Rapid Test and Treat Dolutegravir Plus Lamivudine Study in Newly Diagnosed Human Immunodeficiency Virus (HIV)-1 Infected Adults

Participants were classified as HIV-1 RNA \<50 c/mL using an ITT-E missing = Failure analysis. Participants were classified as 'HIV-1 RNA \< 50 c/mL' if the last viral load within the Week 24 visit window was \<50/c/mL, regardless of the ART regimen they were on at the time of viral load assessment (in other words switch from DTG plus 3TC fixed-dose combination \[FDC\] to another ART was not penalized) and as HIV-1 RNA \>= 50 c/mL in all other cases (i.e. last viral load within Week 24 visit window \>= 50 c/mL, on study but having missing viral load data at Week 24, discontinued early from study due to lost to follow-up (LFU), withdrew consent or any other reason). Confidence intervals (CI) were calculated based on the Exact Clopper-Pearson method. Percentage of participants with plasma HIV-1 RNA \< 50 c/mL based on ITT-E missing = Failure analysis at Week 24 are presented.

Time frame: At Week 24

Population: Intent-To-Treat Exposed (ITT-E) Population was used which comprised of all enrolled participants who received at least one dose of study treatment. ITT-E missing = Failure analysis is mentioned as 'Observed analysis' in the protocol.

Blood samples were collected at specified time points to assess CD4+/CD8+ cell count ratio. It was assessed by flow cyclometry to evaluate the immunologic activity of DTG plus 3TC. Baseline value is defined as the latest pre-dose assessment (Day 1). Change from Baseline was defined as post-dose visit value minus Baseline value.

Time frame: Baseline (Day 1) and Week 24 and Week 48

Population: Intent-to-Treat Exposed Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

CD4+ cells are type of white blood cells that fight infection and as HIV infection progresses, the number of these cells decline. Blood samples were collected at specified time points to assess CD4+. It was evaluated by flow cytometry. Baseline value is defined as the latest pre-dose assessment (Day 1). Change from Baseline was defined as post-dose visit value minus Baseline value.

Time frame: Baseline (Day 1) and Week 24 and Week 48

Population: Intent-to-Treat Exposed Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

Number of participants retained in care for 24 and 48 weeks on study and have HIV-1 RNA \<200 c/mL have been presented.

Time frame: Week 24 and Week 48

Population: Intent-to-Treat Exposed Population

Number of participants who switched from first line regimen of DTG + 3TC FDC due to abnormal Baseline laboratory values or Baseline HIV-1 resistance mutation results are presented.

Time frame: Up to Week 48

Population: Intent-to-Treat Exposed Population

Number of participants who completed 24 and 48 weeks on study are presented.

Time frame: Week 24 and Week 48

Population: Intent-to-Treat Exposed Population

An adverse event is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Number of participants who discontinued the study treatment (DTG plus 3TC) due to AEs are presented.

Time frame: Up to Week 48

Population: Safety Population

An adverse event is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Number of participants who discontinued the study treatment (DTG+3TC FDC) due to drug-related AEs are presented.

Time frame: Up to Week 48

Population: Safety Population

An adverse event is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that; results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, other situations as judged by physician. Number of participants with any SAE and common (\>=2%) non-SAEs are presented.

Time frame: Up to Week 48

Population: Safety Population comprised of all enrolled participants who received at least one dose of study treatment.

HIV-associated conditions were recorded during the study and was assessed according to the 2014 Centers for Disease Control and Prevention (CDC) Classification System for HIV Infection in Adults. CDC classification for HIV were stage 1, 2 and 3. Higher stage indicates more severity. Disease progression summarize participants who had HIV infection stage 3 associated conditions, AIDS and/or death. Number of participants with HIV-1 disease progression to stage 3 HIV-associated conditions, AIDS or death are presented.

Time frame: Up to Week 48

Population: Intent-to-Treat Exposed Population

Blood samples were collected up to Week 48 for the analysis of clinical chemistry parameters: alanine aminotransferase (ALT), albumin, aspartate aminotransferase (AST), Alkaline Phosphatase (ALP), bilirubin, carbon dioxide (CO2), creatinine kinase (CK), creatinine, glomerular filtration rate (GFR) from creatinine adjusted for body surface area (BSA), glucose, hypercalcemia, hyperkalemia, hypernatremia, hypocalcemia, hypokalemia, hyponatremia and phosphate. Any abnormality was graded according to DAIDS toxicity scales from Grade 1 to 4 (1=Mild, 2=Moderate, 3=Severe, 4=Potentially life threatening). Higher grade indicates more severity. Only those participants with maximum post-Baseline emergent chemistry toxicities in any of the chemistry parameters have been presented.

Time frame: Up to Week 48

Population: Safety Population

Blood samples were collected up to Week 48 visit for the analysis of hematology parameters-platelet count, neutrophils, hemoglobin and leukocytes Any abnormality was graded according to Division of Acquired Immunodeficiency Syndrome (DAIDS) toxicity scales from Grade 1 to 4 (1=Mild, 2=Moderate, 3=Severe, 4=Potentially life threatening). Higher grade indicates more severity. Only those participants with maximum post-Baseline emergent hematology toxicities in any of the hematology parameters have been presented.

Time frame: Up to Week 48

Population: Safety Population

Blood samples were collected for genotypic resistance testing post-Baseline when Confirmed Virologic Failure criteria were met or in other occasion as needed (e.g. at time of study withdrawal when HIV-1 RNA \>= 400 c/mL). 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). Number of participants with treatment-emergent resistance associated mutations to any class (INSTI, NNRTI, NRTI, PI) from post-Baseline genotypic resistance data up to Week 48 have been presented.

Time frame: Up to Week 48

Population: HIV-1 Viral Genotypic Population comprised of all participants in the ITT-E Population who had available post-Baseline HIV-1 genotypic resistance data either for DTG + 3TC FDC or any other ART. Only those participants with data available at the specified time points were analyzed.

Blood samples were collected for drug resistance testing post-Baseline when Confirmed Virologic Failure criteria were met or in other occasion as needed (e.g. at time of study withdrawal when HIV-1 RNA \>= 400 c/mL). Assessment of antiviral activity of ART using phenotypic test results was interpreted through a proprietary algorithm (from Monogram Biosciences) and provides the overall susceptibility of the drug. Number of participants with phenotypic resistance to DTG and/or 3TC or any other ART (if treatment is modified) taken during the study in participants with post-Baseline phenotypic resistance data up to Week 48 have been presented.

Time frame: Up to Week 48

Population: HIV-1 Viral Phenotypic Population comprised of all participants in the ITT-E Population who had available post-Baseline HIV-1 phenotypic resistance data either under treatment with DTG + 3TC FDC or any other ART. Only those participants with data available at the specified time points were analyzed.

Participants were classified as HIV-1 RNA \<50 c/mL using an ITT-E Missing = Failure analysis. Participants were classified as 'HIV-1 RNA \< 50 c/mL' if the last viral load within the Week 48 visit window was \<50/c/mL, regardless of the ART regimen they were on at the time of viral load assessment (in other words switch from DTG plus 3TC FDC to another ART was not penalized) and as HIV-1 RNA \>= 50 c/mL in all other cases (i.e. last viral load within Week 48 visit window \>= 50 c/mL, on study but having missing viral load data at Week 48, discontinued early from study due to LFU, withdrew consent or any other reason). CI were calculated based on the Exact Clopper-Pearson method. Percentage of participants with plasma HIV-1 RNA \< 50 c/mL based on ITT-E missing = Failure analysis at Week 48 are presented.

Time frame: At Week 48

Population: Intent-to-Treat Exposed Population

Percentage of participants with HIV-1 RNA\<50 c/mL was obtained using FDA Snapshot algorithm. The Snapshot algorithm treated all participants without HIV-1 RNA data at the visit of interest (either due to missing plasma HIV-1 RNA assessment but on study, or due to permanent discontinuation of study treatment prior to visit window) as virologic non-success, as well as participants who switched from first line regimen of DTG + 3TC FDC for any reason prior to the visit of interest. Confidence intervals were calculated based on the Exact Clopper-Pearson method. Percentage of participants with plasma HIV-1 RNA \<50 c/mL obtained using FDA Snapshot algorithm are presented.

Time frame: At Week 24 and Week 48

Population: Intent-to-Treat Exposed Population

Time of viral suppression for participants who had HIV-1 RNA \>= 50 c/mL at Baseline is defined as the time to first viral load value \< 50 c/mL, irrespective of the ART regimen a participant was on when that occurred. Non parametric Kaplan-Meier method was used. Participants who withdrew for any reason without being suppressed were censored at date of withdrawal. Participants who have not been withdrawn and have not had viral suppression at time of the analysis were censored at last viral load date. Median time (i.e. time when 50% of participants have reached HIV-1 RNA \< 50 c/mL) along with 95% CI is presented.

Time frame: Up to Week 48

Population: Intent-to-Treat Exposed Population. Only those participants with data available at the specified time points were analyzed.

Participants with at least one viral load assessment within Week 24 and 48 visit window have been considered. Participants who discontinued from study prior to Week 24 and Week 48 or who were still on study at Week 24 and Week 48 but with missing viral load assessment have been excluded. Viral load assessments performed under DTG + 3TC FDC treatment or under any Modified ART treatment at Week 24 and Week 48 have been considered. Percentage of participants with HIV-1 RNA \< 50 c/mL at Weeks 24 and 48 among participants with available HIV-1 RNA assessment regardless of ART have been presented.

Time frame: At Week 24 and Week 48

Population: Intent-to-Treat Exposed Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).