The purpose of this study was to evaluate the efficacy of GSK3640254 + DTG relative to lamivudine (3TC) + DTG in treatment-naïve adult participants living with human immunodeficiency virus (HIV)-1. The participants were randomized to one of the three doses of blinded GSK3640254 (100, 150, or 200 milligrams \[mgs\]) or a reference arm of blinded 3TC-each in combination with open label DTG.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
85
GSK3640254 was available as 25 mg or 100 mg tablets administered orally.
DTG was available as 50 mg tablets administered orally.
3TC was available as 300 mg capsules administered orally as a blinded treatment.
Percentage of Participants With Plasma HIV-1 Ribonucleic Acid (RNA) Less Than (<)50 Copies Per Milliliter (c/mL) at Week 24
Percentage of participants with plasma HIV-1 RNA \<50 c/mL at Week 24 using the Food and Drug Administration (FDA) snapshot algorithm was assessed to evaluate the antiviral activity in HIV-1 infected ART (anti-retroviral therapy)-naïve participants.
Time frame: At Week 24
Absolute Values of HIV-1 RNA Through Week 24
Plasma samples were collected for quantitative analysis of HIV-1 RNA. Logarithm to base 10 (log 10) values for plasma HIV-1 RNA has been presented. Baseline is defined as the latest non-missing value prior to first dose of treatment according to date and time including unscheduled visits.
Time frame: At Baseline (Day 1) and Week 24
Change From Baseline in HIV-1 RNA Through Week 24
Plasma samples were collected for quantitative analysis of HIV-1 RNA. Logarithm to base 10 (log 10) values for plasma HIV-1 RNA has been presented. Change from Baseline is defined as post-dose visit value minus Baseline value.
Time frame: At Week 24 compared to baseline (Day 1)
Absolute Values of Cluster of Differentiation 4+ (CD4+) T-cell Counts Through Week 24
Blood samples were collected and CD4+ cell count assessment by flow cytometry was carried out to evaluate the immunologic activity. Baseline is defined as the latest non-missing value prior to first dose of treatment according to date and time including unscheduled visits.
Time frame: At Baseline (Day 1) and Week 24
Change From Baseline in CD4+ T-cell Counts Through Week 24
Blood samples were collected and CD4+ cell count assessment was carried out to evaluate the immunologic activity. Change from Baseline is defined as post-dose visit value minus Baseline value.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
3TC was available as 300 mg tablets administered orally as an unblinded treatment.
GSK Investigational Site
Bakersfield, California, United States
GSK Investigational Site
Palm Springs, California, United States
GSK Investigational Site
Denver, Colorado, United States
GSK Investigational Site
Ft. Pierce, Florida, United States
GSK Investigational Site
Miami, Florida, United States
GSK Investigational Site
Orlando, Florida, United States
GSK Investigational Site
Kansas City, Missouri, United States
GSK Investigational Site
Omaha, Nebraska, United States
GSK Investigational Site
Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina
GSK Investigational Site
Buenos Aires, Argentina
...and 34 more locations
Time frame: At Week 24 compared to baseline (Day 1)
Number of Participants With Serious Adverse Events (SAEs) and Deaths, up to End of Continued Access to Treatment Post-study Termination (Day 478)
An SAE is defined as any serious adverse event that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity and is a congenital anomaly/birth defect. The study was terminated by the sponsor after primary analysis (at week 24). Adverse event data were collected up to end of continued access to treatment post-study termination (Day 478).
Time frame: From Day 1 up to end of continued access to treatment post-study termination (Day 478)
Number of Participants With Adverse Events (AEs) Leading to Discontinuation, up to End of Continued Access to Treatment Post-study Termination (Day 478)
Number of participants who discontinued treatment due to AEs are presented. The study was terminated by the sponsor after primary analysis (at week 24). Adverse event data were collected up to end of continued access to treatment post-study termination (Day 478).
Time frame: From Day 1 up to end of continued access to treatment post-study termination (Day 478)
Number of Participants With Adverse Events of Special Interest (AESIs), up to End of Continued Access to Treatment Post-study Termination (Day 478)
AEs of special interest (AESIs) included AEs related to QT prolongation, gastrointestinal (GI) intolerability/toxicity, psychiatric events, nervous system disorders, skin and subcutaneous tissue disorders and cardiac disorders. The study was terminated by the sponsor after primary analysis (at week 24). Adverse event data were collected up to end of continued access to treatment post-study termination (Day 478).
Time frame: From Day 1 up to end of continued access to treatment post-study termination (Day 478)
Number of Participants Who Develop Genotypic Resistance up to Week 24
Blood samples were collected for drug resistance testing to assess the development of viral resistance to GSK3640254 through Week 24. New mutations were tabulated by drug class: integrase strand transfer inhibitor (INSTI), non-nucleoside reverse transcriptase inhibitor (NNRTI), nucleoside reverse transcriptase inhibitor (NRTI) and protease inhibitor (PI). Protocol-Defined Virologic Failure (PDVF) was defined as having virologic non-response (HIV-1 RNA \<1.0 log10 c/mL reduction from baseline and \<200 copies/mL by Week 12, confirmed levels \>=200 c/mL at or after Week 24 and plasma HIV-1 RNA \<= 50 c/mL from testing on Week 24, virologic rebound (confirmed HIV-1 RNA \>=200 copies/mL after confirmed consecutive HIV-1 RNA \<50 copies/mL).
Time frame: From Day 1 up to Week 24
Number of Participants Who Develop Phenotypic Resistance up to Week 24
Blood samples were collected for drug resistance testing to assess the development of viral resistance to GSK3640254 and other on-study Anti-Retroviral Therapy (ART) in participants experiencing virologic failure through Week 24. Only plasma HIV-1 RNA values determined by the central laboratory were used to assess virologic failure. PDVF was defined as having virologic non-response (HIV-1 RNA \<1.0 log10 c/mL reduction from baseline and \<200 copies/mL by Week 12, confirmed levels \>=200 c/mL at or after Week 24 and plasma HIV-1 RNA \<= 50 c/mL from testing on Week 24, virologic rebound (confirmed HIV-1 RNA \>=200 copies/mL after confirmed consecutive HIV-1 RNA \<50 copies/mL).
Time frame: From Day 1 up to Week 24
Trough Concentration (Ctrough) of GSK3640254 at Weeks 2, 4, 8, 12 and 24
Trough concentration (Ctrough) is the concentration reached by a drug immediately before the next dose is administered. This was determined to assess the steady-state exposure of GSK3640254 when given in combination with DTG.
Time frame: At Weeks 2, 4, 8, 12 (PRE DOSE), 12 (2-6HR POST DOSE), 24 (PRE DOSE), 24 (2-6HR POST DOSE)