Tripe Versus Dual Antiretroviral Therapy in HIV-infected Patients With Virological Suppression (Tridual)

Summary

The persistence of an aberrant state of immune activation and inflammation (pIA) may contribute to the emergence of serious non-AIDS events which carry a higher morbimortality in HIV-infected patients. Although combined antiretroviral treatment (cART) reduces both cellular and soluble activation markers, it fails to completely control pIA despite consistent plasma viral load suppression. One of the mechanisms involved in pIA is may be an incomplete suppression of viral replication not reflected by plasma viral load, which only reflects a balance between viral replication and clearance of HIV-RNA. In addition, low-level viremia detected in most HIV-1-infected patients despite years on cART. Unintegrated 2-LTR HIV-DNA, and cellular associated HIV-RNAs, as products of active integrated DNA transcription, support this issue. Furthermore, the key rationales behind simplifying cART are a reduction of toxicities, lower risk of resistance mutations in case of virological failure and saving costs. One of these simplification strategies is a dual therapy which, based on the data up to date and in our clinical experience, has similar virological efficacy than cART. However, it is unknown if this strategy could increase the persistent HIV-1 replication and, therefore, pIA. The CD4+/CD8+ T cell ratio as a marker of immune recovery, the changes in T cell immune activation, senescence, exhaustion and apoptosis, and the cellular associated HIV-DNA and -RNA would answer the question if simplification to dual therapy would provide less control of residual HIV replication and, therefore, a detriment on pIA compared to triple therapy and, therefore, would worsen the patients' long-term prognosis.

Timeline

Start

2017-06-01

Primary completion

2020-09-15

Completion

2021-02-03

Publications

• Munoz-Muela E, Trujillo-Rodriguez M, Serna-Gallego A, Saborido-Alconchel A, Ruiz-Mateos E, Lopez-Cortes LF, Gutierrez-Valencia A. HIV-1-specific T-cell responses and exhaustion profiles in people with HIV after switching to dual therapy vs. maintaining triple therapy based on integrase inhibitors. Biomed Pharmacother. 2023 Dec;168:115750. doi: 10.1016/j.biopha.2023.115750. Epub 2023 Oct 21.

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