scholarly journals 34. Long-term clinical outcomes following SARS-CoV-2 infection include persistent symptoms and cardiovascular disease beyond 3 months post-infection

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S24-S25
Author(s):  
Stephanie A Richard ◽  
Simon Pollett ◽  
Nusrat J Epsi ◽  
Ryan C Maves ◽  
Ryan C Maves ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Generalized Linear Models ◽  
Symptom Onset ◽  
Linear Models ◽  
Random Effect ◽  
Panel Member ◽  
Organ System ◽  
Review Panel ◽  
Persistent Symptoms

Abstract Background The long-term health effects after SARS-CoV-2 infection remain poorly understood. We evaluated health and healthcare usage after SARS-CoV-2 infection via surveys and longitudinal electronic medical record (EMR) review within the Military Health System (MHS). Methods We studied MHS beneficiaries enrolled in the Epidemiology, Immunology, and Clinical Characteristics of Emerging Infectious Diseases with Pandemic Potential (EPICC) cohort from March to December 2020. COVID-19 illness symptom severity and duration were derived from surveys initiated in late 2020. In addition, multi-year healthcare encounter history before and after onset of COVID-19 symptoms was collected from the MHS EMR. Odds of organ-system clinical diagnoses within the 3 months pre- and post-symptom onset were calculated using generalized linear models, controlling for age, sex, and race, and including participant as a random effect. Results 1,015 participants were included who were SARS-CoV-2 positive, symptomatic, and had 3-month follow-up data available in the EMR (Table 1). 625 of these participants had survey data collected more than 28 days post-symptom onset, among whom 17% and 6% reported persistent symptoms at 28-84 days, and 85+ days, respectively. 9.6% had not resumed normal activities by one month. The most frequently reported symptoms persisting beyond 28 days were dyspnea, loss of smell and/or taste, fatigue, and exercise intolerance (Figure 1A). When compared with the period 61 to 90 days prior to symptom onset, the first month post-symptom onset period was associated with increases of pulmonary (aOR = 57, 95% CI 28-112), renal (aOR = 29, 95% CI 10-84), cardiovascular (aOR = 7, 95% CI 5-11), and neurological diagnoses (aOR = 3, 95% CI 2-4) (Figures 1B and 1C). Cardiovascular disease diagnoses remained elevated through 3 months (aOR = 2, 95% CI 1-3). Table 1. Characteristics of SARS-CoV-2+ EPICC participants, and illness duration among those with 28+ days post-symptom onset survey data collection. Figure 1 Fig1A. Symptoms reported by EPICC participants with illnesses longer than 28 days; 1B. Percent of participants with organ system specific diagnoses on each day, 90 days pre- and post-symptom onset; 1C. Odds of organ system specific diagnoses within each month, +/- 3 months of symptom onset, were calculated using generalized linear models, controlling for age, sex, and race and included participants as a random effect. Odds shown are relative to the earliest period included in the model, 61-90 days before onset. Conclusion In this MHS cohort, a significant proportion of participants had persistent symptoms and cardiovascular disease diagnoses 3 months after COVID-19 illness onset. These findings emphasize the long-term morbidity of COVID-19 and the importance of mitigating SARS-CoV-2 infections. Further analyses will evaluate demographic, clinical, and biomarker predictors of medium-to-long term organ-specific post-acute sequelae. Disclosures Simon Pollett, MBBS, Astra Zeneca (Other Financial or Material Support, HJF, in support of USU IDCRP, funded under a CRADA to augment the conduct of an unrelated Phase III COVID-19 vaccine trial sponsored by AstraZeneca as part of USG response (unrelated work)) Ryan C. Maves, MD, EMD Serono (Advisor or Review Panel member)Heron Therapeutics (Advisor or Review Panel member) David A. Lindholm, MD, American Board of Internal Medicine (Individual(s) Involved: Self): Member of Auxiliary R&D Infectious Disease Item-Writer Task Force. No financial support received. No exam questions will be disclosed ., Other Financial or Material Support

scholarly journals 8. The Adjuvanted Recombinant Zoster Vaccine (RZV) Confers Long-term Protection Against Herpes Zoster: Interim Results of an Extension Study (ZOSTER-049) of Two Clinical Trials (ZOE-50 and ZOE-70)

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S4-S5
Author(s):  
Céline Boutry ◽  
Andrew Hastie ◽  
Meng Shi ◽  
Javier Diez-Domingo ◽  
Juan Carlos Tinoco ◽  
...  
Keyword(s):  
Herpes Zoster ◽  
Research Study ◽  
Panel Member ◽  
Extension Study ◽  
Zoster Vaccine ◽  
Review Panel ◽  
Post Dose ◽  
Study Investigator

Abstract Background Two large-scale phase 3 clinical trials (ZOE-50 [NCT01165177] and ZOE-70 [NCT01165229]) demonstrated that, in adults ≥ 50 years of age followed over a mean period of 3.1 and 3.7 years respectively, the adjuvanted recombinant zoster vaccine (RZV) was efficacious against herpes zoster (HZ), highly immunogenic and had a clinically acceptable safety profile. In this extension study (ZOSTER-049 [NCT02723773]), RZV-induced immunogenicity persistence and long-term vaccine efficacy (VE) against HZ were evaluated; we report interim results after at least 2 years of follow-up (starting and ending ≈5.1 and 7.1 years, respectively, after initial vaccination during the parent studies). Methods The study design is detailed in Figure 1. Primary objective: VE against HZ over the ZOSTER-049 study. Secondary objectives: VE against HZ from 1 month post-dose 2 in ZOE-50/-70 until the end of observation for year (Y)2 of ZOSTER-049, persistence of vaccine-induced humoral immunogenicity (HI) in terms of anti-gE antibody concentrations (by ELISA) and cell-mediated immune (CMI) response in terms of frequency of gE-specific CD4+ T-cells (by intracellular cytokine staining). Figure 1. Study design of the extension study in relation to the parent studies. ZOSTER-049 study procedures, timing, endpoints and cohorts Results Of the 7,413 participants enrolled in ZOSTER-049, 7,277 were included in the VE analysis (Figure 2) and 6,972 reached Y2 of this study. The overall VE against HZ during at least 2 years of follow-up in ZOSTER-049 was 84.0% (95% confidence interval [CI]: 75.9–89.8%). From 1 month post-dose 2 in the ZOE-50/-70 studies until the end of observation for Y2 of ZOSTER-049, the overall VE was 90.9% (95% CI: 88.2–93.2%). Anti-gE antibody concentrations persisted ≈6 times above pre-vaccination levels up to Y8 after vaccination (Figure 3A) and the frequency of gE-specific CD4[2+] T-cells remained above baseline from Y6 to Y8 after vaccination (i.e. until the end of observation for Y2 of ZOSTER-049) (Figure 3B). Figure 2. Demographic characteristics of participants included in the ZOSTER-049 study, for the analysis of vaccine efficacy against herpes zoster (mTVC) Figure 3. Long-term persistence of humoral immunogenicity (HI) and cell-mediated immune (CMI) responses up to year 8 post-vaccination dose 2 administered in the ZOE-50/-70 studies Conclusion RZV demonstrated high VE against HZ until the end of the observation period for this Y2 interim analysis. The HI and CMI responses remained stable and high until the end of observation (i.e. 7.1 years after initial vaccination). Funding: GlaxoSmithKline Biologicals SA Acknowledgements: LA Truta/S Hulsmans (Modis c/o GSK) provided writing/editorial support Disclosures Céline Boutry, PhD, Aixial (Consultant) Andrew Hastie, MD, GSK group of companies (Employee) Meng Shi, MS, GSK group of companies (Employee) Javier Diez-Domingo, MD, GSK group of companies (Board Member, Scientific Research Study Investigator, Advisor or Review Panel member)MSD (Board Member, Scientific Research Study Investigator, Advisor or Review Panel member) Paola Pirrotta, PharmD, GSK group of companies (Employee) George Kalema, PhD, GSK group of companies/Keyrus Biopharma (Consultant) Anne Schuind, MD, GSK (Employee, Other Financial or Material Support, own GSK stock options or restricted shares as part of renumeration)

scholarly journals LB2. Safety and Efficacy of Combination SARS-CoV-2 Monoclonal Neutralizing Antibodies (mAb) BRII-196 and BRII-198 in Non-Hospitalized COVID-19 Patients

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S807-S808
Author(s):  
Teresa H Evering ◽  
Mark Giganti ◽  
Kara W Chew ◽  
Michael Hughes ◽  
Carlee Moser ◽  
...  
Keyword(s):  
High Risk ◽  
Symptom Onset ◽  
Interim Analysis ◽  
Neutralizing Antibodies ◽  
Severe Disease ◽  
Panel Member ◽  
The Philippines ◽  
Research Support ◽  
Review Panel ◽  
Research Grant

Abstract Background SARS-CoV-2 continues to spread and the development of safe and effective therapeutics for the prevention of severe disease remains a priority. BRII-196 and BRII-198 are non-competing anti-SARS-CoV-2 mAbs with YTE triple amino acid substitution in Fc to extend half-life and reduce receptor binding, that are being studied for treatment of COVID-19 in the ACTIV-2 Trial, sponsored by NIAID and led by ACTG. Methods ACTIV-2 evaluates safety/efficacy of investigational agents for treatment of non-hospitalized adults with mild-moderate COVID-19 under a randomized, blinded, controlled adaptive platform. BRII-196/BRII-198 (1000 mg each) as a single dose given as sequential infusions, or placebo to those at high risk of clinical progression (i.e., age ≥ 60 years or presence of other medical conditions) within 10 days of symptom onset and positive test for SARS-CoV-2. The primary endpoint was hospitalization and/or death through day 28. We report Phase 3 BRII-196/BRII-198 trial results per DSMB recommendation following an interim analysis. Results Between January and July 2021, 837 participants (418 active, 419 placebo) from sites in the US (66%), Brazil, South Africa, Mexico, Argentina and the Philippines were randomized and received study product at time of emerging variants. Median age 49 years (Q1, Q3: 39, 58), 51% female, 17% Black/African-American and 49% Hispanic/Latino, with median 6 days from symptom onset. At interim analysis 71% and 97% had a day 28 and 7 visit, respectively. For all available data at interim review, BRII-196/BRII-198 compared to placebo had fewer hospitalizations (12 vs. 45) and deaths (1 vs. 9). At day 28 of follow-up, there was an estimated 78% reduction in hospitalization and/or death (2.4 vs. 11.1%), relative risk 0.22 (95% CI: 0.05, 0.86), P=0.00001 (nominal one-sided). Grade 3 or higher adverse events (AEs) were observed less frequently among BRII-196/BRII-198 participants than placebo (3.8% vs. 13.4%) with no severe infusion reactions or drug related serious AEs. Conclusion BRII-196/BRII-198 was safe, well-tolerated, and demonstrated significant reduction compared to placebo in the risk of hospitalization and/or death among adults with mild-moderate COVID-19 at high risk for progression to severe disease. Disclosures Kara W. Chew, MD, MS, Amgen (Individual(s) Involved: Self): Grant/Research Support; Merck Sharp & Dohme (Individual(s) Involved: Self): Grant/Research Support David Alain Wohl, MD, Gilead Sciences (Individual(s) Involved: Self): Advisor or Review Panel member, Consultant, Research Grant or Support, Scientific Research Study Investigator; Janssen (Individual(s) Involved: Self): Advisor or Review Panel member; Merck (Individual(s) Involved: Self): Advisor or Review Panel member, Research Grant or Support; ViiV (Individual(s) Involved: Self): Advisor or Review Panel member, Research Grant or Support Joseph J. Eron, MD, Gilead Sciences (Consultant, Research Grant or Support)Janssen (Consultant, Research Grant or Support)Merck (Consultant)ViiV (Consultant, Research Grant or Support) David A. Margolis, MD MPH, Brii Biosciences (Employee) Courtney Fletcher, Pharm.D., National Institute of Allergy and Infectious Diseases, NIH (Grant/Research Support) Davey Smith, M.D., Linear Therapies, Matrix Biomed, Bayer (Consultant, Shareholder) Eric Daar, Gilead (Consultant, Grant/Research Support)Merck (Consultant)ViiV (Consultant, Grant/Research Support)

scholarly journals Long Covid in adults discharged from UK hospitals after Covid-19: A prospective, multicentre cohort study using the ISARIC WHO Clinical Characterisation Protocol.

2021 ◽  
Author(s):  
Louise Sigfrid ◽  
Tom M Drake ◽  
Ellen Pauley ◽  
Edwin C Jesudason ◽  
Piero Olliaro ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Cohort Study ◽  
Outcome Measures ◽  
Symptom Onset ◽  
Persistent Symptoms ◽  
Patient Reported ◽  
The Impact

Structured Abstract Objectives: The long-term consequences of severe Covid-19 requiring hospital admission are not well characterised. The objective of this study was to establish the long-term effects of Covid-19 following hospitalisation and the impact these may have on patient reported outcome measures. Design: A multicentre, prospective cohort study with at least 3 months follow-up of participants admitted to hospital between 5th February 2020 and 5th October 2020. Setting: 31 hospitals in the United Kingdom. Participants: 327 hospitalised participants discharged alive from hospital with confirmed/high likelihood SARS-CoV-2 infection. Main outcome measures and comparisons: The primary outcome was self-reported recovery at least ninety days after initial Covid-19 symptom onset. Secondary outcomes included new symptoms, new or increased disability (Washington group short scale), breathlessness (MRC Dyspnoea scale) and quality of life (EQ5D-5L). We compared these outcome measures across age, comorbidity status and in-hospital Covid-19 severity to identify groups at highest risk of developing long-term difficulties. Multilevel logistic and linear regression models were built to adjust for the effects of patient and centre level risk factors on these outcomes. Results: In total 53.7% (443/824) contacted participants responded, yielding 73.8% (327/443) responses with follow-up of 90 days or more from symptom onset. The median time between symptom onset of initial illness and completing the participant questionnaire was 222 days (Interquartile range (IQR) 189 to 269 days). In total, 54.7% (179/327) of participants reported they did not feel fully recovered. Persistent symptoms were reported by 93.3% (305/325) of participants, with fatigue the most common (82.8%, 255/308), followed by breathlessness (53.5%, 175/327). 46.8% (153/327) reported an increase in MRC dyspnoea scale of at least one grade. New or worse disability was reported by 24.2% (79/327) of participants. Overall (EQ5D-5L) summary index was significantly worse at the time of follow-up (median difference 0.1 points on a scale of 0 to 1, IQR: -0.2 to 0.0). Females under the age of 50 years were five times less likely to report feeling recovered (adjusted OR 5.09, 95% CI 1.64 to 15.74), were more likely to have greater disability (adjusted OR 4.22, 95% CI 1.12 to 15.94), twice as likely to report worse fatigue (adjusted OR 2.06, 95% CI 0.81 to 3.31) and seven times more likely to become more breathless (adjusted OR 7.15, 95% CI 2.24 to 22.83) than men of the same age. Conclusions: Survivors of Covid-19 experienced long-term symptoms, new disability, increased breathlessness, and reduced quality of life. These findings were present even in young, previously healthy working age adults, and were most common in younger females. Policymakers should fund further research to identify effective treatments for long-Covid and ensure healthcare, social care and welfare support is available for individuals with long-Covid.  

Evaluation and dynamics of risk of tick-borne viral encephalitis disease in some regions of Ural Federal District

2020 ◽  
pp. 29-32
Author(s):  
V. A. Mishchenko ◽  
I. A. Kshnyasev ◽  
I. V. Vyalykh ◽  
I. P. Bykov ◽  
L. G. Vyatkina
Keyword(s):  
Risk Factors ◽  
Generalized Linear Models ◽  
Odds Ratio ◽  
Viral Encephalitis ◽  
Linear Models ◽  
Federal District ◽  
Logit Regression ◽  
Tick Borne Encephalitis ◽  
External Variables

The regions of the Ural Federal District (UFD) are highly endemic for tick-borne encephalitis (ТВE) territories. The dynamics of morbidity of ТВЕ in the population characterized by complex cyclic, depending on many external variables. Retrospective analysis of the long-term dynamics (2007–2019) of the incidence of ТВЕ in regions of the UFD, taking into account the number of tick affected people was presented. The chances of getting sick in tick affected peoples to quantify the effect of predictors on TBE incidence were calculated. Standard apparatus of the theory of generalized linear models – logit-regression was used. It was established that the regions of the UFD characterized by a similar dynamics in the odds ratio indicator, therefore, TBE incidence with alternating ups and downs with a trend towards a decrease in the chance of TBE getting sick in tick affected people from 2007 to 2019. On average, over 13 years, the chances of developing TBE are statistically significantly different in the studied regions of the UFD, which can be explained by the influence of many risk factors and their combinations on the TBE incidence.

scholarly journals 501. Implementation and Outcomes of a Program to Coordinate and Administer Monoclonal Antibody Therapy to Long-Term Care Facility Residents with COVID-19

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S353-S353
Author(s):  
Andrew B Watkins ◽  
Lisa M Brand ◽  
Michelle Schwedhelm ◽  
Heather L Jensen ◽  
Brandon Scott ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Long Term Care ◽  
Antibody Therapy ◽  
Panel Member ◽  
Care Facility ◽  
Monoclonal Antibody Therapy ◽  
Review Panel ◽  
Term Care ◽  
Long Term Care Facility

Abstract Background Long-term care facility (LTCF) residents are at increased risk of severe COVID-19, with CMS data indicating > 20% mortality. BLAZE-1 trial noted lower hospitalization rates in high-risk patients receiving monoclonal antibody (mAb) vs placebo (4.2% vs 14.6%) for mild to moderate infections, making it a treatment option for LTCF residents; however, many LTCF lack staff to prepare and administer mAb therapy. To address this need, Region VII Disaster Health Response Ecosystem (R7DHRE) coordinated via NE Medical Emergency Operations Center (NEMEOC) an ASPR pilot project to facilitate infusion of COVID-19 mAb therapeutics for LTCF residents in the state. Methods R7DHRE partnered with Great Plains Health, Nebraska DHHS, Nebraska Antimicrobial Stewardship Assessment and Promotion Program (ASAP) and Infection Control Assessment and Promotion Program (ICAP) to surveil cases in the state, establish distribution/administration pathways, and educate providers on mAb therapeutics. A multi-hub-and-spoke model was created to allow LTCF to work with regional hospitals or pharmacy services to administer drug in their facilities, reducing time to therapy and transmission risk associated with patient transport. A centralized request process was created using a REDCap platform and verification of patient eligibility by ASAP. This request link, informational documents, fact sheets, and custom-built order form templates were hosted on a dedicated ASAP webpage, and details were shared during weekly ICAP LTCF webinars. Outcomes data, including 14- and 28-day COVID-related hospitalizations and mortality, were collected using databases from Nebraska Health Information Initiative and Nebraska DHHS. Results Through this program, 513 doses were administered to LTCF residents. Average time from symptom onset to infusion was 2.6 days. COVID- related hospitalization and mortality rates were lower than previously reported for LTCF residents (Table 1). Table 1. Debographics and Outcomes of mAb Infusions Conclusion By utilizing existing relationships with LTCFs in the region, we established a program to promptly distribute, prepare, and administer monoclonal antibody therapy to LTCF residents in need, preventing COVID-related hospitalizations and deaths. Disclosures James Lawler, MD, MPH, FIDSA, Kinsa Health (Advisor or Review Panel member)Takeda Pharmaceuticals (Advisor or Review Panel member) M. Salman Ashraf, MBBS, Merck & Co. Inc (Grant/Research Support, I have recieved grant funding for an investigator initiated research project from Merck & Con. Inc. However, I do not see any direct conflict of interest related to the submitted abstract)

scholarly journals 282 Follow-up of hospitalized COVID-19 survivors: assessment of short- and long-term cardiovascular sequelae after SARS-CoV-2 infection

2021 ◽  
Vol 23 (Supplement_G) ◽  
Author(s):  
Lucia Ilaria Birtolo ◽  
Silvia Prosperi ◽  
Sara Monosilio ◽  
Sara Cimino ◽  
Domenico Filomena ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Systemic Hypertension ◽  
Persistent Symptoms ◽  
Delayed Onset ◽  
Arterial Blood ◽  
Cardiovascular Involvement ◽  
Long Term Follow Up ◽  
Cardiovascular Evaluation

Abstract Aims Cardiovascular sequelae in COVID-19 survivors remain largely unclear and can potentially go unrecognized. Reports on follow-up focused on cardiovascular evaluation after hospital discharge are currently scarce. Aim of this prospective study was to assess cardiovascular sequelae in previously hospitalized COVID-19 survivors. Methods and results The study was conducted at ‘Sapienza’ University of Rome—Policlinico ‘Umberto I’. After 2 months from discharge, n = 230 COVID-19 survivors underwent a follow-up visit at a dedicated ‘post-COVID Outpatient Clinic’. A cardiovascular evaluation including electrocardiogram (ECG), Troponin and echocardiography was performed. Further tests were requested when clinically indicated. Medical history, symptoms, arterial-blood gas, blood tests, chest computed tomography, and treatment of both in-hospital and follow-up evaluation were recorded. A 1-year telephone follow-up was performed. A total of 36 (16%) COVID-19 survivors showed persistence or delayed onset of cardiovascular disease at 2-months follow-up visit. Persistent condition was recorded in 62% of survivors who experienced an in-hospital cardiovascular disease. Delayed cardiovascular involvement included: myocarditis, pericarditis, ventricular disfunction, new onset of systemic hypertension and arrhythmias. At 1-year telephone follow-up, 105 (45%) survivors reported persistent symptoms, with dyspnoea and fatigue being the most frequent. 60% of survivors showed persistent chest CT abnormalities and among those 28% complained of persistent cardiopulmonary symptoms at long term follow-up. Conclusions Our preliminary data showed persistent or delayed onset of cardiovascular involvement (16%) at short-term follow-up and persistent symptoms (45%) at long-term follow-up. These findings suggest the need for monitoring COVID-19 survivors.

scholarly journals Estimating Long-Term Delay Risk with Generalized Linear Models

2018 ◽  
Author(s):  
Marie Milliet de Faverges ◽  
Giorgio Russolillo ◽  
Christophe Picouleau ◽  
Boubekeur Merabet ◽  
Bertrand Houzel
Keyword(s):  
Generalized Linear Models ◽  
Linear Models

scholarly journals Why the Patient-Made Term 'Long Covid' is needed

2020 ◽  
Vol 5 ◽  
pp. 224 ◽  
Author(s):  
Elisa Perego ◽  
Felicity Callard ◽  
Laurie Stras ◽  
Barbara Melville-Jóhannesson ◽  
Rachel Pope ◽  
...  
Keyword(s):  
Public Health ◽  
Severe Acute Respiratory Syndrome ◽  
Patient Experience ◽  
Symptom Onset ◽  
Scientific Literature ◽  
Open Letter ◽  
Persistent Symptoms ◽  
The Media ◽  
Provision Of Care

The patient-made term ‘Long Covid’ is, we argue, a helpful and capacious term that is needed to address key medical, epidemiological and socio-political challenges posed by diverse symptoms persisting beyond four weeks after symptom onset suggestive of coronavirus disease 2019 (COVID-19). An international movement of patients (which includes all six authors) brought the persistence and heterogeneity of long-term symptoms to widespread visibility. The same grassroots movement introduced the term ‘Long Covid’ (and the cognate term ‘long-haulers’) to intervene in relation to widespread assumptions about disease severity and duration. Persistent symptoms following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are now one of the most pressing clinical and public health phenomena to address: their cause(s) is/are unknown, their effects can be debilitating, and the percentage of patients affected is unclear, though likely significant. The term ‘Long Covid’ is now used in scientific literature, the media, and in interactions with the WHO. Uncertainty regarding its value and meaning, however, remains. In this Open Letter, we explain the advantages of the term ‘Long Covid’ and bring clarity to some pressing issues of use and definition. We also point to the importance of centring patient experience and expertise in relation to ‘Long Covid’ research, as well as the provision of care and rehabilitation.

scholarly journals 854. Long-term Outcomes of Participants on F/TAF for Pre-Exposure Prophylaxis: Results for 144 Weeks of Follow-Up in the DISCOVER Trial

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S517-S518
Author(s):  
Moti Ramgopal ◽  
Peter Ruane ◽  
Yongwu Shao ◽  
Ramin Ebrahimi ◽  
Alex Kintu ◽  
...  
Keyword(s):  
Research Study ◽  
Scientific Research ◽  
Panel Member ◽  
Mineral Density ◽  
Research Support ◽  
Review Panel ◽  
Study Investigator ◽  
Research Grant

Abstract Background In DISCOVER, a multinational randomized controlled trial, F/TAF demonstrated noninferior efficacy compared to F/TDF for HIV prevention with improved bone mineral density and renal safety biomarkers at the primary endpoint (when all participants had reached 48 weeks and 50% had reached 96 weeks) and at week (W) 96, the end of the blinded phase. We now report W144 outcomes for participants who were randomized to F/TAF and continued F/TAF in the open-label extension (OLE) phase. Methods All participants who completed the randomized blinded phase could opt to receive F/TAF for at least 48 weeks in the OLE phase. We evaluated HIV incidence in participants on F/TAF through W144 and assessed changes in hip and spine bone mineral density (BMD) and in glomerular function (eGFR) from baseline to W144. Results 2,080 of the 2,694 participants initially randomized to F/TAF opted into the OLE phase, and 1,933 were still on study drug through W144, thereby leading to a total of 7,885 person-years (PY) of follow-up on F/TAF. Eight participants taking F/TAF acquired HIV in the blinded phase and 3 in the OLE phase. Dried blood spot analyses on the 3 OL infections found tenofovir diphosphate levels consistent with low adherence. Genotypic resistance testing showed no relevant resistance mutations for the 3 new infections. Among participants taking F/TAF, HIV incidence was 0.16/100 PY (95% CI 0.06-0.33) at the primary endpoint, 0.16/100 PY (95% CI 0.07-0.31) through 96 weeks and 0.14/100 PY (95% CI 0.07-0.25) through 144 weeks. Participants taking F/TAF had increases in hip BMD (mean percentage change +0.54%) and in spine BMD (mean percentage change +1.02%) from baseline to W144 (Figure 1). Median eGFR increased over 144 weeks, with a median increase of 2.6 mL/min from baseline to week 144. Participants in the F/TAF arm gained a median 2.3 kg (IQR -0.9-5.8) over 3 years of follow up. Figure 1. Changes in hip and spine bone mineral density and in eGFR through Week 144 Conclusion The OLE of DISCOVER allowed for a long-term assessment (144 wks.) of F/TAF for PrEP. HIV incidence remained low with BMD and renal function parameters remaining stable through 144 weeks of follow-up. These findings demonstrate that F/TAF is a safe and effective option for long-term use in people who would benefit from PrEP. Disclosures Moti Ramgopal, MD FACP FIDSA, Abbvie (Scientific Research Study Investigator, Speaker’s Bureau)Gilead (Consultant, Scientific Research Study Investigator, Speaker’s Bureau)Janssen (Consultant, Scientific Research Study Investigator, Research Grant or Support, Speaker’s Bureau)Merck (Consultant, Scientific Research Study Investigator)ViiV (Consultant, Scientific Research Study Investigator, Speaker’s Bureau) Peter Ruane, MD, AbbVie (Consultant, Research Grant or Support)Allergan (Research Grant or Support)Gilead Sciences Inc. (Consultant, Research Grant or Support, Shareholder, Speaker’s Bureau)Merck (Consultant, Research Grant or Support)ViiV Healthcare (Consultant, Research Grant or Support) Yongwu Shao, PhD, Gilead Sciences Inc. (Employee, Shareholder) Ramin Ebrahimi, MSc, Gilead Sciences Inc. (Employee, Shareholder) Alex Kintu, MD, ScD, Gilead Sciences Inc. (Employee, Shareholder) Christoph C. Carter, MD, Gilead Sciences Inc. (Employee, Shareholder) Moupali Das, MD, Gilead Sciences Inc. (Employee, Shareholder) Jared Baeten, MD, PHD, Gilead Sciences Inc. (Employee, Shareholder) Cynthia Brinson, MD, Abbvie (Scientific Research Study Investigator)BI (Scientific Research Study Investigator)Gilead Sciences Inc. (Scientific Research Study Investigator, Advisor or Review Panel member, Speaker’s Bureau, Personal fees)GSK (Scientific Research Study Investigator)Novo Nordisk (Scientific Research Study Investigator)ViiV Healthcare (Scientific Research Study Investigator, Advisor or Review Panel member, Speaker’s Bureau) Peter Shalit, MD, PhD, Abbvie (Grant/Research Support)Gilead Sciences (Consultant, Grant/Research Support, Speaker’s Bureau)Glaxo Smithkline (Consultant, Grant/Research Support)Janssen (Consultant, Grant/Research Support, Speaker’s Bureau)Merck (Grant/Research Support, Speaker’s Bureau)Thera (Speaker’s Bureau)ViiV Healthcare (Speaker’s Bureau) Karam Mounzer, MD, Epividian (Advisor or Review Panel member)Gilead Sciences Inc. (Consultant, Scientific Research Study Investigator, Research Grant or Support, Speaker’s Bureau)Janssen (Consultant, Research Grant or Support, Speaker’s Bureau)Merck (Research Grant or Support, Speaker’s Bureau)ViiV Healthcare (Consultant, Speaker’s Bureau)

Sign in / Sign up

Export Citation Format

Share Document