Pub Date : 2022-04-01DOI: 10.1177/13596535211067606
Taiyin Yang, R. Oliyai, K. Kent
A concept of “all or nothing” inspired the innovation of a one-pill-once-daily HIV treatment. Atripla® was the one pill that combined efavirenz, emtricitabine, and tenofovir disoproxil fumarate to become the first daily single tablet regimen that forever simplified HIV treatment to enhance patient compliance and thus, sustained viral suppression. The making of Atripla incorporated dry granulation and bilayer compression technologies to achieve stability and bioequivalence in an optimal pill size. In 2011, there lacked a standard of care for chronic hepatitis C infections that was safe, simple, short, free of interferon and ribavirin, and with high cure rates. A fixed-dose combination of ledipasvir and sofosbuvir was developed and approved in 2014 to be the first complete daily single tablet regimen for CHC genotype 1 infection. A spray-drying process for particle morphology engineering in a polymer matrix was used for improving bioavailability.
{"title":"The making of the one pill—Developing single tablet regimens for HIV and for HCV","authors":"Taiyin Yang, R. Oliyai, K. Kent","doi":"10.1177/13596535211067606","DOIUrl":"https://doi.org/10.1177/13596535211067606","url":null,"abstract":"A concept of “all or nothing” inspired the innovation of a one-pill-once-daily HIV treatment. Atripla® was the one pill that combined efavirenz, emtricitabine, and tenofovir disoproxil fumarate to become the first daily single tablet regimen that forever simplified HIV treatment to enhance patient compliance and thus, sustained viral suppression. The making of Atripla incorporated dry granulation and bilayer compression technologies to achieve stability and bioequivalence in an optimal pill size. In 2011, there lacked a standard of care for chronic hepatitis C infections that was safe, simple, short, free of interferon and ribavirin, and with high cure rates. A fixed-dose combination of ledipasvir and sofosbuvir was developed and approved in 2014 to be the first complete daily single tablet regimen for CHC genotype 1 infection. A spray-drying process for particle morphology engineering in a polymer matrix was used for improving bioavailability.","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46956706","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 : 2022-04-01DOI: 10.1177/13596535211068617
G. Alton, Clifford Samuel, A. Reddi
Background Gilead Sciences, under Dr. John Martin’s leadership, created its Global Access Program to deliver high-quality, affordable medicines to treat and ultimately eliminate some of the world’s most challenging-to-treat, pervasive, life-limiting diseases not as philanthropy but based on a self-sustaining business model—a highly novel concept in the pharmaceutical realm. John was determined to bring together all key stakeholders from public health officials to doctors and patients around the globe to understand barriers and opportunities in HIV, viral hepatitis, and visceral leishmaniasis (VL) and in so doing, pushed the Gilead team to devise novel strategies to address healthcare disparities in resource-challenged geographies. Purpose This case study provides an overview of the evolution and impact of the Gilead Access to Medicines Program in providing treatments for HIV in low- and lower middle-income countries.
{"title":"Providing access to high-quality, low-cost medicines across low and middle-income countries (LMICs), working with governments and generic manufacturers around the globe - A business case","authors":"G. Alton, Clifford Samuel, A. Reddi","doi":"10.1177/13596535211068617","DOIUrl":"https://doi.org/10.1177/13596535211068617","url":null,"abstract":"Background Gilead Sciences, under Dr. John Martin’s leadership, created its Global Access Program to deliver high-quality, affordable medicines to treat and ultimately eliminate some of the world’s most challenging-to-treat, pervasive, life-limiting diseases not as philanthropy but based on a self-sustaining business model—a highly novel concept in the pharmaceutical realm. John was determined to bring together all key stakeholders from public health officials to doctors and patients around the globe to understand barriers and opportunities in HIV, viral hepatitis, and visceral leishmaniasis (VL) and in so doing, pushed the Gilead team to devise novel strategies to address healthcare disparities in resource-challenged geographies. Purpose This case study provides an overview of the evolution and impact of the Gilead Access to Medicines Program in providing treatments for HIV in low- and lower middle-income countries.","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45379484","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 : 2022-04-01DOI: 10.1177/13596535221076640
C. Pan
Background Since immunoprophylaxis failure can occur if maternal serum hepatitis B virus (HBV) DNA levels are >200,000 IU/ml, tenofovir disoproxil fumarate (TDF) therapy has been investigated for preventing mother to child transmission (PMTCT). Methods A literature search for maternal TDF therapy for PMTCT between 1/1/2015 and 7/1/21 on PUBMED, EMBASE, Cochrane, CNKI, and Wanfang databases was performed. Data from RCTs in English or Chinese were extracted and reviewed. The outcomes of interest included the efficacy and safety of TDF versus placebo for PMTCT. Results Among 11 RCTs identified from the databases, the risk-of-bias was low. All studies demonstrated that maternal TDF therapy initiated from the second or third trimester for highly viremic chronic hepatitis B mothers is highly effective and safe in the PMTCT of HBV, except one RCT performed in Thailand which showed no therapeutic advantage on TDF treatment versus placebo for PMTCT (0% vs 3% transmission). Recent emerging data suggest that maternal TDF therapy initiated at the 2nd or early 3rd trimester in mothers with HBV DNA >200,000 IU/ml achieved viremic control before delivery. In the 4-year long follow-up study for maternal TDF therapy, there were no impacts on infants’ physical growth, psychological or mental development, and bone mineral density after fetal exposure to TDF. In the light of updated efficacy and safety data from RCTs, an algorithm was proposed. The approaches in resource-limit areas were discussed. Conclusions TDF is safe for both mothers and infants as the preferred therapy for PMTCT in highly viremic mothers. TDF should be initiated at the second or early third trimester in the combination of the appropriate infants’ immunoprophylaxis.
{"title":"The role of tenofovir disoproxil fumarate for preventing vertical transmission of hepatitis B","authors":"C. Pan","doi":"10.1177/13596535221076640","DOIUrl":"https://doi.org/10.1177/13596535221076640","url":null,"abstract":"Background Since immunoprophylaxis failure can occur if maternal serum hepatitis B virus (HBV) DNA levels are >200,000 IU/ml, tenofovir disoproxil fumarate (TDF) therapy has been investigated for preventing mother to child transmission (PMTCT). Methods A literature search for maternal TDF therapy for PMTCT between 1/1/2015 and 7/1/21 on PUBMED, EMBASE, Cochrane, CNKI, and Wanfang databases was performed. Data from RCTs in English or Chinese were extracted and reviewed. The outcomes of interest included the efficacy and safety of TDF versus placebo for PMTCT. Results Among 11 RCTs identified from the databases, the risk-of-bias was low. All studies demonstrated that maternal TDF therapy initiated from the second or third trimester for highly viremic chronic hepatitis B mothers is highly effective and safe in the PMTCT of HBV, except one RCT performed in Thailand which showed no therapeutic advantage on TDF treatment versus placebo for PMTCT (0% vs 3% transmission). Recent emerging data suggest that maternal TDF therapy initiated at the 2nd or early 3rd trimester in mothers with HBV DNA >200,000 IU/ml achieved viremic control before delivery. In the 4-year long follow-up study for maternal TDF therapy, there were no impacts on infants’ physical growth, psychological or mental development, and bone mineral density after fetal exposure to TDF. In the light of updated efficacy and safety data from RCTs, an algorithm was proposed. The approaches in resource-limit areas were discussed. Conclusions TDF is safe for both mothers and infants as the preferred therapy for PMTCT in highly viremic mothers. TDF should be initiated at the second or early third trimester in the combination of the appropriate infants’ immunoprophylaxis.","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44075374","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 : 2022-04-01DOI: 10.1177/13596535211067598
U. Schmitz, S. Swaminathan
John Martin’s untimely death in March 2021 was a huge loss for us personally, Gilead Sciences, the company he built over 30 years and the scientific community concerned with antiviral therapies. We wish to honor John’s legacy by retelling the discovery and history of Tamiflu and his contributions to it. Without his vision, persistence, and keen eye for opportunities, Tamiflu would not exist and Gilead’s path would not have been the same. His strategic thinking around the first oral flu drug is still quite relevant today, when we are still in the SARS-CoV-2 pandemic. John explained it simply in an interview with the Science History Institute in May 2020: “…most of my colleagues, we travel with Tamiflu when we go internationally, because it works for treatment and prevention, and hopefully, there will be a solution like that, eventually, for the Covid virus in addition to vaccines. Most people will get a flu vaccine every year, but there is still disease, we need a pill for treatment and prevention.”
{"title":"Discovery and development of oseltamivir at Gilead Sciences","authors":"U. Schmitz, S. Swaminathan","doi":"10.1177/13596535211067598","DOIUrl":"https://doi.org/10.1177/13596535211067598","url":null,"abstract":"John Martin’s untimely death in March 2021 was a huge loss for us personally, Gilead Sciences, the company he built over 30 years and the scientific community concerned with antiviral therapies. We wish to honor John’s legacy by retelling the discovery and history of Tamiflu and his contributions to it. Without his vision, persistence, and keen eye for opportunities, Tamiflu would not exist and Gilead’s path would not have been the same. His strategic thinking around the first oral flu drug is still quite relevant today, when we are still in the SARS-CoV-2 pandemic. John explained it simply in an interview with the Science History Institute in May 2020: “…most of my colleagues, we travel with Tamiflu when we go internationally, because it works for treatment and prevention, and hopefully, there will be a solution like that, eventually, for the Covid virus in addition to vaccines. Most people will get a flu vaccine every year, but there is still disease, we need a pill for treatment and prevention.”","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42691471","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 : 2022-04-01DOI: 10.1177/13596535221082399
Yeqiong Zhang, Zhipeng Li, Q. Luo, Wenxiong Xu, Lu Wang, Shu Zhu, L. Peng, Chang Xie
Background Tenofovir alafenamide (TAF) is a new anti-hepatitis B virus nucleotide analogue that can cause dyslipidaemia in AIDS patients, but the effect of TAF on blood lipids in patients with chronic hepatitis B (CHB) is unknown. This study aimed to evaluate the effect of TAF on blood lipid levels in patients with CHB. Methods One hundred and twenty-one CHB patients were recruited as TAF group, including 69 treatment-naïve patients and 52 patients with nucleoside/nucleotide analogue experience before TAF treatment. All patients were followed up regularly for 48 weeks. Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) levels and the incidence of dyslipidaemia before and after TAF treatment were compared. Results After 48 weeks of TAF treatment, the levels of TC, TGs and LDL-C in TAF group were significantly higher than those in control group. In TAF group, the TC and TG levels were significantly higher than that at baseline. Baseline TC and TGs levels had a significant effect on the incidence of abnormal TC and TG levels after 48 weeks treatment. The LDL-C decreased slightly but not significantly. The proportion of patients with TC abnormalities increased from 20.7% at baseline to 26.3% at week 48, LDL-C abnormalities decreased from 50.4% to 42.5% and TG abnormalities increased from 14.2% to 22.5%. There were no significant differences compared with control group, as well as compared with baseline. Conclusions Tenofovir alafenamide treatment mainly affects the TC and TG level in patients with CHB but has little effect on LDL-C.
{"title":"Changes in blood lipids in patients with chronic hepatitis B after 48 weeks of tenofovir alafenamide treatment: A prospective real-world clinical study","authors":"Yeqiong Zhang, Zhipeng Li, Q. Luo, Wenxiong Xu, Lu Wang, Shu Zhu, L. Peng, Chang Xie","doi":"10.1177/13596535221082399","DOIUrl":"https://doi.org/10.1177/13596535221082399","url":null,"abstract":"Background Tenofovir alafenamide (TAF) is a new anti-hepatitis B virus nucleotide analogue that can cause dyslipidaemia in AIDS patients, but the effect of TAF on blood lipids in patients with chronic hepatitis B (CHB) is unknown. This study aimed to evaluate the effect of TAF on blood lipid levels in patients with CHB. Methods One hundred and twenty-one CHB patients were recruited as TAF group, including 69 treatment-naïve patients and 52 patients with nucleoside/nucleotide analogue experience before TAF treatment. All patients were followed up regularly for 48 weeks. Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) levels and the incidence of dyslipidaemia before and after TAF treatment were compared. Results After 48 weeks of TAF treatment, the levels of TC, TGs and LDL-C in TAF group were significantly higher than those in control group. In TAF group, the TC and TG levels were significantly higher than that at baseline. Baseline TC and TGs levels had a significant effect on the incidence of abnormal TC and TG levels after 48 weeks treatment. The LDL-C decreased slightly but not significantly. The proportion of patients with TC abnormalities increased from 20.7% at baseline to 26.3% at week 48, LDL-C abnormalities decreased from 50.4% to 42.5% and TG abnormalities increased from 14.2% to 22.5%. There were no significant differences compared with control group, as well as compared with baseline. Conclusions Tenofovir alafenamide treatment mainly affects the TC and TG level in patients with CHB but has little effect on LDL-C.","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44319361","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 : 2022-04-01DOI: 10.1177/13596535211062396
Madhuchanda Choudhary, J. Mellors
A co-formulated, one pill once a day antiretroviral regimen (single-tablet regimen), containing efavirenz, emtricitabine, and tenofovir disoproxyl fumarate (Atripla), revolutionized the antiretroviral therapy landscape. Single-tablet regimens provide not only dosing convenience but help optimize adherence and persistence with antiretroviral therapy to achieve durably suppressed viremia with both individual and societal benefits. Given the many excellent options available now, single-tablet regimens are the preferred choice for initiating antiretroviral therapy in almost all patients with rare exceptions for drug interactions and pregnancy, and for simplification of more complex antiretroviral therapy to a single-tablet regimen. In this special commemorative article, we celebrate this astounding advancement in antiretroviral therapy, championed by John C. Martin while CEO of Gilead Sciences, and its transformative impact on HIV care nationally and globally.
{"title":"The transformation of HIV therapy: One pill once a day","authors":"Madhuchanda Choudhary, J. Mellors","doi":"10.1177/13596535211062396","DOIUrl":"https://doi.org/10.1177/13596535211062396","url":null,"abstract":"A co-formulated, one pill once a day antiretroviral regimen (single-tablet regimen), containing efavirenz, emtricitabine, and tenofovir disoproxyl fumarate (Atripla), revolutionized the antiretroviral therapy landscape. Single-tablet regimens provide not only dosing convenience but help optimize adherence and persistence with antiretroviral therapy to achieve durably suppressed viremia with both individual and societal benefits. Given the many excellent options available now, single-tablet regimens are the preferred choice for initiating antiretroviral therapy in almost all patients with rare exceptions for drug interactions and pregnancy, and for simplification of more complex antiretroviral therapy to a single-tablet regimen. In this special commemorative article, we celebrate this astounding advancement in antiretroviral therapy, championed by John C. Martin while CEO of Gilead Sciences, and its transformative impact on HIV care nationally and globally.","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44712129","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 : 2022-04-01DOI: 10.1177/13596535211072672
M. Cornberg, M. Manns
The development of direct-acting antivirals (DAA) has revolutionized the treatment of chronic hepatitis C, enabling cure of hepatitis C virus (HCV) infection in more than 95% of cases. There are essentially no contraindications, so almost any patient can now be successfully treated. The result is the prevention or amelioration of cirrhosis, hepatocellular carcinoma (HCC), and extrahepatic manifestations. Consequently, the 2020 Nobel Prize in Medicine and Physiology was awarded for the discovery of HCV. Due to the high efficacy of therapy, even global HCV elimination is conceivable even without a vaccine. Here, we would like to venture a SWOT analysis of current HCV therapies aimed at HCV elimination.
{"title":"The curing regimens of HCV: A SWOT analysis","authors":"M. Cornberg, M. Manns","doi":"10.1177/13596535211072672","DOIUrl":"https://doi.org/10.1177/13596535211072672","url":null,"abstract":"The development of direct-acting antivirals (DAA) has revolutionized the treatment of chronic hepatitis C, enabling cure of hepatitis C virus (HCV) infection in more than 95% of cases. There are essentially no contraindications, so almost any patient can now be successfully treated. The result is the prevention or amelioration of cirrhosis, hepatocellular carcinoma (HCC), and extrahepatic manifestations. Consequently, the 2020 Nobel Prize in Medicine and Physiology was awarded for the discovery of HCV. Due to the high efficacy of therapy, even global HCV elimination is conceivable even without a vaccine. Here, we would like to venture a SWOT analysis of current HCV therapies aimed at HCV elimination.","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43979178","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: 10.1177/13596535211067600
William A Lee, A. Cheng
Tenofovir alafenamide fumarate is a lipophilic prodrug of tenofovir which is preferentially metabolized in lymphatic tissue resulting in high concentrations of tenofovir (TFV) and its active diphosphate metabolite inside the cells that replicate HIV. Due to its selectivity for these tissues, lower total doses of TAF can be administered relative to tenofovir disoproxil fumarate (TDF) which results in improved bone and renal biomarkers. Tenofovir alafenamide fumarate has become the “backbone” of multiple combination products for the treatment of HIV, combined with emtricitabine for PreP and as a monotherapy for the treatment or HBV.
{"title":"Tenofovir alafenamide fumarate","authors":"William A Lee, A. Cheng","doi":"10.1177/13596535211067600","DOIUrl":"https://doi.org/10.1177/13596535211067600","url":null,"abstract":"Tenofovir alafenamide fumarate is a lipophilic prodrug of tenofovir which is preferentially metabolized in lymphatic tissue resulting in high concentrations of tenofovir (TFV) and its active diphosphate metabolite inside the cells that replicate HIV. Due to its selectivity for these tissues, lower total doses of TAF can be administered relative to tenofovir disoproxil fumarate (TDF) which results in improved bone and renal biomarkers. Tenofovir alafenamide fumarate has become the “backbone” of multiple combination products for the treatment of HIV, combined with emtricitabine for PreP and as a monotherapy for the treatment or HBV.","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45072979","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: 10.1177/13596535211060968
R. Whitley
In the mid 1980’s, I flew from Birmingham, Alabama to San Francisco, rented a car, and drove to Palo Alto so that I could meet with John Martin at Syntex. John, along with Julian Verheyden, synthesized ganciclovir, which had significant in vitro activity against cytomegalovirus (CMV) in vitro. This drug provided my colleagues and me an opportunity to evaluate it as a therapeutic agent for congenital CMV infection, knowing full well that it was mutagenic, teratogenic, and carcinogenic. John in his wisdom convinced the management of Syntex to provide ganciclovir for this disease, allowing me to study this drug in symptomatic congenitally infected children through the NIAID Collaborative Antiviral Study Group (CASG). Certainly, no other person or company would advocate for the use of such a medication in children, regardless of disease severity, because of its toxicity profile. Since these early days, ganciclovir, and subsequently its prodrug valganciclovir, have become the standard of care for the treatment of congenital cytomegalovirus infection. The following commentary defines the need and progress in the development of therapy
{"title":"Commentary: Development of Therapeutics for Congenital Cytomegalovirus Infection","authors":"R. Whitley","doi":"10.1177/13596535211060968","DOIUrl":"https://doi.org/10.1177/13596535211060968","url":null,"abstract":"In the mid 1980’s, I flew from Birmingham, Alabama to San Francisco, rented a car, and drove to Palo Alto so that I could meet with John Martin at Syntex. John, along with Julian Verheyden, synthesized ganciclovir, which had significant in vitro activity against cytomegalovirus (CMV) in vitro. This drug provided my colleagues and me an opportunity to evaluate it as a therapeutic agent for congenital CMV infection, knowing full well that it was mutagenic, teratogenic, and carcinogenic. John in his wisdom convinced the management of Syntex to provide ganciclovir for this disease, allowing me to study this drug in symptomatic congenitally infected children through the NIAID Collaborative Antiviral Study Group (CASG). Certainly, no other person or company would advocate for the use of such a medication in children, regardless of disease severity, because of its toxicity profile. Since these early days, ganciclovir, and subsequently its prodrug valganciclovir, have become the standard of care for the treatment of congenital cytomegalovirus infection. The following commentary defines the need and progress in the development of therapy","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44304098","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: 10.1177/13596535211072673
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":null,"pages":null},"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}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：