Effect of Methamphetamine on Residual Latent HIV Disease Study
Condition: HIV-1-infection; Methamphetamine-dependence
MeSH terms: Acquired Immunodeficiency Syndrome; HIV Infections
Study type: Interventional
Phase: Phase 4

Summary: 
      The most commonly used illicit stimulant in HIV-infected individuals is methamphetamine (MA).
      Prior studies demonstrate strong evidence that MA promotes increased HIV transcription as
      well as immune dysregulation. A challenge in achieving worldwide HIV eradication is targeting
      specific marginalized populations who are most likely to benefit from an HIV cure but possess
      poorer immune responses. For this study, HIV+ infected ART-suppressed individuals with no
      prior history of MA use disorder will be administered oral methamphetamine (the maximum FDA
      approved daily dose for the treatment of childhood obesity) to determine the effects of
      short-term MA exposure on residual virus production, gene expression, and inflammation.
      Measures of MA exposure in urine and serum will then be associated with residual virus
      production, gene expression, cell surface immune marker protein expression, and systemic
      markers of inflammation. The clinical trial data will generate advanced gene expression and
      immunologic data to identify potential novel targets for reversing HIV latency, reducing
      inflammation, and personalizing future therapies in HIV+ individuals who use MA.
    

Detailed description: 
      The most commonly used illicit stimulant in HIV-infected individuals is methamphetamine (MA),
      and prior studies demonstrate strong evidence that MA promotes increased HIV transcription as
      well as immune dysregulation. HIV cure has emerged as an important clinical and research
      priority given evidence of ongoing immune dysfunction in HIV-infected individuals despite
      effective antiretroviral therapy (ART). A challenge in achieving worldwide HIV eradication is
      targeting specific vulnerable populations who are most likely to benefit from an HIV cure but
      possess poorer immune responses as a result of residual viral replication due to suboptimal
      ART adherence and/or direct immune dysfunction from illicit substance use. Prior non-human
      studies demonstrate that MA directly induces HIV production and promotes immune activation
      and inflammation. These preclinical findings suggest that HIV+ individuals who use MA may
      experience greater immune dysfunction and face additional challenges for future HIV
      eradication. This study will investigate the effects of short-term MA exposure in HIV+
      ART-suppressed individuals without a prior history of MA use. Participants will be enrolled
      in an interventional study where they will be administered oral methamphetamine (the maximum
      FDA approved daily dose for the treatment of childhood obesity) to determine the effects of
      short-term MA exposure on residual virus production, gene expression, inflammation, and trace
      amine-associated 1 (TAAR1, a promising drug target for psychostimulant addiction) signaling.
      MA exposure will be quantified with multiple serum samples collected over a 24-hour
      monitoring period and associated with residual viral transcription, host gene and cell
      surface protein expression, and inflammation (plasma inflammatory cytokine levels)
      quantification. The proposed study will be the first human genetic study to directly evaluate
      the effect of MA exposure on residual viral transcription during effective ART. The overall
      goals of the study are to integrate a rigorous clinical study designs with high throughput
      'omics data to identify novel targets for reversing HIV latency, reducing inflammation, and
      personalizing future therapeutic strategies specific to HIV+ ART-suppressed individuals who
      use MA.
    

Intervention name(s): Oral Methamphetamine; Placebo oral capsule
Intervention type(s): Drug; Other
Intervention description(s): In this phase IV open label double-blind randomized crossover study, participants will be randomized to either of two treatment arms, oral methamphetamine or placebo, using a crossover design with a 31-day washout period in between treatment arms. For the oral methamphetamine treatment arm, an initial 10 mg of oral methamphetamine (over-encapsulated to look similar to placebo capsule) study drug will be administered to assess tolerability, followed by a subsequent 15 mg oral dose (over-encapsulated to look similar to placebo capsule) two hours later.; In this phase IV open label double-blind randomized crossover study, participants will be randomized to either of two treatment arms, oral methamphetamine or placebo, using a crossover design with a 31-day washout period in between treatment arms. For placebo treatment phase, one placebo capsule will be administered orally on treatment day, followed by a second oral placebo capsule two hours later.
Other intervention name(s): Desoxyn; Placebo
Intervention MeSH terms: Methamphetamine
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: This is a phase IV open label randomized, double-blinded, placebo-controlled crossover study. A placebo treatment arm will be assigned to participants in a randomized crossover design. HIV+ ART-suppressed individuals with no prior history of MA use disorder will be administered 10mg oral methamphetamine hydrochloride, followed by 15 mg methamphetamine hydrochloride two hours later, for a total of 25mg in one 24-hour period (the maximum FDA approved daily dose for the treatment of childhood obesity). Participants will complete the study twice (once on a placebo treatment arm and once with the oral methamphetamine treatment arm). Which treatment arm occurs first will be randomly assigned and will include a 31-day washout period between the two phases.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: HIV; methamphetamine; viral transcription; inflammation