Only half asleep

The AIDS virus actively replicates and drives immune activation even in patients on antiretroviral therapy, according to a report in this week's Nature Medicine.

Highly active antiretroviral therapy (HAART) results in durable suppression of the AIDS virus (HIV-1), but HIV-1 replication resumes if therapy is interrupted. Active viral replication is generally thought to stop in patients on HAART, though immune activation and inflammation continue at abnormal levels, suggesting continued, low-level viral replication.

Javier Martinez-Picado and his colleagues assessed whether active HIV-1 replication persists in patients on HAART and whether this is what drives immune activation. By intensifying treatment with an extra antiretroviral drug that prevents HIV replication products from integrating into the genome, the scientists were able to detect a specific and transient increase in HIV-1 replication products in a large percentage of patients on HAART.

Importantly, immune activation was higher in these subjects before the addition of the extra drug and was normalized after intensification. These results indicate that, despite suppressive HAART, active replication persists in some patients and drives immune activation. Intensification regimens that target this active replication may therefore accelerate the decay of the HIV-1 reservoirs that persist in HAART-treated patients.

doi: 10.1038/nm.2111

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