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22 February 2017, 09:03

HIV Conserv vaccine achieves long-term viral suppression in 38% of trial recipients

HIV Conserv vaccine achieves long-term viral suppression in 38% of trial recipients - picture 1

For the first time, an “HIV Conserv” vaccine has been shown to achieve long-term viral suppression in a large minority (38%) of recipients who were taken off antiretroviral therapy (ART). That is, the virus is still present, but does not rebound after stopping ART.

One participant has been off ART for seven months and has not yet had to resume it.

Trial participants received two doses of the HIV Conserv vaccine at weeks 0 and 9. At weeks 3, 4, and 5 they received three doses of the drug romidepsin, a latency-reversing drug that stimulates the immune system and has been used in “kick-and-kill” HIV cure experiments. The romidepsin stimulates the virus to reproduce while the patient is on ART. In theory, the immune response provoked by the Conserv vaccine should be strengthened by this experience of viral replication, as the body's anti-HIV CD8 T-cell response grows more powerful and efficient. In all but one participant, this type of response was observed.

The HIV DNA in participants' cells was measured at weeks 0, 3-5 (during the romidepsin infusions), and 9. At weeks 0, 1, 3, 9, 10, and 13 the proportion of HIV-sensitive CD8 cells was measured. At week 17, participants stopped ART. During the Monitored Antiretroviral Pause (MAP) patients were monitored and resumed ART if viral rebound occurred.

To date, 13 of the 15 participants have stopped ART. 8 of 13 experienced a rapid rebound to pre-ART viral load levels within the first 4 weeks and resumed ART. The remaining 5 participants – 38% of the group – experienced only intermittent, low-level viral rebound (fewer than 2000 copies/ml) and stayed off ART for 6, 12, 19, 20, and 28 weeks respectively.

Only 1-2% of people typically spontaneously control their viral load after ending ART, so the 38% of people in this study who experienced long-term viral suppression is a significantly higher proportion. Researchers said that these five participants, unlike the eight whose viral load rebounded after stopping ART, were all within the lower half of viral DNA measurements and a greater proportion of their immune responses were directed at the highly conserved regions of HIV.

Sharon Lewin, Director of the Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Australia, said, “This study is exciting because it is the first to demonstrate post-treatment control. However, we also need to be cautious – there was no control group and we don’t know which part of the intervention was important – the early vaccine? The second vaccine? Romedepsin? All of the above? At the same time, until now, in every other study involving treatment interruption, post-treatment control has been rare and at most happens occasionally. So this is a promising and significant step forward. We definitely need a follow-up study that is larger, has a control group who receive no intervention and a less complicated vaccine schedule. We'd want to understand why some people controlled too – currently they don’t know the answer to this."