Role of Integrase Strand Transfer Inhibitors on Hypertension in People with HIV

About This Grant

PROJECT SUMMARY / ABSTRACT People with HIV on antiretroviral therapy (ART) have a higher prevalence of hypertension than HIV seronegative adults. In the last decade, integrase strand transfer inhibitors (INSTIs) have become the preferred ART class to pair with nucleoside reverse transcriptase inhibitors (NRTIs) to durably suppress viremia in people with HIV. In addition, INSTI-based ARTs and NRTIs backbone agents like tenofovir alafenamide (TAF) are associated with higher BP and increased incidence of hypertension compared with non-INSTI-based ART. Potential mechanisms contributing to higher blood pressure (BP) in people with HIV include off-target effects of ART. INSTI-based ARTs and NRTIs backbone agents like TAF are associated with weight gain, which may lead to chronic conditions including hypertension. Besides traditional risk factors, HIV conditions may also increase the risk of developing hypertension. However, unknown is the incidence of hypertension, if weight gain is a mechanism of hypertension incidence and if HIV and non-HIV risk factors cause hypertension incidence across different INSTI- based ARTs, especially second generation (which are more commonly used) including bictegravir and dolutegravir-based ART overall and with NRTI backbone combinations including TAF, tenofovir disoproxil fumarate (TDF) and others. The objective of the proposed study is to assess hypertension incidence in ART naïve people with HIV after initiation of bictegravir versus dolutegravir-based ART overall and with NRTI combinations (Aim 1); determine if weight gain is associated with incident hypertension in ART naïve people with HIV initiating bictegravir and dolutegravir-based ART overall and with NRTI combinations (Aim 2); and determine if HIV and non-HIV risk factors for incident hypertension in ART naïve people with HIV initiating bictegravir and dolutegravir-based ARTs (Secondary aim). The proposed study, titled “Role of Integrase Strand Transfer Inhibitors on Hypertension in People with HIV” will achieve the aims by analyzing data from Center for AIDS Research Network (CFAR) of Integrated Clinical Systems (CNICS) study. The proposed study is unique in that it will leverage the CNICS study, a well-established diverse large cohort of patients with HIV, that includes clinical data and patient-reported outcomes from 10 sites across the US. The study will evaluate hypertension incidence, weight gain as a mechanism and risk factors (HIV and non-HIV) within 2 years after initiation of bictegravir and dolutegravir-based ART overall and with NRTI combinations from 2018 to 2023.The proposed study can inform strategies to prevent and manage hypertension in people with HIV on second generation INSTIs-based ART. We anticipate that the results from this study will prepare us to propose and lead R01 grants testing risk factors, mechanisms and interventions to prevent the development of hypertension and reduce cardiovascular risk in people with HIV taking INSTI-based ART.