Lack of Reactivation of Cytomegalovirus (CMV) Retinitis after Stopping CMV Maintenance Therapy in AIDS Patients with Sustained Elevations in CD4 T Cells in Response to Highly Active Antiretroviral Therapy

Abstract

The suppression of human immunodeficiency virus (HIV) replication and elevation in CD4 cells observed with protease inhibitor combination regimens known as HAART (highly active antiretroviral therapy) may allow AIDS patients to undergo an immune recovery that allows them to suppress the progression of cytomegalovirus (CMV) retinitis. Eleven AIDS patients receiving HAART with healed CMV retinitis in whom CMV-specific maintenance therapy was discontinued were studied. Median CD4 cell counts were 42 before the initiation of HAART and 183 at discontinuation of anti-CMV therapy. While a median 1.1 log 10 drop in plasma HIV-1 RNA was obtained between starting HAART and withdrawal of maintenance therapy for CMV, only 3 of 11 patients maintained plasma HIV RNA below the limits of detection. Reactivation of CMV retinitis after withdrawal of anti-CMV therapy did not occur in any of the patients observed for a median of 156 days (range, 92 -558).

Withdrawal of maintenance therapy for cytomegalovirus retinitis in AIDS patients exhibiting immunological response to HAART

“…Due to the low recurrence of CMV disease, we conclude, as previous literature reports suggest, that the withdrawal of CMV prophylaxis is a safe procedure in patients on HAART showing immune recovery 2,5,20,25,26,30,36,40,41,43,45 .…”

“…Studies addressing CMV immune recovery were first published in 1998 24,31,44 targeting both humoral 6 and cellular responses 23 . Clinical studies followed, demonstrating a low incidence of recurrence after withdrawal of secondary prophylaxis in small samples 4,5,7,19,25,30,32,36,41,45,46 .…”

Comparative Analysis of Human Cytomegalovirus-Specific CD4 + T-Cell Frequency and Lymphoproliferative Response in Human Immunodeficiency Virus-Positive Patients

“…those patients, possibly due to failure of reconstitution of the complete T-cell-receptor repertoire (4,6,8). In addition, current guidelines suggest maintenance or interruption of anti-HCMV therapy only based upon CD4 ϩ T-cell count (12,13,16,18,24,25,27). Furthermore, as shown in this study, some patients with low CD4 ϩ T-cell counts possess an apparently adequate anti-HCMV immune response and so would not require anti-HCMV therapy.…”

“…However, at least two reasons suggest that careful monitoring of HCMV disease in HIV-infected patients is still important: first, some cases of HCMV disease in patients with relatively high CD4 ϩ T-cell counts have been reported (7,10,11,15); second, the guidelines for the discontinuation of maintenance anti-HCMV therapy are mainly based on the CD4 ϩ T-cell count (12,13,16,18,24,25,27), regardless of any possible information on the reconstitution of the HCMV-specific immune response. Evaluation of specific anti-HCMV immunity could influence the clinical decision to discontinue or maintain anti-HCMV therapy in patients with previous HCMV disease and intermediate CD4 ϩ T-cell counts.…”

Prevención de las infecciones oportunistas en pacientes adultos y adolescentes infectados por el VIH. Recomendaciones de GESIDA/Plan Nacional sobre el Sida. Año 2003

“…En el primero se incluyeron 14 pacientes y no se detectaron recaídas tras una mediana de seguimiento de 16,4 meses 28 . En el segundo estudio, 3 de 22 pacientes que suspendieron la profilaxis secundaria sufrieron una recidiva de la retinitis por CMV 29 . En los 3 casos, los pacientes habían experimentado fracaso al TARGA y tenían una cifra de linfocitos T CD4+ < 50/l en el momento de la recaída.…”