Safe interruption of maintenance therapy against previous infection with four common HIV-associated opportunistic pathogens during potent antiretroviral therapy

Background: The safety of interrupting maintenance therapy for previous opportunistic infections other than Pneumocystis carinii pneumonia among patients with HIV infection who respond to potent antiretroviral therapy has not been well documented. Objective: To assess the safety of interrupting maintenance therapy for cytomegalovirus (CMV) end-organ disease, disseminated Mycobacterium avium complex (MAC) infection, cerebral toxoplasmosis, and extrapulmonary cryptococcosis in patients receiving antiretroviral therapy. Design: Observational study. Setting: Seven European HIV cohorts. Patients: 358 patients taking potent antiretroviral therapy (greater than or equal to3 drugs) who interrupted maintenance therapy at a CD4 lymphocyte count greater than 50 x 10(6) cells/L. Measurements: Recurrence of opportunistic infection after interruption of maintenance therapy. Results: 379 interruptions of maintenance therapy were identified: 162 for CMV disease, 103 for MAC infection, 75 for toxoplasmosis, and 39 for cryptococcosis. During 781 person-years of follow-up, five patients had relapse. Two relapses (one of CMV disease and one of MAC infection) were diagnosed after maintenance therapy was interrupted when the CD4 lymphocyte count was less than 100 x 106 cells/L or when only one recent measurement exceeded this value. Two relapses (one of CMV disease and one of MAC infection) were diagnosed after maintenance therapy was interrupted once CD4 counts were greater than 100 x 106 cells/L for 10 and 8 months, respectively. One relapse (toxoplasmosis) was diagnosed after maintenance therapy interruption at a CD4 lymphocyte count greater than 200 x 106 cells/L for 15 months. The overall incidences of recurrent CMV disease, MAC infection, toxoplasmosis, and cryptococcosis were 0.54 per 100 person-years (95% Cl, 0.07 to 1.95 per 100 person-years), 0.90 per 100 person-years (Cl, 0.11 to 3.25 per 100 person-years), 0.84 per 100 person-years (Cl, 0.02 to 4.68 per 100 person-years), and 0.00 per 100 person-years (Cl, 0.00 to 5.27 per 100 person-years), respectively. Conclusion: Maintenance therapy against previous infection with CMV, MAC, Toxoplasma gondii, or Cryptococcus neoformans in patients with HIV infection can be interrupted after sustained CD4 count increases to greater than 200 (or possibly 100 to 200) x 106 cells/L for at least 6 months after the start of potent antiretroviral therapy.