Scientists have discovered that an anti-cancer drug can revive dormant HIV (human immunodeficiency virus), thereby allowing therapies to act upon the low level inactive virus particles that hide in patients' immune cells and have, until now, been unsusceptible to treatment.
The study, performed by researchers from the University of North Carolina at Chapel Hill, USA, and published in the journal Nature, shows that a single treatment with the drug – called vorinostat – can specifically target dormant virus particles, those which are normally unaffected by standard anti-retroviral therapy.
The current treatment for HIV infection is a cocktail of drugs that suppress HIV replication. However, latent virus particles that aren't replicating evade these therapies by lying dormant in patients' own cells.
During the study, vorinostat, which is normally used to treat lymphoma, was given to eight HIV-positive patients who were already undergoing anti-retroviral therapy. The patients showed an average 4.8-fold increase in viral RNA expression in the cells where dormant HIV is known to hide, a tell-tale sign that the drug had induced the latent HIV to become active. In essence, the drug had forced dormant virus out of its hiding place.
By directly attacking latent HIV infection, this study is another step on the road towards a cure. Dr David Margolis, lead author on the study, said in a press release, 'this research provides new hope for a strategy to eradicate HIV completely from the body'. Steven Deeks, of the University of California, wrote in a Nature Commentary accompanying the main paper, '[this work] is a proof-of-concept study that provides the first evidence that such a cure might be one day feasible'.
To date, Timothy Ray-Brown, the so-called 'Berlin patient', is widely recognised as the only man to have been cured of HIV infection. Brown, who was also suffering from leukaemia, underwent stem cell replacement therapy for his cancer. His doctor was able to find a donor who was naturally resistant to HIV. Thus, the therapy effectively replaced Brown's susceptible cells with resistant cells from the donor. This method cured Brown of HIV infection, and supplied a proof-of-principle that stem cell replacement might be a legitimate pursuit in the fight against HIV.
On the back of this success it was announced this week at the nineteenth International AIDS (acquired immunodeficiency syndrome) conference in Washington DC that two more men receiving stem cell transplants for lymphoma have been effectively cured. One patient is HIV-free after two years, while the second has no detectable HIV DNA in their immune cells three-and-a-half years on. This time, however, the donor cells used were not naturally HIV resistant.
The key seems to have been keeping the patients on anti-retroviral drugs throughout their chemotherapy and transplant. The study was overseen by Dr Daniel Kuritzkes of Brigham and Women's Hospital in Boston, USA. 'We found that immediately before the transplant and after the transplant, HIV DNA was in the cells. As the patients' cells were replaced by the donor cells, the HIV DNA disappeared', Dr Kuritzkes told WITN. In essence, the donor cells replaced the infected cells while the anti-retroviral drugs protected the donor cells from becoming infected themselves.