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ART Soon After Infection Yields Normal Immune Activation Markers in Small Study
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XIX International AIDS Conference, July 22-27, 2012, Washington, DC
Mark Mascolini
Starting antiretroviral therapy (ART) during the first weeks of HIV infection resulted in normal CD8-cell activation after 48 and 96 weeks of treatment when compared with HIV-negative healthy controls in a small pilot study [1]. HIV-positive people attained normal immune activation marker levels regardless of whether they began treatment with 3 or 5 antiretrovirals. Levels of soluble CD14 (sCD14) were normal before and after 48 and 96 weeks of treatment in these recently infected people.
Much research shows that the immune system remains abnormally activated in people responding to long-term ART with an undetectable viral load and a rising CD4 count [2,3]. Researchers at New York's Aaron Diamond AIDS Research Center conducted this study to see if starting ART immediately during acute or early HIV infection affects immune activation. They identified activated CD8 cells as those expressing CD38 and HLA-DR, and they measured sCD14 as another activation marker.
Eleven study participants started a three-drug regimen including tenofovir/emtricitabine plus ritonavir-boosted atazanavir or darunavir. Twenty participants took one of those regimens plus raltegravir and maraviroc. The Aaron Diamond team measured CD38 and HLA-DR expression on CD8 cells and sCD14 at baseline (before treatment began) and after 48 and 96 weeks of treatment. For comparison, the researchers measured these markers once in 13 healthy HIV-negative volunteers.
All antiretroviral participants were men, while 8 of 13 healthy volunteers were men. Median age did not differ substantially between the 3-drug group (41), the 5-drug group (37), or healthy controls (39). Pretreatment viral load stood at 1 million copies in the 3-drug group and about 250,000 copies in the 5-drug group. Respective pretreatment CD4 counts were 405 and 570. All but 1 recently infected person had symptoms of acute infection. Estimated duration of infection was 48 days in the 3-drug group and 54 days in the 5-drug group.
All antiretroviral-treated people had a viral load below 20 copies at weeks 48 and 96. Proportions of activated CD8 cells and levels of sCD14 did not differ significantly by treatment assignment at baseline or at week 48 or week 9.
Before treatment began, both HIV-positive groups had significantly higher proportion of activated CD8 cells than did healthy controls (about 40% activated versus about 5% in controls, P < 0.001). By treatment week 48, CD8 activation levels had become comparable in the two HIV groups and the healthy volunteers (about 5% activated). That comparability persisted through week 96 at the same level.
Levels of sCD14 did not differ significantly between either HIV group and healthy volunteers. Before treatment, sCD14 levels were about 1500 ng/mL in the three study groups. sCD14 concentrations stayed at about that level in the HIV groups after 48 and 96 weeks of treatment.
The Aaron Diamond investigators believe their findings "suggest that very early initiation of combination antiretroviral therapy may overcome perceived limitations of current therapies and could potentially result in superior clinical outcomes." They called for "larger, comprehensive, well-designed" trials to address these issues.
References
1. Markowitz M, Evering T, Figueroa A, et al. Very early initiation of combination antiviral therapy results in normal levels of markers of immune activation. XIX International AIDS Conference. July 22-27, 2012. Abstract TUPDB0204.
2. Plaeger SF, Collins BS, Musib R, Deeks SG, Read S, Embry A. Immune activation in the pathogenesis of treated chronic HIV disease: a workshop summary. AIDS Res Hum Retroviruses. 2012;28:469-477.
3. Rueda CM, Velilla PA, Chougnet CA, Montoya CJ, Rugeles MT. HIV-induced T-cell activation/exhaustion in rectal mucosa is controlled only partially by antiretroviral treatment. PLoS One. 2012;7:e30307. http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0030307.
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