A5053560801- HIV/AIDS drug development and treatment
- HIV Research and Treatment
- HIV/AIDS Research and Interventions
- HIV-related health complications and treatments
- Hepatitis C virus research
- Biochemical and Molecular Research
- Viral-associated cancers and disorders
- Hepatitis B Virus Studies
- Pharmacological Effects and Toxicity Studies
- Pneumocystis jirovecii pneumonia detection and treatment
- Diabetes Treatment and Management
- Blood groups and transfusion
- Metabolism and Genetic Disorders
- Tuberculosis Research and Epidemiology
- Adolescent Sexual and Reproductive Health
- Cytomegalovirus and herpesvirus research
- HIV/AIDS Impact and Responses
Triangle
2006-2017
GlaxoSmithKline (United States)
2004-2014
Research Triangle Park Foundation
2000-2014
Cambridge University Hospitals NHS Foundation Trust
2010
Rutgers, The State University of New Jersey
2004
Rutgers New Jersey Medical School
2004
Duke University
1998-2004
University of Chicago
2004
Cancer Research And Biostatistics
2004
Beth Israel Deaconess Medical Center
2004
Serial human immunodeficiency virus type-1 (HIV-1) isolates were obtained from five individuals with acquired syndrome (AIDS) who changed therapy to 2',3'-dideoxyinosine (ddI) after at least 12 months of treatment 3'-azido-3'-deoxythymidine (zidovudine, AZT). The in vitro sensitivity ddI decreased during the following initiation, whereas AZT increased. Analysis reverse transcriptase coding region revealed a mutation associated reduced ddI. When this was present same genome as known confer...
Background. The pilot phase IIb VIKING study suggested that dolutegravir (DTG), a human immunodeficiency virus (HIV) integrase inhibitor (INI), would be efficacious in INI-resistant patients at the 50 mg twice daily (BID) dose. Methods. VIKING-3 is single-arm, open-label III which therapy-experienced adults with received DTG BID while continuing their failing regimen (without raltegravir or elvitegravir) through day 7, after was optimized ≥1 fully active drug and continued. primary efficacy...
Background. Dolutegravir (DTG; S/GSK1349572), a human immunodeficiency virus type 1 (HIV-1) integrase inhibitor, has limited cross-resistance to raltegravir (RAL) and elvitegravir in vitro. This phase IIb study assessed the activity of DTG HIV-1–infected subjects with genotypic evidence RAL resistance. Methods. Subjects received 50 mg once daily (cohort I) or twice II) while continuing failing regimen (without RAL) through day 10, after which background was optimized, when feasible, for...
Background: Abacavir/lamivudine and tenofovir/emtricitabine fixed-dose combinations are commonly used first-line antiretroviral therapies, yet few studies have comprehensively compared their safety profiles. Methods: Forty-eight-week data presented from this multicenter, randomized, open-label study comparing the profiles of abacavir/lamivudine tenofovir/emtricitabine, both administered with efavirenz, in HLA-B*5701-negative HIV-1-infected adults. Results: Three hundred eighty-five subjects...
Abacavir sulfate/lamivudine (ABC/3TC) and tenofovir DF/emtricitabine (TDF/FTC) are widely used nucleoside reverse transcriptase inhibitors for initial HIV-1 treatment. This is the first completed, randomized clinical trial to directly compare efficacy, safety, tolerability of these agents, each in combination with lopinavir/ritonavir antiretroviral-naive patients.Six hundred eighty-eight antiretroviral-naive, HIV-1-infected patients were this double-blind, placebo-matched, multicenter,...
The Phase III VIKING-3 study demonstrated that dolutegravir (DTG) 50 mg twice daily was efficacious in antiretroviral therapy (ART)-experienced subjects harbouring raltegravir- and/or elvitegravir-resistant HIV-1. VIKING-4 (ING116529) included a placebo-controlled 7-day monotherapy phase to demonstrate short-term antiviral activity attributable DTG.VIKING-4 is randomized, double-blind therapy-experienced adults with integrase inhibitor (INI)-resistant virus randomized DTG or placebo while...
Background: Dolutegravir/Lamivudine is recommended for initial antiretroviral therapy (ART) in adults living with HIV-1; however, no clinical trials have assessed this regimen adolescents, a potentially more challenging population to treat. We evaluated efficacy, safety, and pharmacokinetics of dolutegravir/lamivudine as ART adolescents HIV-1. Setting: Nine centers Thailand, Kenya, South Africa. Methods: In the single-arm, open-label, phase 3b DANCE study (NCT03682848), naive aged ≥12 <18...
P1093 is an ongoing phase I/II multicenter open-label study of dolutegravir plus optimized background regimen in age-defined pediatric cohorts; here we report the long-term safety and virologic efficacy outcomes for oldest cohort.The enrolled human immunodeficiency virus type 1 (HIV-1)-infected treatment-experienced adolescents aged 12 to <18 years, with HIV-1 RNA level ≥1000 copies/mL . Cumulative were assessed once last participant reached 144 weeks follow-up.Among 23 enrolled, 16 remained...
P1093 is a multicenter, open-label, phase I/II study of pharmacokinetics, safety, and tolerability dolutegravir plus an optimized background regimen in pediatric participants aged 4 weeks to <18 years with HIV-1. Most were highly treatment experienced.
We evaluated the responses of HIV-infected children to a single dose split-virus influenza vaccine and relationship viral load other characteristics.Fifty-three ages 1.8 13.2 years were given for 1994 1995 season (Wyeth-Ayerst: A/Texas H1N1, A/Shangdong H3N2 B/Panama). Immunologic virologic factors assessed at time 2 10 weeks after immunization.The differences between pre- postimmunization CD4+ counts, CD4+:CD8+ ratios not significant. Thirty-one 53 (58.4%) had > 2-fold increase 16 (30%)...
Purpose: The KLEAN study extension assessed the long-term efficacy and safety of fosamprenavir-ritonavir (FPV/r) lopinavir-ritonavir (LPV/r), both administered with abacavir/lamivudine (ABC/3TC) fixed dose combination, over 144 weeks. Methods: was an open-label, noninferiority that randomised antiretroviral-naïve patients to FPV/r twice daily (bid) or LPV/r bid ABC/3TC once (qd). Patients a viral load <400 copies/mL at Week 48 were eligible participate in (up weeks) continued their...
Abacavir (ABC) and lamivudine (3TC) administered twice daily were compared with an ABC + 3TC fixed-dose combination (Epzicom, Kivexa; EPZ) once daily, both in a protease inhibitor (PI) or nonnucleoside reverse transcriptase (NNRTI).Two hundred sixty HIV-infected subjects more than 6 months of plus PI NNRTI HIV-1 RNA level less 400 copies/mL for 3 CD4 count greater 50 cells/mm randomized 1:1 to EPZ daily.At baseline, median time on was 22 months, 554 <50 copies/mL, respectively. established...
Background VIKING‐3 aimed to examine efficacy and safety of dolutegravir (DTG) 50 mg twice daily in patients with resistance multiple ARV classes, including integrase inhibitors (INI). Methods RAL and/or EVG‐resistant (current or historical) adult subjects screening plasma HIV‐1 RNA ≥500 c/mL ≥2 other ART classes received open‐label DTG BID while continuing their failing regimen (without RAL/EVG). At Day 8 the background was optimised continued. Activity optimized (OBR) determined by...
ABSTRACT The majority of HIV-1 integrase amino acid sites are highly conserved, suggesting that most necessary to carry out the critical structural and functional roles integrase. We analyzed 34 variable in (>10% variability) showed prevalent polymorphic acids at these positions did not affect susceptibility inhibitor dolutegravir (S/GSK1349572), as demonstrated both vitro (in site-directed mutagenesis studies) vivo a phase IIa study monotherapy HIV-infected individuals). Ongoing clinical...
Objectives. To evaluate the prognostic value of surrogate markers (HIV RNA copy number, CD4 counts and CDC clinical immunologic categories) in HIV-infected children through a 2-year period. Methods. Eighty-six followed by Duke Pediatric HIV Clinic fall 1994 were evaluated for plasma concentration (viral load), lymphocyte percentage, age, antiretroviral treatment status categories. Follow-up evaluations performed ∼2 years, time to progression new category C diagnosis or death was noted....
7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK
Dolutegravir (DTG) is a once-daily HIV-1 integrase inhibitor approved for the treatment of infection in adults and children from 4 weeks age. The posology DTG has been driven by exposure-matching relative to adult dose efficacy safety. However, higher variability pediatric exposures raises concern that may not be reliably extrapolated trials. Therefore, we evaluated relationship between exposure virologic response children.
Background. Highly active antiretroviral therapy (HAART) has brought about rapid declines in HIV-1 RNA concentrations and an increase CD4+ counts HIV-1-infected children. These changes are often accompanied by clinical improvement; however, the extent to which immune reconstitution occurs is not known. Design. We compared two cohorts (n = 35) of children evaluate effects HAART on recovery. Cohort 1 (C1) included clinically well receiving with a CD4 >22% at study initiation. Before all had...
ABSTRACT We evaluated the performance characteristics of a new, real-time nucleic acid sequence-based amplification (NASBA) assay that incorporates molecular beacon technology for detection human immunodeficiency virus type 1 (HIV-1). The quantitative results were comparable to those obtained with three leading commercially available assays. analytical sensitivity was 37 IU/ml. NASBA detected clinically relevant recombinant viruses and all group M HIV-1 subtypes.
Background. Few data are available concerning the impact of antiretroviral resistance in response to antiviral therapy children. We evaluated development genotypic and clinical outcome a subgroup children involved prospective trial (Pediatric AIDS Clinical Trials Group Protocol 152). Design. studied 26 matched case/control pairs. A case was defined as having disease progression during study period; controls did not have progression. Cases were by age CD4+ cell count at baseline. Matched...
To demonstrate that lamivudine and zidovudine, given separately (lamivudine/zidovudine) or as a single combination tablet (Combivir), had equivalent efficacy. evaluate the safety antiretroviral activity of intensification with abacavir in patients treated lamivudine/zidovudine for > = 12 weeks.A 12-week, equivalence study lamivudine/ zidovudine versus Combivir. Patients who completed this could enter 48-week, Combivir plus abacavir.In study, treatment-naive were assessed HIV-1 RNA, CD4 cell...