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  IAS 2013: 7th IAS Conference on HIV
Pathogenesis Treatment and Prevention
June 30 - July 3 2013
Kuala Lumpur, Malaysia
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Immune Activation Tied to Viral Blips in People Taking Suppressive ART
  7th IAS Conference on HIV Pathogenesis, Treatment and Prevention, June 30-July 3, 2013, Kuala Lumpur
Mark Mascolini
Levels of activated (CD3+ HLA-DR+) T cells predicted viral load blips during suppressive antiretroviral therapy (ART), according to results of a case-control study at the University Medical Center Hamburg-Eppendorf [1]. Other signals of immune activation and the inflammation marker C-reactive protein did not predict blips in this 164-patient study.
Blips in people with an undetectable viral load usually represent clinically innocuous random swings around a steady state. But Jan van Lunzen and Hamburg colleagues noted that blips may reflect viral shedding from activated immune cells. Because persistent immune activation may portend HIV disease progression, they conducted this study to analyze potential links between viral blips and systemic immune activation.
The researchers devised a case-control study in their HIV outpatient cohort, with case patients representing those with a blip after at least 180 days of suppressive ART. They matched cases to blip-free controls according to age, sex, CDC stage, and time with complete virologic suppression. The Hamburg team defined blips as intermittent viremia between 50 and 1000 copies, preceded and followed by an undetectable load.
The investigators used flow cytometry to measure CD3, CD4, CD8, HLA-DR, CD16, CD56, and CD19 on cells in longitudinal samples from cases and controls. Then they calculated average areas under the curve (AUC) for these cellular markers. The researchers also recorded levels of C-reactive protein, an inflammation marker, from the first date of complete virologic suppression to the index date (the blip date or the corresponding date in controls). They assessed adherence to ART by measuring nonnucleoside or protease inhibitor plasma concentration at the index date in 57 people with available serum samples.
The analysis involved 82 cases and 82 controls with respective average ages of 46.1 and 47.8. Median duration of complete viral suppression to the index date measured 427 days in cases and 433 days in controls. Proportions taking an NNRTI, a PI, or both were 40.2%, 39.0%, and 15.9% among cases and 60.0%, 26.8%, and 7.3% among controls (P = 0.05). Adherence did not differ between cases and controls: Subtherapeutic antiretroviral concentrations were found in 6 of 23 cases (26.1%) and 12 of 34 controls (35.3%) (P = 0.46).
Multivariate analysis identified only two predictors of blips: Each year of ART raised the odds 47% (adjusted odds ratio 1.47, 95% confidence interval 1.04 to 2.06, P = 0.03). And T-cell activation (CD3+ HLA-DR+ cells) raised the odds 41% (adjusted odds ratio 1.41 for average AUC per 100 cells/mm3 higher, 95% confidence interval 1.09 to 1.83, P = 0.01). Variables that did not affect chances of blips in this analysis were levels of CD4 or CD8 cells, levels of CD3+ CD56+ CD3- natural killer cells, levels of CD19+ B cells, C-reactive protein levels, type of antiretroviral regimen, and subtherapeutic versus therapeutic antiretroviral levels.
The researchers suggested that blips "could help to identify patients with higher levels of immune activation and potentially higher risk for disease progression."
1. van Lunzen J, Kiepe J, Hertling S, et al. Persistent immune activation despite suppressive HAART is associated with higher risk for viral blips in HIV-1 infected individuals. 7th IAS Conference on HIV Pathogenesis, Treatment and Prevention, June 30-July 3, 2013, Kuala Lumpur. Abstract MOPE025.