CMV retinitis recurs after stopping treatment in virological and immunological failures of potent antiretroviral therapy

OBJECTIVES: To determine predictors of clinical relapse of cytomegalovirus (CMV) end-organ disease in a cohort of 17 HIV-infected patients with healed and treated CMV retinitis (CMVR) who responded to HAART with an increase in CD4 cell counts to above 70 cells/mm3 and discontinued CMV maintenance therapy (MT). DESIGN: Seventeen patients were monitored for reactivation of retinitis. The CD4 cell counts, HIV RNA and peripheral blood mononuclear cell (PBMC) lymphoproliferative assays to CMV at 3 month intervals were compared between patients with and without reactivation of CMVR. Positive lymphoproliferative responses were defined as a stimulation index of 3 or greater. RESULTS: Five out of 17 (29%) patients experienced a recurrence of CMVR a mean of 14.5 months after stopping CMV MT and between 8 days and 10 months after CD4 cell counts fell below 50 cells/mm3. Median CD4 cell counts and plasma HIV RNA at reactivation were 37 cells/mm3 and 5.3 log10 copies/ml. Three patients recurred at a previously active site of the retina, one had contralateral CMVR, and one a recurrence of retinitis and pancreatitis simultaneously. Mean lymphoproliferative responses to CMV were 2.4 in patients with reactivation versus 21.0 stimulation index (SI) in patients without reactivation (P= 0.01). A model incorporating four variables (CD4 cell counts and HIV RNA at maintenance discontinuation, highest CD4 cell count, nadir HIV RNA and median lymphoproliferative responses) identified correctly 88% of patients with and without reactivation. CONCLUSION: CMV disease recurs after virological and immunological failure of HAART if CD4 cell counts drop below 50. In this situation, anti-CMV agents should be resumed before clinical reactivation ensues, because of the risk of contralateral retinal involvement and systemic disease

The immune reconstitution inflammatory syndrome related to HIV co-infections: a review

The immune reconstitution inflammatory syndrome (IRIS) is a consequence of an excessive pathogen-specific immune recovery reaction and occurs in a subset of patients on antiretroviral therapy (ART). Infective forms of IRIS may present either as an 'unmasking' of a previously subclinical infection or the paradoxical clinical deterioration of an infection for which the patient received appropriate antimicrobial therapy. The most important risk factors for IRIS are a low CD4+ T-cell count and a short time between treatment of the infection and the commencement of ART. The general approach to the treatment of IRIS is to continue ART and provide antimicrobial therapy for the provoking infection. The majority of cases are self-limiting; however, mortality and hospitalisation rates are particularly high when tuberculosis- or cryptococcal-IRIS affects the central nervous system (CNS). Corticosteroid therapy should be considered in certain forms of IRIS after the exclusion of other conditions that could explain the inflammatory manifestations in the patients. Given that a low CD4+ T-cell count is a major risk factor for the development of IRIS, commencing ART at a CD4+ T-cell count of >350/muL will prevent most cases