SEARCH 018: Adjunctive therapy with telmisartan instituted with ART during acute HIV infection to reduce the establishment of CNS reservoirs of HIV and lymph node fibrosis.
Overview
Current research points toward the establishment of central nervous system (CNS) HIV reservoirs early in HIV infection. HIV has been detected in cerebrospinal fluid (CSF) as early as 8 days after infection. Thus, extremely early intervention may be necessary to prevent establishment of a substantial CNS sanctuary for HIV. We seek to determine whether the establishment of this reservoir might be reduced by strategies aimed to decrease this cellular trafficking as well as maintenance of immune activation within the CNS. In conjunction with antiretroviral therapy (ART), telmisartan therapy has the potential to reduce lymphocyte and monocyte trafficking to the CNS, which can lead to acutely reducing the burden of HIV entering the CNS and limiting the transmigration of inflammatory cells. Furthermore, lymphoid tissue fibrosis may contribute to HIV reservoir persistence. Telmisartan may be able to alleviate the structural damage caused by the lymphoid tissue fibrosis, as it suppresses TGF production, thus preventing collagen deposition in the lymph nodes.
Participants will be recruited from and co-enrolled in SEARCH 010. We will enroll 21 acutely HIV-infected subjects who will be randomized 2:1 to treatment with telmisartan and ART vs. ART alone. Participants will be followed at the Thai Red Cross AIDS Research Centre (TRCARC), a Division of AIDS-certified site in Bangkok, Thailand. Participants will undergo a neurological exam, neuropsychological assessments, quantification of drug use, lumbar punctures, measurement of soluble markers, CSF, blood virology assays, MRI/MRS, and the optional procedure of a lymph node biopsy. Each participant will be followed over the course of 72 weeks.
Current research points toward the establishment of central nervous system (CNS) HIV reservoirs early in HIV infection. HIV has been detected in cerebrospinal fluid (CSF) as early as 8 days after infection. Thus, extremely early intervention may be necessary to prevent establishment of a substantial CNS sanctuary for HIV. We seek to determine whether the establishment of this reservoir might be reduced by strategies aimed to decrease this cellular trafficking as well as maintenance of immune activation within the CNS. In conjunction with antiretroviral therapy (ART), telmisartan therapy has the potential to reduce lymphocyte and monocyte trafficking to the CNS, which can lead to acutely reducing the burden of HIV entering the CNS and limiting the transmigration of inflammatory cells. Furthermore, lymphoid tissue fibrosis may contribute to HIV reservoir persistence. Telmisartan may be able to alleviate the structural damage caused by the lymphoid tissue fibrosis, as it suppresses TGF production, thus preventing collagen deposition in the lymph nodes.
Participants will be recruited from and co-enrolled in SEARCH 010. We will enroll 21 acutely HIV-infected subjects who will be randomized 2:1 to treatment with telmisartan and ART vs. ART alone. Participants will be followed at the Thai Red Cross AIDS Research Centre (TRCARC), a Division of AIDS-certified site in Bangkok, Thailand. Participants will undergo a neurological exam, neuropsychological assessments, quantification of drug use, lumbar punctures, measurement of soluble markers, CSF, blood virology assays, MRI/MRS, and the optional procedure of a lymph node biopsy. Each participant will be followed over the course of 72 weeks.
Collaborators
|
Study Publications
|
Sponsor
|