Prospective clinical trials of HIV therapy and cohort studies typically describe a rapid immunologic response to treatment in the first year of therapy, followed by a slowing and an eventual plateau of the CD4+ cell response. One of the longest prospective clinical studies performed since the introduction of potent combination therapy is the Abbott 720 study, which had seven years of follow-up on treatment-naive patients who initiated a lopinavir/ritonavir (LPV/r, Kaletra)-containing regimen. Here the Abbott researchers have applied statistical methods to describe the phenomenon of the CD4+ cell count plateau based on starting CD4+ cell count.¹

One hundred study participants were included in the analysis. Seventeen of the participants had a baseline CD4+ cell count of less than 50. Nineteen had baselines between 50 and 199, while the remainder had a starting count of 200 or greater. Applying a complex statistical model to the data, the researchers found that the time to CD4+ cell count plateau and level achieved differed based on the starting CD4+ cell count, as shown in the table below:

In summary, patients starting therapy with the lowest counts experienced a longer time before reaching their CD4+ cell count plateau and they never caught up to the groups that started with higher counts. This finding also has been confirmed in other studies.

It is notable that only the group initiating treatment with a CD4+ cell count greater than 200 achieved a plateau level consistently in the normal range. However, whether there is a clinical benefit to having a normal CD4+ cell count on treatment versus one in the 500s is not yet known, but certainly it has been proven that starting therapy prior to severe immunosuppression is associated with a better clinical outcome.

The authors also note that the long-term CD4+ cell increases observed in the study are of a greater magnitude and a longer duration than those described in other studies (a total of nine are cited), suggesting a possible advantage to boosted protease inhibitors in generating greater immune responses.

Footnote

1. King M, Da Silva BA, McMillan F, Niemi K, Hanna GJ. When does the CD4 cell count plateau? Evidence from subjects treated with a lopinavir/ritonavir-based regimen for up to 7 years. In: Program and abstracts of the 46th Interscience Conference on Antimicrobial Agents and Chemotherapy; September 27-30, 2006; San Francisco, Calif. Abstract H-1401.
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