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.


METHODS
Observational study.


METHODS
Seven European HIV cohorts.


METHODS
358 patients taking potent antiretroviral therapy (> or =3 drugs) who interrupted maintenance therapy at a CD4 lymphocyte count greater than 50 x 10(6) cells/L.


METHODS
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 10(6) 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 10(6) 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 10(6) 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% CI, 0.07 to 1.95 per 100 person-years), 0.90 per 100 person-years (CI, 0.11 to 3.25 per 100 person-years), 0.84 per 100 person-years (CI, 0.02 to 4.68 per 100 person-years), and 0.00 per 100 person-years (CI, 0.00 to 5.27 per 100 person-years), respectively.


CONCLUSIONS
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 10(6) cells/L for at least 6 months after the start of potent antiretroviral therapy.
Coordinating Centre of EuroSIDA, Department of Infectious Diseases, Hvidovre Hospital, University of Copenhagen, Kettegaard Alle, 2650 Hvidovre, Denmark. oki@cphiv.dk
Ole
O
Kirk
Peter
P
Reiss
Caterina
C
Uberti-Foppa
Markus
M
Bickel
Jan
J
Gerstoft
Christian
C
Pradier
Ferdinand W
FW
Wit
Bruno
B
Ledergerber
Jens D
JD
Lundgren
Hansjakob
H
Furrer
D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy* / Q000276:immunology; D000328:Adult; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D003453:Cryptococcosis / Q000188:drug therapy / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000188:drug therapy / Q000276:immunology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015270:Mycobacterium avium-intracellulare Infection / Q000188:drug therapy / Q000276:immunology; D017063:Outcome Assessment, Health Care; D012008:Recurrence; D016781:Toxoplasmosis, Cerebral / Q000188:drug therapy / Q000276:immunology
D000890:Anti-Infective Agents