December 18, 2001
The cause and significance of discordant immunological/virological responses in severely immunosuppressed patients on highly active antiretroviral therapy (HAART) is unclear. A prospective study presented at the 41st ICAAC evaluated 187 antiretroviral-naive patients who started protease inhibitor-based HAART with a CD4 T-cell count <200 cells/mL.
One hundred fifty-five of these patients (83 percent) achieved an undetectable viral load within one year of starting HAART. Of these 155 patients, 75 percent were men, and baseline median age, viral load and CD4 T-cell count were 39 years, 5.3 log10 copies/mL and 87 cells/mm3, respectively. AIDS was present in 45 percent of the patients. The percentage of patients with persistent immunosuppression despite an undetectable viral load decreased with duration of HAART, from 45 percent at 12 months to 21 percent and 8 percent at 24 and 36 months, respectively.
Using a univariate analysis, persistent immunosuppression was associated with male gender, prior AIDS diagnosis, and lower CD4 T-cell counts (mean 62 cells/mm3 versus 110 cells/mm3). Using a multivariate analysis persistent immunosuppression was only associated with baseline CD4 T-cell count (p<0.001). The rate of clinical events, admissions and deaths were similar in both groups, but there were significant differences in the number of outpatient visits and admissions per patient, and the time to the first admission.
Herpes zoster and bacterial pneumonia were the most frequent clinical events and tuberculosis was more common in patients with persistent immune suppression (24 percent versus 6 percent). The authors conclude, "Delaying HAART until advanced immunosuppression produces a higher risk of incomplete immunological recovery despite an adequate virological response."
These data are somewhat reassuring for patients who have failed to have significant immune reconstitution while on HAART, since in this study they were not at higher risk for opportunistic infections or other complications of AIDS. This study and other studies make it quite clear, however, that delaying therapy until the patient has significant immune suppression may be a mistake.
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