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Immune Activation Persists Despite Effective ART

In a cohort of HIV-positive patients, markers of immune activation remained elevated despite 6 years of effective antiretroviral therapy. Immune activation was associated with lower CD4-cell counts.

Several species of monkeys, when infected with HIV or related viruses, do not develop disease or CD4-cell decline despite high viral loads. Recent research indicates that the key to viral tolerance in these monkeys may lie in their lack of immune activation. Other studies have suggested that immune activation is also a strong driver of T-cell depletion in human infections.

In the present study, researchers evaluated markers of immune activation in stored serum samples obtained from 63 HIV-positive patients who were enrolled in a long-term study of d4T + 3TC + lopinavir/ritonavir. The samples were drawn at baseline (when all patients were treatment-naive) and at years 3 and 6. All but one patient had an undetectable viral load after 6 years of therapy.

At baseline, study participants generally had significantly higher levels of serum and cellular activation markers than did HIV-negative controls. Surprisingly, most of these differences persisted after 6 years, despite effective antiretroviral therapy. Immune activation was associated with lower CD4-cell counts both at baseline and at year 6.

Comment: Immune activation is not easy to quantify, because certain markers are difficult to measure, especially in stored samples. These authors, however, managed to evaluate 10 different markers. Unfortunately, the HIV-positive patients and HIV-negative controls were not matched at all. A more interesting control group would have been HIV-positive patients who were untreated or receiving contemporary regimens. Nonetheless, if the findings of this study are confirmed, we may want to start evaluating supplementary therapies — that is, medications that interfere with inflammation and immune activation in patients with well-controlled infection but persistent immune activation.

— Helmut Albrecht, MD

Published in Journal Watch HIV/AIDS Clinical Care November 9, 2009

Citation(s):

French MA et al. Serum immune activation markers are persistently increased in patients with HIV infection after 6 years of antiretroviral therapy despite suppression of viral replication and reconstitution of CD4⁺ T cells. J Infect Dis 2009 Oct 15; 200:1212.

• Medline abstract (Free)