Acute HIV Infection, HIV Infections
Conditions
Keywords
Acute HIV infection, Central nervous system, Antiretroviral therapy, Telmisartan, Cerebrospinal fluid
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.
Interventions
DRUGTelmisartan
Sponsors
National Institute of Neurological Disorders and Stroke (NINDS)
SEARCH Research Foundation
University of California, San Francisco
Walter Reed Army Institute of Research (WRAIR)
University of Hawaii
National Institute of Mental Health (NIMH)
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
DOUBLE (Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 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. |
| 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). |
| 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. |
Countries
Thailand
Outcome results
None listed