28 results on '"Chau, Gordon"'
Search Results
2. Identification of Novel UGT1A1 Variants Including UGT1A1 454C>A through the Genotyping of Healthy Participants of the HPTN 077 Study
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Seneviratne, Herana Kamal, Hamlin, Allyson N, Li, Sue, Grinsztejn, Beatriz, Dawood, Halima, Liu, Albert Y, Kuo, Irene, Hosseinipour, Mina C, Panchia, Ravindre, Cottle, Leslie, Chau, Gordon, Adeyeye, Adeola, Rinehart, Alex R, McCauley, Marybeth, Eron, Joseph S, Cohen, Myron S, Landovitz, Raphael J, Hendrix, Craig W, and Bumpus, Namandjé N
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Prevention ,Biotechnology ,Genetics ,Human Genome ,cabotegravir ,long-acting ,human immunodeficiency virus ,pre-exposure prophylaxis ,uridine diphosphate glucuronosyltransferase ,cabotegravir-glucuronide - Abstract
Cabotegravir (CAB) is an integrase strand-transfer inhibitor of HIV that has proven effective for HIV treatment and prevention in a long-acting injectable formulation, typically preceded by an oral formulation lead-in phase. Previous in vitro studies have demonstrated that CAB is primarily metabolized via glucuronidation by uridine diphosphate glucuronosyltransferase (UGT) 1A1 and 1A9. In this study, we performed next-generation sequencing of genomic DNA isolated from the HPTN 077 participants to explore the variants within UGT1A1 and UGT1A9. Additionally, to enable correlation of UGT1A1 and UGT1A9 genotypes with plasma CAB-glucuronide levels, we quantified glucuronidated CAB following both oral administration of CAB and intramuscular injection of long-acting CAB. From these studies, 48 previously unreported variants of UGT1A1 and UGT1A9 were detected. Notably, 5/68 individuals carried a UGT1A1 454C>A variant that resulted in amino acid substitution P152T, and the use of in silico tools predicted a deleterious effect of the P152T substitution. Thus, the impact of this mutant on a range of UGT1A1 substrates was tested using a COS-7 cell-based assay. The glucuronide conjugates of CAB, dolutegravir, and raltegravir, were not formed in the COS-7 cells expressing the UGT1A1 P152T mutant. Further, formation of glucuronides of raloxifene and 7-ethyl-10-hydroxycamptothecin were reduced in the cells expressing the UGT1A1 P152T mutant. Using the same approach, we tested the activities of two UGT1A9 mutants, UGT1A9 H217Y and UGT1A9 R464G, and found that these mutations were tolerated and decreased function, respectively. These data provide insight into previously unreported genetic variants of UGT1A1 and UGT1A9.
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- 2021
3. Immunogenicity and safety of a fourth homologous dose of NVX-CoV2373
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Alves, Katia, Plested, Joyce S., Galbiati, Shirley, Chau, Gordon, Cloney-Clark, Shane, Zhu, Mingzhu, Kalkeri, Raj, Patel, Nita, Smith, Kathy, Marcheschi, Alex, Pfeiffer, Susan, McFall, Heather, Smith, Gale, Glenn, Gregory M., Dubovsky, Filip, and Mallory, Raburn M.
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- 2023
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4. Acceptability of Long-Acting Injectable Cabotegravir (CAB LA) in HIV-Uninfected Individuals: HPTN 077.
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Tolley, Elizabeth, Zangeneh, Sahar, Chau, Gordon, Eron, Joe, Grinsztejn, Beatriz, Humphries, Hilton, Liu, Albert, Siegel, Marc, Bertha, Maseko, Panchia, Ravindre, Li, Sue, Cottle, Leslie, Rinehart, Alex, Margolis, David, Jennings, Andrea, McCauley, Marybeth, and Landovitz, Raphael
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Acceptability ,Clinical trial ,Females ,HIV prevention ,Injectable ,Males ,PrEP ,Adult ,Anti-HIV Agents ,Double-Blind Method ,Female ,HIV Infections ,Humans ,Injections ,Male ,Middle Aged ,Patient Acceptance of Health Care ,Patient Participation ,Pre-Exposure Prophylaxis ,Pyridones ,Treatment Outcome - Abstract
Long-acting injectable PrEP could offer an alternative to daily oral PrEP, improve adherence and protection, if found acceptable, safe and effective. HPTN 077 evaluated injectable cabotegravir safety, tolerability and pharmacokinetics among HIV-uninfected males and females in sequentially-enrolled cohorts of two dosing strategies. We compared acceptability of product attributes, prevention preferences and future interest in injectable PrEP (FIIP) by region, sex-at-birth, arm and cohort and used multivariable analysis to identify FIIP determinants. Baseline injectable PrEP preferences were higher in non-U.S. sites and increased in both regions over time. In multivariable models, FIIP was most strongly associated with acceptability of product attributes, was higher in non-U.S. sites and more altruistic participants. Treatment arm and report of pain were not associated with FIIP. Injectable acceptability was highest in non-U.S. sites. Preferences for injectable versus other PrEP methods were higher among U.S. males than females, but higher among males and females in non-U.S. settings.
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- 2020
5. Brief Report: Hormonal Contraception Use and Cabotegravir Pharmacokinetics in HIV-Uninfected Women Enrolled in HPTN 077.
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Blair, Cheríe S, Li, Sue, Chau, Gordon, Cottle, Leslie, Richardson, Paul, Marzinke, Mark A, Eshleman, Susan H, Adeyeye, Adeola, Rinehart, Alex R, Margolis, David, McCauley, Marybeth, Hendrix, Craig W, and Landovitz, Raphael J
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Reproductive Medicine ,Biomedical and Clinical Sciences ,Clinical Research ,Contraception/Reproduction ,Prevention ,HIV/AIDS ,Infectious Diseases ,Behavioral and Social Science ,Good Health and Well Being ,Brazil ,Contraceptive Agents ,Female ,Drug Interactions ,Female ,HIV Infections ,HIV Integrase Inhibitors ,HIV Seronegativity ,HIV-1 ,Hormonal Contraception ,Humans ,Malawi ,Male ,Pre-Exposure Prophylaxis ,Pyridones ,South Africa ,Young Adult ,hormonal contraception ,pharmacokinetics ,cabotegravir ,HIV ,cisgender women ,HPTN 077 Study Team ,Clinical Sciences ,Public Health and Health Services ,Virology ,Clinical sciences ,Epidemiology ,Public health - Abstract
ObjectivesTo evaluate whether hormonal contraceptive use among cisgender women is associated with differences in pharmacokinetic (PK) parameters of a long-acting injectable formulation of the integrase strand transfer inhibitor, cabotegravir (CAB-LA).SettingThis is a secondary analysis of 85 cisgender women enrolled in HPTN 077, a phase 2a multicenter study that enrolled HIV-uninfected, low-risk individuals in Malawi, Brazil, South Africa, and the United States.MethodsParticipants received 4-week daily oral cabotegravir lead-in, followed by CAB-LA 800 mg injection every 12 weeks (cohort 1) or 600 mg every 8 weeks (after 4-week initial interval between injections, cohort 2), over 41 weeks. Participants were followed 52-76 weeks subsequent to final injection. Generalized estimating equations and linear regression were used to evaluate differences in CAB-LA PK parameters (peak concentration, trough concentration, area under the curve, apparent terminal half-life, and time to lower limit of quantification) and self-reported hormonal contraceptive stratified by type (oral, injectable, implants, and other), controlling for body mass index and cohort.ResultsCompared to women reporting no hormonal contraception (n = 6), oral contraceptive use (n = 18) was associated with lower CAB-LA peak concentration but was not associated with differences in other PK parameters. No other hormonal contraceptive type (injectable, implants, and other) was associated with significant differences in CAB-LA PK parameters.ConclusionAlthough oral contraceptive use was associated with differences in CAB-LA peak concentration, no differences were observed in other PK parameters, suggesting that this association is not likely to be clinically significant. However, these data highlight the need for further research exploring potential drug-drug interactions between CAB-LA and hormonal contraceptives.
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- 2020
6. Cabotegravir Is Not Associated With Weight Gain in Human Immunodeficiency Virus–uninfected Individuals in HPTN 077
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Landovitz, Raphael J, Zangeneh, Sahar Z, Chau, Gordon, Grinsztejn, Beatriz, Eron, Joseph J, Dawood, Halima, Magnus, Manya, Liu, Albert Y, Panchia, Ravindre, Hosseinipour, Mina C, Kofron, Ryan, Margolis, David A, Rinehart, Alex, Adeyeye, Adeola, Burns, David, McCauley, Marybeth, Cohen, Myron S, and Currier, Judith S
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Medical Microbiology ,Biomedical and Clinical Sciences ,Immunology ,HIV/AIDS ,Clinical Trials and Supportive Activities ,Clinical Research ,Nutrition ,Prevention ,Obesity ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Metabolic and endocrine ,Infection ,Good Health and Well Being ,Anti-HIV Agents ,HIV ,HIV Infections ,Humans ,Pyridones ,Weight Gain ,cabotegravir ,CAB ,weight gain ,HIV uninfected ,Biological Sciences ,Medical and Health Sciences ,Microbiology ,Clinical sciences - Abstract
Studies in human immunodeficiency virus (HIV)-infected individuals suggest excess weight gain with integrase inhibitor-based antiretroviral therapy. The HIV Prevention Trials Network Study 077 evaluated changes in weight and fasting metabolic parameters in HIV-uninfected individuals randomized to cabotegravir or a placebo. No differences between arms were found for change in weight or fasting metabolic parameters overall or for subgroups.
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- 2020
7. Immunogenicity and safety of NVX-CoV2373 as a booster: A phase 3 randomized clinical trial in adults
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Raiser, Fritz, Davis, Matthew, Adelglass, Jeffrey, Cai, Miranda R., Chau, Gordon, Cloney-Clark, Shane, Eickhoff, Mark, Kalkeri, Raj, McKnight, Irene, Plested, Joyce, Zhu, Mingzhu, and Dunkle, Lisa M.
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- 2023
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8. Safety and immunogenicity following a homologous booster dose of a SARS-CoV-2 recombinant spike protein vaccine (NVX-CoV2373): a secondary analysis of a randomised, placebo-controlled, phase 2 trial
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Adams, Mark, Arya, Mark, Athan, Eugene, Berger, Ira, Bradley, Paul, Briskin, Toby, Glover II, Richard, Griffin, Paul, Kim, Joshua, Kitchener, Scott, Klein, Terry, Leah, Amber, Leelasena, Indika, Lemech, Charlotte, Lickliter, Jason, Manning, Mary Beth, Napier-Flood, Fiona, Nugent, Paul, Thackwray, Susan, Turner, Mark, Mallory, Raburn M, Formica, Neil, Pfeiffer, Susan, Wilkinson, Bethanie, Marcheschi, Alex, Albert, Gary, McFall, Heather, Robinson, Michelle, Plested, Joyce S, Zhu, Mingzhu, Cloney-Clark, Shane, Zhou, Bin, Chau, Gordon, Robertson, Andreana, Maciejewski, Sonia, Hammond, Holly L, Baracco, Lauren, Logue, James, Frieman, Matthew B, Smith, Gale, Patel, Nita, and Glenn, Gregory M
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- 2022
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9. The Longitudinal Effects of Non-injection Substance Use on Sustained HIV Viral Load Undetectability Among MSM and Heterosexual Men in Brazil and Thailand: The Role of ART Adherence and Depressive Symptoms (HPTN 063)
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Tsuyuki, Kiyomi, Shoptaw, Steven J, Ransome, Yusuf, Chau, Gordon, Rodriguez-Diaz, Carlos E, Friedman, Ruth K, Srithanaviboonchai, Kriengkrai, Li, Sue, Mimiaga, Matthew J, Mayer, Kenneth H, and Safren, Steven A
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Public Health ,Health Sciences ,Behavioral and Social Science ,Depression ,Mental Health ,Clinical Research ,Drug Abuse (NIDA only) ,Substance Misuse ,HIV/AIDS ,Prevention ,Infectious Diseases ,Infection ,Mental health ,Good Health and Well Being ,Adult ,Anti-HIV Agents ,Brazil ,Drug Users ,Female ,HIV Infections ,HIV-1 ,Heterosexuality ,Homosexuality ,Male ,Humans ,Longitudinal Studies ,Male ,Medication Adherence ,Middle Aged ,Substance-Related Disorders ,Thailand ,Viral Load ,Young Adult ,Zambia ,Substance use ,HIV ,Adherence ,Undetectable viral load ,Public Health and Health Services ,Social Work ,Public health - Abstract
The effect of non-injection substance use on HIV viral load (VL) is understudied in international settings. Data are from HPTN063, a longitudinal observational study of HIV-infected individuals in Brazil, Thailand, and Zambia, with focus on men with VL data (Brazil = 146; Thailand = 159). Generalized linear mixed models (GLMM) assessed whether non-injection substance use (stimulants, cannabis, alcohol, polysubstance) was associated with VL undetectability. ART adherence and depressive symptoms were examined as mediators of the association. In Thailand, substance use was not significantly associated with VL undetectability or ART adherence, but alcohol misuse among MSM was associated with increased odds of depression (AOR = 2.75; 95% CI 1.20, 6.32, p = 0.02). In Brazil, alcohol misuse by MSM was associated with decreased odds of undetectable VL (AOR = 0.34; 95% CI 0.13, 0.92, p = 0.03). Polysubstance use by heterosexual men in Brazil was associated with decreased odds of ART adherence (AOR = 0.25; 95% CI 0.08, 0.78, p = 0.02). VL suppression appears attainable among non-injection substance users. Substance use interventions among HIV-positive men should address depression, adherence, and VL undetectability.
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- 2019
10. Safety, tolerability, and pharmacokinetics of long-acting injectable cabotegravir in low-risk HIV-uninfected individuals: HPTN 077, a phase 2a randomized controlled trial.
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Landovitz, Raphael J, Li, Sue, Grinsztejn, Beatriz, Dawood, Halima, Liu, Albert Y, Magnus, Manya, Hosseinipour, Mina C, Panchia, Ravindre, Cottle, Leslie, Chau, Gordon, Richardson, Paul, Marzinke, Mark A, Hendrix, Craig W, Eshleman, Susan H, Zhang, Yinfeng, Tolley, Elizabeth, Sugarman, Jeremy, Kofron, Ryan, Adeyeye, Adeola, Burns, David, Rinehart, Alex R, Margolis, David, Spreen, William R, Cohen, Myron S, McCauley, Marybeth, and Eron, Joseph J
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Humans ,HIV Infections ,Pyridones ,Delayed-Action Preparations ,Anti-HIV Agents ,Drug Monitoring ,Treatment Outcome ,Injections ,Intramuscular ,Drug Administration Schedule ,Risk Assessment ,Risk Factors ,Double-Blind Method ,Adolescent ,Adult ,Aged ,Middle Aged ,Malawi ,South Africa ,United States ,Brazil ,Female ,Male ,Young Adult ,Injections ,Intramuscular ,General & Internal Medicine ,Medical and Health Sciences - Abstract
BackgroundCabotegravir (CAB) is a novel strand-transfer integrase inhibitor being developed for HIV treatment and prevention. CAB is formulated both as an immediate-release oral tablet for daily administration and as a long-acting injectable suspension (long-acting CAB [CAB LA]) for intramuscular (IM) administration, which delivers prolonged plasma exposure to the drug after IM injection. HIV Prevention Trials Network study 077 (HPTN 077) evaluated the safety, tolerability, and pharmacokinetics of CAB LA in HIV-uninfected males and females at 8 sites in Brazil, Malawi, South Africa, and the United States.Methods and findingsHPTN 077 was a double-blind, placebo-controlled phase 2a trial. Healthy individuals age 18-65 years at low HIV risk were randomized (3:1) to receive CAB or placebo (PBO). In the initial oral phase, participants received 1 daily oral tablet (CAB or PBO) for 4 weeks. Those without safety concerns in the oral phase continued and received injections in the injection phase (Cohort 1: 3 injections of CAB LA 800 mg or 0.9% saline as PBO IM every 12 weeks for 3 injection cycles; Cohort 2: CAB LA 600 mg or PBO IM for 5 injection cycles; the first 2 injections in Cohort 2 were separated by 4 weeks, the rest by 8 weeks). The primary analysis included weeks 5 to 41 of study participation, encompassing the injection phase. The cohorts were enrolled sequentially. Primary outcomes were safety and tolerability. Secondary outcomes included pharmacokinetics and events occurring during the oral and injection phases. Between February 9, 2015, and May 27, 2016, the study screened 443 individuals and enrolled 110 participants in Cohort 1 and 89 eligible participants in Cohort 2. Participant population characteristics were as follows: 66% female at birth; median age 31 years; 27% non-Hispanic white, 41% non-Hispanic black, 24% Hispanic/Latino, 3% Asian, and 6% mixed/other; and 6 transgender men and 1 transgender woman. Twenty-two (11%) participants discontinued the oral study product; 6 of these were for clinical or laboratory adverse events (AEs). Of those who received at least 1 CAB LA injection, 80% of Cohort 1 and 92% of Cohort 2 participants completed all injections; injection course completion rates were not different from those in the PBO arm. Injection site reactions (ISRs) were common (92% of Cohort 1 and 88% of Cohort 2 participants who received CAB LA reported any ISR). ISRs were mostly Grade 1 (mild) to Grade 2 (moderate), and 1 ISR event (Cohort 1) led to product discontinuation. Grade 2 or higher ISRs were the only AEs reported more commonly among CAB LA recipients than PBO recipients. Two Grade 3 (severe) ISRs occurred in CAB recipients, 1 in each cohort, but did not lead to product discontinuation in either case. Seven incident sexually transmitted infections were diagnosed in 6 participants. One HIV infection occurred in a participant 48 weeks after last injection of CAB LA: CAB was not detectable in plasma both at the time of first reactive HIV test and at the study visit 12 weeks prior to the first reactive test. Participants in Cohort 2 (unlike Cohort 1) consistently met prespecified pharmacokinetic targets of at least 95% of participants maintaining CAB trough concentrations above PA-IC90, and 80% maintaining trough concentrations above 4× PA-IC90. Study limitations include a modest sample size, a short course of injections, and a low-risk study population.ConclusionsIn this study, CAB LA was well tolerated at the doses and dosing intervals used. ISRs were common, but infrequently led to product discontinuation. CAB LA 600 mg every 8 weeks met pharmacokinetic targets for both male and female study participants. The safety and pharmacokinetic results observed support the further development of CAB LA, and efficacy studies of CAB LA for HIV treatment and prevention are in progress.Trial registrationClinicalTrials.gov Registry: ClinicalTrials.gov Trial number: NCT02178800.
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- 2018
11. Tail-phase safety, tolerability, and pharmacokinetics of long-acting injectable cabotegravir in HIV-uninfected adults: a secondary analysis of the HPTN 077 trial
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Landovitz, Raphael J, Li, Sue, Eron, Joseph J, Jr, Grinsztejn, Beatriz, Dawood, Halima, Liu, Albert Y, Magnus, Manya, Hosseinipour, Mina C, Panchia, Ravindre, Cottle, Leslie, Chau, Gordon, Richardson, Paul, Marzinke, Mark A, Eshleman, Susan H, Kofron, Ryan, Adeyeye, Adeola, Burns, David, Rinehart, Alex R, Margolis, David, Cohen, Myron S, McCauley, Marybeth, and Hendrix, Craig W
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- 2020
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12. Analysis of HIV Diversity in HIV-Infected Black Men Who Have Sex with Men (HPTN 061)
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Chen, Iris, Chau, Gordon, Wang, Jing, Clarke, William, Marzinke, Mark A, Cummings, Vanessa, Breaud, Autumn, Laeyendecker, Oliver, Fields, Sheldon D, Griffith, Sam, Scott, Hyman M, Shoptaw, Steven, del Rio, Carlos, Magnus, Manya, Mannheimer, Sharon, Tieu, Hong-Van, Wheeler, Darrell P, Mayer, Kenneth H, Koblin, Beryl A, and Eshleman, Susan H
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Medical Microbiology ,Biomedical and Clinical Sciences ,Clinical Sciences ,Immunology ,Infectious Diseases ,Sexual and Gender Minorities (SGM/LGBT*) ,Prevention ,Clinical Research ,HIV/AIDS ,Infection ,Good Health and Well Being ,Adult ,Black or African American ,Anti-HIV Agents ,Drug Resistance ,Viral ,Genetic Variation ,HIV ,HIV Infections ,Homosexuality ,Male ,Humans ,Male ,Middle Aged ,United States ,Young Adult ,General Science & Technology - Abstract
BackgroundHIV populations often diversify in response to selective pressures, such as the immune response and antiretroviral drug use. We analyzed HIV diversity in Black men who have sex with men who were enrolled in the HIV Prevention Trials Network 061 study.MethodsA high resolution melting (HRM) diversity assay was used to measure diversity in six regions of the HIV genome: two in gag, one in pol, and three in env. HIV diversity was analyzed for 146 men who were HIV infected at study enrollment, including three with acute infection and 13 with recent infection (identified using a multi-assay algorithm), and for 21 men who seroconverted during the study. HIV diversification was analyzed in a paired analysis for 62 HIV-infected men using plasma samples from the enrollment and 12-month (end of study) visits.ResultsMen with acute or recent infection at enrollment and seroconverters had lower median HRM scores (lower HIV diversity) than men with non-recent infection in all six regions analyzed. In univariate analyses, younger age, higher CD4 cell count, and HIV drug resistance were associated with lower median HRM scores in multiple regions; ARV drug detection was marginally associated with lower diversity in the pol region. In multivariate analysis, acute or recent infection (all six regions) and HIV drug resistance (both gag regions) were associated with lower median HRM scores. Diversification in the pol region over 12 months was greater for men with acute or recent infection, higher CD4 cell count, and lower HIV viral load at study enrollment.ConclusionsHIV diversity was significantly associated with duration of HIV infection, and lower gag diversity was observed in men who had HIV drug resistance. HIV pol diversification was more pronounced in men with acute or recent infection, higher CD4 cell count, and lower HIV viral load.
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- 2016
13. Safety, efficacy, and immunogenicity of the NVX-CoV2373 vaccine
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Underwood, Eddie, primary, Dunkle, Lisa M., additional, Madhi, Shabir A., additional, Gay, Cynthia L., additional, Heath, Paul T., additional, Kotloff, Karen L., additional, Smith, Katherine, additional, Chau, Gordon, additional, Galbiati, Shirley, additional, McGarry, Alice, additional, Woo, Wayne, additional, Cho, Iksung, additional, Alves, Katia, additional, Áñez, Germán, additional, Bennett, Chijioke, additional, Shinde, Vivek, additional, Fries, Louis, additional, Mallory, Raburn M., additional, Glenn, Gregory M., additional, and Toback, Seth, additional
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- 2023
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14. Strong CD4+ T-Cell Responses to Ancestral and Variant Spike Proteins Are Established by NVX-CoV2373 Severe Acute Respiratory Syndrome Coronavirus 2 Primary Vaccination.
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Fries, Louis, Formica, Neil, Mallory, Raburn M, Zhou, Haixia, Plested, Joyce S, Kalkeri, Raj, Moldovan, Ioana, Patel, Nita, Albert, Gary, Robinson, Michelle, Cho, Iksung, Chau, Gordon, Dubovsky, Filip, Glenn, Gregory M, and Group, for the 2019nCoV-101 Study
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SARS-CoV-2 ,COVID-19 ,COVID-19 vaccines ,T cells ,GLYCOPROTEINS - Abstract
Background NVX-CoV2373 is an efficacious coronavirus disease 2019 (COVID-19) vaccine comprising full-length recombinant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (rS) glycoprotein and Matrix-M adjuvant. Phase 2 of a randomized, placebo-controlled, phase 1/2 trial in healthy adults (18–84 years of age) previously reported good safety/tolerability and robust humoral immunogenicity. Methods Participants were randomized to placebo or 1 or 2 doses of 5-µg or 25-µg rS with 50 µg Matrix-M adjuvant 21 days apart. CD4
+ T-cell responses to SARS-CoV-2 intact S or pooled peptide stimulation (with ancestral or variant S sequences) were measured via enzyme-linked immunosorbent spot assay and intracellular cytokine staining. Results A clearly discernable spike antigen-specific CD4+ T-cell response was induced after 1 dose, but markedly enhanced after 2 doses. Counts and fold increases in cells producing Th1 cytokines exceeded those secreting Th2 cytokines, although both phenotypes were clearly present. Interferon-γ responses to rS were detected in 93.5% of 2-dose 5-µg recipients. A polyfunctional CD4+ T-cell response was cross-reactive and of equivalent magnitude to all tested variants, including Omicron BA.1/BA.5. Conclusions NVX-CoV2373 elicits a moderately Th1-biased CD4+ T-cell response that is cross-reactive with ancestral and variant S proteins after 2 doses. Clinical Trials Registration NCT04368988. [ABSTRACT FROM AUTHOR]- Published
- 2023
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15. Immunogenicity of a Fourth Homologous Dose of NVX-CoV2373
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Alves, Katia, primary, Plested, Joyce S., additional, Galbiati, Shirley, additional, Chau, Gordon, additional, Cloney-Clark, Shane, additional, Zhu, Mingzhu, additional, Kalkeri, Raj, additional, Patel, Nita, additional, Smith, Kathy, additional, Marcheschi, Alex, additional, Pfeiffer, Susan, additional, McFall, Heather, additional, Smith, Gale, additional, Glenn, Gregory M., additional, Dubovsky, Filip, additional, and Mallory, Raburn M., additional
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- 2023
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16. Immunogenicity and safety of a 4thhomologous booster dose of a SARS-CoV-2 recombinant spike protein vaccine (NVX-CoV2373): a phase 2, randomized, placebo-controlled trial
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Alves, Katia, primary, Plested, Joyce S, additional, Galbiati, Shirley, additional, Chau, Gordon, additional, Cloney-Clark, Shane, additional, Zhu, Mingzhu, additional, Kalkeri, Raj, additional, Patel, Nita, additional, Smith, Kathy, additional, Marcheschi, Alex, additional, Pfeiffer, Susan, additional, McFall, Heather, additional, Smith, Gale, additional, Glenn, Gregory M., additional, Dubovsky, Filip, additional, and Mallory, Raburn M., additional
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- 2022
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17. Safety and immunogenicity following a homologous booster dose of a SARS-CoV-2 recombinant spike protein vaccine (NVX-CoV2373): a secondary analysis of a randomised, placebo-controlled, phase 2 trial
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Mallory, Raburn M, primary, Formica, Neil, additional, Pfeiffer, Susan, additional, Wilkinson, Bethanie, additional, Marcheschi, Alex, additional, Albert, Gary, additional, McFall, Heather, additional, Robinson, Michelle, additional, Plested, Joyce S, additional, Zhu, Mingzhu, additional, Cloney-Clark, Shane, additional, Zhou, Bin, additional, Chau, Gordon, additional, Robertson, Andreana, additional, Maciejewski, Sonia, additional, Hammond, Holly L, additional, Baracco, Lauren, additional, Logue, James, additional, Frieman, Matthew B, additional, Smith, Gale, additional, Patel, Nita, additional, Glenn, Gregory M, additional, Adams, Mark, additional, Arya, Mark, additional, Athan, Eugene, additional, Berger, Ira, additional, Bradley, Paul, additional, Briskin, Toby, additional, Glover II, Richard, additional, Griffin, Paul, additional, Kim, Joshua, additional, Kitchener, Scott, additional, Klein, Terry, additional, Leah, Amber, additional, Leelasena, Indika, additional, Lemech, Charlotte, additional, Lickliter, Jason, additional, Manning, Mary Beth, additional, Napier-Flood, Fiona, additional, Nugent, Paul, additional, Thackwray, Susan, additional, and Turner, Mark, additional
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- 2022
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18. Characterization of Human Immunodeficiency Virus (HIV) Infections in Women Who Received Injectable Cabotegravir or Tenofovir Disoproxil Fumarate/Emtricitabine for HIV Prevention: HPTN 084
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Eshleman, Susan H, primary, Fogel, Jessica M, additional, Piwowar-Manning, Estelle, additional, Chau, Gordon, additional, Cummings, Vanessa, additional, Agyei, Yaw, additional, Richardson, Paul, additional, Sullivan, Philip, additional, Haines, Casey D, additional, Bushman, Lane R, additional, Petropoulos, Christos, additional, Persaud, Deborah, additional, Kofron, Ryan, additional, Hendrix, Craig W, additional, Anderson, Peter L, additional, Farrior, Jennifer, additional, Mellors, John, additional, Adeyeye, Adeola, additional, Rinehart, Alex, additional, St Clair, Marty, additional, Ford, Susan, additional, Rooney, James F, additional, Mathew, Carrie-Anne, additional, Hunidzarira, Portia, additional, Spooner, Elizabeth, additional, Mpendo, Juliet, additional, Nair, Gonasagrie, additional, Cohen, Myron S, additional, Hughes, James P, additional, Hosseinipour, Mina, additional, Hanscom, Brett, additional, Delany-Moretlwe, Sinead, additional, and Marzinke, Mark A, additional
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- 2022
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19. Combining information to estimate adherence in studies of pre‐exposure prophylaxis for HIV prevention: Application to HPTN 067
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Hughes, James P., primary, Williamson, Brian D., additional, Krakauer, Chloe, additional, Chau, Gordon, additional, Ortiz, Brayan, additional, Wakefield, Jon, additional, Hendrix, Craig, additional, Amico, K. Rivet, additional, Holtz, Timothy H., additional, Bekker, Linda‐Gail, additional, and Grant, Robert, additional
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- 2022
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20. Synthesis and metal complexation properties of bisbenzospiropyran chelators in water
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Kumar, Satish, Chau, Cindy, Chau, Gordon, and McCurdy, Alison
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- 2008
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21. Acceptability of Long-Acting Injectable Cabotegravir (CAB LA) in HIV-Uninfected Individuals: HPTN 077
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Tolley, Elizabeth E, Zangeneh, Sahar Z, Chau, Gordon, Eron, Joe, Grinsztejn, Beatriz, Humphries, Hilton, Liu, Albert, Siegel, Marc, Bertha, Maseko, Panchia, Ravindre, Li, Sue, Cottle, Leslie, Rinehart, Alex, Margolis, David, Jennings, Andrea, McCauley, Marybeth, and Landovitz, Raphael J
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Adult ,Male ,Social Work ,Pyridones ,Anti-HIV Agents ,HIV prevention ,HIV Infections ,Injections ,Acceptability ,Double-Blind Method ,Females ,Clinical Research ,Behavioral and Social Science ,Humans ,Males ,Prevention ,Middle Aged ,Patient Acceptance of Health Care ,PrEP ,Clinical trial ,Treatment Outcome ,Injectable ,Good Health and Well Being ,Public Health and Health Services ,HIV/AIDS ,Female ,Pre-Exposure Prophylaxis ,Public Health ,Patient Participation - Abstract
Long-acting injectable PrEP could offer an alternative to daily oral PrEP, improve adherence and protection, if found acceptable, safe and effective. HPTN 077 evaluated injectable cabotegravir safety, tolerability and pharmacokinetics among HIV-uninfected males and females in sequentially-enrolled cohorts of two dosing strategies. We compared acceptability of product attributes, prevention preferences and future interest in injectable PrEP (FIIP) by region, sex-at-birth, arm and cohort and used multivariable analysis to identify FIIP determinants. Baseline injectable PrEP preferences were higher in non-U.S. sites and increased in both regions over time. In multivariable models, FIIP was most strongly associated with acceptability of product attributes, was higher in non-U.S. sites and more altruistic participants. Treatment arm and report of pain were not associated with FIIP. Injectable acceptability was highest in non-U.S. sites. Preferences for injectable versus other PrEP methods were higher among U.S. males than females, but higher among males and females in non-U.S. settings.
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- 2020
22. Cabotegravir Is Not Associated With Weight Gain in Human Immunodeficiency Virus-uninfected Individuals in HPTN 077.
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Zangeneh, Sahar, Zangeneh, Sahar, Chau, Gordon, Grinsztejn, Beatriz, Eron, Joseph, Dawood, Halima, Magnus, Manya, Liu, Albert, Panchia, Ravindre, Hosseinipour, Mina, Kofron, Ryan, Margolis, David, Rinehart, Alex, Adeyeye, Adeola, Burns, David, McCauley, Marybeth, Cohen, Myron, Currier, Judith, Landovitz, Raphael, Zangeneh, Sahar, Zangeneh, Sahar, Chau, Gordon, Grinsztejn, Beatriz, Eron, Joseph, Dawood, Halima, Magnus, Manya, Liu, Albert, Panchia, Ravindre, Hosseinipour, Mina, Kofron, Ryan, Margolis, David, Rinehart, Alex, Adeyeye, Adeola, Burns, David, McCauley, Marybeth, Cohen, Myron, Currier, Judith, and Landovitz, Raphael
- Abstract
Studies in human immunodeficiency virus (HIV)-infected individuals suggest excess weight gain with integrase inhibitor-based antiretroviral therapy. The HIV Prevention Trials Network Study 077 evaluated changes in weight and fasting metabolic parameters in HIV-uninfected individuals randomized to cabotegravir or a placebo. No differences between arms were found for change in weight or fasting metabolic parameters overall or for subgroups.
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- 2020
23. Microcoaxial Phacoemulsification with Torsional Ultrasound
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Chau, Gordon, primary
- Published
- 2008
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24. Cabotegravir Is Not Associated With Weight Gain in Human Immunodeficiency Virus–uninfected Individuals in HPTN 077
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Landovitz, Raphael J, primary, Zangeneh, Sahar Z, additional, Chau, Gordon, additional, Grinsztejn, Beatriz, additional, Eron, Joseph J, additional, Dawood, Halima, additional, Magnus, Manya, additional, Liu, Albert Y, additional, Panchia, Ravindre, additional, Hosseinipour, Mina C, additional, Kofron, Ryan, additional, Margolis, David A, additional, Rinehart, Alex, additional, Adeyeye, Adeola, additional, Burns, David, additional, McCauley, Marybeth, additional, Cohen, Myron S, additional, and Currier, Judith S, additional
- Published
- 2019
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25. Tail-Phase Safety, Tolerability, and Pharmacokinetics of Long-Acting Injectable Cabotegravir in HIV-Uninfected Adults: HPTN 077
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Landovitz, Raphael, primary, Li, Sue, additional, Eron Jr., Joseph J., additional, Grinsztejn, Beatriz, additional, Dawood, Halima, additional, Liu, Albert Y., additional, Magnus, Manya, additional, Hosseinipour, Mina C., additional, Panchia, Ravindre, additional, Cottle, Leslie, additional, Chau, Gordon, additional, Richardson, Paul, additional, Marzinke, Mark A., additional, Eshleman, Susan, additional, Kofron, Ryan, additional, Adeyeye, Adeola, additional, Burns, David, additional, Rinehart, Alex R., additional, Margolis, David, additional, Cohen, Myron S., additional, McCauley, Marybeth, additional, and Hendrix, Craig W., additional
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- 2019
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- View/download PDF
26. Hormonal Contraception Use and Cabotegravir Pharmacokinetics in HIV-Uninfected Women Enrolled in HPTN 077.
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Blair, Cheríe S., Sue Li, Chau, Gordon, Cottle, Leslie, Richardson, Paul, Marzinke, Mark A., Eshleman, Susan H., Adeyeye, Adeola, Rinehart, Alex R., Margolis, David, McCauley, Marybeth, Hendrix, Craig W., and Landovitz, Raphael J.
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- 2020
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27. Strong CD4+ T-Cell Responses to Ancestral and Variant Spike Proteins Are Established by NVX-CoV2373 Severe Acute Respiratory Syndrome Coronavirus 2 Primary Vaccination.
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Fries L, Formica N, Mallory RM, Zhou H, Plested JS, Kalkeri R, Moldovan I, Patel N, Albert G, Robinson M, Cho I, Chau G, Dubovsky F, and Glenn GM
- Subjects
- Adult, Humans, SARS-CoV-2, Spike Glycoprotein, Coronavirus genetics, Cytokines, Adjuvants, Immunologic, Adjuvants, Pharmaceutic, Antibodies, Viral, CD4-Positive T-Lymphocytes, COVID-19 prevention & control
- Abstract
Background: NVX-CoV2373 is an efficacious coronavirus disease 2019 (COVID-19) vaccine comprising full-length recombinant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (rS) glycoprotein and Matrix-M adjuvant. Phase 2 of a randomized, placebo-controlled, phase 1/2 trial in healthy adults (18-84 years of age) previously reported good safety/tolerability and robust humoral immunogenicity., Methods: Participants were randomized to placebo or 1 or 2 doses of 5-µg or 25-µg rS with 50 µg Matrix-M adjuvant 21 days apart. CD4+ T-cell responses to SARS-CoV-2 intact S or pooled peptide stimulation (with ancestral or variant S sequences) were measured via enzyme-linked immunosorbent spot assay and intracellular cytokine staining., Results: A clearly discernable spike antigen-specific CD4+ T-cell response was induced after 1 dose, but markedly enhanced after 2 doses. Counts and fold increases in cells producing Th1 cytokines exceeded those secreting Th2 cytokines, although both phenotypes were clearly present. Interferon-γ responses to rS were detected in 93.5% of 2-dose 5-µg recipients. A polyfunctional CD4+ T-cell response was cross-reactive and of equivalent magnitude to all tested variants, including Omicron BA.1/BA.5., Conclusions: NVX-CoV2373 elicits a moderately Th1-biased CD4+ T-cell response that is cross-reactive with ancestral and variant S proteins after 2 doses., Clinical Trials Registration: NCT04368988., Competing Interests: Potential conflicts of interest. L. F., R. R. M., H. Z., J. S. P., R. K., N. P., G. A., M. R., I. C., G. C., F. D., and G. M. G. are all salaried employees or contractors of Novavax. N. F. was a contractor for Novavax at the time this study was done, and is currently employed at Formative Health Pty Ltd, Casuarina NSW 2487, Australia. I. M. is an employee of Cellular Technology Ltd. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)
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- 2023
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28. Brief Report: Hormonal Contraception Use and Cabotegravir Pharmacokinetics in HIV-Uninfected Women Enrolled in HPTN 077.
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Blair CS, Li S, Chau G, Cottle L, Richardson P, Marzinke MA, Eshleman SH, Adeyeye A, Rinehart AR, Margolis D, McCauley M, Hendrix CW, and Landovitz RJ
- Subjects
- Brazil, Contraceptive Agents, Female administration & dosage, Drug Interactions, Female, HIV Integrase Inhibitors administration & dosage, HIV Seronegativity, Hormonal Contraception, Humans, Malawi, Pre-Exposure Prophylaxis, Pyridones administration & dosage, South Africa, Young Adult, Contraceptive Agents, Female pharmacology, HIV Infections prevention & control, HIV Integrase Inhibitors pharmacokinetics, HIV-1, Pyridones pharmacokinetics
- Abstract
Objectives: To evaluate whether hormonal contraceptive use among cisgender women is associated with differences in pharmacokinetic (PK) parameters of a long-acting injectable formulation of the integrase strand transfer inhibitor, cabotegravir (CAB-LA)., Setting: This is a secondary analysis of 85 cisgender women enrolled in HPTN 077, a phase 2a multicenter study that enrolled HIV-uninfected, low-risk individuals in Malawi, Brazil, South Africa, and the United States., Methods: Participants received 4-week daily oral cabotegravir lead-in, followed by CAB-LA 800 mg injection every 12 weeks (cohort 1) or 600 mg every 8 weeks (after 4-week initial interval between injections, cohort 2), over 41 weeks. Participants were followed 52-76 weeks subsequent to final injection. Generalized estimating equations and linear regression were used to evaluate differences in CAB-LA PK parameters (peak concentration, trough concentration, area under the curve, apparent terminal half-life, and time to lower limit of quantification) and self-reported hormonal contraceptive stratified by type (oral, injectable, implants, and other), controlling for body mass index and cohort., Results: Compared to women reporting no hormonal contraception (n = 6), oral contraceptive use (n = 18) was associated with lower CAB-LA peak concentration but was not associated with differences in other PK parameters. No other hormonal contraceptive type (injectable, implants, and other) was associated with significant differences in CAB-LA PK parameters., Conclusion: Although oral contraceptive use was associated with differences in CAB-LA peak concentration, no differences were observed in other PK parameters, suggesting that this association is not likely to be clinically significant. However, these data highlight the need for further research exploring potential drug-drug interactions between CAB-LA and hormonal contraceptives.
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- 2020
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