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

Phase 1

Completed

• Conditions: Acute HIV Infection; HIV Infections
• Interventions: Drug: Telmisartan

• Registration Number: NCT02170246
• Lead Sponsor: Yale University

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.

Study Timeline

• Study First Submitted: 2014-05-22
• Study First Submitted QC: 2014-06-19
• Study First Posted: 2014-06-23
• Study Start: 2015-01-28
• Primary Completion: 2018-06-13
• Study Completion: 2018-06-13
• Status Verified: 2020-03
• Last Update Submitted: 2020-03-04
• Last Update Posted: 2020-03-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 21

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ART + Telmisartan	Telmisartan	Acute HIV-infected subjects (n=14) will be randomly assigned to a group that will receive treatment with telmisartan in addition to ART. Subjects will receive 40mg telmisartan daily for 4 weeks, followed by 80mg telmisartan daily for 44 weeks, to be taken in conjunction with ART. Subjects unable to tolerate 80mg of telmisartan will be able to de-escalate to 40mg daily. After telmisartan is stopped, subjects will continue to take ART for an additional 24 weeks (total 72 weeks).

Primary Outcome Measures

Name	Time	Method
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	Change from baseline to 48 weeks following ART initiation	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.

Secondary Outcome Measures

Name	Time	Method
Test scores on HIV neuropsychological battery	Change from baseline to 48 weeks following ART initiation	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 in levels of mast cell progenitor-1 (MCP-1), IP-10, and HIV RNA in the cerebrospinal fluid (CSF)	Change from baseline to 48 weeks following ART initiation	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 in absolute concentrations and ratios with respect to creatine of choline, myoinositol, and n-acetylaspartate (NAA) in specified brain regions	Change from baseline to 48 weeks following ART initiation	These measurements will be made using magnetic resonance spectroscopy (MRS).
Change in blood plasma levels of neopterin, interleukin-6, D-dimers, soluble cluster of differentiation 14 (sCD14), and soluble cluster of differentiation 163 (sCD163)	Change from baseline to 48 weeks following ART initiation	Will assess blood plasma levels of these biomarkers in subjects on ART + telmisartan versus those on ART only.

Trial Locations

Locations (2)

Chulalongkorn University Hospital; 🇹🇭 Bangkok, Thailand

Thai Red Cross AIDS Research Centre; 🇹🇭 Bangkok, Thailand