A highlight of the 2013 Conference on Retroviruses and Opportunistic Infections (CROI) held in Atlanta in March was the session called 'Is There Hope for HIV Eradication?'
Data on the case of the premature baby was presented and generated much media attention. There were also nine other presentations on cure-related topics.
A team of researchers based predominantly in Australia reported one in 20 people on long-term HAART with undetectable VL for a median of five years with a median CD4 count of 721 cells/µL. These participants received 400mg vorinostat once daily for 14 days and their blood plasma and rectal tissues were analysed to determine any changes in cell-associated HIV RNA and HIV DNA. Vorinostat, a histone deacetylase inhibitor, is postulated to purge HIV from reservoirs. The study demonstrated that short-term use of vorinostat was safe and that it increased the sustained expression of HIV by CD4 T-cells in blood and rectal tissue. Unfortunately, it failed to demonstrate any significant change in HIV DNA in any assay from these potential reservoirs. In short, vorinostat did not actually shrink the size of the reservoir, and the study authors suggested that further strategies will be needed to eliminate latently infected cells.
Another paper 2 reported on 47 people who began treatment very early, within 25 days of infection. These people had their total integrated HIV DNA measured in blood and lower gut tissues at the commencement of treatment and after 24 weeks of treatment. In all participants, levels of integrated HIV DNA decreased dramatically. Seventy-two percent of those who began treatment within 25 days achieved undetectable HIV DNA in long-lived memory CD4 T-cells. This study showed that very early treatment restricts the seeding of the HIV reservoir, predominantly in CD4 memory T-cells. Other cell types monocytes, B and or CD8 T-cells were not demonstrated as being significant HIV reservoirs at this early HIV disease stage. This is perhaps of limited general applicability as most people are not identified so close to infection. But it does highlight the very early seeding of reservoirs and how this might be reduced.
One report based on laboratory studies suggested that the size of HIV reservoirs of HIV proviruses, which are capable of initiating replication, may be up to 12 times larger than previously thought 3, while another identified a new subset of memory T-cells (T memory stem cells), which in the long term (over ten years)4 demonstrated an increasing contribution to total HIV reservoirs. This new finding suggests this subset of T-cells may contribute to viral persistence and may contribute to viral rebound when stopping treatment or virological failure.
What does this mean for people receiving HIV treatments?
Advances in understanding the nature and size of HIV reservoirs continue to be made, and the evidence of the benefit for limiting reservoir size by very early treatment has also been advanced. However, the task of purging HIV from its reservoirs proceeds slowly. A Global Scientific Strategy to advance an HIV cure has been published by the International AIDS Society Scientific Working Group on HIV Cure 5. It covers the issues canvassed above and much more and will serve as a background to help understand where the global community is placed.