Adherence, not baseline CD4 cell count, linked to CD4 cell gain on HAART

Patients with the highest levels of adherence experience the best improvements in their CD4 cell counts, irrespective of baseline CD4 cell count, according to a Canadian study published in the March 1^st edition of the Journal of Acquired Immune Deficiency Syndromes. The authors of the study say that their findings may raise confidence in delaying treatment until the CD4 cell count falls near to 200 cells/mm³.

The investigators from the HAART Observational Medical Evaluation and Research (HOMER) study conducted their research because of concerns, reflected in early HAART treatment guidelines, that individuals would experience irreversible immune damage if they delayed initiating HAART until their CD4 cell count fell below 350 cells/mm³. The HOMER investigators were concerned that studies supporting this theory did not take into account the importance of patient adherence to HAART when assessing the degree of CD4 cell gain experienced.

Accordingly, the CD4 cell response to therapy was evaluated by the investigators in 1522 antiretroviral-naïve patients initiating HAART between 1996 and 2000. The patients were followed until March 2002 and were divided into three categories, according to their CD4 cell count at the time they started HAART (category one, patients with very severe immune suppression, a CD4 cell count below 50 cells/mm³; category two, individuals with a high degree of immune damage, a CD4 cell count above 50 cells/mm³ but below 200 cells/mm³; and category three, patients with a CD4 cell count above 200 cells/mm³.

A CD4 cell response was assessed as a CD4 cell gain of 50 or more cells/mm³ in two consecutive tests after starting HIV therapy. Observation was divided into five 15-week periods.

At baseline, data were also gathered on gender, age, history of injecting drug use, and previous AIDS-defining illnesses.

The majority of patients (925, 60.8%) started HAART with a CD4 cell count above 200 cells/mm³ (median 300 cells/mm³), although a little over a quarter (393 patients, 25.8%) had a CD4 cell count between 50 cells/mm³ and 199 cells³ (median 135 cells/mm³). 205 individuals (13.4%) had severe immune suppression and a CD4 cell count below 50 cells/mm³ (median 20 cells/mm³).

Adherence was assessed by analysing the number of prescriptions patients refilled, and individuals refilling at least 75% of their HAART prescriptions were classed as adherent. This measure of adherence is less stringent than methods used in many other studies.

Further analysis showed that individuals assessed to be at least 95% adherent were most likely to achieve a CD4 cell response (93.1% of individuals, against 84% of individuals with adherence between 94% and 75%). 95% adherence has been associated with the best long-term viral load outcomes in several studies.

The investigators found a significant association between CD4 cell gain and adherence. During the fifth 15-week period of observation, absolute CD4 cell counts for adherent patients who had a baseline CD4 cell count below 50 cells/mm³ had increased to 200 cells/mm³ but those of non-adherent patients had only increased to 60 cells/mm³ (p=0.009). The results were similar for patients starting HAART with a CD4 cell count between 50 cells/mm³ and 199 cells/mm³, with absolute CD4 cell count increasing to 300 cells/mm³ amongst adherent patients, compared to only 125 cells/mm³ in individuals filling less than 75% of their prescriptions (p3, adherence was again associated with bigger increases in CD4 cell counts (550 cells/mm³ versus 300 cells/mm³, p3 in two consecutive measurements at month 24) was found to be associated with adherence (p

Although adherence remained the strongest predictor of CD4 cell gain in multivariate analysis (RH 2.88), age (RH 1.01), baseline viral load (RH1.17) and male gender (male versus female, RH 1.37) were also independently associated with CD4 cell response (tested t0 p

”We found that substantial and sustained gains in CD4 cell count were observed among adherent patients, regardless of baseline CD4 cell count,” comment the investigators, adding, “in addition, the time to CD4 cell response was most strongly predicted by patient adherence… even among patients who initiated HAART with CD4 cell counts below 200 cells/mm³.”

These results suggest to the investigators that “previous studies showing that CD4 cell counts 3 may preclude a CD4 cell count response might have been confounded by patient non-adherence.”

They conclude, “our findings do not support the notion that irreversible immune damage precludes a CD4 response to HAART if the CD4 cell count declines below 350 cells/mm³ and may raise confidence in the 200 cell/mm³ threshold for the initiation of HAART.”

Further information on this website

Adherence menu

When to start anti-HIV therapy menu

Factsheets on HIV therapy and adherence

Adherence pdf of the 2003 edition of the booklet in the information for HIV-positive people series. The 2004 edition is available by e-mailing info@nam.org.uk.