchopneumonitis, defined as clinical symptoms suggesting of pneumonia and presence of HSV in BAL fluid ≥105 copies of HSV/106 cells, were compared in patients who received either acyclovir or placebo. Results Eighty-three patients were included; 40 having received preemptive acyclovir and 43 having received a placebo, without differences between groups at admission or at randomization. The number of patients who developed HSV bronchopneumonitis was lower among acyclovir-treated patients than among placebo-treated patients (40% vs. 72%, respectively, p = .003). Results were similar when restricted to patients without HSV detected in the lower respiratory tract at randomization (31% vs. 61%, respectively, p = .03). Conclusions Preemptive acyclovir treatment in mechanically ventilated patients with HSV oropharyngeal reactivation reduces HSV bronchopneumonitis rate.","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46182379","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 : 2022-02-01DOI: 10.1177/13596535221083179
H. Razavi
Background: Tools to eliminate Hepatitis B and C have been available and in 2016, the World Health Assembly endorsed the Global Health Sector Strategy for Viral Hepatitis. However, the adoption of hepatitis elimination programs has remained slow. Research design: The Center for Disease Analysis created a universal registry, the Polaris Observatory, to support informed decision-making at the national, regional, and global level for HCV and HBV elimination. The observatory covers 110 countries for HCV and 135 countries for HBV and provides decision analytics, disease burden modeling, economic impact assessments, and training to help countries with their national hepatitis elimination programs. Results: By providing reliable and up-to-date country specific data and analyses, demonstrating the impact of decisions, and providing costing estimates of national programs, our collaborating countries are making informed decisions. Our economic impact analyses also helped countries fund their elimination programs and negotiate prices. Polaris Observatory is an example of impactful private–public partnership where funding by the John C. Martin Foundation allowed support for informed decision-making by public agencies and national governments who would not/could not support such programs on their own. Conclusions: The catalytic funding allowed the Polaris Observatory to demonstrate the utility of such a program resulting in other donors to support this work. The Polaris Observatory is now supported through a portfolio of funders while our work and outputs remain independent to continue support for viral hepatitis elimination by year 2030.
{"title":"Polaris Observatory—supporting informed decision-making at the national, regional, and global levels to eliminate viral hepatitis","authors":"H. Razavi","doi":"10.1177/13596535221083179","DOIUrl":"https://doi.org/10.1177/13596535221083179","url":null,"abstract":"Background: Tools to eliminate Hepatitis B and C have been available and in 2016, the World Health Assembly endorsed the Global Health Sector Strategy for Viral Hepatitis. However, the adoption of hepatitis elimination programs has remained slow. Research design: The Center for Disease Analysis created a universal registry, the Polaris Observatory, to support informed decision-making at the national, regional, and global level for HCV and HBV elimination. The observatory covers 110 countries for HCV and 135 countries for HBV and provides decision analytics, disease burden modeling, economic impact assessments, and training to help countries with their national hepatitis elimination programs. Results: By providing reliable and up-to-date country specific data and analyses, demonstrating the impact of decisions, and providing costing estimates of national programs, our collaborating countries are making informed decisions. Our economic impact analyses also helped countries fund their elimination programs and negotiate prices. Polaris Observatory is an example of impactful private–public partnership where funding by the John C. Martin Foundation allowed support for informed decision-making by public agencies and national governments who would not/could not support such programs on their own. Conclusions: The catalytic funding allowed the Polaris Observatory to demonstrate the utility of such a program resulting in other donors to support this work. The Polaris Observatory is now supported through a portfolio of funders while our work and outputs remain independent to continue support for viral hepatitis elimination by year 2030.","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44618370","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 : 2022-02-01DOI: 10.1177/13596535211067602
A. Mastroianni, S. Greco, Luciana Chidichimo, M. Mauro, Filippo Urso, V. Vangeli
To The Editor, We read with great interest the review on COVID-19 and hepatitis B infection by Alqahtani SA and Buti M [1] underlining the need for screening and possible prophylaxis for HBV in patients with COVID-19 receiving corticosteroids and other immunosuppressive agents.The risk of HBV reactivation in patients with HBV surface antigen (HBsAg) /HBV core antibody (HBcAb)+ is estimated to be between 1 and 10% if they are taking moderate-dose (10–20 mg prednisone or equivalent) or high dose (>20 mg prednisone daily or equivalent) of corticosteroids daily for >4 weeks [2]. Hepatitis B virus reactivation can occur in HBsAg-negative patients who have only markers of previous exposure to HBV (HBcAb-positive with or without hepatitis B surface antibody [HBsAb]) [3].To investigate retrospectively the incidence of HBV reactivation in HBsAg /HBcAb+ patients, we reviewed the medical files of 450 patients with Covid-19 admitted at “Annunziata” Hub Hospital, a tertiary care hospital in Cosenza, Italy, between 6 March 2020 and 6 July 2021. Hepatitis B virus virologic indicators were determined at baseline. A total of 60 (34 males and 26 females; median age 69 year, range: 39–87) COVID-19 patients showed evidence of resolved HBV (HBsAg-negative, HBsAb-positive, HBcAb-positive). fifty-five of them patients had at least one comorbidity (most commonly hypertension, diabetes mellitus type 2, and cardiovascular diseases). Forty of the 60 patients met the criteria for severe COVID-19. Five were treated in ICU. Out of these 60 patients, all patients were given corticosteroids, 95 patients received tocilizumab, 40 patients received baricitinib, 30 patients were given anakinra, and 16 patients were treated with canakinumab. Hepatitis B virus virologic indicators were determined at baseline. There were no deaths. They all underwent antiviral prophylaxis with tenofovir disoproxil fumarate, for an average duration of 20 days (14–46 days). They also received antiviral therapy to treat the COVID-19 (remdesivir 50 and lopinavir/ritonavir 10 patients). Ten of those 60 patients had ALTabove normal range (i.e. >45 IU/L). In 12 patients with normal values of ALT at the time of admission there was a rise of ALT above normal range during hospitalization. With recovery from COVID-19, liver function gradually returned to baseline. None of the 60 patients with resolved HBV infection developed clinical evidence of HBV reactivation during 3–6 months of follow-up. We did not observe slower SarsCov2 viral clearance in these patients, while patients with higher HBsAb titers developed higher anti-SarsCov2 antibody titers. There were no adverse events attributable to anti HBV viral prophylaxis. Hepatitis B virus reactivation in subjects undergoing immunosuppressive treatment is recognized as a serious clinical problem. Although the risk of
{"title":"Antiviral prophylaxis for hepatitis B virus in COVID-19 patients treated with immunosuppressive drug therapy","authors":"A. Mastroianni, S. Greco, Luciana Chidichimo, M. Mauro, Filippo Urso, V. Vangeli","doi":"10.1177/13596535211067602","DOIUrl":"https://doi.org/10.1177/13596535211067602","url":null,"abstract":"To The Editor, We read with great interest the review on COVID-19 and hepatitis B infection by Alqahtani SA and Buti M [1] underlining the need for screening and possible prophylaxis for HBV in patients with COVID-19 receiving corticosteroids and other immunosuppressive agents.The risk of HBV reactivation in patients with HBV surface antigen (HBsAg) /HBV core antibody (HBcAb)+ is estimated to be between 1 and 10% if they are taking moderate-dose (10–20 mg prednisone or equivalent) or high dose (>20 mg prednisone daily or equivalent) of corticosteroids daily for >4 weeks [2]. Hepatitis B virus reactivation can occur in HBsAg-negative patients who have only markers of previous exposure to HBV (HBcAb-positive with or without hepatitis B surface antibody [HBsAb]) [3].To investigate retrospectively the incidence of HBV reactivation in HBsAg /HBcAb+ patients, we reviewed the medical files of 450 patients with Covid-19 admitted at “Annunziata” Hub Hospital, a tertiary care hospital in Cosenza, Italy, between 6 March 2020 and 6 July 2021. Hepatitis B virus virologic indicators were determined at baseline. A total of 60 (34 males and 26 females; median age 69 year, range: 39–87) COVID-19 patients showed evidence of resolved HBV (HBsAg-negative, HBsAb-positive, HBcAb-positive). fifty-five of them patients had at least one comorbidity (most commonly hypertension, diabetes mellitus type 2, and cardiovascular diseases). Forty of the 60 patients met the criteria for severe COVID-19. Five were treated in ICU. Out of these 60 patients, all patients were given corticosteroids, 95 patients received tocilizumab, 40 patients received baricitinib, 30 patients were given anakinra, and 16 patients were treated with canakinumab. Hepatitis B virus virologic indicators were determined at baseline. There were no deaths. They all underwent antiviral prophylaxis with tenofovir disoproxil fumarate, for an average duration of 20 days (14–46 days). They also received antiviral therapy to treat the COVID-19 (remdesivir 50 and lopinavir/ritonavir 10 patients). Ten of those 60 patients had ALTabove normal range (i.e. >45 IU/L). In 12 patients with normal values of ALT at the time of admission there was a rise of ALT above normal range during hospitalization. With recovery from COVID-19, liver function gradually returned to baseline. None of the 60 patients with resolved HBV infection developed clinical evidence of HBV reactivation during 3–6 months of follow-up. We did not observe slower SarsCov2 viral clearance in these patients, while patients with higher HBsAb titers developed higher anti-SarsCov2 antibody titers. There were no adverse events attributable to anti HBV viral prophylaxis. Hepatitis B virus reactivation in subjects undergoing immunosuppressive treatment is recognized as a serious clinical problem. Although the risk of","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46818328","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 : 2022-02-01DOI: 10.1177/13596535211067605
Rebecca Roediger, Elizabeth Smyth, D. Dieterich
Adefovir, a nucleotide analog developed by John Martin, was a major breakthrough in the treatment of chronic Hepatitis B. Prior to adefovir, Hepatitis B treatment was limited to two therapeutic modalities, either interferon, which carried significant side effects and was efficacious in a minority of patients, or lamivudine which showed no durable effects with short-term use and a high rate of resistance with long-term use. Adefovir was found to be effective in suppressing viral replication and in resolving the hepatic inflammation associated with hepatitis B with only rare instances of resistance. In this article, we appreciate John Martin’s contribution to science and medicine as we review the landmark trials of adefovir that brought forth a new era of treatment of Hepatitis B.
{"title":"Adefovir for lamivudine-resistant hepatitis B","authors":"Rebecca Roediger, Elizabeth Smyth, D. Dieterich","doi":"10.1177/13596535211067605","DOIUrl":"https://doi.org/10.1177/13596535211067605","url":null,"abstract":"Adefovir, a nucleotide analog developed by John Martin, was a major breakthrough in the treatment of chronic Hepatitis B. Prior to adefovir, Hepatitis B treatment was limited to two therapeutic modalities, either interferon, which carried significant side effects and was efficacious in a minority of patients, or lamivudine which showed no durable effects with short-term use and a high rate of resistance with long-term use. Adefovir was found to be effective in suppressing viral replication and in resolving the hepatic inflammation associated with hepatitis B with only rare instances of resistance. In this article, we appreciate John Martin’s contribution to science and medicine as we review the landmark trials of adefovir that brought forth a new era of treatment of Hepatitis B.","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45028259","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 : 2022-02-01DOI: 10.1177/13596535221082773
T. Cihlar, R. Mackman
If a planned path reaches a dead-end, one can simply stop. Or one can turn around, walk back to the last intersection and take another path, or one can consider taking few paths in parallel. The last scenario is reflective of the journey of remdesivir, the first antiviral for the treatment of COVID-19, that was approved by FDA less than 10 months after the isolation of SARS-CoV-2, the virus responsible for the COVID-19 pandemic. As of January 2022, 10 million COVID-19 patients have been treated with remdesivir worldwide, but the journey of this molecule started more than a decade earlier with the search for a cure of hepatitis C virus. The development path of remdesivir before the emergence of COVID-19 represents a valuable example of a preemptive pandemic preparedness, but the pursuit of this path would not have been possible without sustaining support of John C. Martin, whom we will sorely miss for his piercing vision, uncompromising leadership, and genuine compassion for patients suffering around the world.
{"title":"Journey of remdesivir from the inhibition of hepatitis C virus to the treatment of COVID-19","authors":"T. Cihlar, R. Mackman","doi":"10.1177/13596535221082773","DOIUrl":"https://doi.org/10.1177/13596535221082773","url":null,"abstract":"If a planned path reaches a dead-end, one can simply stop. Or one can turn around, walk back to the last intersection and take another path, or one can consider taking few paths in parallel. The last scenario is reflective of the journey of remdesivir, the first antiviral for the treatment of COVID-19, that was approved by FDA less than 10 months after the isolation of SARS-CoV-2, the virus responsible for the COVID-19 pandemic. As of January 2022, 10 million COVID-19 patients have been treated with remdesivir worldwide, but the journey of this molecule started more than a decade earlier with the search for a cure of hepatitis C virus. The development path of remdesivir before the emergence of COVID-19 represents a valuable example of a preemptive pandemic preparedness, but the pursuit of this path would not have been possible without sustaining support of John C. Martin, whom we will sorely miss for his piercing vision, uncompromising leadership, and genuine compassion for patients suffering around the world.","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46473656","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 : 2022-02-01DOI: 10.1177/13596535211067610
Gayatri Marathe, E. Moodie, M. Brouillette, J. Cox, C. Delaunay, C. Cooper, M. Hull, J. Gill, S. Walmsley, N. Pick, M. Klein
Background Psychiatric illness was a major barrier for HCV treatment during the Interferon (IFN) treatment era due to neuropsychiatric side effects. While direct acting antivirals (DAA) are better tolerated, patient-level barriers persist. We aimed to assess the effect of depressive symptoms on time to HCV treatment initiation among HIV–HCV co-infected persons during the IFN (2003–2011) and second-generation DAA (2013–2020) eras. Methods We used data from the Canadian Co-infection Cohort, a multicentre prospective cohort, and its associated sub-study on Food Security (FS). We predicted Center for Epidemiologic Studies Depression Scale-10 (CES-D-10) classes for depressive symptoms indicative of a depression risk using a random forest classifier and corrected for misclassification using predictive value-based record-level correction. We used marginal structural Cox proportional hazards models with inverse weighting for competing risks (death) to assess the effect of depressive symptoms on treatment initiation among HCV RNA-positive participants. Results We included 590 and 1127 participants in the IFN and DAA eras. The treatment initiation rate increased from 9 (95% confidence interval (CI): 7–10) to 21 (95% CI: 19–22) per 100 person-years from the IFN to DAA era. Treatment initiation was lower among those with depressive symptoms compared to those without in the IFN era (hazard ratio: 0.81 (95% CI: 0.69–0.95)) and was higher in the DAA era (1.19 (95% CI: 1.10–1.27)). Conclusion Depressive symptoms no longer appear to be a barrier to HCV treatment initiation in the co-infected population in the DAA era. The higher rate of treatment initiation in individuals with depressive symptoms suggests those previously unable to tolerate IFN are now accessing treatment.
{"title":"Depressive symptoms are no longer a barrier to HCV treatment initiation in the HIV–HCV co-infected population in Canada","authors":"Gayatri Marathe, E. Moodie, M. Brouillette, J. Cox, C. Delaunay, C. Cooper, M. Hull, J. Gill, S. Walmsley, N. Pick, M. Klein","doi":"10.1177/13596535211067610","DOIUrl":"https://doi.org/10.1177/13596535211067610","url":null,"abstract":"Background Psychiatric illness was a major barrier for HCV treatment during the Interferon (IFN) treatment era due to neuropsychiatric side effects. While direct acting antivirals (DAA) are better tolerated, patient-level barriers persist. We aimed to assess the effect of depressive symptoms on time to HCV treatment initiation among HIV–HCV co-infected persons during the IFN (2003–2011) and second-generation DAA (2013–2020) eras. Methods We used data from the Canadian Co-infection Cohort, a multicentre prospective cohort, and its associated sub-study on Food Security (FS). We predicted Center for Epidemiologic Studies Depression Scale-10 (CES-D-10) classes for depressive symptoms indicative of a depression risk using a random forest classifier and corrected for misclassification using predictive value-based record-level correction. We used marginal structural Cox proportional hazards models with inverse weighting for competing risks (death) to assess the effect of depressive symptoms on treatment initiation among HCV RNA-positive participants. Results We included 590 and 1127 participants in the IFN and DAA eras. The treatment initiation rate increased from 9 (95% confidence interval (CI): 7–10) to 21 (95% CI: 19–22) per 100 person-years from the IFN to DAA era. Treatment initiation was lower among those with depressive symptoms compared to those without in the IFN era (hazard ratio: 0.81 (95% CI: 0.69–0.95)) and was higher in the DAA era (1.19 (95% CI: 1.10–1.27)). Conclusion Depressive symptoms no longer appear to be a barrier to HCV treatment initiation in the co-infected population in the DAA era. The higher rate of treatment initiation in individuals with depressive symptoms suggests those previously unable to tolerate IFN are now accessing treatment.","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47764968","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 : 2022-02-01DOI: 10.1177/13596535211067589
S. A. Abdool Karim, C. Baxter, Q. Abdool Karim
Tenofovir-based pre-exposure prophylaxis (PrEP) revolutionized the global HIV prevention landscape. Prior to the proof-of concept trial in 2010, which demonstrated that tenofovir (TFV) could prevent sexual transmission of HIV, prevention options were largely limited to behavior change, condoms, and circumcision. Several subsequent studies evaluating oral tenofovir disoproxil fumarate (TDF) or the TDF/emtricitabine (FTC) combination as PrEP for HIV prevention provided evidence for regulatory approval and inclusion in national and international guidelines. By 2021, 1.5 million people had initiated oral tenofovir-based PrEP, contributing to declines in HIV incidence in some regions. Here we reflect on how oral tenofovir-based PrEP became an important component of combination HIV prevention programs across the globe.
{"title":"Advancing HIV prevention using tenofovir-based pre-exposure prophylaxis","authors":"S. A. Abdool Karim, C. Baxter, Q. Abdool Karim","doi":"10.1177/13596535211067589","DOIUrl":"https://doi.org/10.1177/13596535211067589","url":null,"abstract":"Tenofovir-based pre-exposure prophylaxis (PrEP) revolutionized the global HIV prevention landscape. Prior to the proof-of concept trial in 2010, which demonstrated that tenofovir (TFV) could prevent sexual transmission of HIV, prevention options were largely limited to behavior change, condoms, and circumcision. Several subsequent studies evaluating oral tenofovir disoproxil fumarate (TDF) or the TDF/emtricitabine (FTC) combination as PrEP for HIV prevention provided evidence for regulatory approval and inclusion in national and international guidelines. By 2021, 1.5 million people had initiated oral tenofovir-based PrEP, contributing to declines in HIV incidence in some regions. Here we reflect on how oral tenofovir-based PrEP became an important component of combination HIV prevention programs across the globe.","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47055333","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 : 2022-02-01DOI: 10.1177/13596535221077487
Dannae Brown, R. Kaplan, M. Losso, C. Brites, Ruolan Wang, M. Underwood, J. Hopking, M. Aboud, Jörg Sievers
Background In the DAWNING study, dolutegravir + 2 nucleoside reverse transcriptase inhibitors (NRTIs) demonstrated superior efficacy at Week 48 and a favourable safety profile compared with lopinavir/ritonavir + 2 NRTIs in adults with HIV-1 failing first-line therapy of a non-nucleoside reverse transcriptase inhibitor + 2 NRTIs. Methods Participants at 58 centres in 13 countries were randomised (1:1) to 52 weeks of open-label treatment with dolutegravir or lopinavir/ritonavir combined with 2 investigator-selected NRTIs, including at least one fully active NRTI based on screening resistance testing. The primary endpoint was the proportion of participants achieving HIV-1 RNA <50 copies/ml at Week 48 (Snapshot algorithm). Post-hoc efficacy analyses were performed based on baseline NRTI resistance profile and second-line NRTI use. Results Of 624 participants randomised and treated, 499 (80%) received <2 active NRTIs at Baseline. NRTI resistance was present in 561 participants (90%). Among participants receiving lamivudine or emtricitabine in the presence of M184V/I, 85% (187/220) of participants on dolutegravir versus 72% (152/210) on lopinavir/ritonavir had HIV-1 RNA <50 copies/ml at Week 48 (difference, 12.6%; 95% CI: 4.9–20.3%). High responses were also observed in the dolutegravir group, when zidovudine or tenofovir disoproxil fumarate were included in the background regimen in the presence of thymidine analogue mutations or K65R, respectively; however, participant numbers in these subgroups were small. Conclusions Response rates were high in participants receiving dolutegravir + 2 NRTIs as second-line treatment regardless of pre-existing resistance to one of the NRTIs, including in participants using lamivudine or emtricitabine in the presence of M184V/I.
{"title":"Efficacy of second-line dolutegravir plus 2 nucleoside reverse transcriptase inhibitors by baseline nucleoside reverse transcriptase inhibitor resistance and nucleoside reverse transcriptase inhibitor use in the DAWNING study","authors":"Dannae Brown, R. Kaplan, M. Losso, C. Brites, Ruolan Wang, M. Underwood, J. Hopking, M. Aboud, Jörg Sievers","doi":"10.1177/13596535221077487","DOIUrl":"https://doi.org/10.1177/13596535221077487","url":null,"abstract":"Background In the DAWNING study, dolutegravir + 2 nucleoside reverse transcriptase inhibitors (NRTIs) demonstrated superior efficacy at Week 48 and a favourable safety profile compared with lopinavir/ritonavir + 2 NRTIs in adults with HIV-1 failing first-line therapy of a non-nucleoside reverse transcriptase inhibitor + 2 NRTIs. Methods Participants at 58 centres in 13 countries were randomised (1:1) to 52 weeks of open-label treatment with dolutegravir or lopinavir/ritonavir combined with 2 investigator-selected NRTIs, including at least one fully active NRTI based on screening resistance testing. The primary endpoint was the proportion of participants achieving HIV-1 RNA <50 copies/ml at Week 48 (Snapshot algorithm). Post-hoc efficacy analyses were performed based on baseline NRTI resistance profile and second-line NRTI use. Results Of 624 participants randomised and treated, 499 (80%) received <2 active NRTIs at Baseline. NRTI resistance was present in 561 participants (90%). Among participants receiving lamivudine or emtricitabine in the presence of M184V/I, 85% (187/220) of participants on dolutegravir versus 72% (152/210) on lopinavir/ritonavir had HIV-1 RNA <50 copies/ml at Week 48 (difference, 12.6%; 95% CI: 4.9–20.3%). High responses were also observed in the dolutegravir group, when zidovudine or tenofovir disoproxil fumarate were included in the background regimen in the presence of thymidine analogue mutations or K65R, respectively; however, participant numbers in these subgroups were small. Conclusions Response rates were high in participants receiving dolutegravir + 2 NRTIs as second-line treatment regardless of pre-existing resistance to one of the NRTIs, including in participants using lamivudine or emtricitabine in the presence of M184V/I.","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45593570","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 : 2022-02-01DOI: 10.1177/13596535211068613
A. Chiesa, Micol Pallanza, G. Martinetti, Fabio Lanzi, M. Previsdomini, A. Pagnamenta, L. Elzi
Background There is a paucity of data about the occurrence and risk factors of herpes simplex virus (HSV) reactivation among patients with severe COVID-19 presenting with acute respiratory distress syndrome (ARDS). Methods We performed a nested case-control study among a cohort of SARS-CoV-2 infected patients with ARDS. Between March and April 2020, all consecutive mechanically ventilated patients ≥18 years old with a positive PCR for SARS-CoV-2 on mucocutaneous samples were included in the study. We collected data on demographics, medical history, laboratory variables, administration of antivirals and other agents, respiratory and organ support procedures, microbiological results, and management of ARDS with prone positioning and the use of steroids. Univariate and multivariable Cox regression models were performed in order to identify predictors of HSV reactivation. Results Eighty-three patients with laboratory-confirmed SARS-CoV-2 infection were admitted to the ICU for mechanical ventilation. 18/83 (21.7%) patients developed mucocutaneous herpes simplex virus reactivation after a median of 17 days (IQR, 14–20). Prone positioning was the only independent risk factor for HSV reactivation (adj. hazard ratios, 1.60; 95% CI, 1.11–2.30; P = 0.009). All patients with mucocutaneous HSV reactivation were treated with antivirals. The outcome in terms of ventilator-associated pneumonia, catheter-related bloodstream infections, and in-hospital mortality was similar for patients with and without HSV reactivation. Conclusions HSV reactivation is frequent in COVID-19 patients with ARDS, especially if prolonged invasive mechanical ventilation with prone positioning is needed. Prompt testing for HSV and initiation of antiviral therapy should be performed in case of mucocutaneous lesions in this population.
{"title":"Herpes simplex virus reactivation in patients with COVID-19 and acute respiratory distress syndrome: a prospective cohort study","authors":"A. Chiesa, Micol Pallanza, G. Martinetti, Fabio Lanzi, M. Previsdomini, A. Pagnamenta, L. Elzi","doi":"10.1177/13596535211068613","DOIUrl":"https://doi.org/10.1177/13596535211068613","url":null,"abstract":"Background There is a paucity of data about the occurrence and risk factors of herpes simplex virus (HSV) reactivation among patients with severe COVID-19 presenting with acute respiratory distress syndrome (ARDS). Methods We performed a nested case-control study among a cohort of SARS-CoV-2 infected patients with ARDS. Between March and April 2020, all consecutive mechanically ventilated patients ≥18 years old with a positive PCR for SARS-CoV-2 on mucocutaneous samples were included in the study. We collected data on demographics, medical history, laboratory variables, administration of antivirals and other agents, respiratory and organ support procedures, microbiological results, and management of ARDS with prone positioning and the use of steroids. Univariate and multivariable Cox regression models were performed in order to identify predictors of HSV reactivation. Results Eighty-three patients with laboratory-confirmed SARS-CoV-2 infection were admitted to the ICU for mechanical ventilation. 18/83 (21.7%) patients developed mucocutaneous herpes simplex virus reactivation after a median of 17 days (IQR, 14–20). Prone positioning was the only independent risk factor for HSV reactivation (adj. hazard ratios, 1.60; 95% CI, 1.11–2.30; P = 0.009). All patients with mucocutaneous HSV reactivation were treated with antivirals. The outcome in terms of ventilator-associated pneumonia, catheter-related bloodstream infections, and in-hospital mortality was similar for patients with and without HSV reactivation. Conclusions HSV reactivation is frequent in COVID-19 patients with ARDS, especially if prolonged invasive mechanical ventilation with prone positioning is needed. Prompt testing for HSV and initiation of antiviral therapy should be performed in case of mucocutaneous lesions in this population.","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":"27 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42517366","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 : 2022-01-20DOI: 10.1177/13596535211073235
G. Pierone, J. Fusco, V. Vannappagari, L. Brunet, R. P. Weber, M. Aboud, J. van Wyk, L. Ragone, G. Fusco
Background This study compared the effectiveness and durability of DTG/RPV with commonly prescribed 3-drug regimens (3-DR) in people living with HIV (PLWH) in a real-world setting. Methods Antiretroviral therapy (ART)-experienced, virologically suppressed PLWH who initiated DTG/RPV or a 3-DR in 2018 were identified in the OPERA® database and followed through 6/30/2019. Virologic failure (two consecutive viral loads (VL) ≥ 200 copies/mL or single VL ≥ 200 copies/mL with regimen modification/discontinuation) and maintained virologic suppression (last VL test < 50 or < 200 copies/mL) were described. Kaplan–Meier methods were used to estimate time to virologic failure and treatment discontinuation. Risk of virologic failure was adjusted for age, sex, race/ethnicity, risk of infection, region, baseline CD4 cell count, history of substance abuse or syphilis, and mortality risk score at baseline in a Cox model. Results PLWH initiating DTG/RPV were older and more likely to be Hispanic or have comorbidities than 3-DR initiators. DTG/RPV users experienced fewer discontinuations (15%) and were more likely to be suppressed at study end (98%) than 3-DR users (28% and 96%, respectively). Virologic failure was uncommon; rates per 100 person-years did not differ between the DTG/RPV (1.45, 95% CI: 0.69, 3.03) and 3-DR (2.63, 95% CI: 2.21, 3.14) groups. The risk of virologic failure did not differ significantly between the groups in adjusted Cox models (adjusted hazard ratio 1.32, 95% CI: 0.61, 2.89). Conclusions The findings of this real-world OPERA® study suggest that DTG/RPV can be a viable alternative to standard 3-DRs for ART-experienced, virologically suppressed PLWH.
{"title":"Dolutegravir/rilpivirine 2-drug regimen comparable to commonly prescribed 3-drug regimens up to 18-months in a real-world setting","authors":"G. Pierone, J. Fusco, V. Vannappagari, L. Brunet, R. P. Weber, M. Aboud, J. van Wyk, L. Ragone, G. Fusco","doi":"10.1177/13596535211073235","DOIUrl":"https://doi.org/10.1177/13596535211073235","url":null,"abstract":"Background This study compared the effectiveness and durability of DTG/RPV with commonly prescribed 3-drug regimens (3-DR) in people living with HIV (PLWH) in a real-world setting. Methods Antiretroviral therapy (ART)-experienced, virologically suppressed PLWH who initiated DTG/RPV or a 3-DR in 2018 were identified in the OPERA® database and followed through 6/30/2019. Virologic failure (two consecutive viral loads (VL) ≥ 200 copies/mL or single VL ≥ 200 copies/mL with regimen modification/discontinuation) and maintained virologic suppression (last VL test < 50 or < 200 copies/mL) were described. Kaplan–Meier methods were used to estimate time to virologic failure and treatment discontinuation. Risk of virologic failure was adjusted for age, sex, race/ethnicity, risk of infection, region, baseline CD4 cell count, history of substance abuse or syphilis, and mortality risk score at baseline in a Cox model. Results PLWH initiating DTG/RPV were older and more likely to be Hispanic or have comorbidities than 3-DR initiators. DTG/RPV users experienced fewer discontinuations (15%) and were more likely to be suppressed at study end (98%) than 3-DR users (28% and 96%, respectively). Virologic failure was uncommon; rates per 100 person-years did not differ between the DTG/RPV (1.45, 95% CI: 0.69, 3.03) and 3-DR (2.63, 95% CI: 2.21, 3.14) groups. The risk of virologic failure did not differ significantly between the groups in adjusted Cox models (adjusted hazard ratio 1.32, 95% CI: 0.61, 2.89). Conclusions The findings of this real-world OPERA® study suggest that DTG/RPV can be a viable alternative to standard 3-DRs for ART-experienced, virologically suppressed PLWH.","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2022-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45072224","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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