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Combination broadly neutralizing HIV antibodies given with ART during acute infection to try to induce remission

A Double-Blind, Randomized, Placebo-Controlled Clinical Trial of Combination HIV-Specific Broadly Neutralizing Monoclonal Antibodies Combined With ART Initiation During Acute HIV Infection to Induce HIV Remission

Phase 2 Interventional National Institute of Allergy and Infectious Diseases (NIAID) · NCT05719441

This trial will try giving two HIV-specific broadly neutralizing antibodies along with starting ART to ART-naïve adults with acute HIV infection to see if it delays viral rebound and reduces the viral reservoir.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment48 (estimated)
Ages18 Years to 70 Years
SexAll
SponsorNational Institute of Allergy and Infectious Diseases (NIAID) NIH
Drugs / interventionschemotherapy
Locations36 sites (Birmingham, Alabama and 35 other locations)
Trial IDNCT05719441 on ClinicalTrials.gov

What this trial studies

This is a phase II, randomized, double-blind, placebo-controlled trial that will enroll 48 adults diagnosed during acute HIV infection who have not yet started ART. Participants are randomized to receive combination bNAb therapy (VRC07-523LS and PGT121.414.LS) plus ART or placebo plus ART, with blinded treatment assignments. The trial will monitor safety and compare time to confirmed viral rebound (HIV-1 RNA ≥1,000 copies/mL for four consecutive weeks), along with measurements of viral reservoir size and HIV-specific immune responses. Regular clinic visits and blood sampling will be used to track viral load, immune markers, and reservoir assays over follow-up.

Who should consider this trial

Good fit: Adults very recently diagnosed with acute HIV infection who are ART‑naïve and meet the study's laboratory and timing entry criteria are the intended participants.

Not a fit: People with chronic, well-established HIV infection, those already on ART, or those with viral strains resistant to the study antibodies are unlikely to benefit from this intervention.

Why it matters

Potential benefit: If successful, this approach could let some people treated during acute infection remain off ART longer or achieve periods of remission by reducing the viral reservoir and delaying viral rebound.

How similar studies have performed: Previous trials of single or dual broadly neutralizing antibodies in chronic infection have sometimes delayed viral rebound but results have been mixed, and starting combination bNAbs during acute infection is a relatively new strategy.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

Step 1:

1. Appropriate documentation from medical records of diagnosis of AHI prior to enrollment that includes one of the following:

   1. A detectable HIV-1 RNA within 28 days prior to study entry AND a non-reactive HIV-1 antibody within 7 days prior to entry; OR
   2. A detectable HIV-1 RNA or a reactive HIV-1 antibody within 28 days prior to study entry AND a negative/indeterminate Western Blot (WB) or negative/indeterminate Geenius HIV-1/HIV-2 Supplemental Assay within 7 days prior to entry; OR
   3. A documented non-reactive HIV-1 antibody or negative HIV-1 RNA within 90 days prior to study entry AND a documented reactive HIV-1 antibody or positive WB that is negative for p31 band or a positive Geenius HIV-1/HIV-2 Supplemental Assay that is negative for p31 band within 7 days prior to entry; OR
   4. ARCHITECT or GSCOMBO S/CO ≥10 within 7 days prior to entry AND a non-reactive HIV-1 antibody within 7 days prior to entry; OR
   5. ARCHITECT or GSCOMBO S/CO ≥1 within 7 days prior to entry AND a non-reactive HIV-1 antibody within 7 days prior to entry AND a known prior S/CO \<0.5 within 90 days prior to entry; OR
   6. ARCHITECT or GSCOMBO S/CO \>0.5 but \<10 within 7 days prior to entry AND a non-reactive HIV-1 antibody within 7 days prior to entry AND detectable HIV-1 RNA within 7 days prior to entry
2. The following laboratory values obtained within 21 days prior to entry:

   * Absolute neutrophil count (ANC) ˃1,000/mm3
   * Hemoglobin:

     * \>10 g/dL for cisgender men and transgender women
     * \>9 g/dL for cisgender women and transgender men
   * Platelet count ˃100,000/mm3
   * Estimated glomerular filtration rate (eGFR) ≥50 mL/min/1.73m2 using the Chronic Kidney Disease Epidemiology Collaboration (CKD-Epi) equation, with consideration for lower rates in special circumstances.
   * ALT (SGPT) ≤2.5 x ULN
   * AST (SGOT) ≤2.5 x ULN
   * Total bilirubin \<1.5 x ULN
3. For persons who are able to become pregnant, negative urine or serum pregnancy test within 24 hours prior to study entry.
4. Persons who are able to become pregnant must agree to use two methods of contraception throughout Step 1 if participating in sexual activity that could lead to pregnancy. One contraceptive method must be a highly effective method and the second method of contraception must be a barrier method.
5. Participants of reproductive potential who engage in sexual activity that could lead to their partner's becoming pregnant must agree to use a barrier method of contraception throughout Step 1.
6. Ability and willingness to use a barrier method or abstinence from sexual intercourse with all partners who are vulnerable to HIV or whose HIV serostatus is unknown in order to prevent HIV transmission during Step 2, Step 3, and until plasma HIV-1 RNA is less than the limit of detection after ART restart in Step 4.
7. Age ≥18 and ≤70 years.
8. Ability and willingness to initiate ART at enrollment.
9. Ability and willingness to participate in scheduled study visits, including during the ATI, per Schedule of Evaluations (SOE).
10. Ability and willingness of participant to provide informed consent.

Step 2:

1. Documented negative hepatitis B virus (HBV) surface antigen (HBsAg) obtained within 16 weeks prior to Step 2 registration.
2. Documented negative hepatitis C virus (HCV) antibody (anti-HCV) or negative HCV RNA PCR obtained within 16 weeks prior to Step 2 registration.
3. Receipt of full doses of study infusions at enrollment (VRC07-523LS + PGT121.414.LS or placebo \[Sodium Chloride for Injection USP, 0.9%\]).
4. HIV-1 RNA \<200 copies/mL obtained within 6 weeks prior to Step 2 registration.
5. CD4+ T-cell count ≥450 cells/mm3 obtained within 6 weeks prior to Step 2 registration.
6. For participants who are able to become pregnant, negative serum or urine pregnancy test within 48 hours prior to Step 2 entry.
7. To avoid pregnancy, participants who are able to become pregnant must agree to use contraception or practice abstinence from sexual activity that could lead to pregnancy throughout Step 2.
8. Ability and willingness to use a barrier method or abstinence from sexual intercourse with partners who are vulnerable to HIV or whose HIV serostatus is unknown in order to prevent HIV transmission throughout Step 2.
9. Ability and willingness to interrupt ART.
10. Completion of Step 1.

Step 3:

1. Has not met ART restart criteria.
2. Completion of Step 2.
3. Willing to continue ATI.
4. To avoid pregnancy, participants who are able to become pregnant must agree to use contraception or practice abstinence from sexual activity that could lead to pregnancy throughout Step 3.
5. Ability and willingness to use a barrier method or abstinence from sexual intercourse with all partners who are vulnerable to HIV or whose HIV serostatus is unknown in order to prevent HIV transmission throughout Step 3.

Step 4:

1. Has met any of the ART restart criteria during Step 2 or Step 3. -OR- Has completed Step 3 and is not enrolling to ACTG A5385.
2. To avoid pregnancy, participants who are able to become pregnant must agree to use contraception or practice abstinence from sexual activity that could lead to pregnancy throughout Step 4.
3. Ability and willingness to use a barrier method or abstinence from sexual intercourse with all partners who are vulnerable to HIV or whose HIV serostatus is unknown in order to prevent HIV transmission until plasma HIV-1 RNA is less than the limit of detection after ART restart.

Exclusion Criteria:

Step 1:

1. Previous receipt of immunoglobulin (IgG) therapy.
2. Previous receipt of humanized or human monoclonal antibody whether licensed or investigational (other than for the prevention and/or treatment of SARS-CoV-2/COVID-19).
3. History of a severe allergic reaction with generalized urticaria, angioedema or anaphylaxis in the 2 years prior to enrollment.
4. History of chronic urticaria requiring daily treatment.
5. Receipt of investigational study agent within 28 days prior to enrollment.
6. Past participation in an investigational study of a candidate HIV vaccine or immune prophylaxis for HIV-1 infection with receipt of active product or with receipt of active product or placebo and remains blinded to what they actually received.
7. Active or recent non-HIV-associated malignancy requiring systemic chemotherapy or surgery in the preceding 36 months or for whom such therapies are expected in the subsequent 12 months.
8. Use of any immunomodulatory medications within 6 months of study entry including systemic corticosteroids (long-term), immunosuppressants, anti-cancer, interleukins, systemic interferons, systemic chemotherapy, or other medications that the site investigator feels could have an immune modulatory effect.
9. Use of ART for any reason, including pre- or post-exposure prophylaxis, within 60 days prior to study entry.
10. Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
11. Known history of active Hepatitis B or Hepatitis C infection.
12. Any acute, chronic, or recent and clinically significant medical condition that, in the opinion of the site investigator, would interfere with adherence to study requirements or jeopardize the safety or rights of the participant.
13. History of or current clinical atherosclerotic cardiovascular disease (ASCVD) as defined by 2013 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines, including a previous diagnosis of any of the following:

    * Acute myocardial infarction
    * Acute coronary syndromes
    * Stable or unstable angina
    * Coronary or other arterial revascularization
    * Stroke
    * TIA
    * Peripheral arterial disease presumed to be of atherosclerotic origin
14. Currently breastfeeding or pregnant.
15. Weight \>115 kg.
16. Use of prohibited medications for bictegravir, emtricitabine, and tenofovir alafenamide (refer to protocol section 5.8) within 7 days prior to entry, or planned use of prohibited medications during the period of study participation.
17. Absence of adequate venous access for the administration of infusion or for phlebotomy to assess for the primary study endpoint.

Step 2:

1. Viral failure, as defined in protocol section 6.2.4, after Step 1 week 24.
2. Failure to initiate ART in Step 1.
3. Receipt of any non-nucleoside reverse transcriptase inhibitor (NNRTI) or long-acting ART (any therapy dosed at an interval less than daily), such as cabotegravir or rilpivirine injections, after Step 1 entry.
4. Receipt of any immunoglobulin therapy or immunomodulatory medications after Step 1 entry including systemic corticosteroids (long-term), immunosuppressants, anti-cancer, interleukins, systemic interferons, systemic chemotherapy, or other medications that the site investigator feels could have an immune modulatory effect.
5. Does not have HIV-1.
6. Participant was in Fiebig stage VI at the time of study entry.
7. Failure by the participant to attend three consecutive Step 1 study visits.
8. Intercurrent illness, new medical diagnosis, laboratory abnormality, sign, or symptom that, in the opinion of the site investigator, would place participant at higher risk of morbidity during ATI.
9. Pregnancy or breastfeeding.
10. Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.

Step 3:

1. Transfer to A5385 (The Post-Intervention Cohort Study).
2. ART restart in Step 2.
3. Intercurrent illness, new medical diagnosis, laboratory abnormality, sign, or symptom that, in the opinion of the site investigator, would place participant at higher risk of morbidity during analytic treatment interruption.
4. Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.

Step 4:

1\. Unwillingness or inability to restart ART after meeting an ART restart criterion in Step 2 or Step 3.

Where this trial is running

Birmingham, Alabama and 35 other locations

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Acute HIV Infection
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.