Incomplete Peripheral CD4+ Cell Count Restoration in HIV-Infected Patients Receiving Long-Term Antiretroviral Treatment

In most HIV-positive patients, antiretroviral therapy can fully restore a normal CD4+ cell count of more than 500 cells/mm3. However, the researchers note, it is not clear whether all patients can achieve normalization of their CD4+ cell count, in part because no study has followed up patients for more than seven years.

The subjects of the current study were 366 patients from five clinical cohorts who maintained a plasma HIV RNA level of no more than 1,000 copies/mL for at least four years after initiation of antiretroviral therapy. Mixed-effects modeling, spline-smoothing regression, and Kaplan-Meier techniques were used to evaluate changes in CD4+ cell count.

Most (83 percent) of the subjects were men; the subjects' median age was 47. At the time of therapy initiation, the median CD4+ cell count was 201 (interquartile range, 72-344 cells/mm3). The median follow-up period was 7.5 years (interquartile range, 5.5-9.7 years).

Throughout the follow-up period, CD4+ cell counts continued to increase, though slowly after year 4. Almost all (95 percent) of patients who started therapy with a CD4+ cell count of at least 300 were able to attain a CD4+ cell count of 500 or more; however, 44 percent of those who started therapy with a CD4+ cell count of less than 100, and 25 percent of those who started therapy with a CD4+ count of 100-200, were unable to achieve a CD4+ count of more than 500 over a mean duration of 7.5 years. Many did not reach this threshold by year 10. Among patients with a CD4+ cell count of less than 500 at year 4, 24 percent had evidence of a CD4+ cell count plateau after year 4. The frequency of detectable viremia, or "blips," after year 4 was not associated with the magnitude of the CD4+ cell count change.

"A substantial proportion of patients who delay therapy until their CD4+ cell count decreases to <200 cells/mm3 do not achieve a normal CD4+ cell count, even after a decade of otherwise effective antiretroviral therapy," the authors concluded. "Although the majority of patients have evidence of slow increases in their CD4+ cell count over time, many do not. These individuals may have an elevated risk of non-AIDS-related morbidity and mortality."