Lowest-Ever CD4 Cell Count Predicts Both AIDS-defining and Non-AIDS-related Illnesses

By Liz Highleyman

It is well known that CD4 cell count, a marker for immune function, predicts the risk of developing opportunistic infections or AIDS-defining illness in people with HIV. But recent data suggest that lowest-ever (nadir) CD4 cell count also predicts the chances of developing non-AIDS-defining conditions.

Researchers with the large CASCADE Collaboration, which includes more than 10,600 participants in more than 20 cohorts of HIV seroconverters in Europe, Canada, and Australia, conducted a study to assess the relationship between markers of HIV disease progression and 5 specific causes of death in patients followed since 1996. Results were reported at the recent 4th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention in Sydney, Australia (July 22-25, 2007).

The investigators measured the time from seroconversion to specific causes of death (or censoring date). Potential determinants were nadir CD4 cell count, HIV viral load, AIDS stage C, age at seroconversion, sex, HIV transmission category, hepatitis C virus (HCV) serostatus, and type of first-line antiretroviral therapy.

Results

• Among 10,661 cohort participants, 665 deaths were reported during 83,830 persons-year of follow-up.

• 186 deaths (28%) were AIDS-related and 366 (55%) were non-AIDS-related.

• The deaths classified as non-AIDS-related included:

- 51 non-AIDS-defining infections (7.6% of all deaths);
- 49 cases of liver diseases (7.4%);
- 47 non-AIDS-defining malignancies (7.1%);
- 40 cases of cardiovascular diseases (6.0%);
- 113 deaths of unknown cause (17%).

• As expected, AIDS-related deaths were strongly associated with nadir CD4 count, HIV viral load, AIDS stage C.

• Similarly, fatal non-AIDS infections were associated with nadir CD4 cell count < 50 cells/mm3, viral load ? 5 log copies/ml, and AIDS stage C.

• Fatal liver disease was associated with nadir CD4 count < 200 cells/mm3 and HCV coinfection.

• Fatal non-AIDS-defining malignancies were associated with nadir CD4 count or 200-349 or < 200 cells/mm3, AIDS stage C, and age greater than 35 years.

• Fatal cardiovascular disease was associated with AIDS stage and age greater than 35 years.

Conclusion

In [the combination antiretroviral therapy] era, death due to non-AIDS infections, liver diseases, non-AIDS malignancies and cardiovascular diseases are frequent and associated with either laboratory or clinical markers of HIV progression," the researchers concluded. "Earlier initiation of [combination antiretroviral therapy] might have an impact on other fatal morbidities than AIDS."

INSERM U593, Bordeaux, France; INSERM U875, Bordeaux, France; INSERM U720, Paris, France; Istituto Superiore di Sanita, Rome, Italy; Basel Institute for Clinical Epidemiology, Basel, Switzerland; Robert Koch-Institute, Berlin, Germany; MRC Clinical Trial Unit, London, UK.

08/31/07

Reference
B Marin, R Thiébaut, V Rondeau, and others. Association between CD4 and HIV RNA with non AIDS-related causes of death in the era of combination antiretroviral therapy (cART). 4th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention. Sydney, Australia, July 22-25, 2007. Abstract WEPEB019.