Latency Reversing Agents and the Road to an HIV Cure

HIV-1 infection cannot be cured due to the presence of HIV-1 latently infected cells. These cells do not produce the virus, but they can resume virus production at any time in the absence of antiretroviral therapy. Therefore, people living with HIV (PLWH) need to take lifelong therapy. Strategies have been coined to eradicate the viral reservoir by reactivating HIV-1 latently infected cells and subsequently killing them. Various latency reversing agents (LRAs) that can reactivate HIV-1 in vitro and ex vivo have been identified. The most potent LRAs also strongly activate T cells and therefore cannot be applied in vivo. Many LRAs that reactivate HIV in the absence of general T cell activation have been identified and have been tested in clinical trials. Although some LRAs could reduce the reservoir size in clinical trials, so far, they have failed to eradicate the reservoir. More recently, immune modulators have been applied in PLWH, and the first results seem to indicate that these may reduce the reservoir and possibly improve immunological control after therapy interruption. Potentially, combinations of LRAs and immune modulators could reduce the reservoir size, and in the future, immunological control may enable PLWH to live without developing HIV-related disease in the absence of therapy.