Combination therapies currently under investigation in phase I and phase II clinical trials for HIV-1

Introduction: HIV infection is manageable through the use of antiretroviral drugs. However, HIV reservoirs that are constituted early during infection are resistant to treatment. HIV persistence under treatment necessitates life-long treatment and is associated with various co-morbidities. Two significant research avenues are explored through the development of either new antiretroviral drugs or interventions aimed at stimulating the immune system to eradicate HIV reservoirs. Areas covered: This report provides a review of investigational drugs and cell-based interventions against HIV infection that are currently under Phase I or Phase II clinical trials. We report on new antiretroviral drugs, antibodies directed against viral or host targets, reactivating agents, immune modulators and immune checkpoint inhibitors, and cell-based interventions. These new therapies are often tested in combination, including with current antiretroviral drugs. Expert opinion: Islatravir and GS-6207 are promising antiretroviral drugs that are expected to perform well in phase III trials. Whether the host immune system can be activated sufficiently to reduce HIV reservoirs remains unknown. Additional research is needed to identify surrogate markers of success for curative interventions. Given the current safety and efficacy of antiretroviral treatment, risk-benefits should be carefully evaluated before interventions that risk triggering high levels of immune stimulation.