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Vaccine gives HIV patients a long-term boost
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,
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%.
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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.
Newly discovered gene predicts HCV interferon response
The finding helps to explain why African Americans are less likely to respond to interferon treatment than European or Asian patients, and could lead to new treatments.
"We've identified a new gene that may help us better understand response to viral infection and the new genetic marker may transition to clinical practice because it predicts treatment outcome for African-American patients better than the current genetic test," said Thomas O'Brien (National Cancer Institute, Bethesda, Maryland, USA) in a press statement.
The researchers treated human liver cells with a synthetic mimic of HCV RNA to imitate HCV infection and carried out RNA sequencing.
The novel gene was discovered in a region of the genome already known to contain the genes for several types of interferons which suppress HCV replication. Variation in this region has already been strongly associated with HCV clearance.
The newly named IFNL4 is created by a single base deletion in the DNA, resulting in expression of a protein not found in the cells of those without the deletion.
Using data from previous studies of HCV-infected patients, the authors show that the expression of the INFL4 protein is associated with poorer clearance of the virus and poorer response to pegylated interferon and ribavirin treatment than those without the allele.
An alternative allele, that includes an additional base, prevents the IFNL4 protein being expressed and the authors say it appears to have been selected for throughout evolution, becoming particularly common in Asian and European populations.
The authors say that the inhibition of IFNL4 could now present a future treatment strategy for HCV, as well as other diseases.
"By using RNA sequencing we looked outside the box to search for something beyond what was already known in this region ," said Ludmila Prokunina-Olsson, also from the National Cancer Institute. "We hit the jackpot with the discovery of a new gene."