Use CD4 cell count, not CD4 cell percentage to guide treatment decisions in all patients with HIV, even those with cirrhosis

CD4 cell counts and not CD4 cell percentages should be used to guide antiretroviral treatment decisions in all HIV-positive patients, including those with cirrhosis, according to Italian research published in the September 1^st edition of Clinical Infectious Diseases.

It had been hypothesised that CD4 cell percentages would provide a more accurate guide to the immune status of HIV-infected patients with cirrhosis, but analysis of almost 6,000 patients in a large Italian cohort revealed that CD4 cell count was a more accurate predictor than CD4 percentage of a patient’s risk of progressing to AIDS.

The study also found that even when the degree of immune damage was controlled for, patients with cirrhosis were statistically more likely to progress to AIDS than those without.

A study recently showed that HIV-negative individuals with cirrhosis had low CD4 cell counts, but normal CD4 cell percentages.

An editorial accompanying the study hypothesised that the same characteristics might be present in HIV-positive individuals and, as a result, CD4 cell percentages rather than CD4 cell counts should be used to guide decisions about the initiation of antiretroviral therapy in patients with advanced liver disease. But delaying the initiation of anti-HIV treatment in patients with low CD4 cell counts could have serious clinical implications. Therefore the author of the editorial called for studies evaluating the relationship between CD4 cell count and CD4 cell percentage in HIV-positive patients with cirrhosis. You can read the aidmap.com report on the study and editorial, here.

Researchers from the Italian Cohort of Antiretroviral-Naïve Patients (ICoNA) therefore compared CD4 cell counts with CD4 cell percentages as a means of predicting the risk of progression to AIDS in HIV-positive patients with cirrhosis.

Investigators assessed the risk of progression to AIDS in patients with cirrhosis or other serious liver disease and those without. At enrollment, all patients were antiretroviral-naïve. a

The investigators divided their patients into three groups. Group one comprised individuals without liver disease, defined as the absence of either hepatitis B or hepatitis C and normal ALT levels. Group two included patients with hepatitis B or C but no evidence of cirrhosis. And patients in group three had a clinical or histological diagnosis of cirrhosis.

Data were collected on CD4 cell counts and CD4 cell percentages and the incidence of new AIDS-defining illnesses.

A total of 5917 individuals were included in the investigators’ analysis. Median CD4 cell count at baseline was 427 cells/mm³ and median CD4 cell cont was 23%. Hepatitis C coinfection was present in 38% of patients, and a further 5% were coinfected with hepatitis B. At baseline 4% of patients had an AIDS defining illness and 154 patients were cirrhotic, with a further 85 patients progressing to this diagnosis during follow-up.

During 25,000 patient years of follow-up, 402 patients progressed to AIDS providing an incidence of 1.6 per 100 person years.

Unsurprisingly, in each of the three groups of patients, individuals with a CD4 cell count below 200 cells/mm³ were significantly more likely than those with a CD4 cell count above 500 cells/mm³ to progress to AIDS. This difference was most noticeable for patients in group 1 (p < 0.01). Similarly, patients with a CD4 cell percentage below 14% were much more likely than those with a normal CD4 cell percentage, above 28%, to progress to AIDS. This difference was most noticeable amongst patients in group three (p = 0.03).

The investigators then looked at CD4 cell count and CD4 percentage a continuous variables for the risk of progressing to AIDS for patients in each of the three groups.

For patients in group one, they found that higher CD4 cell counts, (p = 0.006 for every 100 cell/mm³ increase), but not higher CD4 cell percentages were protective against the risk of progressing to AIDS.

For patients in both group two and group three, a low CD4 cell count predicted the risk of progressing to AIDS (p = 0.001 per 100 cells/mm³). They also found that a low CD4 cell percentage predicted a risk of HIV disease progression for patients in these groups (p = 0.006 per 10% for patients in group three), but not to the same extent as CD4 cell count.

Cirrhotic patients had a higher risk of progression to AIDS (p = 0.009) than other patients, even when adjusting for the current degree of immune suppression.

“We found, that for each study group, the CD4 cell count was a better predictor of the risk of developing an AIDS-defining illness than CD4 cell percentage” write the investigators. They conclude, “our data confirm that HIV-infected patients with cirrhosis are at a higher risk of developing an AIDS-defining illness than are HIV-infected patients without cirrhosis. These findings suggest that the absolute CD4 cell count should be used to guide therapy decisions for all HIV-infected patients.”