Safety and Efficacy of Fixed Dose Combination Dolutegravir/Abacavir/Lamivudine FDC Initiated During Acute HIV Infection (PHI 05)
Verified April 2018 by University of North Carolina, Chapel Hill
University of North Carolina, Chapel Hill
Information provided by (Responsible Party)
University of North Carolina, Chapel Hill
First received: March 4, 2015
Last updated: April 6, 2018
Last Verified: April 2018
History of Changes
This is a multicenter, single arm, 96-week open-label study of the safety and virologic efficacy of fixed dose combination Dolutegravir/Lamivudine/Abacavir (DTG/3TC/ABC FDC) initiated during acute HIV infection (AHI).
Acute HIV Infection
Drug : DTG/3TC/ABC FDC
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||IGHID 11417 - The Safety and Efficacy of Fixed Dose Combination Dolutegravir/Abacavir/Lamivudine FDC Initiated During Acute HIV Infection: Impact on the Latent HIV Reservoir and Long-Term Immunologic Effect|
Further study details as provided by University of North Carolina, Chapel Hill:
Primary Outcome Measures
- Viral load measurement of <200 copies/mL [ Time Frame: week 24 ]
- Occurrence of Grade 3 or higher adverse event (AE)
[ Time Frame: baseline through week 96 ]
sign/symptom, lab toxicity, or clinical events, or Grade 1 or higher AE that is definitely, probably, or possibly related to study treatment
- Virologic efficacy of DTG/3TC/ABC FDC given once daily to participants with acute HIV as determined by the proportion of treated participants with HIV-1 RNA to <50 copies/mL [ Time Frame: week 48 ]
- Rate of virologic decline in the first 24 weeks of treatment [ Time Frame: week 24 ]
|Study Start Date:||September 2015|
|Estimated Study Completion Date:||July 2021|
|Estimated Primary Completion Date:||July 2021 (Final data collection date for primary outcome measure)|
Dolutegravir (DTG 50 mg), abacavir sulfate (ABC 600 mg) and lamivudine (3TC 300 mg) formulated in a single tablet fixed dose combination (FDC) (DTG/ABC/3TC, GSK2619619), administered orally, once daily
DTG/3TC/ABC FDC as initial therapy for AHI
The study will be conducted at the University of North Carolina in Chapel Hill, NC and Duke
University in Durham, NC. All forty (40) participants will be enrolled for 96 weeks and will
receive DTG/3TC/ABC FDC.
We propose to evaluate the efficacy and time to viral suppression with DTG/3TC/ABC FDC as initial therapy for AHI (acute HIV infection), as well as the feasibility of prompt administration using a rapid HLA-B57 (human leukocyte antigen) screening antibody assay. In addition to validating the restriction of RCI (resting cell infection) by ART (antiretroviral therapy) including a DTG-based regimen initiated during AHI, we will seek correlations between low RCI, residual GALT (gastrointestinal associated lymphoid tissue) HIV expression, and measures of immune activation. We hypothesize that rapid reduction in plasma viremia with this regimen will limit the area under the pre-ART viral load curve, and thus reduce the latent reservoir size as measured by a viral outgrowth assay one to two years following ART start, and as compared with the latent reservoir size in acutely infected individuals started on regimens without an integrase inhibitor based regimen. In addition, we will examine the longitudinal impact of the proposed integrase-based regimen initiated during the acute period on immune activation through week 96. If residual viral expression and persistent immune dysfunction is related to the burden of the latent viral reservoir (and presumably its periodic activation) these abnormalities should be ameliorated by early ART with rapid viral suppression. Finally, we will evaluate dolutegravir levels in plasma and GALT and whether rapid viral suppression with the proposed dolutegravir-based ART regimen impacts HIV RNA levels in GALT.
|Ages Eligible for Study:||18 Years and older|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- Documentation of Acute HIV infection at or within 30 days of study entry.
- Men and women age ≥18 years.
- ART naive, defined as ≤14 days of antiretroviral treatment at any time prior to entry.
The only exceptions are:
- Pre-exposure prophylaxis (PrEP) and documented as HIV-1 negative at least 1 month prior to AHI diagnosis during PrEP, and
- Post-exposure prophylaxis (PEP) provided the participant was documented as HIV-1 negative at least 3-6 months following completion of PEP treatment.
- Lab values obtained within 30 days prior to study entry:
- Absolute neutrophil count >500/mm3
- Hemoglobin > 8.5 g/dL for men and > 8.0 g/dL for women
- Platelet count >50,000/mm3
- Lipase ≤ 3 X upper limit of normal (ULN), single repeat test is allowed to determine eligibility
- Calculated creatinine clearance (Cockcroft-Gault formula) ≥ 50mL/min:
CrCl = (140-age) x body weight (kg) (x 0.85 if female) Serum creatinine [mg/dL] x (72)
- Is of non-childbearing potential defined as either post-menopausal (12 months of spontaneous amenorrhea and ≥ 45 years of age) or physically incapable of becoming pregnant with documented tubal ligation, hysterectomy or bilateral oophorectomy; or,
- Is of child-bearing potential, with a negative pregnancy test at screening and at enrollment, who agrees to use one of the methods of contraception listed below.
- Complete abstinence from intercourse from 2 weeks prior to administration of study medication, throughout the study, and for at least 2 weeks after discontinuation of all study medication;
- Double barrier method (male condom/spermicide, male condom/diaphragm, diaphragm/spermicide);
- Approved hormonal contraception - used alone is not considered a sufficient form of contraception for the study see Protocol Appendix 1 for a listing of examples of approved hormonal contraception;
- Any intrauterine device (IUD) with published data showing that the expected failure rate is <1% per year; see Protocol Appendix 2 for a listing of IUDs meeting this criterion;
- Male partner sterilization confirmed prior to the female participant's entry into the study, and this male is the sole partner for that patient;
- Any other method with published data showing that the expected failure rate is <1% per year.
- Any contraception method must be used consistently, in accordance with the approved product label and for at least 2 weeks after discontinuation of the study medication.
- Dofetilide is prohibited, as DTG may inhibit its renal tubular secretion resulting in increased dofetilide concentrations and potential for toxicity.
- Prednisone at a daily dose of 10 mg or less (physiologic replacement dose) is permitted.
NOTE: Oral candidiasis, vaginal candidiasis, mucocutaneous herpes simplex, and other minor illnesses (as judged by the site investigator) have no restriction.
Contacts and LocationsChoosing 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, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02384395
|Contact: JoAnn Kuruc, MSN, RNfirstname.lastname@example.org|
|Contact: Kristen Hancock, RNemail@example.com|
Locations Show More
|United States, North Carolina|
|University of North Carolina||Recruiting|
|Chapel Hill, North Carolina, United States, 27599|
|Duke University Health System||Recruiting|
|Durham, North Carolina, United States, 27710|
Contact: Kara McGee, MSPH, PA-C  919-668-0242  firstname.lastname@example.org
Principal Investigator: Mehri McKellar, MD
Sponsors and CollaboratorsUniversity of North Carolina, Chapel Hill
|Principal Investigator:||Cindy Gay, MD, MPH||University of North Carolina|
Additional Information:University of North Carolina website
|Responsible Party:||University of North Carolina, Chapel Hill|
|ClinicalTrials.gov Identifier:||NCT02384395 History of Changes|
|Other Study ID Numbers:||14-0549|
|Study First Received:||March 4, 2015|
|Last Updated:||April 6, 2018|
|Individual Participant Data|
|Plan to Share IPD:||No|
Keywords provided by University of North Carolina, Chapel Hill:Dolutegravir
acute HIV infection
human leukocyte antigen
latent HIV reservoir
fixed dose combination
Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
ClinicalTrials.gov processed this data on July 19, 2018
This information is provided by ClinicalTrials.gov.