Analysis of Telmisartan Administered With Antiretroviral Therapy (ART) in Patients With Acute HIV Infection

HIV Infections Clinical Trial

— SEARCH018  

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]

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02170246
• Other study ID #: 1401013214
• Secondary ID: 1R01NS084911-01W
• Status: Completed
• Phase: Phase 1
• Start date: January 28, 2015
• Est. completion date: June 13, 2018

Study information

• Verified date: March 2020
• Source: Yale University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: June 13, 2018
• Est. primary completion date: June 13, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• Acute HIV Infection
• Communicable Diseases
• HIV Infections
• Infection

Intervention

Drug:
• Telmisartan

Locations

Country	Name	City	State
Thailand	Chulalongkorn University Hospital	Bangkok
Thailand	Thai Red Cross AIDS Research Centre	Bangkok

Sponsors (7)

Lead Sponsor	Collaborator
Yale University	National Institute of Mental Health (NIMH), National Institute of Neurological Disorders and Stroke (NINDS), South East Asia Research Collaboration with Hawaii, University of California, San Francisco, University of Hawaii, Walter Reed Army Institute of Research (WRAIR)

Country where clinical trial is conducted

Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Neopterin is a biological marker of immune activation. Its presence in the CSF provides information on the establishment and persistence of HIV viral reservoirs within the central nervous system of HIV-positive patients.	Change from baseline to 48 weeks following ART initiation
Secondary	Change in levels of mast cell progenitor-1 (MCP-1), IP-10, and HIV RNA in the cerebrospinal fluid (CSF)	Will assess CSF levels of MCP-1, IP-10, and HIV RNA. Absolute levels of these compounds will be compared between subjects on ART + telmisartan versus those on ART only.	Change from baseline to 48 weeks following ART initiation
Secondary	Change in blood plasma levels of neopterin, interleukin-6, D-dimers, soluble cluster of differentiation 14 (sCD14), and soluble cluster of differentiation 163 (sCD163)	Will assess blood plasma levels of these biomarkers in subjects on ART + telmisartan versus those on ART only.	Change from baseline to 48 weeks following ART initiation
Secondary	Change in absolute concentrations and ratios with respect to creatine of choline, myoinositol, and n-acetylaspartate (NAA) in specified brain regions	These measurements will be made using magnetic resonance spectroscopy (MRS).	Change from baseline to 48 weeks following ART initiation
Secondary	Test scores on HIV neuropsychological battery	The assessments to be used in this study have been tested for use with native Thai speakers and will be consistent with other SEARCH study tests. SEARCH employs a HIV neurocognitive battery designed to minimize cultural bias, which has been tested in Bangkok.	Change from baseline to 48 weeks following ART initiation

External Links

•   Website: South East Asia Research Collaboration with Hawaii