Remission possible

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11 Sep 2014

While a cure for HIV remains elusive, sustained remission maybe the next best thing. Neil McKeller-Stewart reports.

To date, there have been several instances of HIV remission (remission being when the virus is not active enough to require treatment).

Arguably the most famous case is the ‘Berlin patient’ — Timothy Brown — who, after a bone marrow transplant, remains off treatment and virus-free six years on. And, as revealed at AIDS 2014, two Australian HIV patients have also been discovered to be virus-free.

The latest science on remission strategies was very much the focus of a two-day, pre-conference satellite symposium, Towards an HIV Cure, attended by around 300 researchers and community representatives from around the world. 

Whilst antiretroviral treatment (ART) drives HIV viral load to undetectable levels, some HIV remains circulating in the blood. Additionally, a ‘reservoir’ of long-lived immune system cells containing HIV persists indefinitely. HIV can awaken from this reservoir and enter the circulation system. That’s why — as recently evidenced by the ‘Mississippi baby’ and the ‘Boston patients’ — viral load rapidly returns to pre-treatment levels once ART is discontinued.

But what if this latent reservoir of HIV could be awakened, attacked and killed? A Danish trial — headed by Ole Søgaard of
Aarhus University Hospital, Denmark — assessed the safety of a cancer drug called romidepsin and to what extent it can reactivate HIV from latency. This was a small non-randomised interventional trial involving six patients with HIV who were given romidepsin three times a day for 14 days.

The results were mixed: promising as far as safety and the effect on inducing reactivation from latency; and perhaps disappointing as far as revealing any significant change in reservoir size. Still, the Danish study is regarded as a big step
forward to finding a vaccine for HIV. A clinical trial combining a therapeutic vaccine (Vacc-4x) and romidepsin is ongoing.

Meanwhile, Dr Vicente Planelles of the University of Utah, USA, reported on a new family of heterocyclic compounds
(benzotriazole analogues), which in laboratory studies very effectively reactivated latent cells containing HIV. One of the appealing features of these compounds is that they don’t increase some of the chemical messengers that cause inflammation and other cell damage.

When tested with T cells from HIV-positive people, one of these compounds was able to reactivate virus from people with
undetectable viral loads. The symposium heard of other compounds under lab investigation which stimulate HIV replication through different mechanisms. Together, these new compounds add a whole new range of possibilities in shocking HIV out of latency.

Other research presented at the symposium related to work being done on targeting and killing HIV sanctuaries in tissues.
It has been known for almost a decade that lymph-node follicles produce a range of immune cells and are sites where HIV
replication is active and where substantial reservoirs of HIV are located.

Dr Rama Amara (Yerkes National Primate Research Centre, Emory University, US) reported research in rhesus macaque monkeys which were vaccinated against, and then challenged by, infection with SIV (the monkey form of HIV). Compared to the unvaccinated monkeys, the vaccinated macaques had much lower proportions of HIV-infected cells (in blood, lymph nodes and rectal tissues). They were also found to have higher proportions of CD8 cells able to kill HIV-infected CD4 cells.

This data suggests it may be possible to develop vaccine-based therapies to reduce or eliminate virus-infected cells. Exciting news indeed, indicating that much more is being discovered about, not only where HIV hides but, more crucially, how to eradicate it. 

Conference chair Françoise Barré-Sinoussi — who discovered the HIV virus  — believes remission is more achievable than cure. And while acknowledging there will be rebounds along the way, she remains optimistic that sustained
remission strategies will be found.

“To achieve long-term HIV remission we will likely need to tackle the problem on multiple fronts,” said Barré-Sinoussi.
“Lowering as much as possible the number of long-lived, latently infected cells present in the body, as well as bolstering the host defence. One cannot be done without the other.”

Expect to hear a lot more about interventions that might lead to sustained HIV remission. Australia is more than lifting its
weight in this regard, continuing to contribute funding and expertise to remission research. As the cure symposium showed,
progress towards remission is accelerating and the latest research suggests that the prospect of an AIDS-free generation is indeed within reach.