Discontinuation of maintenance therapy for cryptococcal meningitis in HIV-1-infected persons receiving highly active antiretroviral therapy

Background. Little is known on whether HIV-infected persons with cryptococcal meningitis can discontinue maintenance therapy following HAART-induced immune-reconstitution. The present study is a longitudinal multicentre observational study which aims to determine the incidence of relapses of cryptococcal meningitis among persons undergoing HAART. Methods. The study was conducted by reviewing the clinical charts of HIV-positive adults who had ever attended, as consecutive outpatients, 10 hospital-based infectious-disease clinics located throughout Italy. We included all of the persons who had recovered from at least one episode of cryptococcal meningitis, and who were currently undergoing HAART. The study group consisted of those persons who had discontinued maintenance therapy for cryptococcal meningitis; the, control group consisted of those persons who were still undergoing maintenance therapy. Of the 45 study participants, 24 had discontinued maintenance therapy and 21 had continued. At the time of discontinuation, for the discontinuing participants, the mean CD4 cell count was 113.5 cells/mL, although 12 (50.0%) of them had less than 100 cells/mL; the mean plasma viral load was 2.48 log10 copies/mL; and 12 of them (50.0%) were seropositive for cryptococcal antigen. Results. At the end of the observation period, for the discontinuing participants, the mean CD4 count was 330 cells/mL (compared to 240 cells/mL for the continuing participants); the mean plasma viral load was 2.34 log10 copies/mL (compared to <1.90 log10 copies/mL for the continuing participants); and 2 of the discontinuing participants were seropositive for cryptococcal antigen (compared to 13 continuing participants) (p<0.01). After a mean observation time of 27.5 months for the discontinuing participants (57.9 person-years), no relapse of cryptococcal meningitis was observed or even suspected. Conclusions. This study suggests that persons receiving HAART could consider safety discontinuing maintenance therapy for cryptococcal meningitis, as has been previously described for other opportunistic infections.