Acute HIV Infection
Conditions
Keywords
Acute HIV Infection, Broadly Neutralizing Antibodies, Analytical Treatment Interruption, Viral Reservoir
Brief summary
A5388 is a phase II, two-arm, randomized, double-blind, placebo-controlled study that will enroll 48 antiretroviral therapy (ART)-naïve adults with acute HIV infection (AHI) in order to determine whether: * Administration of combination HIV-specific broadly neutralizing antibody (bNAb) therapy in addition to ART during acute HIV infection (AHI) will be safe. * Participants who receive combination bNAb therapy in addition to ART during AHI will be more likely to demonstrate a delay in time to HIV-1 RNA ≥1,000 copies/mL for 4 consecutive weeks during an Analytical Treatment Interruption (ATI) compared to participants who receive placebo plus ART. * Participants who receive combination bNAb therapy in addition to ART during AHI will demonstrate lower viral reservoirs and enhanced HIV-specific immunity compared to participants who receive placebo plus ART.
Interventions
BIOLOGICALVRC07-523LS
10 mg/kg intravenous infusion over approximately 15 to 30 minutes once at entry
BIOLOGICALPGT121.414.LS
5 mg/kg intravenous infusion over approximately 30 to 60 minutes once at entry
OTHERPlacebo
Sodium Chloride for Injection USP, 0.9%
DRUGART
Bictegravir 50 mg/emtricitabine 200 mg/tenofovir alafenamide 25 mg tablet orally once daily with or without food
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Between 18 and 70 years of age * Body weight under 115 kg (approximately 253 pounds) * Evidence of recently acquiring HIV * Not pregnant or breastfeeding * No recent use of medications to prevent or treat HIV * Able and willing to provide informed consent to study and its procedures which include * initiating HIV medications (also called antiretroviral treatment or ART) following enrollment, * A later, monitored pause in HIV medications (also called an analytical treatment interruption, or ATI) * While pausing HIV treatment per study guidelines until resuppressed following treatment restart, agree to using barrier contraception to prevent HIV acquisition in sexual partners * Agree to use effective contraception to prevent pregnancy in oneself and sexual partners who may become pregnant.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Occurrence of Grade ≥2 AE or SAE that are possibly, probably, or definitely related to the study bNAbs during initial ART treatment | Week 0 to end of initial ART treatment (scheduled to be 60 weeks) |
| Time from ART discontinuation to HIV-1 RNA ≥1,000 copies/mL for 4 consecutive weekly measurements during analytical treatment interruption (ATI) | From start of ATI through 24 weeks after ART interruption |
Secondary
| Measure | Time frame |
|---|---|
| Time from ART discontinuation to first documented HIV-1 RNA viral rebound of ≥50 copies/mL during ATI | From start of ATI through 24 weeks after ART interruption |
| Time from ART discontinuation to first documented HIV-1 RNA viral rebound of ≥200 copies/mL during ATI | From start of ATI through 24 weeks after ART interruption |
| Time from ART discontinuation to first documented HIV-1 RNA viral rebound of ≥1000 copies/mL during ATI | From start of ATI through 24 weeks after ART interruption |
| Proportion of study participants who undergo ATI with HIV-1 RNA <200 copies/mL at 24 weeks after ART interruption, without indication of ART restart | From start of ATI through 24 weeks after ART interruption |
| Time from ART discontinuation to ART restart for an HIV-related reason (virologic, immunologic and clinical criteria) during ATI | From start of ATI through 24 weeks after ART interruption |
| Frequency of participants maintained off ART at each visit during ATI | From start of ATI through 24 weeks after ART interruption |
| Change in CD4+/CD8+ T-cell counts during ATI | From start of ATI through 24 weeks after ART interruption |
| Area under the curve (AUC) of VRC07-523LS and PGT121.414.LS when administered together | Week 0 to end of ATI |
| Half-life of VRC07-523LS and PGT121.414.LS when administered together | Week 0 to end of ATI |
| Cmax of VRC07-523LS and PGT121.414.LS when administered together | Week 0 to end of ATI |
| Cmin of VRC07-523LS and PGT121.414.LS when administered together | Week 0 to end of ATI |
| Clearance (Cl/F) of VRC07-523LS and PGT121.414.LS when administered together | Week 0 to end of ATI |
| Volume of distribution of VRC07-523LS and PGT121.414.LS when administered together | Week 0 to end of ATI |
Countries
Brazil, Peru, United States
Contacts
STUDY_CHAIRTrevor Crowell, MD, PhD
U.S. Military HIV Research Program CTU
STUDY_CHAIRRoberto Arduino, MD
Houston AIDS Research Team CRS
Outcome results
None listed