Antiviral Therapy最新文献

{"title":"Dynamics of HBV surface antigen related end points in chronic hepatitis B infection: a systematic review and meta-analysis.","authors":"Yusi Chen,&nbsp;Justin Jinhui Li,&nbsp;Rong Chen,&nbsp;Gailing Li,&nbsp;Jia Ji","doi":"10.3851/IMP3366","DOIUrl":"https://doi.org/10.3851/IMP3366","url":null,"abstract":"<p><strong>Background: </strong>In chronic hepatitis B (CHB) treatment, hepatitis B surface antigen (HBsAg) is regarded as a promising clinical end point associated with long-term clinical outcomes. We performed a meta-analysis to characterize the dynamics and influencing factors of HBsAg.</p><p><strong>Methods: </strong>Literature search was conducted through PubMed from January 1995 to May 2015 for papers reporting HBsAg in patients receiving various antiviral treatments. We conducted weighted linear regression to select for potential influencing factors on maximum HBsAg loss percentage, and subgroup analysis to calculate the pooled estimates of maximum HBsAg loss and seroconversion percentage following treatment of interferon (IFN), nucleoside analogue (NUC) or combination therapies (NUC+IFN), respectively. Study heterogeneity was assessed through sensitivity test and I-square statistics.</p><p><strong>Results: </strong>We collected data from 24 papers involving 6,674 adult CHB patients. In most studies, average HBsAg level decreased during treatment but relapsed after treatment cessation, while HBsAg loss or seroconversion percentage continued to increase or remained stable after treatment cessation. No strong relationship was observed between maximum HBsAg change and its baseline level. The pooled estimates of maximum HBsAg loss percentage for IFN (5.3%, 2.7-7.9%) and NUC+IFN (5.2%, 3.1-7.4%) were significantly higher than that of NUC (0.93%, 0.29-1.6%). Higher maximum HBsAg loss percentage is associated with longer peak time. Pooled maximum HBsAg seroconversion percentage estimates were 1.6%, 0.56% and 6.2% for IFN, NUC and NUC+IFN.</p><p><strong>Conclusions: </strong>With respect to HBsAg lowering, this meta-analysis confirmed the importance of longer treatment duration and addition of IFN, which revealed the potential value of immune-based therapies.</p>","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":"25 4","pages":"203-215"},"PeriodicalIF":1.2,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38105572","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}

{"title":"Genital secretion HIV RNA shedding in HIV-positive patients on ritonavir-boosted protease inhibitor monotherapy or standard combination ART: a cross-sectional sub-study from the PIVOT Trial.","authors":"Alejandro Arenas-Pinto, Wolfgang Stöhr, Saye Khoo, Amanda Clarke, Nicholas Beeching, Zoe Warwick, Vincent Lee, Laura Else, Rebecca Wiggins, Bridget Ferns, Eleni Nastouli, David Dunn, Charles J Lacey, Nicholas I Paton","doi":"10.3851/IMP3340","DOIUrl":"10.3851/IMP3340","url":null,"abstract":"<p><strong>Background: </strong>Protease inhibitors (PI) have relatively low penetration into the genital tract, raising concerns about the potential for genital HIV RNA shedding in patients taking PI-based regimens, particularly PI monotherapy (PI-mono).</p><p><strong>Methods: </strong>We measured HIV RNA and PI drug concentrations in samples of semen, cervico-vaginal and rectal mucosa secretions, and plasma in patients after 48-96 weeks on PI-mono or standard triple therapy.</p><p><strong>Results: </strong>A total of 85 participants were recruited. Of the 43 participants on PI-mono (70% on darunavir [DRV]/ritonavir [r]), 3 had detectable virus in semen or vaginal secretions (all below quantification limit), and none in rectal mucosa or plasma. Among those taking triple therapy, five had detectable virus in semen or vaginal secretions (HIV RNA >50 copies/ml in one), none in rectal mucosa and one in plasma. The median (IQR) concentration of DRV and atazanavir in semen (659.7 [339-1,089] and 128.8 [63-368] ng/ml, respectively) and cervico-vaginal samples (2,768 [312-7,879] and 1,836 [359-3,314] ng/ml, respectively) exceeded their protein adjusted median inhibition concentration (MIC₅₀). DRV concentration in rectal secretions showed higher variability compared with concentration in the other sites, with particularly high rectal secretion/blood ratios (median 8.4, IQR 2.6-68.7:1).</p><p><strong>Conclusions: </strong>We found no substantive evidence of HIV shedding in patients taking PI-mono, suggesting that PIs provide adequate control of virus in the genital compartment and are unlikely to lead to ongoing sexual transmission.</p>","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":"25 1","pages":"55-59"},"PeriodicalIF":1.3,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37762794","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}

{"title":"Effect of vitamin D₃ and calcium carbonate supplementation on muscle strength in postmenopausal women living with HIV.","authors":"Michael T Yin,&nbsp;Mariana Bucovsky,&nbsp;John Williams,&nbsp;Danielle Brunjes,&nbsp;Arindam RoyChoudhury,&nbsp;Ivelisse Colon,&nbsp;David C Ferris,&nbsp;Susan Olender,&nbsp;P Christian Schulze,&nbsp;Anjali Sharma,&nbsp;Cosmina Zeana,&nbsp;Barry Zingman,&nbsp;Elizabeth Shane","doi":"10.3851/IMP3386","DOIUrl":"https://doi.org/10.3851/IMP3386","url":null,"abstract":"<p><strong>Background: </strong>Both falls and fractures are increased in older persons living with HIV (PLWH). Low serum total 25-hydroxyvitamin D (25-OHD) levels have been associated with falls, fractures and poor muscle strength. We hypothesized that vitamin D (VitD) supplementation would improve muscle strength in postmenopausal PLWH.</p><p><strong>Methods: </strong>In a 12-month prospective, randomized, double-blind, study of 69 African American and Hispanic postmenopausal PLWH on antiretroviral therapy with 25-OHD ≥10 ng/ml and ≤32 ng/ml, we investigated the effects of daily low (1,000 IU; n=31) and moderate (3,000 IU; n=38) cholecalciferol doses on lean mass and strength. Change in lean body mass was assessed by dual-energy X-ray absorptiometry (DXA), and isometric and isokinetic muscle strength in the dominant lower extremity was assessed using the Biodex System 4 Pro.</p><p><strong>Results: </strong>Mean age was 56 ±5 years, median CD4⁺ T-cell count 722 cells/mm³ and 74% had HIV RNA≤50 copies/ml. Serum 25-OHD did not differ at baseline, but was higher in the moderate than low VitD group at 6 and 12 months. In both groups, there were significant increases in lower extremity isokinetic torque, work and power at 12 months, with no change in lean mass.</p><p><strong>Conclusions: </strong>VitD supplementation was associated with a modest increase in lower extremity strength in postmenopausal PLWH, without a concomitant increase in muscle mass. Magnitude of increase in strength were similar with 3,000 IU and 1,000 IU daily. Future larger studies will be required to determine the optimal dose of VitD to improve muscle strength and to determine whether supplementation reduces the risk of falls and fractures in PLWH.</p>","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":"25 8","pages":"411-418"},"PeriodicalIF":1.2,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9372923/pdf/nihms-1824030.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25464095","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}

{"title":"Cytomegalovirus infection associated with severe intraocular inflammation in an HIV patient: a case report.","authors":"Viviana P Lezcano Carduz,&nbsp;Nicolás Alejandre Alba,&nbsp;Elena Guzmán Almagro,&nbsp;Olga Sánchez Pernaute","doi":"10.3851/IMP3381","DOIUrl":"https://doi.org/10.3851/IMP3381","url":null,"abstract":"<p><p>This is a report of a case of severe intraocular inflammation associated with cytomegalovirus in an untreated HIV+ patient with a marked CD4⁺ T-cell depletion. The atypical presentation shown could confuse and delay the diagnosis. Early suspicion and appropriate treatment (ganciclovir, valganciclovir, HAART) increase the likelihood of a favourable outcome.</p>","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":"25 6","pages":"341-344"},"PeriodicalIF":1.2,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25565994","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}

{"title":"Differences in social and mental well-being of long-term survivors among people who inject drugs and other participants in the Swiss HIV Cohort Study: 1980-2018.","authors":"Katharina Kusejko,&nbsp;Alex Marzel,&nbsp;Huyen Nguyen,&nbsp;Sandra E Chaudron,&nbsp;Nadine Bachmann,&nbsp;Rainer Weber,&nbsp;Philip Bruggmann,&nbsp;Jan A Roth,&nbsp;Enos Bernasconi,&nbsp;Alexandra Calmy,&nbsp;Matthias Cavassini,&nbsp;Andrea Bregenzer,&nbsp;Jürg Böni,&nbsp;Sabine Yerly,&nbsp;Thomas Klimkait,&nbsp;Matthieu Perreau,&nbsp;Laura N Walti,&nbsp;Huldrych F Günthard,&nbsp;Roger D Kouyos","doi":"10.3851/IMP3347","DOIUrl":"https://doi.org/10.3851/IMP3347","url":null,"abstract":"<p><strong>Background: </strong>People living with HIV who were diagnosed before highly active antiretroviral therapy became available in 1996 and who survived at least 15 years after HIV diagnosis, termed long-term survivors (LTS), form a particularly vulnerable population. We study social, clinical and mental factors of LTS in the Swiss HIV Cohort Study, with a particular focus on people who inject drugs (PWID).</p><p><strong>Methods: </strong>We quantified differences between PWID LTS, and men who have sex with men (MSM) and heterosexual (HET) LTS. Using phylogenetic methods, we distinguished between heterosexual LTS who most likely shared a social network with PWID at the time of infection, termed clusteredHET, and those who did not, termed HET not clustered (HETnc). The analysis was performed using data collected at least 15 years post diagnosis.</p><p><strong>Results: </strong>Overall, 1,663 of 5,686 (29.2%) PWID were LTS. We found significant differences between PWID LTS and MSM/HETnc LTS regarding self-reported depression (59.4% versus 43.3%; odds ratio [OR]=1.8; P<0.001), incarceration (30.6% versus 7.0%; OR=6.9; P<0.001) and full work ability (25.4% versus 59.0%; OR=0.27; P<0.001). ClusteredHET were less vulnerable with respect to these variables than PWID LTS but more at risk compared with MSM/HETnc LTS, indicating that clusteredHET are closer to PWID with regard to social and mental aspects compared with all MSM/HETnc.</p><p><strong>Conclusions: </strong>Even more than 15 years post HIV diagnosis, special care for HIV-positive PWID is needed, with emphasis on mental health and social integration of PWID LTS.</p>","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":"25 1","pages":"43-54"},"PeriodicalIF":1.2,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37790463","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}

{"title":"Early low-molecular-weight heparin administration is associated with shorter time to SARS-CoV-2 swab negativity.","authors":"Mattia Trunfio,&nbsp;Elena Salvador,&nbsp;Alberto Gaviraghi,&nbsp;Sabrina Audagnotto,&nbsp;Letizia Marinaro,&nbsp;Ilaria Motta,&nbsp;Riccardo Casciaro,&nbsp;Valeria Ghisetti,&nbsp;Carmen Fava,&nbsp;Stefano Bonora,&nbsp;Giovanni Di Perri,&nbsp;Andrea Calcagno","doi":"10.3851/IMP3377","DOIUrl":"https://doi.org/10.3851/IMP3377","url":null,"abstract":"<p><strong>Background: </strong>Antiviral and immune-modulating properties of low-molecular-weight heparin (LMWH) against Coronaviridae have been reported by in vitro studies, but no in vivo evidence is yet available. We sought to know whether the timing of prophylactic doses of LMWH during the course of COVID-19 may affect the time to SARS-CoV-2 nasal-oropharyngeal swab negativization.</p><p><strong>Methods: </strong>Retrospective monocentric cross-sectional study on patients requiring sub-intensive ward admission due to first SARS-CoV-2 infection and undergoing early (EH; within 7 days from COVID-19 signs and symptoms onset) versus delayed prophylactic LMWH (DH; after 7 days). SARS-CoV-2 RNA was measured by reverse transcription real-time PCR according to scheduled time points: first swab after 2 weeks from COVID-19 onset, then at 1-week intervals until negativity.</p><p><strong>Results: </strong>Time to SARS-CoV-2 swab negativity was shorter in EH (38 patients) compared with DH (55 patients): 22 versus 37 days (P=0.004). The number of confirmative negative swabs in EH was significantly higher compared with DH at week 2 (21.1% versus 3.6%; P=0.017) and 4 (60.0% versus 19.6%; P<0.001). At univariate, EH differed from DH for several disease severity and clinical management parameters. Nevertheless, after accounting for the differences, Cox regression showed early LMWH administration (hazard ratio [HR] 2.91 [1.51, 5.63]; P=0.002) and higher lymphocytes nadir (HR 1.04 [1.01, 1.08]; P=0.020) as predictors of shorter time to swab negativity.</p><p><strong>Conclusions: </strong>This potential antiviral and/or immune-modulating activity of LMWH needs further in vivo confirmations by randomized controlled trials.</p>","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":"25 6","pages":"327-333"},"PeriodicalIF":1.2,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38868938","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}

{"title":"Efficacy of elbasvir/grazoprevir therapy in HCV genotype-1 with or without HIV infection: role of HCV core antigen monitoring and improvement of liver stiffness and steatosis.","authors":"Maneerat Chayanupatkul,&nbsp;Salyavit Chittmittraprap,&nbsp;Pornpitra Pratedrat,&nbsp;Natthaya Chuaypen,&nbsp;Anchalee Avihingsanon,&nbsp;Pisit Tangkijvanich","doi":"10.3851/IMP3370","DOIUrl":"https://doi.org/10.3851/IMP3370","url":null,"abstract":"<p><strong>Background: </strong>The combination of elbasvir and grazoprevir (EBR/GZR) has been approved for treating HCV infection. This study aimed to evaluate the efficacy of EBR/GZR in terms of sustained virological response (SVR) and improvement of liver fibrosis in Thai patients with HCV genotype-1 (GT1). The utility of serum HCV core antigen (HCVcAg) as an alternative to HCV RNA in assessing SVR was also investigated.</p><p><strong>Methods: </strong>A total of 101 HCV GT1-infected patients (65 monoinfection and 36 HIV coinfection) who received EBR/GZR for 12-16 weeks were included. Liver stiffness (LS) and controlled attenuation parameter (CAP) were measured by transient elastography. Serum HCVcAg was measured in parallel with HCV RNA.</p><p><strong>Results: </strong>The overall SVR12 and SVR24 rates in the cohort were 98.0% and 95.0%, respectively. SVR24 rates were consistently high (90.0% to 100%) across all subgroups of patients. A significant LS decline ³30% was observed more frequently in cirrhotic than non-cirrhotic individuals who achieved SVR (63.3% versus 30.3%; P=0.003). The magnitude of LS decline following HCV eradication was comparable between HCV monoinfection and HCV-HIV coinfection. The reduction of CAP was also observed in responders who had significant steatosis at baseline. Compared with HCV RNA, HCVcAg testing displayed high sensitivity (100%) and specificity (99.0-100%) in determining SVR12 and SVR24.</p><p><strong>Conclusions: </strong>This study confirms that EBR/GZR is effective for HCV GT1-infected Thai patients with or without HIV infection. HCV eradication is associated with LS and CAP improvement regardless of HIV status. HCVcAg testing could be a potential replacement for HCV RNA for assessing SVR in resource-limited settings.</p>","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":"25 6","pages":"305-314"},"PeriodicalIF":1.2,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38460874","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}

{"title":"Factors influencing hair lamivudine concentration among people living with HIV in Guangxi, China.","authors":"Quan Zhang,&nbsp;Xiaoming Li,&nbsp;Shan Qiao,&nbsp;Zhiyong Shen,&nbsp;Yuejiao Zhou","doi":"10.3851/IMP3360","DOIUrl":"https://doi.org/10.3851/IMP3360","url":null,"abstract":"<p><strong>Background: </strong>Hair antiretroviral concentration has served as an innovative and objective measure of antiretroviral adherence. However, some factors (for example, pharmacokinetics and hair characteristics) may contribute to the variability of hair antiretroviral concentration that may threaten the validity and reliability of the hair measure as a biomarker of adherence. This study aimed to examine the potential factors that may influence the measure of hair antiretroviral concentration.</p><p><strong>Methods: </strong>Hair samples from a cohort of 372 people living with HIV (PLHIV) receiving lamivudine (300 mg/day) in Guangxi, China. Lamivudine concentration was analysed using liquid chromatography-tandem mass spectrometry. Multivariable linear regression was used to evaluate the associations of hair lamivudine concentration with age, sex, ethnicity, height, weight, body mass index, duration of HIV diagnosis, duration of current regimen, dosing schedule, concomitant antiretroviral medications, frequency of hair washing, hair care products use, hair cosmetic treatment and self-reported adherence.</p><p><strong>Results: </strong>Multivariable models revealed that frequency of hair washing (β=-0.221, P=0.001), dosing schedule (β=0.141, P=0.036) and self-reported adherence (β=0.160, P=0.002) were associated with hair lamivudine concentration.</p><p><strong>Conclusions: </strong>We observed that, among those potential factors, hair lamivudine concentration was influenced by frequency of hair washing and dosing schedule. Therefore, frequency of hair washing and dosing schedule should be considered in future research using hair lamivudine concentration as a measure of lamivudine exposure and biomarker of adherence.</p>","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":"25 3","pages":"143-149"},"PeriodicalIF":1.2,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37996020","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}

{"title":"Perillyl alcohol and perillic acid exert efficient action upon HSV-1 maturation and release of infective virus.","authors":"Camilly Pires Mello,&nbsp;Thereza Quirico-Santos,&nbsp;Lídia Fonte Amorim,&nbsp;Viveca Giongo Silva,&nbsp;Lucianne Madeira Fragel,&nbsp;David C Bloom,&nbsp;Izabel Palmer Paixão","doi":"10.3851/IMP3315","DOIUrl":"https://doi.org/10.3851/IMP3315","url":null,"abstract":"<p><strong>Background: </strong>Infection by herpes simplex type-1 virus (HSV-1) causes several pathological processes, including cutaneous, oral and genital infections, fatal encephalitis and cognitive dysfunction due to grey matter loss. Acyclovir is the reference compound used as HSV-1 antiviral therapy. However, with the emergence of HSV-resistant strains to current antiviral drugs, development of new antiviral agents with distinct modes of action is urgently needed.</p><p><strong>Methods: </strong>In this study, we examined the mechanism of action of monoterpenes perillyl alcohol (POH) and perillic acid (PA) upon in vitro replication of HSV-1 KOS wild-type and the syn-mutant 17+ strain on Vero cells by plaque assay.</p><p><strong>Results: </strong>The cytotoxicity of POH and PA was measured by MTT assay and indicated that both compounds had high anti-HSV-1 activities in a concentration range that was not toxic for Vero cells. In addition, PCR analysis showed that POH and PA did not inhibit viral genome replication, but rather the release of infective virion particles from Vero cells.</p><p><strong>Conclusions: </strong>Such findings suggest that POH and PA exert action upon late stages of HSV-1 maturation, therefore, indicating a promising perspective to its application in clinical investigation as effective anti-HSV-1 therapy preventing intermittent reactivation and progressive grey matter loss.</p>","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":"25 1","pages":"1-11"},"PeriodicalIF":1.2,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3851/IMP3315","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37252197","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}

{"title":"The protease inhibitor lopinavir, boosted with ritonavir, as treatment for COVID-19: a rapid review.","authors":"Jienchi Dorward, Oghenekome Gbinigie, Ting Cai, Nia W Roberts, Nigel Garrett, Gail Hayward, Christopher C Butler","doi":"10.3851/IMP3385","DOIUrl":"10.3851/IMP3385","url":null,"abstract":"<p><strong>Background: </strong>The HIV protease inhibitor lopinavir, boosted with ritonavir, has been used off-label to treat COVID-19. We aimed to synthesize the clinical evidence for lopinavir/ritonavir as a treatment for COVID-19.</p><p><strong>Methods: </strong>We performed a rapid review by searching databases including PubMed, GoogleScholar, medRxiv, ClinicalTrials.gov and the Cochrane COVID-19 Study Register, for COVID-19 studies comparing outcomes between patients who did and did not receive lopinavir/ritonavir. The quality of evidence was assessed using the GRADE criteria.</p><p><strong>Results: </strong>We identified five completed randomized controlled trials (RCTs) and 14 retrospective cohort studies. Two large RCTs of 5,040 and 2,771 hospitalized adults with COVID-19 found no evidence that lopinavir/ritonavir influenced the primary outcome of mortality, or secondary outcomes including progression to mechanical ventilation or time to discharge. Results remained similar in all sub-group analyses including by age, gender, baseline ventilation and time since symptom onset. The three smaller RCTs (n=86-199) also found no evidence of a benefit in the primary outcomes of time to clinical improvement or time to viral clearance. The 14 observational studies included between 50 and 415 participants, and were limited by a lack of adjustment for potential confounding variables. The majority of these studies found no evidence that lopinavir/ritonavir was associated with improved mortality or other clinical outcomes, although results regarding viral clearance were mixed.</p><p><strong>Conclusions: </strong>Good evidence from large clinical trials does not support using lopinavir/ritonavir to treat COVID-19 amongst hospitalized patients.</p>","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":"25 7","pages":"365-376"},"PeriodicalIF":1.3,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25461961","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}