Non-ARV Based Interventions to Combat HIV/AIDS: New Insights and Initiatives Yves Lévy Inserm, VRI

Summary of the AIDS epidemic 2016

Necessity to go beyond cART Since the introduction of ART 20 years ago, improved survival and increased life expectancy of ART-treated HIV individuals. Life expectancy in people with HIV is nearly the same as that in the general population, except for in some important minority groups (eg, African Americans) (The Antiretroviral Therapy Cohort Collaboration, 2017 Lancet HIV doi.org/10.1016/S2352-3018(17)30066-8) However, chronic HIV infection leads to premature ageing in the cART era (Goodkin K et al., 2017 Lancet HIV doi.org/10.1016/S2352-3018(17)30098-X) PREVAGAY study reveals still a high HIV prevalence in the MSM community in France (14,3% in the total MSM and 6% in the <30 year- old MSM) despite PrEP and prevention methods In addition, a high incidence of bacterial sexually transmitted infections (STIs) has been reported in several PrEP trials The vaccine is still necessary despite PrEP and cART Consequence of PrEP on the long run is not known Activation & inflammation linked to HIV and toxicity linked to cART have consequences on an ageing population

Vaccines will be needed to sustainably halt HIV infection and end AIDS Opportunities in the development of effective HIV vaccines Experimental vaccines confer protection to SIV-infected monkeys and certain vaccine candidates induce potent immune responses in vaccinees There is evidence that HIV-1-specific immune responses may confer protection (e.g. exposed non-infected subjects) A small percentage (<5%) of HIV-1-infected subjects show no signs of disease progression and/or spontaneous control of viral replication (e.g. long-term nonprogressors and “HIV Controllers” Results of the large proof-of-concept Thai trial demonstrate that protection against HIV acquisition is possible

Vaccine against HIV Vaccines (prophylactic and therapeutic) remain a priority in HIV research Classical vaccines approaches have been unsuccessful in HIV Neutralizing antibodies remain the gold standard to reach for a prophylactic vaccine. While these Ab may exist during natural HIV infection, their induction through vaccination remains a challenge. Induction of specific T cell responses may control viral replication during natural HIV infection and represent therefore the target of therapeutic vaccines which represent an important weapon in HIV cure strategies

science and biostatistics. EHVA consortium Project Started Jan 1st, 2016 EHVA is a grant of 28 million Euros with 22 million Euros from the European Commission and 6 million Euros supplemented by the Swiss government for the Swiss partners. 39 partners from 11 countries in Europe, 4 in Sub-Sahara Africa and the US, with leading scientists in the fields of molecular biology, structure biology, vectorology, adjuvants, delivery, immunology, clinical science and biostatistics.

Primary Goals To Develop a Multidisciplinary Vaccine Platform (MVP) in the fields of Prophylactic and Therapeutic HIV Vaccines To move at least two novel prophylactic vaccine candidates to clinical development To identify immune correlates associated with control of HIV replication following immunological intervention To establish strong scientific basis for further development of EHVA vaccine candidates in larger clinical trials

Multivalent Vaccine Platform Discovery Immune Profiling Data Mgmt Integration Down-Selection Clinical Trials MVP – a platform approach to facilitate: Early selection of the most promising vaccine candidates Acceleration of the development process Identification of biological/immunological signatures for the selection of future vaccine candidates

EHVA Symposium Program Program topics Clinical development for preventative and therapeutic vaccines Development of new vaccine candidates: advances and challenges Virological and immunological markers

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