RV630 - Approach to Control HIV With Immune Enhancement and Vaccination (ACHIEV
Phase 1
Not yet recruiting
- Conditions
- Acute HIV InfectionHIV InfectionsPLWHART
- Interventions
- Biological: VRC07-523LSBiological: PGDM1400LSOther: PlaceboBiological: ChAdOx1.tHIVconsv1Biological: ChAdOx1.HIVconsv62Biological: MVA.tHIVconsv4Biological: A244d11 gp120Biological: ALFQ
- Registration Number
- NCT06484335
- Lead Sponsor
- Henry M. Jackson Foundation for the Advancement of Military Medicine
- Brief Summary
This is a phase I, randomized, double-blind, placebo-controlled clinical trial to investigate the safety of VRC07-523LS and PGDM1400LS in combination with ChAdOx1.tHIVconsv1, ChAdOx1.HIVconsv62 prime, MVA.tHIVconsv4 and A244d11gp120/ALFQ vaccination, and the impact on viral load setpoint during analytic treatment interruption (ATI) in people living with human immunodeficiency virus-1 (HIV-1, PLWH) who have initiated or will initiate antiretroviral therapy (ART) during acute HIV-1 infection (AHI).
- Detailed Description
This is a phase I, randomized, double-blinded, placebo-controlled clinical trial to investigate the safety of VRC07-523LS and PGDM1400LS in combination with ChAdOx1.tHIVconsv1, ChAdOx1.tHIVconsv62, MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination, and the impact on viral load setpoint during ATI in PLWH who initiated ART during AHI.
To evaluate the primary objectives, the study will enroll up to 40 adults already enrolled in the RV 254/WRAIR #1494 study who initiated ART during Fiebig I-V acute HIV-1 infection, with plasma HIV-1 RNA \< 50 copies/mL for ≥ 48 weeks, CD4 T-cell counts ≥ 400 cells/mm3, viruses susceptible to VRC07-523LS and/or PGDM1400LS, and the absence of known protective HLA allele (Groups 1 and 2).
Participants currently on ART who meet study entry criteria will be randomized (Section 6.2) in a 1:1 allocation to the Active (Group 1) or Comparator (Group 2) Arms prior to entering Step 1.
To evaluate exploratory objectives, the study will also enroll up to 8 adults who are newly enrolled in the RV 254/WRAIR #1494 study, diagnosed during Fiebig I-V AHI, and have not yet initiated ART (Group 3).
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 48
Inclusion Criteria
Not provided
Exclusion Criteria
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Active Arm ALFQ For the primary objectives and endpoints, this study will enroll PLWH aged 18-60 years who initiated ART during Fiebig I-V AHI, are virologically suppressed (HIV-1 RNA \<50 copies/ml for ≥48 weeks) on uninterrupted ART, and who meet study inclusion criteria into Groups 1 and 2. • Active Arm - Group 1 will receive: i. VRC07-523LS and PGDM1400LS at Step 2, Week 0 ii. ART starting at Step 2, Week 1 iii. ChAdOx1.tHIVconsv1 and ChAdOx1.HIVconsv62 vaccination at Step 2, Week 4 iv. MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination at Step 2, Weeks 12 and 20 Active Arm PGDM1400LS For the primary objectives and endpoints, this study will enroll PLWH aged 18-60 years who initiated ART during Fiebig I-V AHI, are virologically suppressed (HIV-1 RNA \<50 copies/ml for ≥48 weeks) on uninterrupted ART, and who meet study inclusion criteria into Groups 1 and 2. • Active Arm - Group 1 will receive: i. VRC07-523LS and PGDM1400LS at Step 2, Week 0 ii. ART starting at Step 2, Week 1 iii. ChAdOx1.tHIVconsv1 and ChAdOx1.HIVconsv62 vaccination at Step 2, Week 4 iv. MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination at Step 2, Weeks 12 and 20 Active Arm A244d11 gp120 For the primary objectives and endpoints, this study will enroll PLWH aged 18-60 years who initiated ART during Fiebig I-V AHI, are virologically suppressed (HIV-1 RNA \<50 copies/ml for ≥48 weeks) on uninterrupted ART, and who meet study inclusion criteria into Groups 1 and 2. • Active Arm - Group 1 will receive: i. VRC07-523LS and PGDM1400LS at Step 2, Week 0 ii. ART starting at Step 2, Week 1 iii. ChAdOx1.tHIVconsv1 and ChAdOx1.HIVconsv62 vaccination at Step 2, Week 4 iv. MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination at Step 2, Weeks 12 and 20 Comparator Arm Placebo For the primary objectives and endpoints, this study will enroll PLWH aged 18-60 years who initiated ART during Fiebig I-V AHI, are virologically suppressed (HIV-1 RNA \<50 copies/ml for ≥48 weeks) on uninterrupted ART, and who meet study inclusion criteria into Groups 1 and 2. • Comparator Arm - Group 2 will receive: i. VRC07-523LS and PGDM1400LS at Step 2, Week 0 ii. ART starting at Step 2, Week 1 iii. Placebo vaccination at Step 2, Weeks 4, 12 and 20 Active Arm VRC07-523LS For the primary objectives and endpoints, this study will enroll PLWH aged 18-60 years who initiated ART during Fiebig I-V AHI, are virologically suppressed (HIV-1 RNA \<50 copies/ml for ≥48 weeks) on uninterrupted ART, and who meet study inclusion criteria into Groups 1 and 2. • Active Arm - Group 1 will receive: i. VRC07-523LS and PGDM1400LS at Step 2, Week 0 ii. ART starting at Step 2, Week 1 iii. ChAdOx1.tHIVconsv1 and ChAdOx1.HIVconsv62 vaccination at Step 2, Week 4 iv. MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination at Step 2, Weeks 12 and 20 Active Arm ChAdOx1.HIVconsv62 For the primary objectives and endpoints, this study will enroll PLWH aged 18-60 years who initiated ART during Fiebig I-V AHI, are virologically suppressed (HIV-1 RNA \<50 copies/ml for ≥48 weeks) on uninterrupted ART, and who meet study inclusion criteria into Groups 1 and 2. • Active Arm - Group 1 will receive: i. VRC07-523LS and PGDM1400LS at Step 2, Week 0 ii. ART starting at Step 2, Week 1 iii. ChAdOx1.tHIVconsv1 and ChAdOx1.HIVconsv62 vaccination at Step 2, Week 4 iv. MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination at Step 2, Weeks 12 and 20 Exploratory Arm MVA.tHIVconsv4 This study will also enroll an Exploratory arm of PLWH aged 18-60 years who are diagnosed during Fiebig I-V AHI, have not yet initiated ART, and meet all study inclusion criteria into Group 3. • Exploratory Arm - Group 3 will receive: i. VRC07-523LS and PGDM1400LS at Step 2, Week 0 ii. ART starting at Step 2, Week 0 iii. ChAdOx1.tHIVconsv1 and ChAdOx1.HIVconsv62 vaccination at Step 2, Week 12 iv. MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination at Step 2, Weeks 20 and 28 Active Arm ChAdOx1.tHIVconsv1 For the primary objectives and endpoints, this study will enroll PLWH aged 18-60 years who initiated ART during Fiebig I-V AHI, are virologically suppressed (HIV-1 RNA \<50 copies/ml for ≥48 weeks) on uninterrupted ART, and who meet study inclusion criteria into Groups 1 and 2. • Active Arm - Group 1 will receive: i. VRC07-523LS and PGDM1400LS at Step 2, Week 0 ii. ART starting at Step 2, Week 1 iii. ChAdOx1.tHIVconsv1 and ChAdOx1.HIVconsv62 vaccination at Step 2, Week 4 iv. MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination at Step 2, Weeks 12 and 20 Exploratory Arm ChAdOx1.tHIVconsv1 This study will also enroll an Exploratory arm of PLWH aged 18-60 years who are diagnosed during Fiebig I-V AHI, have not yet initiated ART, and meet all study inclusion criteria into Group 3. • Exploratory Arm - Group 3 will receive: i. VRC07-523LS and PGDM1400LS at Step 2, Week 0 ii. ART starting at Step 2, Week 0 iii. ChAdOx1.tHIVconsv1 and ChAdOx1.HIVconsv62 vaccination at Step 2, Week 12 iv. MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination at Step 2, Weeks 20 and 28 Exploratory Arm ChAdOx1.HIVconsv62 This study will also enroll an Exploratory arm of PLWH aged 18-60 years who are diagnosed during Fiebig I-V AHI, have not yet initiated ART, and meet all study inclusion criteria into Group 3. • Exploratory Arm - Group 3 will receive: i. VRC07-523LS and PGDM1400LS at Step 2, Week 0 ii. ART starting at Step 2, Week 0 iii. ChAdOx1.tHIVconsv1 and ChAdOx1.HIVconsv62 vaccination at Step 2, Week 12 iv. MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination at Step 2, Weeks 20 and 28 Active Arm MVA.tHIVconsv4 For the primary objectives and endpoints, this study will enroll PLWH aged 18-60 years who initiated ART during Fiebig I-V AHI, are virologically suppressed (HIV-1 RNA \<50 copies/ml for ≥48 weeks) on uninterrupted ART, and who meet study inclusion criteria into Groups 1 and 2. • Active Arm - Group 1 will receive: i. VRC07-523LS and PGDM1400LS at Step 2, Week 0 ii. ART starting at Step 2, Week 1 iii. ChAdOx1.tHIVconsv1 and ChAdOx1.HIVconsv62 vaccination at Step 2, Week 4 iv. MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination at Step 2, Weeks 12 and 20 Comparator Arm PGDM1400LS For the primary objectives and endpoints, this study will enroll PLWH aged 18-60 years who initiated ART during Fiebig I-V AHI, are virologically suppressed (HIV-1 RNA \<50 copies/ml for ≥48 weeks) on uninterrupted ART, and who meet study inclusion criteria into Groups 1 and 2. • Comparator Arm - Group 2 will receive: i. VRC07-523LS and PGDM1400LS at Step 2, Week 0 ii. ART starting at Step 2, Week 1 iii. Placebo vaccination at Step 2, Weeks 4, 12 and 20 Comparator Arm VRC07-523LS For the primary objectives and endpoints, this study will enroll PLWH aged 18-60 years who initiated ART during Fiebig I-V AHI, are virologically suppressed (HIV-1 RNA \<50 copies/ml for ≥48 weeks) on uninterrupted ART, and who meet study inclusion criteria into Groups 1 and 2. • Comparator Arm - Group 2 will receive: i. VRC07-523LS and PGDM1400LS at Step 2, Week 0 ii. ART starting at Step 2, Week 1 iii. Placebo vaccination at Step 2, Weeks 4, 12 and 20 Exploratory Arm VRC07-523LS This study will also enroll an Exploratory arm of PLWH aged 18-60 years who are diagnosed during Fiebig I-V AHI, have not yet initiated ART, and meet all study inclusion criteria into Group 3. • Exploratory Arm - Group 3 will receive: i. VRC07-523LS and PGDM1400LS at Step 2, Week 0 ii. ART starting at Step 2, Week 0 iii. ChAdOx1.tHIVconsv1 and ChAdOx1.HIVconsv62 vaccination at Step 2, Week 12 iv. MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination at Step 2, Weeks 20 and 28 Exploratory Arm A244d11 gp120 This study will also enroll an Exploratory arm of PLWH aged 18-60 years who are diagnosed during Fiebig I-V AHI, have not yet initiated ART, and meet all study inclusion criteria into Group 3. • Exploratory Arm - Group 3 will receive: i. VRC07-523LS and PGDM1400LS at Step 2, Week 0 ii. ART starting at Step 2, Week 0 iii. ChAdOx1.tHIVconsv1 and ChAdOx1.HIVconsv62 vaccination at Step 2, Week 12 iv. MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination at Step 2, Weeks 20 and 28 Exploratory Arm PGDM1400LS This study will also enroll an Exploratory arm of PLWH aged 18-60 years who are diagnosed during Fiebig I-V AHI, have not yet initiated ART, and meet all study inclusion criteria into Group 3. • Exploratory Arm - Group 3 will receive: i. VRC07-523LS and PGDM1400LS at Step 2, Week 0 ii. ART starting at Step 2, Week 0 iii. ChAdOx1.tHIVconsv1 and ChAdOx1.HIVconsv62 vaccination at Step 2, Week 12 iv. MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination at Step 2, Weeks 20 and 28 Exploratory Arm ALFQ This study will also enroll an Exploratory arm of PLWH aged 18-60 years who are diagnosed during Fiebig I-V AHI, have not yet initiated ART, and meet all study inclusion criteria into Group 3. • Exploratory Arm - Group 3 will receive: i. VRC07-523LS and PGDM1400LS at Step 2, Week 0 ii. ART starting at Step 2, Week 0 iii. ChAdOx1.tHIVconsv1 and ChAdOx1.HIVconsv62 vaccination at Step 2, Week 12 iv. MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination at Step 2, Weeks 20 and 28 Active Arm VRC07-523LS Active Arm (Group 1) will have 20 participants. For the primary objectives and endpoints, this study will enroll participants of the RV 254/WRAIR #1494 study, who are PLWH aged 18 - 60 years, initiated ART during Fiebig I-V AHI, are virologically suppressed (HIV-1 RNA \< 50 copies/mL for ≥ 48 weeks) on uninterrupted ART, and who meet study inclusion criteria into Groups 1 and 2. For Active Arm: Group 1 will receive: i. VRC07-523LS and PGDM1400LS at Step 2, Week 0 ii. ART starting at Step 2, Week 1 iii. ChAdOx1.tHIVconsv1 and ChAdOx1.HIVconsv62 vaccination at Step 2, Week 4 iv. MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination at Step 2, Weeks 12 and 20 Active Arm PGDM1400LS Active Arm (Group 1) will have 20 participants. For the primary objectives and endpoints, this study will enroll participants of the RV 254/WRAIR #1494 study, who are PLWH aged 18 - 60 years, initiated ART during Fiebig I-V AHI, are virologically suppressed (HIV-1 RNA \< 50 copies/mL for ≥ 48 weeks) on uninterrupted ART, and who meet study inclusion criteria into Groups 1 and 2. For Active Arm: Group 1 will receive: i. VRC07-523LS and PGDM1400LS at Step 2, Week 0 ii. ART starting at Step 2, Week 1 iii. ChAdOx1.tHIVconsv1 and ChAdOx1.HIVconsv62 vaccination at Step 2, Week 4 iv. MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination at Step 2, Weeks 12 and 20 Active Arm ChAdOx1.tHIVconsv1 Active Arm (Group 1) will have 20 participants. For the primary objectives and endpoints, this study will enroll participants of the RV 254/WRAIR #1494 study, who are PLWH aged 18 - 60 years, initiated ART during Fiebig I-V AHI, are virologically suppressed (HIV-1 RNA \< 50 copies/mL for ≥ 48 weeks) on uninterrupted ART, and who meet study inclusion criteria into Groups 1 and 2. For Active Arm: Group 1 will receive: i. VRC07-523LS and PGDM1400LS at Step 2, Week 0 ii. ART starting at Step 2, Week 1 iii. ChAdOx1.tHIVconsv1 and ChAdOx1.HIVconsv62 vaccination at Step 2, Week 4 iv. MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination at Step 2, Weeks 12 and 20 Active Arm ChAdOx1.HIVconsv62 Active Arm (Group 1) will have 20 participants. For the primary objectives and endpoints, this study will enroll participants of the RV 254/WRAIR #1494 study, who are PLWH aged 18 - 60 years, initiated ART during Fiebig I-V AHI, are virologically suppressed (HIV-1 RNA \< 50 copies/mL for ≥ 48 weeks) on uninterrupted ART, and who meet study inclusion criteria into Groups 1 and 2. For Active Arm: Group 1 will receive: i. VRC07-523LS and PGDM1400LS at Step 2, Week 0 ii. ART starting at Step 2, Week 1 iii. ChAdOx1.tHIVconsv1 and ChAdOx1.HIVconsv62 vaccination at Step 2, Week 4 iv. MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination at Step 2, Weeks 12 and 20 Active Arm ALFQ Active Arm (Group 1) will have 20 participants. For the primary objectives and endpoints, this study will enroll participants of the RV 254/WRAIR #1494 study, who are PLWH aged 18 - 60 years, initiated ART during Fiebig I-V AHI, are virologically suppressed (HIV-1 RNA \< 50 copies/mL for ≥ 48 weeks) on uninterrupted ART, and who meet study inclusion criteria into Groups 1 and 2. For Active Arm: Group 1 will receive: i. VRC07-523LS and PGDM1400LS at Step 2, Week 0 ii. ART starting at Step 2, Week 1 iii. ChAdOx1.tHIVconsv1 and ChAdOx1.HIVconsv62 vaccination at Step 2, Week 4 iv. MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination at Step 2, Weeks 12 and 20 Comparator Arm PGDM1400LS Comparator Arm (Group 2) will have 20 participants. For the primary objectives and endpoints, this study will enroll participants of the RV 254/WRAIR #1494 study, who are PLWH aged 18 - 60 years, initiated ART during Fiebig I-V AHI, are virologically suppressed (HIV-1 RNA \< 50 copies/mL for ≥ 48 weeks) on uninterrupted ART, and who meet study inclusion criteria into Groups 1 and 2. For Comparator Arm - Group 2 will receive: i. VRC07-523LS and PGDM1400LS at Step 2, Week 0 ii. ART starting at Step 2, Week 1 iii. Placebo vaccination at Step 2, Weeks 4, 12 and 20 Active Arm MVA.tHIVconsv4 Active Arm (Group 1) will have 20 participants. For the primary objectives and endpoints, this study will enroll participants of the RV 254/WRAIR #1494 study, who are PLWH aged 18 - 60 years, initiated ART during Fiebig I-V AHI, are virologically suppressed (HIV-1 RNA \< 50 copies/mL for ≥ 48 weeks) on uninterrupted ART, and who meet study inclusion criteria into Groups 1 and 2. For Active Arm: Group 1 will receive: i. VRC07-523LS and PGDM1400LS at Step 2, Week 0 ii. ART starting at Step 2, Week 1 iii. ChAdOx1.tHIVconsv1 and ChAdOx1.HIVconsv62 vaccination at Step 2, Week 4 iv. MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination at Step 2, Weeks 12 and 20 Exploratory Arm VRC07-523LS Exploratory Arm (Group 3) will have 8 participants. This study will also enroll an Exploratory arm of newly enrolled participants of the RV 254/ WRAIR #1494 study, who are PLWH aged 18 - 60 years, diagnosed during Fiebig I-V AHI, have not yet initiated ART, and meet all study inclusion criteria into Group 3. For the Exploratory Arm - Group 3 will receive: iv. VRC07-523LS and PGDM1400LS at Step 2, Week 0 v. ART starting at Step 2, Week 0 vi. ChAdOx1.tHIVconsv1 and ChAdOx1.HIVconsv62 vaccination at Step 2, Week 12 vii. MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination at Step 2, Weeks 20 and 28 Active Arm A244d11 gp120 Active Arm (Group 1) will have 20 participants. For the primary objectives and endpoints, this study will enroll participants of the RV 254/WRAIR #1494 study, who are PLWH aged 18 - 60 years, initiated ART during Fiebig I-V AHI, are virologically suppressed (HIV-1 RNA \< 50 copies/mL for ≥ 48 weeks) on uninterrupted ART, and who meet study inclusion criteria into Groups 1 and 2. For Active Arm: Group 1 will receive: i. VRC07-523LS and PGDM1400LS at Step 2, Week 0 ii. ART starting at Step 2, Week 1 iii. ChAdOx1.tHIVconsv1 and ChAdOx1.HIVconsv62 vaccination at Step 2, Week 4 iv. MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination at Step 2, Weeks 12 and 20 Comparator Arm VRC07-523LS Comparator Arm (Group 2) will have 20 participants. For the primary objectives and endpoints, this study will enroll participants of the RV 254/WRAIR #1494 study, who are PLWH aged 18 - 60 years, initiated ART during Fiebig I-V AHI, are virologically suppressed (HIV-1 RNA \< 50 copies/mL for ≥ 48 weeks) on uninterrupted ART, and who meet study inclusion criteria into Groups 1 and 2. For Comparator Arm - Group 2 will receive: i. VRC07-523LS and PGDM1400LS at Step 2, Week 0 ii. ART starting at Step 2, Week 1 iii. Placebo vaccination at Step 2, Weeks 4, 12 and 20 Exploratory Arm PGDM1400LS Exploratory Arm (Group 3) will have 8 participants. This study will also enroll an Exploratory arm of newly enrolled participants of the RV 254/ WRAIR #1494 study, who are PLWH aged 18 - 60 years, diagnosed during Fiebig I-V AHI, have not yet initiated ART, and meet all study inclusion criteria into Group 3. For the Exploratory Arm - Group 3 will receive: iv. VRC07-523LS and PGDM1400LS at Step 2, Week 0 v. ART starting at Step 2, Week 0 vi. ChAdOx1.tHIVconsv1 and ChAdOx1.HIVconsv62 vaccination at Step 2, Week 12 vii. MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination at Step 2, Weeks 20 and 28 Comparator Arm Placebo Comparator Arm (Group 2) will have 20 participants. For the primary objectives and endpoints, this study will enroll participants of the RV 254/WRAIR #1494 study, who are PLWH aged 18 - 60 years, initiated ART during Fiebig I-V AHI, are virologically suppressed (HIV-1 RNA \< 50 copies/mL for ≥ 48 weeks) on uninterrupted ART, and who meet study inclusion criteria into Groups 1 and 2. For Comparator Arm - Group 2 will receive: i. VRC07-523LS and PGDM1400LS at Step 2, Week 0 ii. ART starting at Step 2, Week 1 iii. Placebo vaccination at Step 2, Weeks 4, 12 and 20 Exploratory Arm ChAdOx1.tHIVconsv1 Exploratory Arm (Group 3) will have 8 participants. This study will also enroll an Exploratory arm of newly enrolled participants of the RV 254/ WRAIR #1494 study, who are PLWH aged 18 - 60 years, diagnosed during Fiebig I-V AHI, have not yet initiated ART, and meet all study inclusion criteria into Group 3. For the Exploratory Arm - Group 3 will receive: iv. VRC07-523LS and PGDM1400LS at Step 2, Week 0 v. ART starting at Step 2, Week 0 vi. ChAdOx1.tHIVconsv1 and ChAdOx1.HIVconsv62 vaccination at Step 2, Week 12 vii. MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination at Step 2, Weeks 20 and 28 Exploratory Arm ChAdOx1.HIVconsv62 Exploratory Arm (Group 3) will have 8 participants. This study will also enroll an Exploratory arm of newly enrolled participants of the RV 254/ WRAIR #1494 study, who are PLWH aged 18 - 60 years, diagnosed during Fiebig I-V AHI, have not yet initiated ART, and meet all study inclusion criteria into Group 3. For the Exploratory Arm - Group 3 will receive: iv. VRC07-523LS and PGDM1400LS at Step 2, Week 0 v. ART starting at Step 2, Week 0 vi. ChAdOx1.tHIVconsv1 and ChAdOx1.HIVconsv62 vaccination at Step 2, Week 12 vii. MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination at Step 2, Weeks 20 and 28 Exploratory Arm MVA.tHIVconsv4 Exploratory Arm (Group 3) will have 8 participants. This study will also enroll an Exploratory arm of newly enrolled participants of the RV 254/ WRAIR #1494 study, who are PLWH aged 18 - 60 years, diagnosed during Fiebig I-V AHI, have not yet initiated ART, and meet all study inclusion criteria into Group 3. For the Exploratory Arm - Group 3 will receive: iv. VRC07-523LS and PGDM1400LS at Step 2, Week 0 v. ART starting at Step 2, Week 0 vi. ChAdOx1.tHIVconsv1 and ChAdOx1.HIVconsv62 vaccination at Step 2, Week 12 vii. MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination at Step 2, Weeks 20 and 28 Exploratory Arm A244d11 gp120 Exploratory Arm (Group 3) will have 8 participants. This study will also enroll an Exploratory arm of newly enrolled participants of the RV 254/ WRAIR #1494 study, who are PLWH aged 18 - 60 years, diagnosed during Fiebig I-V AHI, have not yet initiated ART, and meet all study inclusion criteria into Group 3. For the Exploratory Arm - Group 3 will receive: iv. VRC07-523LS and PGDM1400LS at Step 2, Week 0 v. ART starting at Step 2, Week 0 vi. ChAdOx1.tHIVconsv1 and ChAdOx1.HIVconsv62 vaccination at Step 2, Week 12 vii. MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination at Step 2, Weeks 20 and 28 Exploratory Arm ALFQ Exploratory Arm (Group 3) will have 8 participants. This study will also enroll an Exploratory arm of newly enrolled participants of the RV 254/ WRAIR #1494 study, who are PLWH aged 18 - 60 years, diagnosed during Fiebig I-V AHI, have not yet initiated ART, and meet all study inclusion criteria into Group 3. For the Exploratory Arm - Group 3 will receive: iv. VRC07-523LS and PGDM1400LS at Step 2, Week 0 v. ART starting at Step 2, Week 0 vi. ChAdOx1.tHIVconsv1 and ChAdOx1.HIVconsv62 vaccination at Step 2, Week 12 vii. MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination at Step 2, Weeks 20 and 28
- Primary Outcome Measures
Name Time Method To evaluate the safety of VRC07-523LS and PGDM1400LS in combination with ChAdOx1.tHIVconsv1, ChAdOx1.HIVconsv62, MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination in PLWH who initiated ART during AHI. Measured from enrollment to a minimum of 50 weeks to a maximum of 100 weeks per participant Occurrence of ≥ grade 3 AE or SAE that are possibly, probably, or definitely related to the IPs during the study
To evaluate the impact of VRC07-523LS and PGDM1400LS in combination with ChAdOx1.tHIVconsv1, ChAdOx1.HIVconsv62, MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination on viral load setpoint after viral rebound during ATI. Measured for 50 weeks from entry into step 3 (treatment interruption and last mAb administration) Viral Load setpoint after 2 weeks post viral rebound during ATI.
- Secondary Outcome Measures
Name Time Method To evaluate the impact of VRC07-523LS and PGDM1400LS in combination with ChAdOx1.tHIVconsv1, ChAdOx1.HIVconsv62, MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination on time to first documented HIV-1 RNA viral rebound of ≥50 copies/mL following ATI. Measured for 50 weeks from entry into step 3 (treatment interruption and last mAb administration) Time (days) from ATI to first documented HIV-1 RNA viral rebound of ≥50 copies/mL
To evaluate the impact of VRC07-523LS and PGDM1400LS in combination with ChAdOx1.tHIVconsv1, ChAdOx1.HIVconsv62, MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination on viral rebound dynamics during ATI. Measured for 50 weeks from entry into step 3 (treatment interruption and last mAb administration) Peak viral load, nadir viral load, and viral load area under the curve (AUC) during the first 8 weeks after viral rebound.
To evaluate the impact of VRC07-523LS and PGDM1400LS in combination with ChAdOx1.tHIVconsv1, ChAdOx1.HIVconsv62, MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination on time to first documented HIV-1 RNA viral rebound of ≥1000 copies/mL following ATI. Measured for 50 weeks from entry into step 3 (treatment interruption and last mAb administration) Time (days) from ATI to first documented HIV-1 RNA viral rebound of ≥1000 copies/mL
To assess the impact of VRC07-523LS and PGDM1400LS in combination with ChAdOx1.tHIVconsv1, ChAdOx1.HIVconsv62, MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination on total HIV-1 DNA levels prior to ATI Measured for 50 weeks from entry into step 3 (treatment interruption and last mAb administration) Total HIV-1 DNA levels prior to ATI.
To assess the effects of VRC07-523LS and PGDM1400LS in combination with ChAdOx1.tHIVconsv1, ChAdOx1.HIVconsv62, MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination on HIV-1 specific cellular immune responses prior to ATI. Measure during step 2: from the initial administration of bNab therapy through week 22 in arms 1 and 2 and through week 30 in arm 3. Magnitude, breadth, cytokine production, cytotoxicity, proliferation and related functions of HIV-1 specific CD4 and CD8 T-cells prior to ATI.
To evaluate the impact of VRC07-523LS and PGDM1400LS in combination with ChAdOx1.tHIVconsv1, ChAdOx1.HIVconsv62, MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination on the number of participants with plasma HIV-1 RNA < 1000 copies/mL at 12 and 24 weeks of Measured for 50 weeks from entry into step 3 (treatment interruption and last mAb administration) The number of participants with plasma HIV-1 RNA \< 1000 copies/mL at 12 and 24 weeks of ATI.
To evaluate the impact of VRC07-523LS and PGDM1400LS in combination with ChAdOx1.tHIVconsv1, ChAdOx1.HIVconsv62, MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination on time to ART resumption for an HIV-related (virologic, immunologic, or clinical) reason d i. Measured for 50 weeks from entry into step 3 (treatment interruption and last mAb administration) Time (days) from ATI to ART resumption during Step 3
To measure the effects of VRC07-523LS and PGDM1400LS in combination with ChAdOx1.tHIVconsv1, ChAdOx1.HIVconsv62, MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination on HIV-1 RNA levels while on ART. Measured for 50 weeks from entry into step 3 (treatment interruption and last mAb administration) HIV-1 RNA levels using single copy assay while on ART
To assess the effects of VRC07-523LS andPGDM1400LSin combination withChAdOx1.tHIVconsv1, ChAdOx1.HIVconsv62,MVA.tHIVconsv4 and A244d11 gp120/ALFQvaccination on HIV-1 specific humoral immuneresponses. Measure at week 0 of Step 3 in all groups, just prior to ATI. Binding antibodies to HIV-1, ADCC, ADCP andother functional ab-mediated responses prior toATI.
To assess the impact of VRC07-523LS andPGDM1400LS in combination withChAdOx1.tHIVconsv1, ChAdOx1.HIVconsv62,MVA.tHIVconsv4 and A244d11 gp120/ALFQvaccination on the HIV-1 reservoir prior to ATI Measure at week 0 of Step 3 in all groups, just prior to ATI. Measurements of HIV-1 reservoir using assaysbased on contemporary literature that may includebut are not limited to total and/or intact HIV-1DNA, quantitative infectious virus outgrowth(qVOA), cell- associated HIV-1 RNA, and relatedassays prior to ATI.
To characterize the pharmacokinetics of VRC07-523LS and PGDM1400LS. Measured for 50 weeks from entry into step 3 (treatment interruption and last mAb administration) Concentration of PGDM1400LS during ATI by MSD
To describe the neurological, neuroimaging andneuro-cognitive effects that occur after receiptof VRC07-523LS and PGDM1400LS incombination with ChAdOx1.tHIVconsv1,ChAdOx1.HIVconsv62, MVA.tHIVconsv4 andA244d11 gp120/ALFQ vaccination and ATI Measure at week 0 of Step 3 in all groups, just prior to ATI. Findings on CSF examination, MRI/MRS,neurological and neurocognitive testing before andafter receipt of study products and ATI
To assess the effects of VRC07-523LS and PGDM1400LSin combination with ChAdOx1.tHIVconsv1, ChAdOx1.HIVconsv62, MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination on HIV-1 specific humoral immune responses. Measure at week 0 of Step 3 in all groups, just prior to ATI. Measure Antibody Dependent Cellular Phagocytosis using clade AE protein coated target cells
To assess the impact of VRC07-523LS and PGDM1400LS in combination with ChAdOx1.tHIVconsv1, ChAdOx1.HIVconsv62, MVA.tHIVconsv4 and A244d11 gp120/ALFQ vaccination on the HIV-1 reservoir prior to ATI Measure at week 0 of Step 3 in all groups, just prior to ATI. Total HIV cell associate RNA measured by the quantitative RNA PCR
Trial Locations
- Locations (1)
The Faculty of Medicine, Chulalongkorn University/ King Chulalongkorn Memorial Hospital
🇹🇭Pathum Wan, Bangkok, Thailand