While antiretroviral therapy (ART) has clearly improved life for millions of people living with HIV, ART is not a cure. This is because HIV persists in a dormant or “latent” state in a small number of cells throughout the body. These cells, called “HIV reservoirs,” can become reactivated at any time to produce infectious virus. As a result, people living with HIV must maintain ART for life. Our goal is to achieve a cure for HIV. One promising approach to reduce or eliminate HIV reservoirs involves latency reversing agents (LRAs) to “activate” HIV reservoirs, which can then be eliminated naturally or therapeutically. Unfortunately, this strategy has not yet succeeded in humans. New LRAs are urgently needed that have more activity and are better tolerated by people. To address this, we have taken an unconventional approach to document and characterize extracts and chemical compounds from medicinal plants that are traditionally used to manage infections in Sub-Saharan Africa. We found that one of these extracts (“Mukungulu”, a bark extract of Croton megalobotrys) is a robust LRA in cultures of blood cells taken from donors living with HIV, as well as in mice infected with HIV, with no major toxicities. In this proposal, we are studying how Mukungulu and its major chemical compound (“Namushen-1”) work and how they may affect HIV reservoir-containing cells. Further understanding of Mukungulu and Namushen-1 has the potential for developing new HIV cure therapies and profound impacts on the lives of people living with HIV.
Dr. Ian Tietjen, left, works alongside Tarek Olabi (right) during a Biomedical Technician Training program class at The Wistar Institute. Dr. Tietjen has been working to isolate and extract chemical compounds from medicinal plants as part of a project that may lead to new treatments for HIV. W. W. Smith Charitable Trust Research Project: “Mukungulu: A novel HIV latency reversing agent to reduce persistence of HIV”