Adjunctive Therapy With Telmisartan Instituted With ART During Acute HIV Infection to Reduce the Establishment of CNS Reservoirs of HIV and Lymph Node Fibrosis
Adjunctive Therapy With Telmisartan Instituted With ART During Acute HIV Infection to Reduce the Establishment of CNS Reservoirs of HIV and Lymph Node Fibrosis
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.
Clinical assessments:
Neurological exam: South East Asia Research Collaboration with Hawaii (SEARCH) employs the AIDS Clinical Trials Group (ACTG)-derived HIV macroneurological examination, a physician rated symptoms assessment of cognitive features typical of HAND and peripheral neuropathy
Neuropsychological assessments: SEARCH employs the HIV neurocognitive battery originally developed by Maj et al. designed to minimize cultural bias and tested in Bangkok. All subjects will have the full SEARCH battery as previously published, avoiding evaluations following invasive procedures.
Quantification of Drug use: Drug and alcohol use are assessed with a structured interview including methamphetamine, heroin, and marijuana based on a Thai Red Cross study defining frequently abused drugs in Bangkok. Urine is stored at each visit and may be later tested for illicit drugs. Evidence of intoxication is documented so that neuropsychological data can be censored.
Lumbar punctures are completed per standard clinical procedures using a Sprotte® (pencil-point) needle to minimize complications. Standard assessments of CSF and serum, protein and cell count are completed and approximately 20cc are collected and ultra-centrifuged, Cell pellets of both blood and CSF will be cryopreserved for future potential studies, with subject consent. Supernatants are divided into 0.5cc aliquots, and frozen to -80oC on the same day. Venereal Disease Research Laboratory test (VDRL)/Rapid Plasma Reagin (RPR) will be assessed at baseline and in follow up if risk for new syphilis exposure is reported. Participant hospitalization for hydration will be completed, if needed. Participants will be compensated for their time based on Institutional Review Board (IRB)-approved rates.
Inclusion Criteria:
Exclusion Criteria: