HIV Vaccine Induces Sustained HIV Remission in Proof-of-Concept Study
February 27, 2017
After treatment of primary HIV infection, two doses of a therapeutic HIV vaccine plus three infusions of romidepsin, an HIV latency reactivator, allowed five of 13 trial participants to stay off antiretroviral therapy (ART) without rebound for up to 28 weeks in a Spanish proof-of-concept study. BCN02-Romi is the first immune intervention trial showing that manipulating cytotoxic T lymphocyte (CTL) immunodominance patterns may allow off-ART viral control in some people.
Researchers in Barcelona's IrsiCaixa group note that ART during primary HIV infection may promote immune recovery and limit size of the latent HIV reservoir. Conserved HIV vaccines aim to reduce viral diversity driven by immune escape. The BCN01 trial gave two conserved vaccines in a prime-boost sequence to people who began antiretrovirals early in the course of their infection. This strategy did not affect HIV reservoir size.
BCN02-Romi enrolled people who completed BCN01, had an undetectable viral load for at least three years (including the four weeks before enrollment while taking raltegravir [Isentress] or dolutegravir [Tivicay, DTG]) and a CD4 count of at least 500 cells/mm3. Fifteen participants received the MVA.HIVconsv vaccine on weeks zero and nine and romidepsin on weeks three, four and five. They had a median age of 43 years, began ART 28 to 164 days after infection and had taken ART for 3.03 to 3.77 years.
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All participants completed all HIVconsv immunizations and romidepsin infusions. Fourteen of 15 participants reported grade 1 or 2 headache or fatigue, 11 reported grade 1 or 2 nausea and nine reported grade 1 or 2 anorexia. Grade 1 or 2 thrombocytopenia affected five participants, and four had grade 1 hypophosphatemia. HIVconsv responses, measured as interferon-gamma spot-forming cells per million peripheral blood mononuclear cells (PBMCs), rose in 13 of 15 participants and significantly exceeded responses during the BCN01 trial (P = .0381). CTL immunodominance patterns shifted toward conserved regions, with more than two-thirds of total T-cell responses directed to conserved regions.
After the first HIVconsv immunization, nine of 15 participants (60%) had detectable HIV RNA in plasma. After romidepsin infusions, 14 of 15 (93%) had at least one viral load above 20 copies/mL. Proviral DNA declined significantly during one year of continued ART after BCN01 (P = .0064) and remained around that level after administration of HIVconsv and romidepsin and during the planned ART interruption. At ART interruption, median proviral DNA stood at 144 copies/million CD4 cells and was detectable in all participants.
At the time the data were presented, 13 of 15 participants had interrupted ART. Eight of the 13 had rebounded above 2000 copies/mL within four weeks and resumed ART according to the study protocol. Five participants (38%) had maintained viral control for 6, 14, 19, 21 and 28 weeks without ART, although low-level viremia could be detected in all of them.
The researchers conclude that this strategy lowers viral diversity and viral escape while promoting functional T cells and off-ART viral control in some individuals. They suggest that "viral control can be achieved by an effective redirection of CTLs towards conserved regions in the context of a limited viral reservoir."
Mark Mascolini writes about HIV infection.
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