Early ART to Limit Infection and Establishment of Reservoir

• Status: Active, not recruiting
• Trial end date: 2023-09-08
• Target enrollment: 0
• Participant gender: All

Summary

The study is being done to:

• start ART early in those recently or acutely infected with HIV-1

• see how starting ART as soon as the infection is found affects the amount of HIV-1 in blood and how well the body fights the HIV-1 infection

• look at the amount of HIV-1 DNA (genetic material for HIV-1) seen in CD4+ T-cells (infection-fighting cells in blood) after 48 weeks of ART

• see how early treatment for HIV affects the numbers of HIV-1 infection fighting cells (CD4+ and CD8+ T-cells) in blood

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: AIDS Clinical Trials Group
• Collaborator: National Institute of Allergy and Infectious Diseases (NIAID)
• Treatments: Anti-Retroviral Agents; Cobicistat; Elvitegravir; Emtricitabine; Emtricitabine tenofovir alafenamide; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Tenofovir

Criteria

Inclusion Criteria:

• Appropriate documentation from medical records of diagnosis of acute HIV-1 infection (AHI) within 7 days 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 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

NOTE A: HIV-1 RNA result must be reported from an FDA-approved or CE-marked assay.

NOTE B: Since characterization of Fiebig stage using samples at the time of ART initiation will be performed with results known within 12 weeks based on standardized, centralized testing, an estimated Fiebig group at enrollment based on inclusion criteria as shown in the table above will provide additional real-time monitoring for accruals into each study group. The protocol team will notify the sites if some criteria may no longer be used because accrual is completed in certain Fiebig groups.

NOTE C: Specimens for the testing specified above may be collected on the day of study entry provided the testing result is available prior to enrollment.

• Ability and willingness of candidate to provide written informed consent.

• Ability and willingness to initiate ART at enrollment.

• Ability and willingness to participate in scheduled study visits for up to 72 weeks.

• Female candidates of reproductive potential who are not pregnant at the time of enrollment and who will receive the study-provided EVG/COBI/FTC/TAF and must agree not to participate in the conception process (ie, active attempt to become pregnant, in vitro fertilization), and if participating in sexual activity that could lead to pregnancy, the female candidate must agree to use at least one reliable form of contraceptive while receiving study-provided treatment.

Female candidates are considered to be of reproductive potential if any of the following conditions apply:

• Candidate has experienced menarche.

• Candidate has not undergone bilateral tubal ligation, bilateral oophorectomy, or hysterectomy.

• Candidate has not experienced menopause, defined as lack of menstruation within the preceding 12 months.

Acceptable contraceptive methods include:

• Condoms (male or female) with or without a spermicidal agent

• Diaphragm or cervical cap with spermicide

• Intrauterine device

• Hormonal contraceptive

Female candidates who are not of reproductive potential or whose male partner(s) has documented azoospermia are not required to use contraceptives. Any statement of self-reported sterility or that of her partner must be entered in the source documents.

NOTE: Acceptable documentation of lack of reproductive potential is oral or written documentation from the individual.

Female candidates who are prescribed a non-study-provided ARV regimen should discuss the safety of that regimen during conception and pregnancy with the prescribing physician. Such individuals should follow medical guidance regarding any potential need for contraception while using the non-study-provided ARV regimen.

NOTE: Pregnant and breastfeeding women may enroll in the study provided that they meet the eligibility requirements and have access to non-study-provided ARV regimens.

Exclusion Criteria:

• Positive HIV-1 antibody test ≥90 days prior to study entry.

• Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.

• 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.

• Receipt of an investigational study agent within 28 days prior to enrollment

• Chronic or recurrent use of medications that modify host immune response, eg, oral or parenteral steroids, cancer chemotherapy.

• AHI diagnosis within 60 days after receiving any investigational ARV or HIV-1 vaccine or immune prophylaxis for HIV-1 infection.

• Use of ARVs for pre- or post-exposure prophylaxis within 60 days prior to the diagnosis of AHI.

NOTE: The rationale for this exclusion is to minimize the impact of therapy on the primary endpoint.