Christoph D. Spinner

This Prime Session offered a brief overview on the current state of the art, challenges and perspectives of antiviral therapy. Advantages, challenges, and upcoming aspects have been introduced in the talk and briefly discussed afterwards. In the last part of the session the IAS/ANRS prices have been awarded.

After the opening of the 5th Prime Session by Eckhart von Hirschausen, Jennifer Hoy started with a nice and precise overview on the history of ART and the current discussion on 2- and 3-drug (2DR and 3DR) combination in antiviral therapy (ART). She introduced the different PROs and CONs of 2- and 3-drug ART combinations. She discussed briefly advantages and disadvantages of novel drugs, novel combinations, and the current state of the art in ART. Hereby, alternative dosing options and cost implications have been reflected as well. While long-acting injectable drugs contains several advantages for people living with HIV (PLWH), a few challenges, such as monitoring, delivery, dosing and drug tail, remain. She ended up with a perspective of upcoming drug options to individualize ART. A very interactive discussion followed. Bruno Spire awarded the IAS/ANRS prices in the third part of the session. The Young Investigator prices have been awarded in track-A to Basiel Cole (Belgium), track-B to Ayokunle Olanrewaju (USA), track-C “Johanna Chapin-Bardales (USA)” to and track-D to Thomas Carpino (USA).

Major improvement in the availability, efficacy and tolerability of ART has been made within the recent years. Although 2DR combination have nowadays proven evidence of comparable efficacy to 3DR, several pitfalls exist. Hereby populations with advanced disease, poor adherence and/or hepatitis B-coinfection might not be suitable for 2DR. Despite all efforts of ART, several side effects (e.g. weight gain, bone and renal issues and more) require further improvement and development! This is also the case for making ART dosing and delivery easier. The sum of all improvements should pave the way to individualized treatment.

Marta Massanella

This session, chaired by the president of IAS, Adeeba KAMARULZAMAN, discussed about changing the current paradigm of triple combination therapy to 2 drug-regimens (initial ART or treatment switch) or the use of long acting injectables. There are several advantages at different levels, but also some challenges to overcome.

Jennifer HOY explained several advantages of 2-drug regimens for initial ART or treatment switch, such as that they are as potent and durable as triple combination, they show no difference in adherence or adverse effects and, importantly, at lower cost. Double therapy suppresses viral load in ART-naïve individuals as rapidly as 3-drug regimens and no residual viremia is observed. Long acting injectables have shown long-term viral suppression, and virological failure is uncommon. They present some implementation challenges, such as the adverse effect (if any) cannot be removed after administration and the long pharmacokinetic tail, which may cause viral resistances in case of suboptimal adherence. Importantly, not all PWH can benefit from these new treatments (i.e., pregnant women, chronic hepatitis B, high VL, low CD4 counts). It is time to change the paradigm, but always embracing all options to individualize ART to specific needs.

2-drug regimens (and long acting injectables) seem to be the new paradigm for treating HIV. However, there are still some gaps that needs to be addressed. First, more studies are required to evaluate the impact on the size of the HIV reservoir and the residual viral replication, which can occur in anatomical sanctuaries where drugs cannot penetrate. The levels of immune activation should also be monitored to avoid the appearance of more premature o accentuated comorbidities, especially in the long run. Besides, the generation of resistance mutations is worrying, particularly in injectables, and should be studied carefully.