HIVPHI-05NCT02384395
Safety and Efficacy of Fixed Dose Combination Dolutegravir/Abacavir/Lamivudine FDC Initiated During Acute HIV Infection
A study testing Dolutegravir 50 mg, Lamivudine 300 mg and Abacavir 600 mg in people with HIV and Acute HIV Infection, run by University of North Carolina, Chapel Hill at 2 sites in United States.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV, Acute HIV Infection
- What is being tested?
- Dolutegravir 50 mg, Lamivudine 300 mg and Abacavir 600 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 2 sitesUnited States
- Study dates
- Sep 2015to 17 Sep 2021
- Phase
- Interventional
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- Absolute neutrophil count >500/mm^3
- Hemoglobin > 8.5 g/dL for men and > 8.0 g/dL for women
- Platelet count >50,000/mm^3
- Lipase ≤ 3 X upper limit of normal (ULN), single repeat test is allowed to determine eligibility
- Calculated creatinine clearance (CrCl, Cockcroft-Gault formula) ≥ 50 mL/min:
- CrCl = (140-age) x body weight (kg) (x 0.85 if female) Serum creatinine [mg/dL] x (72)
- Testing for HBsAg is pending. Note: Participants who test positive for HBsAg will be terminated from the study prior to starting study treatment.
- Testing for HLA-B57 and/or HLA-B*5701 is pending. Note: Participants who test positive for HLA-B*5701 will be terminated from the study prior to starting study treatment.
- A female is eligible to enter and participate in the study if she:
- 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.
- Females who meet the post-menopausal definition, noted in inclusion criterion 7, will have a follicle stimulation hormone (FSH) test to verify menopause,
- Ability and willingness of participant to give written informed consent.
Who cannot join
- Alanine Transaminase (ALT) ≥ 5 times Upper Limit of Normal (≥5xULN)
- Aspartate Aminotransferase (AST) ≥ 3x ULN
- Bilirubin ≥1.5x ULN (with >35% direct bilirubin)
- Weight <40 kg
- Women who are breast-feeding.
- Women with a positive pregnancy test on enrollment or prior to study drug administration.
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- Women and men of child bearing potential unwilling to agree to use an effective methods of contraception required by the study.
- History or presence of allergy to the study drugs or their components.
- Requires or is anticipated to require any of the prohibited concomitant therapy: barbiturates, dofetilide, fampridine (dalfampridine), modafinil, oxcarbazepine, pioglitazone, pilsicainide, pimozide, rifampin, rifapentine, phenytoin, phenobarbital, carbamazepine, and St. John's wort.
- Dofetilide, fampridine, and pilsicainide are prohibited, as DTG may inhibit its renal tubular secretion resulting in increased dofetilide concentrations and potential for toxicity.
- Unable to discontinue any current medications that are excluded during study treatment.
- Use of immunomodulators (e.g., interleukins, interferons, cyclosporine), radiation therapy, HIV vaccine, systemic cytotoxic chemotherapy, or investigational therapy within 30 days prior to study entry.
- Prednisone at a daily dose of 10 mg or less (physiologic replacement dose) is permitted.
- Treatment with radiation therapy or cytotoxic chemotherapeutics agents within 28 days prior to screening or has an anticipated need for these agents during the study.
- Administration of an HIV-1 immunotherapeutic vaccine within 90 days prior to screening.
- Prior treatment with any other experimental drug for any indication (within 30 days of initiating study treatment).
- Difficulty swallowing capsules/tablets.
- Inability to communicate effectively with study personnel.
- Incarceration; prisoner recruitment and participation are not permitted.
- Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements or confound the analysis of study endpoints.
- Any condition (including but not limited to alcohol and drug use) or any active clinically significant disease or findings during screening of medical history or physical examination, which, in the opinion of the Investigator would interfere with patient safety or compliance.
- Serious illness requiring systemic treatment and/or hospitalization until patient either completes therapy or is clinically stable on therapy, in the opinion of the site investigator, for at least 7 days prior to study entry.
- Note: Oral candidiasis, vaginal candidiasis, mucocutaneous herpes simplex, and other minor illnesses (as judged by the site investigator) have no restriction.
- A life expectancy less than twelve months.
- Acute viral hepatitis, including, but not limited to, hepatitis A, B, or C.
- History of myocardial infarction or diagnosis of coronary artery disease.
- History of ongoing or clinically relevant pancreatitis within the previous 6 months.
- Chronic hepatitis C infection with an anticipated need for treatment during the study period (through week 96).
- Chronic hepatitis B infection (see inclusion criterion 5).
- Evidence for moderate to severe hepatic impairment (as defined by the presence of cirrhosis, ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice or Child-Pugh class B or greater hepatic impairment).
- Evidence of biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- Any verified grade 4 laboratory abnormality with exception of ALT as defined in exclusion criterion 1
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of North Carolina
Chapel Hill, North Carolina, 27599
Duke University Health System
Durham, North Carolina, 27710
About this study
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
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).
Read the detailed description
The study will be conducted at the University of North Carolina in Chapel Hill, NC and Duke University in Durham, NC. The investigators plan to enroll up to 44 participants who will be enrolled for 96 weeks and will receive DTG/3TC/ABC FDC.
The investigators propose to evaluate the efficacy and time to viral suppression with DTG/3TC/ABC FDC as initial therapy for acute HIV infection (AHI), as well as the feasibility of prompt administration using a rapid human leukocyte antigen-B57 (HLA-B57) screening antibody assay. In addition to validating the restriction of resting cell infection (RCI) by antiretroviral therapy (ART) including a DTG-based regimen initiated during AHI, the investigators will seek correlations between low RCI, residual gastrointestinal associated lymphoid tissue (GALT) HIV expression, and measures of immune activation. The investigators 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, the investigators 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. The investigators hypothesize that earlier treatment coupled with more rapid ART-mediated virus suppression will be associated with better long-term T cell function, specifically better T cell function after 2 years of durable HIV suppression.
- Conditions
- HIV, Acute HIV Infection
- Being tested
- Dolutegravir 50 mg, Lamivudine 300 mg, Abacavir 600 mg
- Keywords
- Dolutegravir, Abacavir, Lamivudine, acute HIV infection, human leukocyte antigen, latent HIV reservoir, integrase-based regimen, viremia, antiretroviral therapy, fixed dose combination
- Medical subject headings
- Viremia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dolutegravir 50 mgDrug
Also called DTG, Tivicay
Initial therapy for AHI
Lamivudine 300 mgDrug
Also called 3TC, Epivir
Initial therapy for AHI
Abacavir 600 mgDrug
Also called ABC, Ziagen
Initial therapy for AHI
| Study group | Role | What they receive |
|---|---|---|
| DTG/3TC/ABC FDC | Experimental | 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 Receives: Drug: Dolutegravir 50 mg; Drug: Lamivudine 300 mg; Drug: Abacavir 600 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Viral Load Measurement <200 Copies/mL at Week 24
Total number of participants on study at Week 24 with an HIV-1 RNA level less than 200 copies/mL
Measured: Week 24
Secondary outcomes (3)
Number of Participants With Grade 3 or Higher Adverse Event (AE)
Sign/symptom, lab toxicity, or clinical events, or Grade 3 or higher AE that is definitely, probably, or possibly related to study treatment
Measured: Baseline through Week 96
Proportion of Treated Participants With HIV-1 RNA to <50 Copies/mL at Week 48
Proportion of participants completing Week 48 with an HIV-1 RNA level less than 50 copies/mL
Measured: Week 48
Median Change HIV-1 RNA Level Among Participants Completing Week 24 Visit
Measured: Baseline, Week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Mar 2015 (estimated)
- Study startSep 2015
- Primary completion6 Mar 2020
- Study completion17 Sep 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (50)Papers the sponsor has linked to this study.
- Other trials for HIVStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of North Carolina, Chapel Hill
- Sponsor type
- University, hospital or other
- Collaborators
- ViiV Healthcare
- Responsible party
- Sponsor
- Investigators
- Cindy Gay, MD, MPH, Principal investigator, University of North Carolina
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02384395
- Sponsor's protocol ID
- 14-0549
- Acronym
- PHI-05
- Status last verified
- Oct 2021
- First submitted
- 4 Mar 2015
- Last updated
- 22 Nov 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Adolescents. PoAGfAa. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. In: Department of Health and Human Servies.; 2013
Ortiz GM, Nixon DF, Trkola A, Binley J, Jin X, Bonhoeffer S, Kuebler PJ, Donahoe SM, Demoitie MA, Kakimoto WM, Ketas T, Clas B, Heymann JJ, Zhang L, Cao Y, Hurley A, Moore JP, Ho DD, Markowitz M. HIV-1-specific immune responses in subjects who temporarily contain virus replication after discontinuation of highly active antiretroviral therapy. J Clin Invest. 1999 Sep;104(6):R13-8. doi: 10.1172/JCI7371.
PubMed 10491418Pilcher CD, Eron JJ Jr, Galvin S, Gay C, Cohen MS. Acute HIV revisited: new opportunities for treatment and prevention. J Clin Invest. 2004 Apr;113(7):937-45. doi: 10.1172/JCI21540.
PubMed 15057296Pires A, Hardy G, Gazzard B, Gotch F, Imami N. Initiation of antiretroviral therapy during recent HIV-1 infection results in lower residual viral reservoirs. J Acquir Immune Defic Syndr. 2004 Jul 1;36(3):783-90. doi: 10.1097/00126334-200407010-00004.
PubMed 15213561Ramratnam B, Ribeiro R, He T, Chung C, Simon V, Vanderhoeven J, Hurley A, Zhang L, Perelson AS, Ho DD, Markowitz M. Intensification of antiretroviral therapy accelerates the decay of the HIV-1 latent reservoir and decreases, but does not eliminate, ongoing virus replication. J Acquir Immune Defic Syndr. 2004 Jan 1;35(1):33-7. doi: 10.1097/00126334-200401010-00004.
PubMed 14707789Chamberland A, Sylla M, Boulassel MR, Baril JG, Cote P, Thomas R, Trottier B, Rouleau D, Routy JP, Tremblay C; Investigators of the Primary HIV-Infection Cohort of Montreal. Effect of antiretroviral therapy on HIV-1 genetic evolution during acute infection. Int J STD AIDS. 2011 Mar;22(3):146-50. doi: 10.1258/ijsa.2010.010292.
PubMed 21464451Gay CL, Mayo AJ, Mfalila CK, Chu H, Barry AC, Kuruc JD, McGee KS, Kerkau M, Sebastian J, Fiscus SA, Margolis DM, Hicks CB, Ferrari G, Eron JJ; Duke-UNC Acute HIV Infection Consortium. Efficacy of NNRTI-based antiretroviral therapy initiated during acute HIV infection. AIDS. 2011 Apr 24;25(7):941-9. doi: 10.1097/QAD.0b013e3283463c07.
PubMed 21487250Cossarini F, Boeri E, Canducci F, Salpietro S, Bigoloni A, Galli L, Spagnuolo V, Castagna A, Clementi M, Lazzarin A, Gianotti N. Integrase and fusion inhibitors transmitted drug resistance in naive patients with recent diagnosis of HIV-1 infection. J Acquir Immune Defic Syndr. 2011 Feb 1;56(2):e51-4. doi: 10.1097/QAI.0b013e3181fcc0f1. No abstract available.
PubMed 21233631Markowitz M, Nguyen BY, Gotuzzo E, Mendo F, Ratanasuwan W, Kovacs C, Prada G, Morales-Ramirez JO, Crumpacker CS, Isaacs RD, Campbell H, Strohmaier KM, Wan H, Danovich RM, Teppler H; Protocol 004 Part II Study Team. Sustained antiretroviral effect of raltegravir after 96 weeks of combination therapy in treatment-naive patients with HIV-1 infection. J Acquir Immune Defic Syndr. 2009 Nov 1;52(3):350-6. doi: 10.1097/QAI.0b013e3181b064b0.
PubMed 19648823Cohen C, Elion R, Ruane P, Shamblaw D, DeJesus E, Rashbaum B, Chuck SL, Yale K, Liu HC, Warren DR, Ramanathan S, Kearney BP. Randomized, phase 2 evaluation of two single-tablet regimens elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate versus efavirenz/emtricitabine/tenofovir disoproxil fumarate for the initial treatment of HIV infection. AIDS. 2011 Mar 27;25(6):F7-12. doi: 10.1097/QAD.0b013e328345766f.
PubMed 21412057Archin NM, Vaidya NK, Kuruc JD, Liberty AL, Wiegand A, Kearney MF, Cohen MS, Coffin JM, Bosch RJ, Gay CL, Eron JJ, Margolis DM, Perelson AS. Immediate antiviral therapy appears to restrict resting CD4+ cell HIV-1 infection without accelerating the decay of latent infection. Proc Natl Acad Sci U S A. 2012 Jun 12;109(24):9523-8. doi: 10.1073/pnas.1120248109. Epub 2012 May 29.
PubMed 22645358Vinikoor MJ, Cope A, Gay CL, Ferrari G, McGee KS, Kuruc JD, Lennox JL, Margolis DM, Hicks CB, Eron JJ. Antiretroviral therapy initiated during acute HIV infection fails to prevent persistent T-cell activation. J Acquir Immune Defic Syndr. 2013 Apr 15;62(5):505-8. doi: 10.1097/QAI.0b013e318285cd33.
PubMed 23314410Lennox JL, Dejesus E, Berger DS, Lazzarin A, Pollard RB, Ramalho Madruga JV, Zhao J, Wan H, Gilbert CL, Teppler H, Rodgers AJ, Barnard RJ, Miller MD, Dinubile MJ, Nguyen BY, Leavitt R, Sklar P; STARTMRK Investigators. Raltegravir versus Efavirenz regimens in treatment-naive HIV-1-infected patients: 96-week efficacy, durability, subgroup, safety, and metabolic analyses. J Acquir Immune Defic Syndr. 2010 Sep;55(1):39-48. doi: 10.1097/QAI.0b013e3181da1287.
PubMed 20404738Raffi F, Rachlis A, Stellbrink HJ, Hardy WD, Torti C, Orkin C, Bloch M, Podzamczer D, Pokrovsky V, Pulido F, Almond S, Margolis D, Brennan C, Min S; SPRING-2 Study Group. Once-daily dolutegravir versus raltegravir in antiretroviral-naive adults with HIV-1 infection: 48 week results from the randomised, double-blind, non-inferiority SPRING-2 study. Lancet. 2013 Mar 2;381(9868):735-43. doi: 10.1016/S0140-6736(12)61853-4. Epub 2013 Jan 8.
PubMed 23306000Siliciano JD, Kajdas J, Finzi D, Quinn TC, Chadwick K, Margolick JB, Kovacs C, Gange SJ, Siliciano RF. Long-term follow-up studies confirm the stability of the latent reservoir for HIV-1 in resting CD4+ T cells. Nat Med. 2003 Jun;9(6):727-8. doi: 10.1038/nm880. Epub 2003 May 18.
PubMed 12754504