Multi Interventional Approaches to Mitigate HIV Reservoirs for the Sustained HIV Remission Without Antiretrovirals

Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18-65
SponsorFederal University of São Paulo

About this trial

A modern and urgent challenge in fighting HIV infection is to achieve sustained HIV remission without the use of antiretrovirals. The investigators' preliminary data indicate that the use of combined strategies to mitigate the HIV proviral reservoir size among individuals with suppressive antiretroviral treatment achieved unprecedented results in the reduction of HIV DNA present in these cells and in the reduction of CD4 + and CD8 + T cell activation. Combined interventions include intensified antiretroviral treatment to mitigate residual HIV replication, use of a histone deacetylase inhibitor to interrupt viral latency, use of an anti-proliferative medication to reduce long-lived T cells that harbor HIV and a personalized dendritic cell therapy vaccine to eliminate cells with latent HIV infection or cells present in viral sanctuaries. Due to the good results obtained in the exploratory stage of the project, the investigators propose to expand it by recruiting a larger number of patients to confirm the previously obtained results and to generate new insights related to the mechanisms involved in viral latency, latency disruption and the effects of analytical treatment interruption of antiretrovirals among patients undergoing all above mentioned interventions.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

None

Disqualifiers

None

Trial design

Design model

Parallel

Treatments tested in this trial

  • Maraviroc

    Drug

    antiretroviral intensification

  • Dolutegravir

    Drug

    antiretroviral intensification

  • Dendritic Cell Vaccine

    Biological/Vaccine

    therapeutic vaccination

  • Auranofin

    Drug

    purging

  • Sirtuin Histone deacetylase inhibitor

    Drug

    latency disruption

Treatment groups

70 Participants
are divided into 2 treatment groups
Group A: Antiretroviral Treated (ART) GroupNo intervention 0 interventions
Group B: ART Intensification GroupExperimental treatment 5 interventions

Trial outcomes

Primary outcomes

1

Evolution of viral load of HIV RNA over the time frame of study

Viral load count by qPCR at each time point to measure the viral persistence in each participant

Time frame
baseline, weeks 12, 24, 36 and 48 and every 3 weeks after the antiretroviral ATI up to 36 months after antiretroviral ATI
2

Evolution of total DNA and episomal HIV in PBMCs

Quantification of total DNA and episomal HIV in a virological assay

Time frame
baseline, weeks 12, 24, 36 and 48 and every 3 weeks after the antiretroviral ATI up to 36 months after antiretroviral ATI
3

Evolution of cell-associated HIV RNA in PBMCs over the study time frame

Quantification of HIV RNA in PBMCs by qPCR

Time frame
baseline, weeks 12, 24, 36 and 48 and every 3 weeks after the antiretroviral ATI up to 36 months after antiretroviral ATI
4

Evolution of total DNA and episomal HIV DNA in lymphoid tissue (rectal biopsy)

Quantification by in-house virological assay

Time frame
baseline, week 48, after resurgence of viremia in the analytical interruption of antiretrovirals, or after 24 and 96 weeks after analytical interruption of antiretrovirals.

Secondary outcomes

Other outcomes

Sponsors and contacts

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Federal University of São Paulo

Lead sponsor

Conselho Nacional de Desenvolvimento Científico e Tecnológico

Collaborator

Weill Medical College of Cornell University

Collaborator

Fundação de Amparo à Pesquisa do Estado de São Paulo

Collaborator