'Stepping up the pace' for a cure!

In keeping with the main theme of the AIDS 2014 conference ‘Stepping up the pace’, the first day of plenaries, oral abstracts and symposia sessions (amongst many other activities) focused on the so-called ‘Holy Grail’ of HIV medicine – finding a cure!

This largely focused on how can we identify HIV viral reservoirs and how we can eradicate them. While much of the science presented seems well beyond the scope of primary care, I felt the theme underpins the current debate of whether commencing treatment sooner rather than later is of individual benefit.

The opening plenary by Salim S Abdool Karim (Director of the Centre for the AIDS program of Research in South Africa) summarised the global response to HIV/AIDS over the last 30 years and pleasingly showed a global decrease in the number of new HIV infections in adults and children since the early 2000s. Less pleasingly though was the noticeable decrease in condom use in MSM in Australia between 2007 and 2011.

He also did theorise that the concept of elimination and eradication is not readily applicable to AIDS with the millions of people living with HIV/AIDS and that there is no cure available and that the key to the end of AIDS is ‘epidemic control’.

Jintanat Ananworanich, a paediatrician, immunologist and HIV researcher and now the Associate Director of HIV Therapeutic Trials at the US Military HIV research program in Maryland, USA, then outlined where we are in terms of an HIV Cure and where are we going. She introduced us to the concepts of the persistence of HIV in latent reservoirs and the difficulties of monitoring the elimination of HIV due to the fact that we do not have biomarkers to determine HIV remission.

She suggested that success will likely require combination approaches including early antiretroviral treatment.

This theme was continued in a special session on ‘The Future of Science in the HIV Response’ by Dr Anthony Fauci, Director, National Institute of Allergy and Infectious Diseases, National Institute of Health, Bethseda, USA, where he further outlined the complexity of the HIV reservoir in terms of having qualitative and quantitative characteristics. Qualitative components including the body (e.g. gut, peripheral lymphoid cells, brain), cell type (naiive and memory CD4 cells, monocytes, macrophages and follicular dendritic cells) and the status of the virus (defective or replication competent) and the quantitative aspect simply indicating the quantity of viral reservoir which increases after infection.

HIV viral latency is believed to form very early in HIV infection and the various methods to eradicate HIV include:

• ‘flush out’ the virus or the so called ‘shock and kill’ method (use of latency activator therapies such as Panobinastat)
• immunotoxic therapy
• stem cell transplant
• gene therapy to eliminate CCR5 (Zinc-finger-nuclease modification of CCR5)

Dr Fauci also emphasised that a combination approach would be needed to achieve sustained virologic remission; early treatment initiation would “stack the deck in favour of eradication” by limiting the seeding of the reservoir, while use of novel immunotherapies (including passive transfer of HIV specific antibodies or therapeutic vaccination) would help eliminate HIV and HIV-infected cells. In addition, he outlined that recent advances in our understanding of the ‘broadly neutralising antibody response’ as particularly important in controlling the virus.

These concepts were further discussed in an afternoon abstract session that will be covered in another post.