A functional cure for HIV-1 seems feasible after research shows that an immunotherapeutic vaccine demonstrated long-term efficacy at reducing viral load when administered to patients in the early stages of disease.
In a study of chronic HIV-1 patients who interrupted their combination antiretroviral therapy (cART) to receive therapeutic dendritic cell (DC) vaccines instead, there was a significant boost in immune response against the virus that allowed control of viral replication for 24 weeks.
"To our knowledge, these are the best virological responses to any therapeutic vaccine used to date," remark Felipe Garcia (University of Barcelona, Spain) and colleagues.
Furthermore, although the viral load response to the vaccine waned after 24 weeks, Garcia and team suggest that "a new strategy including booster doses after cART interruption could potentially avoid this decline of the vaccine effect."
The concept of "functional cure," defined as the control of HIV replication without cART, is based on the observation that a few individuals who have been persistently infected with HIV for decades are able to control HIV replication so effectively that they remain aviremic, explain the authors in Science Translational Medicine.
In the 48-week study, patients treated with high doses of DCs that were primed with heat-inactivated HIV-1 experienced significant drops in plasma viral load after cART interruption than those who received unprimed DCs (controls).
The protocol endpoint for the control of plasma viral load (≥1 log10) was achieved in 12 (55%) of 22 vaccine recipients at week 12, but in only one (9%) of 11 controls. At 24 weeks, the corresponding proportions of individuals achieving this endpoint were 35% and 0%.
The decrease in plasma viral load in vaccinated patients was significantly associated with a consistent increase in HIV-1 specific T-cell responses. At different time points, the researchers observed greater increases in activation markers such as CD38 and HLA-DR on CD4 T cells from the vaccinated recipients than in those from the unvaccinated controls.
"This is a proof-of-concept study justifying further investigation of new candidates and/or new optimized strategies of vaccination with the final objective of obtaining a functional cure as an alternative to cART for life," concludes the team.
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