Clinical trial NCT02170246: Analysis of Telmisartan Administered With Antiretroviral Therapy (ART) in Patients With Acute HIV Infection
Official title: Adjunctive Therapy With Telmisartan Instituted With ART During Acute HIV Infection to Reduce the Establishment of Central Nervous System Reservoirs of HIV and Lymph Node Fibrosis [Southeast Asia Research Collaboration With Hawaii (SEARCH) 018]
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Acute HIV Infection
HIV Infections
Keywords: Acute HIV infection
Central nervous system
Antiretroviral therapy
Telmisartan
Cerebrospinal fluid
Lead sponsor: Yale University
Sponsor class: OTHER
Collaborators: name: National Institute of Neurological Disorders and Stroke (NINDS)
name: SEARCH Research Foundation
name: University of California, San Francisco
name: Walter Reed Army Institute of Research (WRAIR)
name: University of Hawaii
name: National Institute of Mental Health (NIMH)
First posted: 2014-06-23
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: This research project will study whether the drug telmisartan administered in conjunction with antiretroviral therapy (ART) will help reduce nervous system infection with HIV. The investigators are studying the effect of this treatment in people who have contracted HIV infection within the past three weeks, and thus have a form of HIV called acute HIV infection. The investigators will measure biological markers of immune activation in the blood and cerebrospinal fluid to see if telmisartan may reduce the spread of HIV reservoirs in affected patients.

Detailed description: Note regarding the primary purpose of the study: In the Study Design section, this protocol is classified as "Other", since it is specifically designed to examine the effect of telmisartan administered in conjunction with ART on the size of HIV reservoirs in the central nervous system.

Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years old
* Have protocol-defined acute HIV-1 infection
* Be part of the SEARCH 010/RV 254 study in Bangkok, Thailand
* Ability and willingness to start ART immediately after diagnosis
* Availability for follow-up for the duration of the planned study
* Systolic blood pressure ≥ 110 mmHg
* Agree to undergo lumbar puncture at weeks 0, 48 and 72
* Ability and willingness to provide informed consent. Subjects must understand the study and sign the consent form. Persons who cannot read will have the consent form read to them by a member of the study staff and may then give informed consent by using making a thumb print.

Exclusion Criteria:

* Pregnancy (current or within the last 6 months) or breastfeeding
* Uncontrolled hypertension
* Use of thiazolidinediones or other angiotensin receptor blockers class \[losartan, irbesartan, olmesartan, valsartan, candesartan (washout permitted)\]
* Screening laboratory values: absolute neutrophil count \< 750 cells/mm3, hemoglobin \<10 gm/dL creatinine clearance \<30 mL/min (estimated by the Cockcroft-Gault equation using ideal body weight)
* Known renal artery stenosis
* Known cirrhosis or severe liver disease
* Unstable coronary artery disease/angina or decompensated congestive heart failure
* Any history of intolerance to any angiotensin receptor blocker
* Need for ongoing potassium supplementation
* Any contraindication to lumbar puncture such as history of bleeding diathesis or cerebral mass lesion

Primary outcomes:
measure: Change in level of neopterin in the cerebrospinal fluid (CSF) of patients placed on antiretroviral therapy (ART) administered in conjunction with telmisartan, versus those placed on ART only
timeFrame: Change from baseline to 48 weeks following ART initiation
Secondary outcomes:
measure: Change in levels of mast cell progenitor-1 (MCP-1), IP-10, and HIV RNA in the cerebrospinal fluid (CSF)
timeFrame: Change from baseline to 48 weeks following ART initiation
measure: Change in blood plasma levels of neopterin, interleukin-6, D-dimers, soluble cluster of differentiation 14 (sCD14), and soluble cluster of differentiation 163 (sCD163)
timeFrame: Change from baseline to 48 weeks following ART initiation
measure: Change in absolute concentrations and ratios with respect to creatine of choline, myoinositol, and n-acetylaspartate (NAA) in specified brain regions
timeFrame: Change from baseline to 48 weeks following ART initiation
measure: Test scores on HIV neuropsychological battery
timeFrame: Change from baseline to 48 weeks following ART initiation
Other outcomes:
Locations:
city: Bangkok
country: Thailand
facility: Chulalongkorn University Hospital
city: Bangkok
country: Thailand
facility: Thai Red Cross AIDS Research Centre
Study officials:
affiliation: Yale University
name: Serena Spudich, MD, MA
role: PRINCIPAL_INVESTIGATOR
affiliation: U.S. Military HIV Research Program, Bethesda, Maryland
name: Jintanat Ananworanich, MD, PhD
role: STUDY_CHAIR
affiliation: Thai Red Cross AIDS Research Centre, Bangkok, Thailand
name: Nittaya Phanuphak, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: