Pub Date : 2022-06-01DOI: 10.1177/13596535221092182
European Pregnancy And Paediatric Infections Cohort Collaboration Eppicc, Alex Lyons, Lindsay Thompson, Elizabeth Chappell, Luminita Ene, Luisa Galli, Tessa Goetghebuer, Gonzague Jourdain, Antoni Noguera-Julian, Christian R Kahlert, Christoph Königs, Pope Kosalaraksa, Pagakrong Lumbiganon, Magdalena Marczyńska, Laura Marques, Marissa Navarro, Lars Naver, Liubov Okhonskaia, Filipa Prata, Thanyawee Puthanakit, Jose T Ramos, Anna Samarina, Claire Thorne, Evgeny Voronin, Anna Turkova, Carlo Giaquinto, Ali Judd, Intira J Collins
Background: Etravirine (ETR) is approved as a component of second or third-line antiretroviral treatment (ART) for children living with HIV. We assessed the outcomes of ETR-based ART in children in routine care in Europe and Thailand.
Methods: Data on children aged <18 years at ETR start were pooled from 17 observational cohorts. Characteristics at ETR start, immunological and virological outcomes at 12 months, discontinuations, adverse events (AEs) and serious adverse events (SAEs) were described. Follow-up was censored at ETR discontinuation, death or last visit.
Results: 177 children ever received ETR. At ETR start, median [IQR] age was 15 [12,16] years, CD4 count 480 [287, 713] cells/mm3, 70% had exposure to ≥3 ART classes and 20% had viral load (VL) <50 copies/mL. 95% received ETR in combination with ≥1 potent drug class, mostly protease inhibitor-based regimens. Median time on ETR was 24 [7, 48] months. Amongst those on ETR at 12 months (n=141), 69% had VL<50 copies/mL. Median CD4 increase since ETR start (n=83) was 147 [16, 267] cells/mm3. Overall, 81 (46%) discontinued ETR by last follow-up. Median time to discontinuation was 23 [8, 47] months. Common reasons for discontinuation were treatment simplification (19%), treatment failure (16%) and toxicity (12%). Eight children (5%) had AEs causally associated with ETR, all dermatological/hypersensitivity reactions. Two were SAEs, both Stevens-Johnson Syndrome in children on regimens containing ETR and darunavir and were causally related to either drugs; both resolved following ART discontinuation.
Conclusion: Children receiving ETR were predominantly highly treatment-experienced, over two-thirds were virally suppressed at 12 months.
{"title":"Outcomes of etravirine-based antiretroviral treatment in treatment-experienced children and adolescents living with HIV in Europe and Thailand.","authors":"European Pregnancy And Paediatric Infections Cohort Collaboration Eppicc, Alex Lyons, Lindsay Thompson, Elizabeth Chappell, Luminita Ene, Luisa Galli, Tessa Goetghebuer, Gonzague Jourdain, Antoni Noguera-Julian, Christian R Kahlert, Christoph Königs, Pope Kosalaraksa, Pagakrong Lumbiganon, Magdalena Marczyńska, Laura Marques, Marissa Navarro, Lars Naver, Liubov Okhonskaia, Filipa Prata, Thanyawee Puthanakit, Jose T Ramos, Anna Samarina, Claire Thorne, Evgeny Voronin, Anna Turkova, Carlo Giaquinto, Ali Judd, Intira J Collins","doi":"10.1177/13596535221092182","DOIUrl":"https://doi.org/10.1177/13596535221092182","url":null,"abstract":"<p><strong>Background: </strong>Etravirine (ETR) is approved as a component of second or third-line antiretroviral treatment (ART) for children living with HIV. We assessed the outcomes of ETR-based ART in children in routine care in Europe and Thailand.</p><p><strong>Methods: </strong>Data on children aged <18 years at ETR start were pooled from 17 observational cohorts. Characteristics at ETR start, immunological and virological outcomes at 12 months, discontinuations, adverse events (AEs) and serious adverse events (SAEs) were described. Follow-up was censored at ETR discontinuation, death or last visit.</p><p><strong>Results: </strong>177 children ever received ETR. At ETR start, median [IQR] age was 15 [12,16] years, CD4 count 480 [287, 713] cells/mm<sup>3</sup>, 70% had exposure to ≥3 ART classes and 20% had viral load (VL) <50 copies/mL. 95% received ETR in combination with ≥1 potent drug class, mostly protease inhibitor-based regimens. Median time on ETR was 24 [7, 48] months. Amongst those on ETR at 12 months (<i>n</i>=141), 69% had VL<50 copies/mL. Median CD4 increase since ETR start (<i>n</i>=83) was 147 [16, 267] cells/mm<sup>3</sup>. Overall, 81 (46%) discontinued ETR by last follow-up. Median time to discontinuation was 23 [8, 47] months. Common reasons for discontinuation were treatment simplification (19%), treatment failure (16%) and toxicity (12%). Eight children (5%) had AEs causally associated with ETR, all dermatological/hypersensitivity reactions. Two were SAEs, both Stevens-Johnson Syndrome in children on regimens containing ETR and darunavir and were causally related to either drugs; both resolved following ART discontinuation.</p><p><strong>Conclusion: </strong>Children receiving ETR were predominantly highly treatment-experienced, over two-thirds were virally suppressed at 12 months.</p>","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":"27 3","pages":"13596535221092182"},"PeriodicalIF":1.2,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7614682/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9703809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-06-01DOI: 10.1177/13596535221102690
Gentille Musengimana, Elysee Tuyishime, Athanase Kiromera, Samuel S Malamba, Augustin Mulindabigwi, Madjid R Habimana, Cyprien Baribwira, Muhayimpundu Ribakare, Savio D Habimana, Josh DeVos, Richard C N Mwesigwa, Eugenie Kayirangwa, Jules M Semuhore, Gallican N Rwibasira, Amitabh B Suthar, Eric Remera
Background: We assessed the prevalence of acquired HIV drug resistance (HIVDR) and associated factors among patients receiving first-line antiretroviral therapy (ART) in Rwanda.
Methods: This cross-sectional study included 702 patients receiving first-line ART for at least 6 months with last viral load (VL) results ≥1000 copies/mL. Blood plasma samples were subjected to VL testing; specimens with unsuppressed VL were genotyped to identify HIVDR-associated mutations. Data were analysed using STATA/SE.
Results: Median time on ART was 86.4 months (interquartile range [IQR], 44.8-130.2 months), and median CD4 count at ART initiation was 311 cells/mm3 (IQR, 197-484 cells/mm3). Of 414 (68.2%) samples with unsuppressed VL, 378 (88.3%) were genotyped. HIVDR included 347 (90.4%) non-nucleoside reverse transcriptase inhibitor- (NNRTI), 291 (75.5%) nucleoside reverse transcriptase inhibitor- (NRTI) and 13 (3.5%) protease inhibitor (PI) resistance-associated mutations. The most common HIVDR mutations were K65R (22.7%), M184V (15.4%) and D67N (9.8%) for NRTIs and K103N (34.4%) and Y181C/I/V/YC (7%) for NNRTIs. Independent predictors of acquired HIVDR included current ART regimen of zidovudine + lamivudine + nevirapine (adjusted odds ratio [aOR], 3.333 [95% confidence interval (CI): 1.022-10.870]; p = 0.046) for NRTI resistance and current ART regimen of tenofovir + emtricitabine + nevirapine (aOR, 0.148 [95% CI: 0.028-0.779]; p = 0.025), zidovudine + lamivudine + efavirenz (aOR, 0.105 [95% CI: 0.016-0.693]; p = 0.020) and zidovudine + lamivudine + nevirapine (aOR, 0.259 [95% CI: 0.084-0.793]; p = 0.019) for NNRTI resistance. History of ever switching ART regimen was associated with NRTI resistance (aOR, 2.53 [95% CI: 1.198-5.356]; p = 0.016) and NNRTI resistance (aOR, 3.23 [95% CI: 1.435-7.278], p = 0.005).
Conclusion: The prevalence of acquired HIV drug resistance (HIVDR) was high among patient failing to re-suppress VL and was associated with current ART regimen and ever switching ART regimen. The findings of this study support the current WHO guidelines recommending that patients on an NNRTI-based regimen should be switched based on a single viral load test and suggests that national HIV VL monitoring of patients receiving ART has prevented long-term treatment failure that would result in the accumulation of TAMs and potential loss of efficacy of all NRTI used in second-line ART as the backbone in combination with either dolutegravir or boosted PIs.
{"title":"Acquired HIV drug resistance among adults living with HIV receiving first-line antiretroviral therapy in Rwanda: A cross-sectional nationally representative survey.","authors":"Gentille Musengimana, Elysee Tuyishime, Athanase Kiromera, Samuel S Malamba, Augustin Mulindabigwi, Madjid R Habimana, Cyprien Baribwira, Muhayimpundu Ribakare, Savio D Habimana, Josh DeVos, Richard C N Mwesigwa, Eugenie Kayirangwa, Jules M Semuhore, Gallican N Rwibasira, Amitabh B Suthar, Eric Remera","doi":"10.1177/13596535221102690","DOIUrl":"https://doi.org/10.1177/13596535221102690","url":null,"abstract":"<p><strong>Background: </strong>We assessed the prevalence of acquired HIV drug resistance (HIVDR) and associated factors among patients receiving first-line antiretroviral therapy (ART) in Rwanda.</p><p><strong>Methods: </strong>This cross-sectional study included 702 patients receiving first-line ART for at least 6 months with last viral load (VL) results ≥1000 copies/mL. Blood plasma samples were subjected to VL testing; specimens with unsuppressed VL were genotyped to identify HIVDR-associated mutations. Data were analysed using STATA/SE.</p><p><strong>Results: </strong>Median time on ART was 86.4 months (interquartile range [IQR], 44.8-130.2 months), and median CD4 count at ART initiation was 311 cells/mm<sup>3</sup> (IQR, 197-484 cells/mm<sup>3</sup>). Of 414 (68.2%) samples with unsuppressed VL, 378 (88.3%) were genotyped. HIVDR included 347 (90.4%) non-nucleoside reverse transcriptase inhibitor- (NNRTI), 291 (75.5%) nucleoside reverse transcriptase inhibitor- (NRTI) and 13 (3.5%) protease inhibitor (PI) resistance-associated mutations. The most common HIVDR mutations were K65R (22.7%), M184V (15.4%) and D67N (9.8%) for NRTIs and K103N (34.4%) and Y181C/I/V/YC (7%) for NNRTIs. Independent predictors of acquired HIVDR included current ART regimen of zidovudine + lamivudine + nevirapine (adjusted odds ratio [aOR], 3.333 [95% confidence interval (CI): 1.022-10.870]; p = 0.046) for NRTI resistance and current ART regimen of tenofovir + emtricitabine + nevirapine (aOR, 0.148 [95% CI: 0.028-0.779]; p = 0.025), zidovudine + lamivudine + efavirenz (aOR, 0.105 [95% CI: 0.016-0.693]; p = 0.020) and zidovudine + lamivudine + nevirapine (aOR, 0.259 [95% CI: 0.084-0.793]; p = 0.019) for NNRTI resistance. History of ever switching ART regimen was associated with NRTI resistance (aOR, 2.53 [95% CI: 1.198-5.356]; <i>p</i> = 0.016) and NNRTI resistance (aOR, 3.23 [95% CI: 1.435-7.278], p = 0.005).</p><p><strong>Conclusion: </strong>The prevalence of acquired HIV drug resistance (HIVDR) was high among patient failing to re-suppress VL and was associated with current ART regimen and ever switching ART regimen. The findings of this study support the current WHO guidelines recommending that patients on an NNRTI-based regimen should be switched based on a single viral load test and suggests that national HIV VL monitoring of patients receiving ART has prevented long-term treatment failure that would result in the accumulation of TAMs and potential loss of efficacy of all NRTI used in second-line ART as the backbone in combination with either dolutegravir or boosted PIs.</p>","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":"27 3","pages":"13596535221102690"},"PeriodicalIF":1.2,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/80/71/nihms-1812025.PMC9263597.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10507332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-06-01DOI: 10.1177/13596535221093856
E. Gane, M. Yuen, T. Kakuda, Tetsuro Ogawa, Yasushi Takahashi, N. Goeyvaerts, I. Lonjon‐Domanec, Tamisha Y. Vaughan, T. Schluep, J. Hamilton, E. Njumbe Ediage, V. Hillewaert, J. Snoeys, O. Lenz, W. Talloen, M. Biermer
Background JNJ-73763989 comprises two hepatitis B virus (HBV)-specific, liver-targeted N-galactosamine-conjugated short interfering RNA triggers, JNJ-73763976 and JNJ-73763924. JNJ-73763989 pharmacokinetics, safety and tolerability were assessed in two phase 1 studies: Japanese (NCT04002752), and non-Japanese healthy participants and chronic hepatitis B (CHB) patients also receiving the HBV capsid assembly modulator JNJ-56136379 and a nucleos(t)ide analogue (NA) (NCT03365947). Methods Healthy participant cohorts were double-blind and randomized to receive a single subcutaneous JNJ-73763989 dose (non-Japanese participants, 35, 100, 200, 300 or 400 mg; Japanese participants, 25, 100 or 200 mg) or placebo. JNJ-73763976 and JNJ-73763924 plasma concentrations were assessed over 48 h. CHB patients received JNJ-73763989 200 mg every 4 weeks plus daily oral JNJ-56136379 250 mg and NA in an open-label fashion. Safety and tolerability were assessed through Day 28 (healthy participants) or Day 112 (patients). Results Thirty non-Japanese (n = 4/dose; placebo, n = 10) and 24 Japanese healthy participants (n = 6/dose; placebo, n = 6) were randomized. JNJ-73763976 and JNJ-73763924 exposure generally increased in a dose-proportional manner. Mean plasma half-life was 4–9 h. No differences between pharmacokinetic parameters were apparent between non-Japanese and Japanese healthy participants. In the 12 CHB patients, mean JNJ-73763976, JNJ-73763924 and JNJ-56136379 plasma concentrations 2 h post-dose on Day 29 were 663, 269 and 14,718 ng/mL, respectively. In both studies, all adverse events were mild/moderate. Conclusion JNJ-73763976 and JNJ-73763924 had short plasma half-lives and exposure generally increased in a dose-proportional manner; there were no pharmacokinetic differences between Japanese and non-Japanese healthy adults. JNJ-73763989 with or without JNJ-56136379 and NA was generally safe and well tolerated.
{"title":"JNJ-73763989 pharmacokinetics and safety: Liver-targeted siRNAs against hepatitis B virus, in Japanese and non-Japanese healthy adults, and combined with JNJ-56136379 and a nucleos(t)ide analogue in patients with chronic hepatitis B","authors":"E. Gane, M. Yuen, T. Kakuda, Tetsuro Ogawa, Yasushi Takahashi, N. Goeyvaerts, I. Lonjon‐Domanec, Tamisha Y. Vaughan, T. Schluep, J. Hamilton, E. Njumbe Ediage, V. Hillewaert, J. Snoeys, O. Lenz, W. Talloen, M. Biermer","doi":"10.1177/13596535221093856","DOIUrl":"https://doi.org/10.1177/13596535221093856","url":null,"abstract":"Background JNJ-73763989 comprises two hepatitis B virus (HBV)-specific, liver-targeted N-galactosamine-conjugated short interfering RNA triggers, JNJ-73763976 and JNJ-73763924. JNJ-73763989 pharmacokinetics, safety and tolerability were assessed in two phase 1 studies: Japanese (NCT04002752), and non-Japanese healthy participants and chronic hepatitis B (CHB) patients also receiving the HBV capsid assembly modulator JNJ-56136379 and a nucleos(t)ide analogue (NA) (NCT03365947). Methods Healthy participant cohorts were double-blind and randomized to receive a single subcutaneous JNJ-73763989 dose (non-Japanese participants, 35, 100, 200, 300 or 400 mg; Japanese participants, 25, 100 or 200 mg) or placebo. JNJ-73763976 and JNJ-73763924 plasma concentrations were assessed over 48 h. CHB patients received JNJ-73763989 200 mg every 4 weeks plus daily oral JNJ-56136379 250 mg and NA in an open-label fashion. Safety and tolerability were assessed through Day 28 (healthy participants) or Day 112 (patients). Results Thirty non-Japanese (n = 4/dose; placebo, n = 10) and 24 Japanese healthy participants (n = 6/dose; placebo, n = 6) were randomized. JNJ-73763976 and JNJ-73763924 exposure generally increased in a dose-proportional manner. Mean plasma half-life was 4–9 h. No differences between pharmacokinetic parameters were apparent between non-Japanese and Japanese healthy participants. In the 12 CHB patients, mean JNJ-73763976, JNJ-73763924 and JNJ-56136379 plasma concentrations 2 h post-dose on Day 29 were 663, 269 and 14,718 ng/mL, respectively. In both studies, all adverse events were mild/moderate. Conclusion JNJ-73763976 and JNJ-73763924 had short plasma half-lives and exposure generally increased in a dose-proportional manner; there were no pharmacokinetic differences between Japanese and non-Japanese healthy adults. JNJ-73763989 with or without JNJ-56136379 and NA was generally safe and well tolerated.","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47071541","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: 10.1177/13596535211068957
Cheng-En Wu, Chun-Hsien Wu, S. Tsai, Wen-I Liao
Ergotism is a rare cause of peripheral vasoconstriction with varying presentation depending on the affected vessels. Coronary vasospasm is a rare, potentially fatal manifestation of ergotism. Cytochrome P-450 isoenzyme CYP3A metabolizes ergot alkaloids and their derivatives; thus, concomitant use of ergotamine and CYP3A inhibitors significantly increases ergotism risk. The antiretroviral drug darunavir boosted with cobicistat potently inhibits CYP3A. A few deleterious interactions are described in the literature when combining ergotamine with boosted human immunodeficiency virus protease inhibitors. Herein, we describe a patient who presented to the emergency department with profound coronary vasospasm arising from ergotamine’s interaction with darunavir and cobicistat. Emergency coronary angiography revealed no critical atherosclerotic stenosis, but prolonged coronary artery spasm. After prompt cardiopulmonary resuscitation, intravenous vasodilator treatment, and 14-day extracorporeal membrane oxygenation application, the patient fully recovered and was discharged. Concomitant use of ergot alkaloids and their derivatives could be disastrous for patients treated with cobicistat-boosted darunavir.
{"title":"A rare complication of coronary vasospasm associated with concomitant use of ergotamine, cobicistat, and darunavir","authors":"Cheng-En Wu, Chun-Hsien Wu, S. Tsai, Wen-I Liao","doi":"10.1177/13596535211068957","DOIUrl":"https://doi.org/10.1177/13596535211068957","url":null,"abstract":"Ergotism is a rare cause of peripheral vasoconstriction with varying presentation depending on the affected vessels. Coronary vasospasm is a rare, potentially fatal manifestation of ergotism. Cytochrome P-450 isoenzyme CYP3A metabolizes ergot alkaloids and their derivatives; thus, concomitant use of ergotamine and CYP3A inhibitors significantly increases ergotism risk. The antiretroviral drug darunavir boosted with cobicistat potently inhibits CYP3A. A few deleterious interactions are described in the literature when combining ergotamine with boosted human immunodeficiency virus protease inhibitors. Herein, we describe a patient who presented to the emergency department with profound coronary vasospasm arising from ergotamine’s interaction with darunavir and cobicistat. Emergency coronary angiography revealed no critical atherosclerotic stenosis, but prolonged coronary artery spasm. After prompt cardiopulmonary resuscitation, intravenous vasodilator treatment, and 14-day extracorporeal membrane oxygenation application, the patient fully recovered and was discharged. Concomitant use of ergot alkaloids and their derivatives could be disastrous for patients treated with cobicistat-boosted darunavir.","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47449408","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: 10.1177/13596535211067599
Raymond F Schinazi, Dharmeshkumar Patel, Maryam Ehteshami
The advent of antiretroviral combination therapy has significantly impacted the HIV/AIDS epidemic. No longer a death sentence, HIV infection can be controlled and suppressed using cocktail therapies that contain two or more small molecule drugs. This review aims to highlight the discovery, development, and impact of one such molecule, namely, emtricitabine (FTC, emtriva), which is one of the most successful drugs in the fight against HIV/AIDS and has been taken by over 94% of individuals infected with HIV in the USA. We also pay tribute to Dr. John C. Martin, former CEO and Chairman of Gilead Sciences, who unexpectedly passed away in 2021. A true visionary, he was instrumental in delivering FTC, as part of combination therapy with TDF (tenofovir, viread) to the global stage. As the fight to eradicate HIV marches on, we honor Dr. Martin's legacy of collaboration, achievement, and hope.
抗逆转录病毒联合疗法的出现极大地影响了艾滋病毒/艾滋病的流行。使用含有两种或两种以上小分子药物的鸡尾酒疗法可以控制和抑制艾滋病病毒感染，而不再是死刑。本综述旨在重点介绍恩曲他滨（FTC，emtriva）这类分子药物的发现、开发和影响，恩曲他滨是抗击艾滋病毒/艾滋病最成功的药物之一，在美国，超过 94% 的艾滋病毒感染者都服用了这种药物。我们还要向 2021 年意外去世的吉利德科学公司前首席执行官兼董事长约翰-马丁博士（Dr. John C. Martin）致敬。作为一位真正的远见卓识者，他在将 FTC 作为 TDF（替诺福韦、韦瑞德）联合疗法的一部分推向全球舞台方面发挥了重要作用。在根除艾滋病的斗争中，我们向马丁博士留下的合作、成就和希望致敬。
{"title":"The best backbone for HIV prevention, treatment, and elimination: Emtricitabine+tenofovir.","authors":"Raymond F Schinazi, Dharmeshkumar Patel, Maryam Ehteshami","doi":"10.1177/13596535211067599","DOIUrl":"10.1177/13596535211067599","url":null,"abstract":"<p><p>The advent of antiretroviral combination therapy has significantly impacted the HIV/AIDS epidemic. No longer a death sentence, HIV infection can be controlled and suppressed using cocktail therapies that contain two or more small molecule drugs. This review aims to highlight the discovery, development, and impact of one such molecule, namely, emtricitabine (FTC, emtriva), which is one of the most successful drugs in the fight against HIV/AIDS and has been taken by over 94% of individuals infected with HIV in the USA. We also pay tribute to Dr. John C. Martin, former CEO and Chairman of Gilead Sciences, who unexpectedly passed away in 2021. A true visionary, he was instrumental in delivering FTC, as part of combination therapy with TDF (tenofovir, viread) to the global stage. As the fight to eradicate HIV marches on, we honor Dr. Martin's legacy of collaboration, achievement, and hope.</p>","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":"27 2","pages":"13596535211067599"},"PeriodicalIF":1.2,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9200445","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: 10.1177/13596535211067592
I. Waked
Background Although Egypt was the country with the highest prevalence of hepatitis C in the world, the availability of sofosbuvir based therapies enabled Egypt to be the first country to eliminate hepatitis C and cure more than 4 million chronically infected patients. Purpose This is a small tribute to John Martin. Methodology and conclusion Here I present a summary of the HCV problem in Egypt, and how we, through Gilead's Access program under his leadership, were able to eliminate the disease.
{"title":"Case study of hepatitis C virus control in Egypt: impact of access program","authors":"I. Waked","doi":"10.1177/13596535211067592","DOIUrl":"https://doi.org/10.1177/13596535211067592","url":null,"abstract":"Background Although Egypt was the country with the highest prevalence of hepatitis C in the world, the availability of sofosbuvir based therapies enabled Egypt to be the first country to eliminate hepatitis C and cure more than 4 million chronically infected patients. Purpose This is a small tribute to John Martin. Methodology and conclusion Here I present a summary of the HCV problem in Egypt, and how we, through Gilead's Access program under his leadership, were able to eliminate the disease.","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44911207","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: 10.1177/13596535211067895
Lillian L Lou, A. Flood, Taiyin Yang, R. Whitley
{"title":"Commentary: John C. Martin (1951–2021)","authors":"Lillian L Lou, A. Flood, Taiyin Yang, R. Whitley","doi":"10.1177/13596535211067895","DOIUrl":"https://doi.org/10.1177/13596535211067895","url":null,"abstract":"","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44650912","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: 10.1177/13596535211067606
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":" ","pages":""},"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: 10.1177/13596535221076640
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":" ","pages":""},"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: 10.1177/13596535211068617
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":" ","pages":""},"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}
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