Effects of protease inhibitors on the course of CMV retinitis in relation to CD4+ lymphocyte responses in HIV+ patients

Abstract

Aim: To gain insight into the course of CMV retinitis (CMVR) in AIDS patients receiving protease inhibitors (PI), and to evaluate whether certain patterns of CD4 response are indicative of the clinical outcome and the risk of recurrence.

Methods: 15 consecutive AIDS patients receiving maintenance therapy for CMVR were included in a prospective observational cohort study at the university hospital between July and October 1996. Patients were evaluated for signs of CMVR activity and intraocular inflammation. CMVR recurrence was defined as the primary clinical endpoint. Follow up was performed until July 1997. No patient was lost to follow up. Clinical outcome was related to CD4+ lymphocyte counts, which were monitored every 6 weeks. Highly active antiretroviral treatment regimen including PI was started at study entry.

Results: All recurrences (n = 7) were in patients who failed to have a sustained increase in CD4 counts, whereas CMVR remained inactive during a follow up of 42-52 weeks in those who were able permanently to restore their CD4 values to 100 x 10(6)/l or more (n = 5). The remaining three patients died after 12, 16, and 50 weeks, respectively, without recurrences. All relapses of CMVR were seen after 6-16 weeks, and at CD4 counts well below 100 x 10(6)/l.

Conclusions: The beneficial effects of PI treatment correlate with the pattern of CD4 response. Sustained increases in CD4 counts achieved in the first 16 weeks of treatment are associated with a prolonged period of CMVR quiescence. Poor initial response is associated with a high risk of CMVR recurrence.

Figure 1

Top: CD4 responses to protease inhibitor (PI) treatment. Individual counts are given at baseline, at 6-8, and at 12-16 weeks. (A) Non-responders. (B) Biphasic responders: an initial increase is followed by a return back to initial values. (C) Sustained responders: after an initial increase, a higher level is reached at 16 weeks and maintained for a prolonged period (up to 52 weeks). Bottom: Outcome with respect to CMVR: R=recurrence; S=smouldering; C=completely inactive. Patient 13, whose retinitis remained smouldering, was non-compliant with respect to his PI and anti-CMV medications, and died after 16 weeks of follow up. Vitritis is indicated by an asterisk.