Enhancement by Poly-ICLC During HIV-1 Infection
Condition: HIV-1 Infected Adults With Chronic HIV-1 Infection
MeSH terms: Infections; Communicable Diseases; HIV Infections
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      This study involves researching new approaches to treating HIV infection. Currently, HIV
      infection is treated with combinations of drugs called antiretrovirals. These drugs protect
      cells from infection by interfering with the viruses' ability to make copies of itself by
      infecting new target cells. Though these drugs are very effective, they cannot cure HIV
      infection and must be taken each and every day at prescribed doses to maintain their
      beneficial effect. This research study is investigating a new approach that involves an
      addition to existing medications.

      The study is investigating a medication called Poly-ICLC (Hiltonol®, Oncovir), which is an
      adjuvant. Adjuvants are medications that are designed to boost your body's immune responses
      resulting from a vaccine. The investigators want to test whether Poly-ICLC is an adjuvant
      that is effective in HIV-infected patients. A vaccine is not given in this study, but just
      investigating the adjuvant, Poly-ICLC, to determine whether it may be safe and useful in
      future vaccines that could be used to treat HIV, called therapeutic vaccines. One goal of
      future therapeutic vaccines is to reduce the virus that remains persistently inside of cells
      in a dormant or resting state despite treatment with HIV medications. This persistent pool is
      termed the "latent virus pool" or "viral reservoir". One tactic to reduce this viral
      reservoir is to first stimulate HIV to start replicating in order to force it out of hiding.
      Once viral replication occurs, the infected cells may then be recognized and killed by cells
      of the immune system. Therefore, we also want to see what effect Poly-ICLC has on the virus
      that lives inside of cells. Specifically, the investigators want to look at whether Poly-ICLC
      increases the level of virus inside your cells while also improving your immune system's
      responses.

      The investigators are doing this research in hope to find new ways to treat HIV infection
      that may reduce exposure to medications that are called antiretrovirals. Antiretrovirals are
      medications used to treat HIV infection. They are very effective but have side effects and
      have to be taken each and every day and cannot cure HIV.
    

Detailed description: 
      Effective combination antiretroviral therapy (cART) has dramatically altered the morbidity
      and mortality associated with human immunodeficiency virus (HIV-1) infection. Nevertheless,
      the current treatment paradigm of lifelong antiviral therapy with near perfect patient
      adherence to avoid the emergence of drug resistant HIV remains less than ideal and this
      therapeutic approach has clear limitations.

      In addition to long term toxicities associated with currently preferred therapies,
      combination therapy for HIV-1 infection cannot address the issue of viral persistence. HIV-1
      persists in both blood and tissue despite long-term suppression with antiretroviral agents
      (ARVs). Eradication strategies for HIV-1 are likely to require a multi-faceted approach to
      reduce the latent reservoir, with key components focusing upon both the disruption of viral
      latency and the enhancement of cytotoxic T lymphocyte (CTL) function to promote killing of
      infected cells. In order to successfully achieve these objectives, agents that safely
      stimulate replication of the latent reservoir AND explore approaches to enhance HIV-specific
      adaptive immunity to augment CTL function must be investigated. The investigators propose
      that this may be accomplished with a single therapeutic modality that is devised
      appropriately. Certain adjuvants may possess immunostimulatory properties that trigger
      transient activation of viral transcription while simultaneously enhancing HIV-specific CTL
      function and, thus, may play an important role in such a vaccine.

      Here, the investigators propose a proof of concept clinical trial to determine the ability of
      Poly-ICLC (Hiltonol®, Oncovir), to safely activate the latent viral reservoir and enhance
      innate immunity when administered to HIV-infected individuals. This randomized,
      double-blinded, placebo-controlled study will administer two doses of Poly-ICLC to
      HIV-infected individuals whom are virologically suppressed on combination anti-retroviral
      therapy (cART). The investigators hypothesize that Poly-ICLC will be safe and well-tolerated
      and will transiently disrupt viral latency while enhancing innate immune responses. Should
      this be the case, then Poly-ICLC would be an ideal modality to combine with a therapeutic HIV
      vaccine to reduce the number of latently infected CD4+ T cells in treated HIV-1 infected
      individuals.
    

Intervention name(s): Arm A: Poly-ICLC; Arm B: Normal Saline
Intervention type(s): Drug; Drug
Intervention description(s): Poly-ICLC (Hiltonol®, Oncovir) Administration - On days 1 and 2, patients randomized to this arm will be injected subcutaneously in the arm with 1.4 mg of Poly-ICLC (Hiltonol®, Oncovir). Each subject will receive a total of 2 SC doses of Poly-ICLC. The volume of each injection is 0.7ml. The investigators who are blinded will not be present at the time of injection by the study nurse.; Normal Saline - On days 1 and 2, patients randomized to this arm will be injected subcutaneously in the arm with normal saline obtained from the Rockefeller University Pharmacy. Each subject will receive a total of 2 SC doses of normal saline. The volume of each injection is 0.7ml. The investigators who are blinded will not be present at the time of injection by the study nurse.
Other intervention name(s): Poly-ICLC (Hiltonol®, Oncovir); Placebo
Intervention MeSH terms: Poly I-C; Carboxymethylcellulose Sodium; Poly ICLC
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Human immunodeficiency virus 1; Combined Antiretroviral Therapy; Poly-ICLC; Adjuvant