Evaluation of Safety, Immunogenicity and Efficacy of a Triple Immune Regimen in Adults Initiated on ART During Acute HIV-1

Launched by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES (NIAID) · Oct 4, 2023

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment approach for adults with HIV-1 who started their antiretroviral therapy (ART) during the early stages of infection. The goal is to evaluate the safety and effectiveness of a combination of vaccines and antibodies, along with a medication that helps stimulate the immune system. By giving this treatment, the researchers hope to see if it can help control the virus when participants temporarily stop their usual medication.

To join the study, participants need to be adults who started ART within 28 days of being diagnosed with HIV and have been stable on their treatment for at least 6 weeks. They should have a good immune system, indicated by specific blood tests, and must agree to follow the study guidelines. Participants will receive either the active treatment or a placebo (a treatment that looks the same but has no active ingredients) and will be closely monitored throughout the trial. It's important for potential participants to understand that they need to commit to attending all study visits and adhere to the treatment plan.

Gender

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Eligibility criteria

• • Inclusion Criteria
• • Provision of written informed consent.
• • History of Initiation of combination ART within 90 days of acute HIV diagnosis
• • No known ART interruption \>14 consecutive days since initiation of ART.
• • ART with an integrase inhibitor-based regimen with two NRTIs or dolutegravir/lamivudine regimen for at least 6 weeks prior to study entry.
• • Willingness to participate in the ATI and willingness to restart ART according to study guidelines.
• • Willingness to adhere to protocol therapy and complete all study visits.
• • Weight ≥50 kg and ≤150 kg at Screening.
• • CD4 cell count ≥500 cells/mm3 obtained within 60 days prior to study Entry.
• • HIV-1 RNA \<50 copies/mL (or below the assay limit of quantification if local assay lower limit of quantification is \>50 copies/mL) since initial viral suppression on ART and for at least 1 year and within 60 days prior to study Entry.
• • Select laboratory results within 60 days of study entry
• • For cisgender women and transgender men of reproductive potential, negative urine or serum pregnancy test within 48 hours prior to or at study Entry.
• • Participants who are able to become pregnant and who are engaging in sexual activity that could lead to pregnancy must agree to use two methods of contraception, one of which must be a highly effective methods for contraception. Barrier methods of contraception are required for the second method of contraception.
• • Availability of results of HLA typing (required for randomization).
• • Completion of pre-entry leukapheresis or LVBD.
• • Exclusion Criteria
• • Currently pregnant or breastfeeding or planning to become pregnant during study participation.
• • Prior receipt of anti-HIV broadly neutralizing antibody therapy.
• • Receipt of any non-HIV monoclonal antibody therapy within 1 year prior to study entry.
• • Prior receipt of a latency-reversing agent (LRA).
• • Receipt of HIV-1 or other investigational vaccines within 6 months prior to study Entry.
• • Receipt of a live-virus vaccine within 60 days or any vaccination within 14 days prior to entry.
• • Prior receipt of any simian adenovirus-vectored vaccine (e.g., anti-COVID-19 AZD1222).
• • Known allergy/sensitivity or any hypersensitivity to components of study treatments or their formulations.
• • Known severe chicken egg allergy.
• • Known history of a severe reaction or anaphylaxis to prior vaccinations or antibody preparations (e.g., intravenous immunoglobulin).
• • Significant drug sensitivity or drug allergy (such as anaphylaxis or hepatoxicity).
• • Any history of anaphylaxis and related symptoms such as hives, respiratory difficulty, or angioedema.
• • Previous or current history of bleeding factor deficiency, coagulopathy or platelet disorder or on chronic anticoagulation.
• • History of inflammatory neurologic diseases.
• • History of pregnancy, head trauma or major surgery within 90 days prior to study Entry.
• • History of use of any immunomodulatory medications within the 6 months prior to study entry.
• • Significant serious skin disease, such as but not limited to active rash, eczema, psoriasis, or urticaria.
• • Autoimmune disease (e.g., lupus, multiple sclerosis, and others) requiring ongoing immunosuppression.
• • Known history of CDC Stage 3 opportunistic infection (OI).
• • Any history of an HIV-associated malignancy.
• • Known or suspected active or untreated latent Mycobacterium tuberculosis infection.
• • Active or recent non-HIV-associated malignancy.
• • Serious illness requiring systemic treatment and/or hospitalization within 90 days prior to study entry.
• • Known resistance to one or more drugs in two or more ARV drug classes.
• • History of or current clinical atherosclerotic cardiovascular disease
• • Current advanced liver disease.
• • Use of complementary or alternative medicines within 14 days prior study entry.