Elevated CD8 cell count associated with HIV treatment failure

An elevated CD8 cell count is associated with an increased risk of HIV treatment failure for patients who initially achieve an undetectable viral load, investigators from the US military report in the online edition of the Journal of Acquired Immune Deficiency Syndromes.

Their retrospective study involved 817 people who started antiretroviral therapy between 1996 and 2008.

Both an elevated CD8 cell count after a year of viral suppression and CD8 cell count in the period preceding viral load rebound were associated with virologic failure.

“Clinically relevant tools that are readily available to predict treatment failure are needed,” write the authors; “in this study we have highlighted the potential of the total CD8 count as one such tool.”

Most patients taking modern HIV therapy achieve and maintain an undetectable viral load. However, a significant proportion of patients experience a rebound in their viral load, necessitating a change of treatment.

Poor adherence is the major risk factor for virological failure, but other factors may also be involved.

One potential predictor is CD8 cell count. These immune system cells have an important role in fighting untreated HIV infection. However, an overstimulation of CD8 response and an elevated cell count has been associated with accelerated HIV disease progression.

Investigators from the US Military’s HIV Natural History study postulated that a high CD8 cell count (over 1200 cells/mm³) in the context of initial suppression of viral load could be associated with subsequent treatment failure.

They therefore analysed the clinical records of patients who had an undetectable viral load (below 400 copies/ml) one year after starting treatment, and analysed the association between viral rebound and CD8 cell count.

Just over half the patients (54%) started therapy between 1996 and 1999. There have been significant improvements in HIV treatment since then. Therefore these years are often defined as the 'early antiretroviral therapy era'.

One year after starting treatment, patients had experienced a median fall in their baseline CD8 cell count  of 61 cells/mm³. Greater decreases were observed in patients who started therapy after 2000 (median decrease 109 cells/mm³ vs 32 cells/mm³; p < 0.001).

Individuals were followed for a median of four years, and two years after suppression of HIV a total of 12% of individuals had experienced a rebound in viral load. Rates of rebound were higher among patients who started therapy in the early treatment era than among those initiating therapy after 2000 (15 vs 9%). The overall rate of virologic failure was 5.6 per 100 person-years.

For people who started therapy after 2000, a higher CD8 cell count after one year of viral suppression was associated with a significant increase in the risk of subsequent viral rebound (above 1200 cells/mm³ vs below 600 cells/mm³, hazard ratio [HR] = 2.68, 95% CI, 1.13 to 6.35).

Almost a third of patients (31%) whose viral load rebounded had an elevated CD8 cell at 20% of their clinic visits in the period before treatment failure. These individuals were over 50% more likely to experience a rebound in viral load than patients whose CD8 cell count was elevated at fewer than 20% of visits (HR = 1.53, 95% CI, 1.14 to 2.06).

CD8 cell count increased by a median of 51 cells/mm³ among patients whose viral load became detectable, compared to a fall of 108 cells/mm³ for patients who maintained an undetectable viral load.

The investigators calculated that patients who experienced an increase in their CD8 cell count of 4% or more were 71% more likely to have virologic failure than other individuals (HR = 1.71; 95% CI, 1.28 to 2.28).

“We found that elevated total CD8 cell counts were associated with greater risk of future virologic failure,” comment the investigators.

They believe that their findings are of clinical relevance and write: “an elevated CD8 count may be one of the few indicators of future virologic failure among virally suppressed individuals who may not otherwise be viewed as at high risk of failure”.

The investigators therefore conclude: “by identifying those patients at increased risk of virologic failure, targeted efforts to confirm treatment adherence or increase the frequency of monitoring could be implemented with the goal of preventing virologic failure among those who are currently maintaining viral suppression.”

Krantz EM et al. Elevated CD8 counts during HAART are associated with HIV virologic treatment failure. J Acquir Immune Defic Syndr, online edition: doi: 10.1097/QAI.0b013e318221c62a, 2011 (click here for the free abstract).