December 18, 2001
Discontinuation of maintenance therapy for certain opportunistic infections has become relatively routine in patients who have significant immune reconstitution with highly active antiretroviral therapy (HAART). A prospective cohort study presented at the 41st ICAAC evaluated the safety of discontinuing maintenance therapy for cytomegalovirus retinitis (CMVR) in patients who have experienced a significant immune response with HAART and evaluated virologic and immunologic predictors of relapse.
Patients were eligible for the study if they had non-zone 1 CMVR which had been inactive for >3 months while on maintenance therapy and were on a stable HAART regimen with a CD4 T-cell count >50 cells/mm3. The enrolled patients were followed very carefully, with frequent ophthalmological evaluations, CMV blood and urine cultures, blood CMV antigenemia and PCR assays. CD4 T-cell counts, HIV viral loads and CMV lymphoproliferative assays (LPA) on peripheral blood mononuclear cells (PBMCs) were performed at baseline and every three months.
Of the 17 patients enrolled in the study, CMVR was diagnosed a mean of 33 months before study entry. The mean CD4 T-cell count at entry was 446 cells/mm3 (range 78-1270), and 14 patients had an HIV viral load of <50 copies/ml. After a mean follow-up of 12 months, the mean CD4 T-cell count had risen to 526 cells/mm3 and 14 patients had a viral load of <50 copies/mL. Five patients, none of whom relapsed, were intermittently or continuously urine-culture-positive for CMV. All CMV blood cultures, CMV antigenemia assays and PCR assays were negative. One patient with a CD4 T-cell count of 607 cells/mm3 and an HIV viral load <50 copies/mL experienced a reactivation of CMVR 12 months after discontinuing CMVR maintenance therapy and responded to reinitiation of ganciclovir.
Of 10 patients with complete LPA data available, three did not have a significant proliferative response to CMV after six months of follow-up, including the patient that ultimately relapsed. The authors concluded, "Only one of 17 patients who had responded to HAART and discontinued CMV maintenance therapy experienced a reactivation. Urine cultures appear to be a poor predictor for relapse, whereas the lack of a proliferative response to CMV may be associated with an increased risk of reactivation."
Due to the burden and risk of maintenance therapy for CMVR, many clinicians and patients contemplate discontinuing it once significant reconstitution has occurred. Some prior studies have shown this practice to be relatively safe; however, this study raises a red flag against viewing it as routine. Unfortunately, LPA for CMV are not routinely available and while this study indicated that failure to develop an LPA may be a risk factor for developing CMVR (which makes sense), these will not be available to most clinicians or patients struggling with this issue. The bottom line seems to be that if a decision is made to discontinue CMVR maintenance therapy, patients should be closely followed for evidence of a relapse.