Analysis of Telmisartan Administered With Antiretroviral Therapy (ART) in Patients With Acute HIV Infection (SEARCH018)

Yale University

Status and phase: Completed; Phase 1

Conditions: Acute HIV Infection; HIV Infections

Treatments: Drug: Telmisartan

Study type: Interventional

Funder types: Other; Other U.S. Federal agency; NIH

Identifiers

NCT02170246

W81XWH-11-2-0174 (Other Identifier)

R01MH095613 (U.S. NIH Grant/Contract)

1401013214

R01MH104141 (U.S. NIH Grant/Contract)

1R01NS084911-01 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 21 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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21 participants in 2 patient groups

Antiretroviral Therapy (ART) only

No Intervention group

Description:

Acute HIV-infected subjects (n=7) will be randomly assigned to a group that will receive antiretroviral therapy (the current standard of care for HIV patients) for 72 weeks.

ART + Telmisartan

Experimental group

Description:

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).

Treatment:

Drug: Telmisartan