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}
Pub Date : 2021-11-01DOI: 10.1177/13596535211059895
Yuqing Fang, Xiaoyan Xu, F. Hou, Wei Jia
Background Few models to predict antiviral response of peginterferon were used in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B patients and the prediction efficacy was unsatisfied. Quantitative antibody to hepatitis B core antigen (anti-HBc) is a new predictor of treatment response. We aimed to develop a new model to identify HBeAg-positive Chinese patients who were more likely to respond to peginterferon. Methods Data from 140 peginterferon recipients with HBeAg-positive were applied with generalized additive models and multiple logistic regression analysis to develop a baseline scoring system to predict serological response (SR: HBeAg loss and HBeAg seroconversion 24 weeks post-treatment) and combined response (CR: SR plus serum HBV DNA levels <2000 IU/mL 24 weeks post-treatment). Results Anti-HBc levels, alanine aminotransferase ratio, and HBeAg were retained in the final model. The new model scored from 0 to 3. Among patients with scores of 0, 1, or ≥2, SR was achieved in 6.45% (2/31), 13.21% (7/51), and 55.36% (31/56), respectively, and CR in 3.23% (1/31), 9.43% (5/53), and 25.00% (14/56), respectively. Our model has a higher AUROC for SR comparing to Chan’s (Z = 2.77 > 1.96, p < 0.05) and Lampertico’s (Z = 2.06 > 1.96, p < 0.05) model. The negative predictive value for SR and CR were both 100% in patients with score 0 and hepatitis B surface antigen ≥20,000 IU/mL at week 12. Conclusions Patients with higher scores at baseline were more likely to respond to peginterferon. This new model may predict the treatment response.
{"title":"A baseline model including quantitative anti-HBc to predict response of peginterferon in HBeAg-positive chronic hepatitis B patients","authors":"Yuqing Fang, Xiaoyan Xu, F. Hou, Wei Jia","doi":"10.1177/13596535211059895","DOIUrl":"https://doi.org/10.1177/13596535211059895","url":null,"abstract":"Background Few models to predict antiviral response of peginterferon were used in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B patients and the prediction efficacy was unsatisfied. Quantitative antibody to hepatitis B core antigen (anti-HBc) is a new predictor of treatment response. We aimed to develop a new model to identify HBeAg-positive Chinese patients who were more likely to respond to peginterferon. Methods Data from 140 peginterferon recipients with HBeAg-positive were applied with generalized additive models and multiple logistic regression analysis to develop a baseline scoring system to predict serological response (SR: HBeAg loss and HBeAg seroconversion 24 weeks post-treatment) and combined response (CR: SR plus serum HBV DNA levels <2000 IU/mL 24 weeks post-treatment). Results Anti-HBc levels, alanine aminotransferase ratio, and HBeAg were retained in the final model. The new model scored from 0 to 3. Among patients with scores of 0, 1, or ≥2, SR was achieved in 6.45% (2/31), 13.21% (7/51), and 55.36% (31/56), respectively, and CR in 3.23% (1/31), 9.43% (5/53), and 25.00% (14/56), respectively. Our model has a higher AUROC for SR comparing to Chan’s (Z = 2.77 > 1.96, p < 0.05) and Lampertico’s (Z = 2.06 > 1.96, p < 0.05) model. The negative predictive value for SR and CR were both 100% in patients with score 0 and hepatitis B surface antigen ≥20,000 IU/mL at week 12. Conclusions Patients with higher scores at baseline were more likely to respond to peginterferon. This new model may predict the treatment response.","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":"26 1","pages":"126 - 133"},"PeriodicalIF":1.2,"publicationDate":"2021-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46812543","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 : 2021-11-01DOI: 10.1177/13596535211062388
J. Molina, L. Ene, P. Cahn, G. Fätkenheuer, E. van Wijngaerden, J. Lombaard, N. Zakharova, V. van Eygen, S. Vanveggel, R. van Solingen-Ristea
Background To evaluate the long-term safety and efficacy of rilpivirine (RPV), a non-nucleoside reverse transcriptase inhibitor (NNRTI), in combination with nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) in human immunodeficiency virus (HIV)–infected patients. Methods RPV-treated HIV-infected patients from phase 2b or 3 studies rolled-over into this phase 3, open-label study and received RPV 25 mg once daily (QD) with choice of two NRTIs. Adverse events (AEs), plasma viral load, CD4+ cell count, and antiviral resistance were evaluated. Results Of the 482 patients treated, 437 (>90%) patients discontinued study treatment; 371 (77%) had switched to commercially available RPV, 14 (2.9%) discontinued due to AEs, and 6 (1.2%) had virologic failure. In this rollover study, patients were followed up to week 336, although data was limited beyond 288 weeks. Forty-five (9.3%) patients were still undergoing treatment at the time of data cut-off for the current analysis (8 February 2018). The most frequently reported AEs were pregnancy in 7 (1.5%) patients and syphilis in 5 (1.0%) patients. Grade 3–4 AEs were reported in 17 (3.5%) patients, and AEs possibly related to RPV in 23 (4.8%) patients. Over 288 weeks of treatment, 80.1% (95% CI: 74.9%; 84.3%) of patients maintained virologic suppression (HIV-1 RNA <50 copies/mL). The absolute CD4+ cell count increased over time until week 192 and remained constant thereafter. Conclusions RPV 25 mg QD in combination with an investigator-selected background regimen of two NRTIs demonstrated sustained long-term virologic suppression. The treatment was well-tolerated with no new safety findings.
{"title":"Long-term safety and efficacy of rilpivirine in combination with nucleoside/nucleotide reverse transcriptase inhibitors in HIV-1 infected patients: 336-week rollover study of phase 2b and 3 clinical studies","authors":"J. Molina, L. Ene, P. Cahn, G. Fätkenheuer, E. van Wijngaerden, J. Lombaard, N. Zakharova, V. van Eygen, S. Vanveggel, R. van Solingen-Ristea","doi":"10.1177/13596535211062388","DOIUrl":"https://doi.org/10.1177/13596535211062388","url":null,"abstract":"Background To evaluate the long-term safety and efficacy of rilpivirine (RPV), a non-nucleoside reverse transcriptase inhibitor (NNRTI), in combination with nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) in human immunodeficiency virus (HIV)–infected patients. Methods RPV-treated HIV-infected patients from phase 2b or 3 studies rolled-over into this phase 3, open-label study and received RPV 25 mg once daily (QD) with choice of two NRTIs. Adverse events (AEs), plasma viral load, CD4+ cell count, and antiviral resistance were evaluated. Results Of the 482 patients treated, 437 (>90%) patients discontinued study treatment; 371 (77%) had switched to commercially available RPV, 14 (2.9%) discontinued due to AEs, and 6 (1.2%) had virologic failure. In this rollover study, patients were followed up to week 336, although data was limited beyond 288 weeks. Forty-five (9.3%) patients were still undergoing treatment at the time of data cut-off for the current analysis (8 February 2018). The most frequently reported AEs were pregnancy in 7 (1.5%) patients and syphilis in 5 (1.0%) patients. Grade 3–4 AEs were reported in 17 (3.5%) patients, and AEs possibly related to RPV in 23 (4.8%) patients. Over 288 weeks of treatment, 80.1% (95% CI: 74.9%; 84.3%) of patients maintained virologic suppression (HIV-1 RNA <50 copies/mL). The absolute CD4+ cell count increased over time until week 192 and remained constant thereafter. Conclusions RPV 25 mg QD in combination with an investigator-selected background regimen of two NRTIs demonstrated sustained long-term virologic suppression. The treatment was well-tolerated with no new safety findings.","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":"26 1","pages":"95 - 105"},"PeriodicalIF":1.2,"publicationDate":"2021-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45063080","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 : 2021-11-01DOI: 10.1177/13596535211058262
A. Rivera, Stephen Machenry, Jonathan Okpokwu, B. Olatunde, Placid Ugoagwu, M. Auwal, H. Sule, P. Agaba, O. Agbaji, C. Thio, Robert L Murphy, C. Hawkins
Background In Nigeria, the effect of Hepatitis B virus (HBV) on long-term liver outcomes in persons with HIV (PLH) has not been described. We determined changes in liver stiffness measure (LSM) using transient elastography over 6 years in HIV mono-infected and HIV-HBV co-infected Nigerians initiating antiretroviral therapy (ART) and factors associated with LSM decline. Methods This single centre, cohort study enrolled ART-naïve HIV mono- and HIV-HBV co-infected adults (≥18 years) at the APIN Public Health Initiatives–supported HIV Care and Treatment Centre at Jos University Teaching Hospital, Nigeria, from 7/2011 to 2/2012. LSM at baseline, Years 3 and 6 were analysed using longitudinal models to estimate changes over time and their predictors. Results Data from 100 (31%) HIV-HBV co-infected and 225 (69%) HIV mono-infected participants were analysed. Median LSM at baseline was 6.10 (IQR: 4.60–7.90) kPa in co-infected and 5.10 (IQR: 4.40–6.10) kPa in mono-infected participants. In adjusted analyses, average LSM was not significantly different between Year 0 and 3 (β = 0.02, −0.22 to 0.26, p = 0.87 and Year 0 and 6 (β = −0.02, −0.23 to 0.27, p = 0.88) in both groups (p>0.05), but co-infected participants had significantly higher LSM than mono-infected throughout follow-up (β = 0.018, 0.019–0.28, p < 0.001). Year 3 LSM differed according to ART initiation status by Year 3 (initiators - non-initiators: −0.87, −1.70 to −0.29). Conclusion In this cohort, LSM remained higher among HIV-HBV co-infected versus HIV mono-infected participants throughout follow-up. Our findings emphasize the continuing need for monitoring of liver outcomes in HIV-HBV co-infected populations on ART and the importance of preventing HBV infection among PLH to optimize liver health.
{"title":"HBV co-infection is associated with persistently elevated liver stiffness measurement in HIV-positive adults: A 6-year single-centre cohort study in Nigeria","authors":"A. Rivera, Stephen Machenry, Jonathan Okpokwu, B. Olatunde, Placid Ugoagwu, M. Auwal, H. Sule, P. Agaba, O. Agbaji, C. Thio, Robert L Murphy, C. Hawkins","doi":"10.1177/13596535211058262","DOIUrl":"https://doi.org/10.1177/13596535211058262","url":null,"abstract":"Background In Nigeria, the effect of Hepatitis B virus (HBV) on long-term liver outcomes in persons with HIV (PLH) has not been described. We determined changes in liver stiffness measure (LSM) using transient elastography over 6 years in HIV mono-infected and HIV-HBV co-infected Nigerians initiating antiretroviral therapy (ART) and factors associated with LSM decline. Methods This single centre, cohort study enrolled ART-naïve HIV mono- and HIV-HBV co-infected adults (≥18 years) at the APIN Public Health Initiatives–supported HIV Care and Treatment Centre at Jos University Teaching Hospital, Nigeria, from 7/2011 to 2/2012. LSM at baseline, Years 3 and 6 were analysed using longitudinal models to estimate changes over time and their predictors. Results Data from 100 (31%) HIV-HBV co-infected and 225 (69%) HIV mono-infected participants were analysed. Median LSM at baseline was 6.10 (IQR: 4.60–7.90) kPa in co-infected and 5.10 (IQR: 4.40–6.10) kPa in mono-infected participants. In adjusted analyses, average LSM was not significantly different between Year 0 and 3 (β = 0.02, −0.22 to 0.26, p = 0.87 and Year 0 and 6 (β = −0.02, −0.23 to 0.27, p = 0.88) in both groups (p>0.05), but co-infected participants had significantly higher LSM than mono-infected throughout follow-up (β = 0.018, 0.019–0.28, p < 0.001). Year 3 LSM differed according to ART initiation status by Year 3 (initiators - non-initiators: −0.87, −1.70 to −0.29). Conclusion In this cohort, LSM remained higher among HIV-HBV co-infected versus HIV mono-infected participants throughout follow-up. Our findings emphasize the continuing need for monitoring of liver outcomes in HIV-HBV co-infected populations on ART and the importance of preventing HBV infection among PLH to optimize liver health.","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":"26 1","pages":"106 - 116"},"PeriodicalIF":1.2,"publicationDate":"2021-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46096286","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 : 2021-11-01DOI: 10.1177/13596535211058267
C. Pressiat, Evelyne Dainguy, J. Treluyer, C. Yonaba, S. Urien, F. Eboua, F. Foissac, D. Dahourou, N. Bouazza, K. Malateste, Sophie Desmonde, A. Pruvost, V. Leroy, D. Hirt, The Anrs-Pediacam Study Group
Background Few pharmacokinetic data were reported on dispersible tablets despite their increasing use. One hundred fifty HIV-infected children receiving lamivudine were enrolled in the MONOD ANRS 12,206 trial. Three galenic forms were administered: liquid formulation, tablet form and dispersible scored tablet. Method HIV-infected children <4 years old were enrolled in the MONOD ANRS 12,206 trial designed to assess the simplification of a successful 12-months lopinavir-based antiretroviral treatment with efavirenz. Lamivudine plasma concentrations were analysed using nonlinear mixed effects modelling approach. Results One hundred and fifty children (age: 2.5 years (1.9–3.2), weight 11.1 (9.5–12.5) kg (median (IQR)) were included in this study. Over the study period, 79 received only the syrup form, 29 children switched from syrup form to tablet 3TC/AZT form, 36 from syrup to the orodispersible ABC/3TC form and two from the 3TC/AZT form to the orodispersible ABC/3TC form. The 630 lamivudine concentrations were best described by a two-compartment model allometrically scaled. Galenic form had no significant effect on 3TC pharmacokinetic. Conclusion This trial provided an opportunity to compare three galenic forms (liquid formulation, tablet form and dispersible scored tablet) of lamivudine in the target population of young HIV–1-infected children. Galenic form had no significant effect on lamivudine pharmacokinetics.
{"title":"Comparison of three galenic forms of lamivudine in young West African children living with Human Immunodeficiency Virus","authors":"C. Pressiat, Evelyne Dainguy, J. Treluyer, C. Yonaba, S. Urien, F. Eboua, F. Foissac, D. Dahourou, N. Bouazza, K. Malateste, Sophie Desmonde, A. Pruvost, V. Leroy, D. Hirt, The Anrs-Pediacam Study Group","doi":"10.1177/13596535211058267","DOIUrl":"https://doi.org/10.1177/13596535211058267","url":null,"abstract":"Background Few pharmacokinetic data were reported on dispersible tablets despite their increasing use. One hundred fifty HIV-infected children receiving lamivudine were enrolled in the MONOD ANRS 12,206 trial. Three galenic forms were administered: liquid formulation, tablet form and dispersible scored tablet. Method HIV-infected children <4 years old were enrolled in the MONOD ANRS 12,206 trial designed to assess the simplification of a successful 12-months lopinavir-based antiretroviral treatment with efavirenz. Lamivudine plasma concentrations were analysed using nonlinear mixed effects modelling approach. Results One hundred and fifty children (age: 2.5 years (1.9–3.2), weight 11.1 (9.5–12.5) kg (median (IQR)) were included in this study. Over the study period, 79 received only the syrup form, 29 children switched from syrup form to tablet 3TC/AZT form, 36 from syrup to the orodispersible ABC/3TC form and two from the 3TC/AZT form to the orodispersible ABC/3TC form. The 630 lamivudine concentrations were best described by a two-compartment model allometrically scaled. Galenic form had no significant effect on 3TC pharmacokinetic. Conclusion This trial provided an opportunity to compare three galenic forms (liquid formulation, tablet form and dispersible scored tablet) of lamivudine in the target population of young HIV–1-infected children. Galenic form had no significant effect on lamivudine pharmacokinetics.","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":"26 1","pages":"134 - 140"},"PeriodicalIF":1.2,"publicationDate":"2021-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42982142","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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