Abstract Body

The ‘pipeline’ of candidate anti-HIV drugs includes novel classes, novel mechanisms of action, biologics and broadly neutralizing monoclonal antibodies. Formulations under development include a diverse range of options such as long-acting oral weekly products and implants capable of providing treatment for several months. Patient acceptability survey outcomes of LA/ER injectable Cabotegravir-Rilpivirine in phase III trials have been very positive. Importantly, drugs are also being developed for patients with extensive anti-viral resistance. Moving towards the future, it is important to examine the efficacy of current ART regimes in first line therapy and beyond, including when switching virologically suppressed patients. In 2018, is efficacy driven mainly by virological factors (high baseline viral load and emergence of resistance) or by tolerability and simplicity? How do we address the data gaps in RCTs, which largely enroll well, young male patients and very few women, transgender, co-infected, complex or ethnically diverse patients? With a future moving towards reducing drug exposure can we ‘simplify’ ART? Near-normal life expectancy of people living with HIV makes it ever more important to use regimens that safeguard against future comorbidity. Advances in the triple therapy TAF-based backbone have reduced treatment-related discontinuations related to bone and renal toxicity, while maintaining efficacy rates of > 90% in treatment-naïve studies. Second generation integrase inhibitors, recommended in the first-line guidelines of ALL well-resourced settings, have reduced emergent resistance toward zero and offer options which avoid booster-related drug interactions. Successful ART simplification is determined by critical pharmacological, biological and behavioural factors including potency, the genetic barrier, adherence and duration of suppression. Attempts to reduce toxicity by using certain two-drug (2DR) combinations in first line therapy and in switch studies have produced unexpectedly disappointing results. However, other 2DR combinations (such as bPI+3TC and NNRTI+INSTI) have demonstrated efficacy similar to triple therapy in switch studies. Large first-line 2DR studies will soon report outcomes. Some data on the safety benefits of 2DR regimens vs TDF-containing regimes have been reported but more are needed. Improving simplicity, tolerability, acceptability while reducing toxicity will be key areas of focus for the ART regimes of the future.