05 Mar 2018
Trial finds no evidence of ongoing virus replication in people living with HIV on ART
Findings from a clinical trial conducted in Melbourne, Australia have provided significant evidence that virus replication in people living with HIV on antiretroviral therapy (ART) is highly unlikely
ART has led to dramatic improvements in life expectancy in people living with HIV, but treatment is needed lifelong and there is no cure. Whether HIV is able to replicate in people living with the virus receiving effective ART has been controversial over many years, the answer to which is important as it guides where research needs to be directed in attempts to find a cure for HIV.
Embarking on a randomised, double-blind, placebo-controlled clinical trial involving 40 HIV-infected individuals on ART, researchers from the Peter Doherty Institute for Infection and Immunity (a joint venture of The University of Melbourne and The Royal Melbourne Hospital), in partnership with The Alfred hospital and the Melbourne Sexual Health Centre, added an additional antiviral drug or placebo to the participant’s routine antiviral drug combination. The additional drug, dolutegravir, comes from a family of drugs called integrase inhibitors, which block the virus from entering cells.
Presenting the results at a media conference at the annual Conference on Retroviruses and Opportunistic Infections (CROI) in Boston, Massachusetts today, Investigator and Physician from Aarhus University Hospital in Denmark, Dr Thomas Rasmussen (formerly from the Doherty Institute), said the results were clearly negative.
“We recorded no significant differences between the placebo and the dolutegravir arm,” said Rasmussen. “Randomised, placebo-controlled trials are the gold standard in study design, and our study definitively demonstrated that intensifying standard ART with dolutegravir did not reveal or impact residual virus replication.”
Dr James McMahon, Investigator and Infectious Diseases Physician from The Alfred, said two previous studies on the impact of ART intensification on residual virus replication had been positive.
“These studies trialled another integrase inhibitor, raltegravir, and were done many years ago when standard antiviral treatment was less potent,” he explained.
“In our study, we examined cells in the blood at very frequent intervals after adding in dolutegravir. It is still possible there is ongoing replication in tissue sites, but we think this is doubtful given there was no change in multiple different measurements of both the virus and immune system that we performed.’’
Professor Sharon Lewin, Principal Investigator of the study and Director of the Doherty Institute, said that finding an answer to the age-old question of whether there is ongoing viral replication on ART is important for how future HIV cure studies are designed.
“We know that ART is unable to cure HIV due to the persistence of the virus in a sleeping form in blood and tissues, known as HIV latency,” she said.
“If we try waking up that virus, the last thing we want is for it to infect new cells, and this study tells us that this is very unlikely to happen,” she said.
The clinical trial was an investigator-initiated study funded by ViiV Healthcare.