Safety and Efficacy of Fixed Dose Combination Dolutegravir/Abacavir/Lamivudine FDC Initiated During Acute HIV Infection

Not Applicable

Completed

• Conditions: HIV; Acute HIV Infection
• Interventions: Drug: Dolutegravir 50 mg; Drug: Lamivudine 300 mg; Drug: Abacavir 600 mg

• Registration Number: NCT02384395
• Lead Sponsor: University of North Carolina, Chapel Hill

Brief 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).

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.

Study Timeline

• Study First Submitted: 2015-03-04
• Study First Submitted QC: 2015-03-04
• Study First Posted: 2015-03-10
• Study Start: 2015-09
• Primary Completion: 2020-03-06
• Study Completion: 2021-09-17
• Results First Submitted: 2021-09-28
• Status Verified: 2021-10
• Results First Submitted QC: 2021-10-22
• Last Update Submitted: 2021-10-22
• Results First Posted: 2021-11-22
• Last Update Posted: 2021-11-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
DTG/3TC/ABC FDC	Lamivudine 300 mg	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	Abacavir 600 mg	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	Dolutegravir 50 mg	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

Primary Outcome Measures

Name	Time	Method
Number of Participants With Viral Load Measurement <200 Copies/mL at Week 24	Week 24	Total number of participants on study at Week 24 with an HIV-1 RNA level less than 200 copies/mL

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Grade 3 or Higher Adverse Event (AE)	Baseline through Week 96	Sign/symptom, lab toxicity, or clinical events, or Grade 3 or higher AE that is definitely, probably, or possibly related to study treatment
Median Change HIV-1 RNA Level Among Participants Completing Week 24 Visit	Baseline, Week 24
Proportion of Treated Participants With HIV-1 RNA to <50 Copies/mL at Week 48	Week 48	Proportion of participants completing Week 48 with an HIV-1 RNA level less than 50 copies/mL

Trial Locations

Locations (2)

University of North Carolina; 🇺🇸 Chapel Hill, North Carolina, United States

Duke University Health System; 🇺🇸 Durham, North Carolina, United States