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Safety and Efficacy of Dolutegravir/Lamivudine (DTG/3TC) in Therapy-naive Human Immunodeficiency Virus-1 (HIV-1) Infected Adolescents

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03682848
Recruitment Status : Not yet recruiting
First Posted : September 25, 2018
Last Update Posted : September 25, 2018
Sponsor:
Information provided by (Responsible Party):
ViiV Healthcare

Brief Summary:
First-line antiretroviral regimens are highly efficacious and generally well tolerated. However, as these regimens need to be taken life-long, there is growing concern about long-term toxicities associated with these regimens. Thus, there is great interest from subjects and clinicians in unique regimens that might avoid such toxicities by minimizing the number of antiretrovirals without sacrificing long-term antiviral efficacy. DTG plus 3TC is a novel, well-tolerated first-line regimen for HIV-infected treatment- naive subjects, limiting the risk of many common adverse reactions associated with other antiretroviral drugs. Thus, this study is designed to evaluate the efficacy and safety of DTG/3TC as a FDC, in ART-naive HIV-1-infected adolescents, who weigh at least 40 kilograms. The study will consists of Screening Phase (up to 28 days prior to the first dose of drug) followed by Treatment Phase (up to 48 weeks). Subjects who successfully complete 48 weeks of therapy and who continue to receive benefit from DTG/3TC FDC may enter a 96-week study Extension Phase. All subjects will receive the FDC of DTG/3TC (50/300 milligrams) for once daily. Approximately 30 subjects will be enrolled in the study.

Condition or disease Intervention/treatment Phase
HIV Infections Drug: DTG + 3TC FDC Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Intervention Model: Single Group Assignment
Intervention Model Description: All subjects will receive the FDC of DTG/3TC (50/300 milligrams) for once daily dosing in this single arm study.
Masking: None (Open Label)
Masking Description: This will be an open-label study. Hence, there will be no masking.
Primary Purpose: Treatment
Official Title: An Open-label, Single Arm Study to Evaluate the Week 48 Efficacy and Safety of a Two-drug Regimen of Dolutegravir/Lamivudine (DTG/3TC) as a Fixed Dose Combination (FDC), in Antiretroviral Therapy (ART)-Naive HIV-1-infected Adolescents, ≥12 to <18 Years of Age Who Weigh at Least 40 kg
Estimated Study Start Date : October 29, 2018
Estimated Primary Completion Date : July 31, 2020
Estimated Study Completion Date : December 29, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Experimental: Subjects receiving DTG + 3TC FDC
Eligible subjects will receive FDC of DTG + 3TC FDC 50/300 milligrams, given orally once daily.
Drug: DTG + 3TC FDC
DTG + 3TC FDC will be available as 50/300 milligrams tablet to be given orally once daily.




Primary Outcome Measures :
  1. Proportion of subjects with plasma HIV-1 ribonucleic acid (RNA) less than 50 copies per milliliter (c/mL) at Week 48 [ Time Frame: Week 48 ]
    Proportion of subjects with plasma HIV-1 RNA <50 c/mL in the intent to treat-exposed (ITT-E) population will be assessed at Week 48 according to the Food and Drug Administration (FDA) Snapshot algorithm.


Secondary Outcome Measures :
  1. Proportion of subjects with plasma HIV-1 RNA <200 c/mL at Week 24 [ Time Frame: Week 24 ]
    Proportion of subjects with plasma HIV-1 RNA <200 c/mL in the ITT-E population will be assessed at Week 24 according to the FDA's Snapshot algorithm.

  2. Proportion of subjects with plasma HIV-1 RNA <200 c/mL at Week 96 [ Time Frame: Week 96 ]
    Proportion of subjects with plasma HIV-1 RNA <200 c/mL in the ITT-E population will be assessed at Week 96 according to the FDA's Snapshot algorithm.

  3. Proportion of subjects with plasma HIV-1 RNA <200 c/mL at Week 144 [ Time Frame: Week 144 ]
    Proportion of subjects with plasma HIV-1 RNA <200 c/mL in the ITT-E population will be assessed at Week 144 according to the FDA's Snapshot algorithm.

  4. Proportion of subjects with plasma HIV-1 RNA <50 c/mL at Week 24 [ Time Frame: Week 24 ]
    Proportion of subjects with plasma HIV-1 RNA <50 c/mL in the ITT-E population will be assessed at Week 24 according to the FDA's Snapshot algorithm.

  5. Proportion of subjects with plasma HIV-1 RNA <50 c/mL at Week 96 [ Time Frame: Week 96 ]
    Proportion of subjects with plasma HIV-1 RNA <50 c/mL in the ITT-E population will be assessed at Week 96 according to the FDA's Snapshot algorithm.

  6. Proportion of subjects with plasma HIV-1 RNA <50 c/mL at Week 144 [ Time Frame: Week 144 ]
    Proportion of subjects with plasma HIV-1 RNA <50 c/mL in the ITT-E population will be assessed at Week 144 according to the FDA's Snapshot algorithm.

  7. Proportion of subjects with plasma HIV-1 RNA <200 c/mL at Week 48 [ Time Frame: Week 48 ]
    Proportion of subjects with plasma HIV-1 RNA <200 c/mL in the ITT-E population will be assessed at Week 48 according to the FDA's Snapshot algorithm.

  8. Number of subjects with adverse events through 144 weeks [ Time Frame: Up to 144 weeks ]
    An adverse event is any untoward medical occurrence in a clinical study subject, temporally associated with the use of a study treatment, whether or not considered related to the study treatment.

  9. Number of subjects with severity of adverse events through 144 weeks [ Time Frame: Up to 144 weeks ]
    An adverse event is any untoward medical occurrence in a clinical study subject, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. The Division of acquired immunodeficiency syndrome (AIDS) table for grading the severity of adult and pediatric adverse events will be used to assess severity.

  10. Number of subjects with abnormal findings for hematology laboratory parameters through 144 weeks [ Time Frame: Up to 144 weeks ]
    Blood samples will be collected from subjects for analysis of hematology parameters including platelet count, red blood cell count, neutrophils, white blood cell count, lymphocytes, hemoglobin, monocytes, hematocrit, eosinophils, mean corpuscular volume, basophils, and mean corpuscular hemoglobin.

  11. Number of subjects with abnormal findings for clinical chemistry laboratory parameters through 144 weeks [ Time Frame: Up to 144 weeks ]
    Blood samples will be collected from subjects for analysis of clinical chemistry parameters including blood urea nitrogen, potassium, aspartate aminotransferase, total bilirubin, creatinine, chloride, alanine aminotransferase (ALT), albumin, glucose, total carbon dioxide, alkaline phosphatase, creatine phosphokinase, sodium, phosphate, glomerular filtration rate/ creatinine clearance, calcium, protein and cystatin-C.

  12. Number of subjects with abnormal findings for fasting lipids through 144 weeks [ Time Frame: Up to 144 weeks ]
    Lipid assessments including total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol and triglycerides will be performed.

  13. Number of subjects with abnormal findings for urinalysis parameters through 144 weeks [ Time Frame: Up to 144 weeks ]
    Urine samples will be collected from subjects for the analysis of urinalysis parameters including specific gravity, potential of hydrogen (pH) of urine, presence of glucose, protein, blood and ketones in urine by dipstick test along with urine albumin/creatinine ratio, urine protein/creatinine ratio, urine phosphate.

  14. Number of subjects who discontinue treatment due to adverse events through 144 weeks [ Time Frame: Up to 144 weeks ]
    An adverse event is any untoward medical occurrence in a clinical study subject, temporally associated with the use of a study treatment, whether or not considered related to the study treatment.

  15. Number of subjects with adverse events through 96 weeks [ Time Frame: Up to 96 weeks ]
    An adverse event is any untoward medical occurrence in a clinical study subject, temporally associated with the use of a study treatment, whether or not considered related to the study treatment.

  16. Number of subjects with severity of adverse events through 96 weeks [ Time Frame: Up to 96 weeks ]
    An adverse event is any untoward medical occurrence in a clinical study subject, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. The Division of AIDS table for grading the severity of adult and pediatric adverse events will be used to assess severity.

  17. Number of subjects with abnormal findings for hematology laboratory parameters through 96 weeks [ Time Frame: Up to 96 weeks ]
    Blood samples will be collected from subjects for analysis of hematology parameters including platelet count, red blood cell count, neutrophils, white blood cells, lymphocytes, hemoglobin, monocytes, hematocrit, eosinophils, mean corpuscular volume, basophils, and mean corpuscular hemoglobin.

  18. Number of subjects with abnormal findings for clinical chemistry laboratory parameters through 96 weeks [ Time Frame: Up to 96 weeks ]
    Blood samples will be collected from subjects for analysis of clinical chemistry parameters including blood urea nitrogen, potassium, aspartate aminotransferase, total bilirubin, creatinine, chloride, ALT, albumin, glucose, total carbon dioxide, alkaline phosphatase, creatine phosphokinase, sodium, phosphate, glomerular filtration rate/ creatinine clearance, calcium, protein and cystatin-C.

  19. Number of subjects with abnormal findings for fasting lipids through 96 weeks [ Time Frame: Up to 96 weeks ]
    Lipid assessments including total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol and triglycerides will be performed.

  20. Number of subjects with abnormal findings for urinalysis parameters through 96 weeks [ Time Frame: Up to 96 weeks ]
    Urine samples will be collected from subjects for the analysis of urinalysis parameters including specific gravity, pH of urine, presence of glucose, protein, blood and ketones in urine by dipstick test along with urine albumin/creatinine ratio, urine protein/creatinine ratio, urine phosphate.

  21. Number of subjects undergoing viral load monitoring from Week 48 through 144 weeks [ Time Frame: Week 48 and up to 144 weeks ]
    Viral load monitoring of subjects will be performed.

  22. Change from Baseline in cluster of differentiation 4+ (CD4+) cell count at Week 24 [ Time Frame: Baseline and Week 24 ]
    Lymphocyte subsets including CD4+ cell counts will be collected for assessment by flow cytometry.

  23. Change from Baseline in CD4+ cell count at Week 48 [ Time Frame: Baseline and Week 48 ]
    Lymphocyte subsets including CD4+ cell counts will be collected for assessment by flow cytometry.

  24. Change from Baseline in CD8+ cell count at Week 24 [ Time Frame: Baseline and Week 24 ]
    Lymphocyte subsets including CD8+ cell counts will be collected for assessment by flow cytometry.

  25. Change from Baseline in CD8+ cell count at Week 48 [ Time Frame: Baseline and Week 48 ]
    Lymphocyte subsets including CD8+ cell counts will be collected for assessment by flow cytometry.

  26. Change from Baseline in ratio of CD4+ and CD8+ at Week 24 [ Time Frame: Baseline and Week 24 ]
    The ratio of CD4+ cells to CD8+ cells will be assessed.

  27. Change from Baseline in ratio of CD4+ and CD8+ at Week 48 [ Time Frame: Baseline and Week 48 ]
    The ratio of CD4+ cells to CD8+ cells will be assessed.

  28. Number of subjects with disease progression from Week 24 through 48 weeks [ Time Frame: Week 24 and up to 48 weeks ]
    The number of subjects with disease progression including HIV-associated conditions, AIDS, and death will be assessed.

  29. Number of subjects with adverse events from Week 24 through 48 weeks [ Time Frame: Week 24 and up to 48 weeks ]
    An adverse event is any untoward medical occurrence in a clinical study subject, temporally associated with the use of a study treatment, whether or not considered related to the study treatment.

  30. Number of subjects with severity of adverse events from Week 24 through 48 weeks [ Time Frame: Week 24 and up to 48 weeks ]
    An adverse event is any untoward medical occurrence in a clinical study subject, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. The Division of AIDS table for grading the severity of adult and pediatric adverse events will be used to assess severity.

  31. Number of subjects with abnormal findings for hematology laboratory parameters from Week 24 through 48 weeks [ Time Frame: Week 24 and up to 48 weeks ]
    Blood samples will be collected from subjects for analysis of hematology parameters including platelet count, red blood cell count, neutrophils, white blood cells, lymphocytes, hemoglobin, monocytes, hematocrit, eosinophils, mean corpuscular volume, basophils, and mean corpuscular hemoglobin.

  32. Number of subjects with abnormal findings for clinical chemistry laboratory parameters from Week 24 through 48 weeks [ Time Frame: Week 24 and up to 48 weeks ]
    Blood samples will be collected from subjects for analysis of clinical chemistry parameters including blood urea nitrogen, potassium, aspartate aminotransferase, total bilirubin, creatinine, chloride, ALT, albumin, glucose, total carbon dioxide, alkaline phosphatase, creatine phosphokinase, sodium, phosphate, glomerular filtration rate/ creatinine clearance, calcium, protein and cystatin-C.

  33. Number of subjects with abnormal findings for fasting lipids from Week 24 through 48 weeks [ Time Frame: Week 24 and up to 48 weeks ]
    Lipid assessments including total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol and triglycerides will be performed.

  34. Number of subjects with abnormal findings for urinalysis parameters from Week 24 through 48 weeks [ Time Frame: Week 24 and up to 48 weeks ]
    Urine samples will be collected from subjects for the analysis of urinalysis parameters including specific gravity, pH of urine, presence of glucose, protein, blood and ketones in urine by dipstick test along with urine albumin/creatinine ratio, urine protein/creatinine ratio, urine phosphate.

  35. Number of subjects who discontinue treatment due to adverse events from Week 24 through 48 weeks [ Time Frame: Week 24 and up to 48 weeks ]
    An adverse event is any untoward medical occurrence in a clinical study subject, temporally associated with the use of a study treatment, whether or not considered related to the study treatment.

  36. Maximum observed plasma concentration (Cmax) following dosing with DTG and 3TC [ Time Frame: Pre-dose, 0.5, 1.0, 1.5, 2, 3, 4, 6, 10, and 24 hours post-dose on Day 5 and Day 10 ]
    Blood samples will be collected on a subset of subjects for intensive pharmacokinetic analysis.

  37. Time of maximum observed plasma concentration (tmax) following dosing with DTG and 3TC [ Time Frame: Pre-dose, 0.5, 1.0, 1.5, 2, 3, 4, 6, 10, and 24 hours post-dose on Day 5 and Day 10 ]
    Blood samples will be collected on a subset of subjects for intensive pharmacokinetic analysis.

  38. Area under the plasma concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration (AUC [0-t]) following dosing with DTG and 3TC [ Time Frame: Pre-dose, 0.5, 1.0, 1.5, 2, 3, 4, 6, 10, and 24 hours post-dose on Day 5 and Day 10 ]
    Blood samples will be collected on a subset of subjects for intensive pharmacokinetic analysis.

  39. AUC over the dosing interval (AUC [0-tau]] following dosing with DTG and 3TC [ Time Frame: Pre-dose, 0.5, 1.0, 1.5, 2, 3, 4, 6, 10, and 24 hours post-dose on Day 5 and Day 10 ]
    Blood samples will be collected on a subset of subjects for intensive pharmacokinetic analysis.

  40. Apparent terminal half-life (t1/2) following dosing with DTG and 3TC [ Time Frame: Pre-dose, 0.5, 1.0, 1.5, 2, 3, 4, 6, 10, and 24 hours post-dose on Day 5 and Day 10 ]
    Blood samples will be collected on a subset of subjects for intensive pharmacokinetic analysis.

  41. Observed pre-dose (trough) concentration (C0) following dosing with DTG and 3TC [ Time Frame: Pre-dose, 0.5, 1.0, 1.5, 2, 3, 4, 6, 10, and 24 hours post-dose on Day 5 and Day 10 ]
    Blood samples will be collected on a subset of subjects for intensive pharmacokinetic analysis.

  42. Observed plasma concentration at the end of 24 hours of dosing interval (C24) [ Time Frame: Pre-dose, 0.5, 1.0, 1.5, 2, 3, 4, 6, 10, and 24 hours post-dose on Day 5 and Day 10 ]
    Blood samples will be collected on a subset of subjects for intensive pharmacokinetic analysis.

  43. Number of subjects with observed genotypic resistance to DTG and 3TC [ Time Frame: Up to 144 weeks ]
    Genotypic resistance to DTG and 3TC in subjects with protocol-defined virologic failure.

  44. Number of subjects with observed phenotypic resistance to DTG and 3TC [ Time Frame: Up to 144 weeks ]
    Phenotypic resistance to DTG and 3TC in subjects with protocol-defined virologic failure will be assessed.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   12 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • HIV-1 infected adolescents >=12 to <18 years of age at the time of signing the informed consent form.
  • Weight >=40 kilograms at the time of signing the informed consent form.
  • Screening plasma HIV-1 RNA between 1,000 and <=500,000 c/mL.
  • Antiretroviral-naive (defined as no prior therapy with any antiretroviral agent for the treatment of HIV following a diagnosis of HIV-1 infection). Subjects who received ART for prevention of mother to child transmission of HIV in the first 3 months of life are allowed.
  • Male and female subjects will be included. A female subject is eligible to participate if she is not pregnant (as confirmed by a negative serum human chorionic gonadotrophin [hCG] test at Screening and negative urine hCG test before Enrollment) and not lactating. Female subjects who are of child bearing potential and who are engaging in sexual activity that could lead to pregnancy, must agree to use a highly effective method of birth control from 28 days prior to the first dose of study medication, and until 4 weeks after the final dose of study medication. Condoms are recommended in addition, because their appropriate use is the only contraception method effective for preventing HIV-1 transmission. The investigator is responsible for ensuring that subjects understand how to properly use these methods of contraception. All subjects participating in the study should also be counselled on safer sexual practices, including the use and benefit/risk of effective barrier methods (example given [e.g.] male condom), and on the risk of HIV transmission to an uninfected partner.
  • The subject's parent(s) or legal guardian or the subject is capable of giving signed informed consent.

Exclusion Criteria:

  • Females who are breastfeeding or plan to become pregnant or breastfeed during the study.
  • Any evidence of an active Centers for Disease Control and Prevention (CDC) Stage 3 and/or Category C or World Health Organization (WHO) Stage 3 or 4 disease, except cutaneous Kaposi's sarcoma not requiring systemic therapy and historical or current CD4 cell counts less than 200 cells per cubic millimeter (cells/mm3) or CD4 percent <15 percent.
  • Subjects with severe hepatic impairment (Class C) as determined by Child-Pugh classification.
  • Unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice), cirrhosis, known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
  • Evidence of hepatitis B virus (HBV) infection based on the results of testing at Screening for HBV surface antigen (HBsAg), HBV core antibody (anti-HBc), HBV surface antibody (anti-HBs or HBsAb), and HBV Deoxyribonucleic acid (DNA) as follows: subjects positive for HBsAg are excluded; subjects negative for anti-HBs but positive for anti-HBc (negative HBsAg status) and positive for HBV DNA are excluded. Subject's positive for anti-HBc (negative HBsAg status) and positive for anti-HBs (past and/or current evidence) are immune to HBV and are not excluded.
  • Anticipated need for any HCV therapy during the first 48 weeks of the study and for HCV therapy based on interferon or any drugs that have a potential for adverse drug: drug interactions with study treatment throughout the entire study period.
  • Untreated syphilis infection (positive rapid plasma reagin [RPR] at Screening without clear documentation of treatment). Subjects who are at least 14 days post completed treatment are eligible.
  • History or sensitivity to any of the study medications or their components or drugs of their class, or a history of drug or other allergy that in the opinion of the Investigator or Medical Monitor contraindicates participation.
  • Ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous cell carcinoma, or cervical, anal or penile intraepithelial neoplasia; other localized malignancies require agreement between the investigator and the Study Medical Monitor for inclusion of the subject.
  • Subjects who in the investigator's judgment, poses a significant suicidality risk. Recent history of suicidal behavior and/or suicidal ideation may be considered as evidence of serious suicide risk.
  • Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of Screening.
  • Treatment with any of the following agents within 28 days of Screening radiation therapy, cytotoxic chemotherapeutic agents, any systemic immune suppressant.
  • Treatment with any agent with documented activity against HIV-1 in vitro within 28 days of first dose of study treatment.
  • Receipt of any prohibited medication and inability or unwillingness to switch to an alternative medication.
  • Exposure to an experimental drug or experimental vaccine within either 28 days, 5 half-lives of the test agent, or twice the duration of the biological effect of the test agent, whichever is longer, prior to the first dose of study treatment.
  • Any evidence of pre-existing viral resistance based on the presence of any major resistance-associated mutation in the Screening result or, if known, in any historical resistance test result.
  • Any verified Grade 4 laboratory abnormality. A single repeat test is allowed during the Screening period to verify a result.
  • Any acute laboratory abnormality at Screening, which, in the opinion of the Investigator, would preclude the subject's participation in the study of an investigational compound.
  • ALT >=5 times the upper limit of normal (ULN) or ALT >=3 times ULN and bilirubin >=1.5 times ULN (with >35 percent direct bilirubin).
  • Creatinine clearance of <50 milliliters per minute per 1.73 meter^2 (mL/min/1.73 m2) using the Schwartz equation method.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03682848


Contacts
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Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com

Sponsors and Collaborators
ViiV Healthcare
Investigators
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Study Director: GSK Clinical Trials ViiV Healthcare

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Responsible Party: ViiV Healthcare
ClinicalTrials.gov Identifier: NCT03682848     History of Changes
Other Study ID Numbers: 205861
First Posted: September 25, 2018    Key Record Dates
Last Update Posted: September 25, 2018
Last Verified: September 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints of the study.
Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
URL: http://clinicalstudydatarequest.com

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by ViiV Healthcare:
Viral load
Dolutegravir
Lamivudine
HIV-1
Fixed dose combination

Additional relevant MeSH terms:
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HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Lamivudine
Dolutegravir
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Anti-HIV Agents
HIV Integrase Inhibitors
Integrase Inhibitors