A Clinical Trial of Combination HIV-Specific Broadly Neutralizing Monoclonal Antibodies Combined With ART Initiation During Acute HIV Infection to Induce HIV Remission

Inclusion Criteria47

• Step 1:
• Appropriate documentation from medical records of diagnosis of AHI prior to enrollment that includes one of the following:
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• For persons who are able to become pregnant, negative urine or serum pregnancy test within 24 hours prior to study entry.
• 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.
• 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.
• 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.
• Age ≥18 and ≤70 years.
• Ability and willingness to initiate ART at enrollment.
• Ability and willingness to participate in scheduled study visits, including during the ATI, per Schedule of Evaluations (SOE).
• Ability and willingness of participant to provide informed consent.
• Step 2:
• Documented negative hepatitis B virus (HBV) surface antigen (HBsAg) obtained within 16 weeks prior to Step 2 registration.
• Documented negative hepatitis C virus (HCV) antibody (anti-HCV) or negative HCV RNA PCR obtained within 16 weeks prior to Step 2 registration.
• Receipt of full doses of study infusions at enrollment (VRC07-523LS + PGT121.414.LS or placebo \[Sodium Chloride for Injection USP, 0.9%\]).
• HIV-1 RNA \<200 copies/mL obtained within 6 weeks prior to Step 2 registration.
• CD4+ T-cell count ≥450 cells/mm3 obtained within 6 weeks prior to Step 2 registration.
• For participants who are able to become pregnant, negative serum or urine pregnancy test within 48 hours prior to Step 2 entry.
• 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.
• 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.
• Ability and willingness to interrupt ART.
• Completion of Step 1.
• Step 3:
• Has not met ART restart criteria.
• Completion of Step 2.
• Willing to continue ATI.
• 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.
• 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:
• 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.
• 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.
• 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.