Phase II Trial of Tesamorelin for Cognition in Aging HIV-Infected Persons

HIV infection can result in memory and thinking difficulties in some people, even those
successfully treated with antiretroviral medications. Tesamorelin is an injectable medication
already approved by the U.S. FDA to treat abdominal fat accumulation in HIV. Abdominal fat
accumulation is linked to memory and thinking difficulties, and previous studies have
suggested that tesamorelin also may be beneficial for memory and thinking, but this has not
been tested in HIV. The aim of this study is to test whether tesamorelin, in combination with
a text-messaging application to help with motivation and adherence, will significantly
improve memory and thinking in HIV. We plan to enroll 100 volunteers with HIV infection at 2
sites - the University of California, San Diego and the University of Southern California and
the satellite site, Borrego Health Stonewall Medical Center. Before entry, volunteers will be
required to show evidence of abdominal obesity and a minimum level of memory and thinking
difficulties on cognitive tests. This is a randomized trial in which each volunteer will have
a 60% chance of initially receiving tesamorelin (the immediate group) and a 40% chance of
initially receiving no treatment (the deferred group). Subsequently, the deferred group
(those who initially received no treatment) will receive tesamorelin for 6 months and those
who initially received tesamorelin will receive no treatment for 6 months. Volunteers will be
trained in the use of a 2-way text-messaging system that will help the research team to
support volunteers' ability to take the study medication as directed. We will measure
volunteers' memory and thinking skills before and at the end of treatment. We will collect
blood at various points during the study to check for safety of the treatment and to
determine its effects on the body. Volunteers will also be asked to have magnetic resonance
scans of the head and abdomen to monitor the effects of the study medication on brain
chemistry and abdominal fat.

Inclusion Criteria:

- HIV-1 infection documented by any FDA licensed clinical test including HIV
enzyme/antigen test or chemiluminescence immunoassay (E/CIA) or plasma HIV-1 RNA viral
load.

- Antiretroviral therapy: Patient currently receiving a combination antiretroviral
therapy (cART) regimen ≥12 weeks with no interruptions longer than 7 days and HIV <500
copies/ml during that time.

- Men or women 40 years of age and older

- Abdominal minimal waist circumference ≥ 95cm for men and ≥94cm for women or minimal
waist to hip ratio of ≥ 0.88 for women (each based on an average of three separate
measurements)

- Screening neuropsychological Global Deficit Score of ≥ 0.35

- The following laboratory values obtained within 90 days prior to entry by any CLIA
certified laboratory.

- Absolute neutrophil count (ANC) ≥750/mm3

- Hemoglobin ≥8.0 g/dL

- Platelet count ≥50,000/mm3

- HgbA1C ≤7.0%

- Calculated creatinine clearance of ≥20 mL/min as estimated by the Cockroft-Gault
formula

- Aspartate aminotransferase (AST) (SGOT), alanine aminotransferase (ALT) (SGPT) <5
X upper limit of normal (ULN) and alkaline phosphatase <3 X upper limit of normal
(ULN) without evidence of active liver disease other than non-alcoholic fatty
liver disease (NAFLD) or hepatitis C requiring treatment.

- Total bilirubin ≤2.5 x ULN (if the participant is receiving atazanavir, a total
bilirubin of ≤5 x ULN is acceptable).

- For females of reproductive potential, negative serum or urine pregnancy test within
30 days prior to entry by any test performed by a CLIA certified laboratory or is
using a point of care (POC)/ CLIA-waived test.

- Contraception requirements: For females of reproductive potential, she or male partner
is willing to use a contraceptive during sexual intercourse.

- Ability and willingness of participant or legal guardian/representative to provide
informed consent

Exclusion Criteria:

- Clinical contraindications

- History of neurocognitive confounding conditions that explain current impairment
including but not limited to stroke, head injury, psychotic disorder, active
substance use disorder by DSM, or opportunistic CNS infection

- Hepatitis C virus infection defined as HCV antibody positive requiring treatment
and plans for treatment during study therapy

- Active or relapsing autoimmune disorder that may require immunotherapy during
this treatment trial

- Active malignancy other than basal or squamous skin cancer.

- Breastfeeding or pregnancy

- Excluded medications used within the last 90 days: active or planned use of rhGH,
anabolic steroids (other than replacement doses of testosterone), anti-TNFa therapy or
other biologic (tocilizumab, Xelijanz, etc.)

- Anticipated need to start new daily anti-inflammatory therapy such as NSAIDs
(excluding aspirin for vascular prophylaxis), systemic corticosteroids, or
anti-malarials, or plan to discontinue regular dosing with these drugs during study
treatment.

- Known allergy/sensitivity or any hypersensitivity to tesamorelin

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

- Acute or serious illness requiring systemic treatment and/or hospitalization within 60
days prior to entry

- Use of tesamorelin in the last 6 months