Reduced Immune Activation Predicts Better Response to Salvage Therapy for Highly Treatment-experienced HIV Patients

Immune system structures - The immune system protects the body from potentially harmful substances. The inflammatory response (inflammation) is part of innate immunity. It occurs when tissues are injured by bacteria, trauma, toxins, heat or any other cause.

Improved antiretroviral drugs have led to better outcomes for heavily treatment-experienced people with HIV, and researchers continue to learn more about factors that predict good response to treatment.

Antiretroviral therapy that leads to "calming" of the immune system's response to HIV is linked to better response to salvage therapy for such patients, according to a study in the June 1, 2008 Journal of Acquired Immune Deficiency Syndromes.

Because effective antiretroviral therapy reduces immune activation, the authors hypothesized that early changes in such activation might be associated with subsequent virological response to therapy.

To test this theory, they conducted an observational cohort study of 34 heavily pre-treated patients (mostly white men) at an institutional HIV clinic, most of whom had been on antiretroviral drugs for at least a decade. Participants were all experiencing virological failure on their current antiretroviral regimen, and switched to a salvage regimen selected by their physicians.

The study investigators looked at measures of immune activation at baseline and at weeks 2, 4, 8, and 24 after enrollment. These included the T-cell markers CD38 and CD95, which are associated with elevated immune activation. Data were analyzed using proportional hazards models.

Results

• The models showed that reductions in T-cell expression of CD38 or CD95 between baseline and week 2 were associated with increased likelihood of achieving virological suppression (P = 0.02).

• Kaplan-Meier analysis demonstrated that patients who had reductions in expression of either CD38 or CD95 within the first 2 weeks were more likely to achieve viral suppression than those who did not (P = 0.003 and 0.008, respectively).

"Reduced CD4 T-cell expression of CD38 and CD95 occurring within 2 weeks of [starting] salvage therapy is associated with subsequent viral suppression," the study authors concluded. "Monitoring CD38 and CD95 may allow earlier assessment of the response to antiretroviral therapy."

Measuring these markers soon after starting therapy may offer a quicker method of determining whether patients will ultimately respond to therapy - well before the several weeks or months needed to achieve undetectable HIV viral load or an increase in CD4 cells - which would be especially beneficial for individuals on failing therapy.

Mayo Clinic, Rochester, MN; University of Toronto, Toronto, Ontario, Canada; Maple Leaf Medical Clinic, Toronto, Ontario, Canada; University Health Network, Toronto, Ontario, Canada; National HIV Laboratory, Ottawa, Ontario, Canada; Ottawa Health Research Institute, Ottawa, Ontario, Canada.

6/24/08

Reference
BD Shepard, MR Loutfy, J Raboud, and others. Early changes in T-cell activation predict antiretroviral success in salvage therapy of HIV infection. Journal of Acquired Immune Deficiency Syndromes 48(2): 149-155. June 1, 2008.