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Elevated CD8 Cell Count Predicts HIV Treatment Failure

High or rising CD8 T-cell counts after starting combination antiretroviral therapy appears to predict virological treatment failure.

By Liz Highleyman

CD4 "helper" T-cells are the primary target of HIV and CD4 cell count is a key measure of immune system health and response to antiretroviral therapy. But CD8 "killer" T-cells also play a role in immune response against HIV and give important information about disease progression.

As described in the May 11, 2011, advance online edition of the Journal of Acquired Immune Deficiency Syndromes, Elizabeth Krantz from the Uniformed Services University of the Health Sciences and colleagues evaluated whether elevated CD8 cell counts are associated with increased risk of virological treatment failure in people with HIV.

This retrospective cohort study included 817 HIV positive participants in the U.S. Military HIV Natural History Study, comprised of service members, veterans, and their families, who started highly active antiretroviral therapy (HAART) between 1996 and 2008. About half started during 1996-1999, soon after the advent of effective combination therapy using protease inhibitors.

Participants had undetectable HIV RNA (below 400 copies/mL) at 6 and 12 months after starting treatment. They also had at least 2 subsequent viral load tests and available baseline CD8 count information. The median follow-up period was about 4 years.


The overall median CD8 count fell by 61 cells/mm3 during the first year on HAART.
12% of participants experienced a total of 216 treatment failures (defined as confirmed HIV RNA >400 copies/mL), for a rate of 5.6 per 100 person-years.
Virological failure was more common among people who started HAART during the early part of the study period, before 2000.
Among participants who initiated HAART during 2000-2008, patients with elevated baseline CD8 cell counts (defined as > 1200 cells/mm3) had significantly greater risk of virological failure than those with baseline CD8 counts < 600 cells/mm3 (hazard ratio 2.68, or nearly 3 times higher risk).
Participants with elevated CD8 counts at more than 20% of prior follow-up visits had significantly greater risk of treatment failure at the current visit than those who did not (hazard ratio 1.53).
People whose CD8 cell counts increased after starting HAART had significantly greater risk of virological failure than those with decreasing or stable CD8 counts.
People who experienced treatment failure had a median increase of 51 CD8 cells/mm3, while those who maintained undetectable viral load had a median decrease of 108 CD8 cells/mm3.

Based on these findings, the study authors concluded, "Initial or serial elevated CD8 counts while on HAART or an increase in CD8 counts from HAART initiation may be early warnings for future treatment failure."

Investigator affiliations: Infectious Disease Clinical Research Program, Uniformed Services University of the Health Sciences, Bethesda, MD; Division of Biostatistics, University of Minnesota, Minneapolis, MN; San Antonio Military Medical Center, Fort Sam Houston, TX; Walter Reed Army Medical Center, Washington, DC; Naval Medical Center San Diego, San Diego, CA; National Naval Medical Center, Bethesda, MD; Tripler Army Medical Center, Honolulu, HI; 8 Naval Health Research Center, San Diego, CA.


EM Krantz, KH Hullsiek, JF Okulicz, et al. Elevated CD8 counts during HAART are associated with HIV virologic treatment failure. Journal of Acquired Immune Deficiency Syndromes (abstract). May 11, 2011 (Epub ahead of print).



















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