Daniel Kuritzkes Lecture at the 2016 ISHEID
The 2016 International Symposium on HIV and Emerging Infectious Diseases took place in Marseille, France, 25-27 May.
One of the invited lecture was on the progress toward a HIV cure.
We had the great honor to wellcome Professor Daniel Kuritzkes to give this lecture.
Daniel Kuritzkes is Professor of Medicine at Brigham & Women's Hospital in Cambridge, MA, USA, and an unanimously recognized expert in the field.
Daniel Kuritzkes (Harvard Medial School, Boston, USA) developed his vision of progress towards HIV cure (J Virus Eradic 2016; 2 (suppl 1): 5 (abstract S18)).
We currently experience a substantial reduction in AIDS-related mortality under ART and a tremendous increase in adult life expectancy in developing countries (Bor et al, Science 2013).
Nevertheless, a treatment that led to durable drug-free remission or eradication (cure) of HIV-1 could reduce the burden, cost, toxicities and stigma associated with long-term ART, and might lower immune activation and the associated risk of non-AIDS clinical events.
The search for a cure therefore remains a high priority for clinicians, investigators and patients. To date, only a single individual (Mr Timothy Ray Brown, known as the "Berlin" patient) has had apparent cure of HIV infection (Hütter et al, N Engl J Med 2009). HIV did not rebound after ART interruption and has remained undetectable during more than 7 years of follow-up.
Attempts to repeat this approach in other patients have been unsuccessful to date (Hütter et al, N Engl J Med 2014; Henrich et al, Ann Intern Med 2014)). Current efforts at eradicating HIV infection or inducing long-term-ART-free remission include activation of HIV transcription in latently infected CD4+ T-cells (latency reversal agents, mainly Histone deacetylase inhibitors or HDACi) (Archin et al, Nature 2012; Elliott et al, PLoS Pathog 2014; Rasmussen et al, Lancet HIV 2014; Søgaard et al, PLoS Pathog 2015); enhancing HIV-specific immunity in order to target and destroy cells harboring latent infectious proviruses (immune activation with TLR-7 agonists or use of anti-PD-L1 agents for instance)( Whitney et al CROI 2016 , Boston, MA, February 22-25; Eron et al CROI 2016 , Boston, MA, February 22-25); and cell-based therapies using genetically modified CD4+ T-cells (gene therapy) or hematopoietic stem cells transplantation.
Several exploratory pilot studies are underway with each of these approaches. Major challenges include the lack of surrogate markers of cure (difficulty of quantifying the HIV reservoir for instance during the monitored ART pause or "test of cure")(Li JZ et al, AIDS 2014; Li JZ et al, AIDS 2016; Ho et al, Cell 2013), the uncertain safety of the experimental treatments under study, and the need to balance the risk of these interventions against the generally well tolerated and proven efficacy of long-term ART.
Key words: HIV cure, ISHEID, Kuritzkes