Using Telmisartan With ART During Acute HIV Infection to Reduce the CNS Reservoirs of HIV and Lymph Node Fibrosis

• Status: Completed
• Trial end date: 2018-02-01
• Target enrollment: 0
• Participant gender: All

Summary

Primary objective: To compare telmisartan therapy + antiretroviral therapy (ART) versus ART alone during acute Human Immunodeficiency Virus (HIV)a infection in reducing systemic immune activation and trafficking of activated and HIV-infected cells to the central nervous system (CNS), and limiting establishment and persistence of the CNS reservoir of HIV.

At 48 weeks (during the telmisartan therapy) and 72 weeks (~6 months after cessation of telmisartan augmentation), the investigator expect subjects in the telmisartan group will have reduced levels of blood and CSF immune activation markers, reduced brain inflammation, lower CSF HIV ribonecleic acid (RNA) and improved neuropsychological testing performance.

Secondary objective: In subjects who are willing to undergo the optional inguinal lymph node biopsy, the study will determine whether subjects receiving telmisartan plus ART for 48 weeks develop less lymphoid tissue fibrosis than subjects receiving ART alone for 48 weeks.

Subject population: Male and female subjects age ≥ 18 years old with acute HIV infection who are identified and enrolled in SEARCH 010/RV254 protocol will be asked to co-enroll in this study.

Number of subjects: 21

Duration of follow-up: 72 weeks

Study design: 21 acutely HIV-infected subjects will be randomized 2:1 to treatment with telmisartan + ART (n=14) vs. ART alone (n=7) for the first 48 weeks followed by ART alone in both arms to week 72. Blood and CSF, magnetic resonance imaging (MRI), and neuropsychological testing and exam will be collected at baseline, week 48 and week 72. Inguinal lymph node biopsy is an optional procedure that will be offered at baseline and week 48.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: South East Asia Research Collaboration with Hawaii
• Collaborator: National Institute of Neurological Disorders and Stroke (NINDS)
• Treatments: Efavirenz; Lamivudine; Telmisartan; Tenofovir

Criteria

Inclusion Criteria:

1. Age ≥ 18 years old

2. Have protocol-defined acute HIV-1 infection (Tested 4th generation HIV enzyme immunoassay [EIA] negative and NAT positive or tested 4th generation HIV EIA positive, negative by less sensitive EIA and nucleic acid testing [NAT] positive)

3. Be part of the SEARCH 010/RV 254 study

4. Ability and willingness to start ART immediately after diagnosis

5. Understand the study and sign informed 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

6. Availability for follow-up for the duration of the planned study

7. Systolic blood pressure ≥ 110 mmHg

8. Agree to undergo lumbar puncture at weeks 0, 48 and 72

9. Ability and willingness to provide informed consent

Exclusion Criteria:

1. Pregnancy (current or within the last 6 months) or breastfeeding

2. Uncontrolled hypertension

3. Use of thiazolidinediones or other angiotensin receptor blockers class [losartan, irbesartan, olmesartan, valsartan, candesartan (washout permitted)]

4. Screening laboratory values: absolute neutrophil count (ANC) < 750 cells/mm3, hemoglobin <10 gm/dL creatinine clearance<30mL/min (estimated by the Cockcroft-Gault equation using ideal body weight)

5. Known renal artery stenosis

6. Known cirrhosis or severe liver disease

7. Unstable coronary artery disease/angina or decompensated congestive heart failure

8. Any history of intolerance to any angiotensin II receptor blocker (ARB)

9. Need for ongoing potassium supplementation

10. Any contraindication to lumbar puncture such as history of bleeding diathesis or known cerebral mass lesion