A Randomized, Double‐Blind Trial of Valaciclovir Prophylaxis for Cytomegalovirus Disease in Patients with Advanced Human Immunodeficiency Virus Infection

Feinberg, Judith; Hurwitz, Shelley; Cooper, David A.; Sattler, Fred R.; MacGregor, Rob Roy; Powderly, William; Holland, Gary N.; Griffiths, Paul; Pollard, Richard B.; Youle, Michael; Gill, M John; Holland, F. J.; Power, Maureen; Owens, Susan; Coakley, Dion F.; Fry, John; Jacobson, Mark A.

doi:10.1086/513804

Cited by 125 publications

(50 citation statements)

References 25 publications

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“…22 Furthermore, an impact of acyclovir on survival was seen in patients with advanced HIV disease. 23 The safety profile of valacyclovir was similar to that of high-dose acyclovir; adverse events were comparable between the groups. In particular the increased risk for TMA reported in a study of human immunodeficiency-infected patients 23,24 was not seen in this study.…”

Section: Discussionmentioning

confidence: 78%

“…23 The safety profile of valacyclovir was similar to that of high-dose acyclovir; adverse events were comparable between the groups. In particular the increased risk for TMA reported in a study of human immunodeficiency-infected patients 23,24 was not seen in this study. The low incidence (17%) of acute GVHD grades 2 to 4 in this study of CMV-seropositive patients (or negative with a positive donor) is interesting because several studies have shown an association between pretransplantation CMV seropositivity and the probability for GVHD.…”

Section: Discussionmentioning

confidence: 78%

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Randomized study of valacyclovir as prophylaxis against cytomegalovirus reactivation in recipients of allogeneic bone marrow transplants

Ljungman¹,

Cámara²,

Milpied³

et al. 2002

Blood

172

122

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Oral valacyclovir for cytomegalovirus (CMV) prophylaxis in bone marrow transplantation (BMT) was investigated in a randomized, double-blind, acyclovircontrolled, multicenter clinical trial in recipients of allogeneic BMT who were CMV seropositive (or donor positive) before transplantation and were aged 13 years or older. Patients were randomized before BMT. All initially received intravenous acyclovir (500 mg/m 2 ) 3 times daily until day 28 after transplantation or after discharge, then oral valacyclovir (2 g) or acyclovir (800 mg) 4 times daily until week 18 after transplantation. Evidence of CMV infection, CMV disease, and death were documented for 22 weeks. Primary end points were time to CMV infection (detection of CMV in blood, bronchoalveolar lavage) or CMV disease and survival. Preemptive CMV therapy was permitted. Seven hundred twenty-seven patients were evaluable for efficacy. After the administration of intravenous acyclovir, valacyclovir was significantly more effective than oral acyclovir in reducing the incidence of CMV infection. CMV infection or disease developed in 102 (28%) valacyclovir patients, compared with 143 (40%) acyclovir patients (HR, 0.59; 95% CI, 0.46-0.76; P < .0001). Survival did not differ between treatments (76% and 75% in the valacyclovir and acyclovir groups, respectively). The safety of oral valacyclovir was similar to that of high-dose oral acyclovir. Valacyclovir was more effective than acyclovir in preventing CMV reactivation in BMT recipients and showed a similar safety profile. CMV disease incidence was low, and no differences were observed between oral valacyclovir and acyclovir. Survival was similar in each group. Valacyclovir prophylaxis provides a clinically valuable intervention but must be part of an overall strategy for CMV prevention in BMT. (Blood. 2002;99: 3050-3056)

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Section: Discussionmentioning

confidence: 78%

Section: Discussionmentioning

confidence: 78%

Randomized study of valacyclovir as prophylaxis against cytomegalovirus reactivation in recipients of allogeneic bone marrow transplants

Ljungman¹,

Cámara²,

Milpied³

et al. 2002

Blood

172

122

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“…All subjects received herpesvirus prophylaxis with valaciclovir (500 mg orally daily if not receiving GCV), a regimen with limited anti-CMV activity. 24 …”

Section: Diagnosis and Clinical Management Of CMV Reactivationmentioning

confidence: 99%

Cytomegalovirus reactivation following allogeneic stem cell transplantation is associated with the presence of dysfunctional antigen-specific CD8+ T cells

Özdemir

John

Gillespie

et al. 2002

Blood

192

162

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Cytomegalovirus (CMV) infection causes significant morbidity and mortality in the setting of immunodeficiency, including the immune reconstitution phase following allogeneic stem cell transplantation (SCT). We assessed CMV-specific CD4 ؉ and CD8 ؉ T-cell responses in 87 HLA-A*0201-positive (A2؉) and/or B*0702-positive (B7؉) allogeneic stem cell transplant recipients using HLA-peptide tetramer staining and cytokine flow cytometry (CFC) to examine the association of CMV-specific immune reconstitution and CMV antigenemia following SCT. Strong CMV-specific T-cell responses recovered in most subjects (77 of 87, 88%) after SCT. Frequencies of CMV-specific CD8 ؉ T cells were significantly higher in those subjects who experienced early antigenemia relative to those who did not (2.2% vs 0.33%, P ‫؍‬ .0002), as were frequencies of CMV-specific CD4 ؉ T cells (1.71% vs 0.75%, P ‫؍‬ .002). Frequencies of CMV-specific CD8 ؉ T cells were also higher in subjects experiencing late antigenemia (2.4% vs 0.57%). When we combined tetramer staining and an assessment of cytokine production in a single assay, we found that individuals who experienced CMV antigenemia had lower tumor necrosis factor-␣ (TNF-␣)-producing fractions of tetramer-staining CMVspecific CD8 ؉ T cells than subjects who did not (25% vs 65%, P ‫؍‬ .015). Furthermore, individuals at high risk for CMV reactivation, including patients with acute graft-versus-host disease and those receiving steroids, had low fractions of cytokine-producing CMV-specific CD8 ؉ T cells (25% and 27%, respectively). These data suggest that the inability to control CMV reactivation following allogeneic SCT is due to the impaired function of antigenspecific CD8 ؉ T cells rather than an inability to recover sufficient numbers of CMV-specific T cells. (Blood. 2002;100: 3690-3697)

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“…[13][14][15] Recent prospective randomized studies using valacyclovir for the prophylactic treatment of CMV infection have shown safety and efficacy in patients with renal transplants and AIDS. [16][17][18][19] However, the benefit of this approach for CMV prophylaxis in SCT recipients has not been reported. We hypothesized that valacyclovir could be useful in the prevention of primary CMV reactivation (drug administered prior to CMV reactivation) or after successful treatment of reactivation with either ganciclovir or foscarnet (secondary prophylaxis) in patients who remain at risk for future reactivation.…”

mentioning

confidence: 99%

Valacyclovir for the prevention of cytomegalovirus infection after allogeneic stem cell transplantation: a single institution retrospective cohort analysis

Vusirikala

Wolff

Stein

et al. 2001

Bone Marrow Transplant

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Summary:A retrospective single center study was performed to evaluate the safety and efficacy of valacyclovir for prevention of cytomegalovirus (CMV) infection (reactivation) after allogeneic stem cell transplantation (SCT). We compared a group of 31 patients at risk for CMV reactivation (donor, recipient or both seropositive for CMV) who received valacyclovir at an oral dose of 1 g three times a day for CMV prophylaxis with a matched cohort of 31 patients who did not receive the drug or any other form of CMV prophylaxis. Valacyclovir was used as primary prophylaxis in 12 patients and as secondary prophylaxis (after a prior CMV reactivation was effectively treated with either ganciclovir or foscarnet and without CMV antigenemia at the start of valacyclovir) in the remaining 19 patients. The two treatment groups were well matched for the donorrecipient CMV serological status and other pre-transplant characteristics. CMV reactivation was detected by blood antigenemia testing using a commercially available immunofluorescence assay for CMV lower matrix protein pp65 in circulating leukocytes. For primary prophylaxis, 3/12 patients who received valacyclovir reactivated CMV compared to 24/31 patients in the control group (P Ͻ 0.001). For secondary prophylaxis, 5/19 valacyclovir patients reactivated compared to 16/24 control patients (P Ͻ 0.05). Valacyclovir was well tolerated except for infrequent and mild gastrointestinal sideeffects. There was no difference in the incidence of CMV disease in the two groups. Prophylaxis with valacyclovir appears to be safe and efficacious in preventing both primary and secondary CMV reactivation in at-risk patients after allogeneic SCT. Larger prospective randomized studies will be required to confirm these observations. Bone Marrow Transplantation (2001) 28, 265-270.

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A Randomized, Double‐Blind Trial of Valaciclovir Prophylaxis for Cytomegalovirus Disease in Patients with Advanced Human Immunodeficiency Virus Infection

Cited by 125 publications

References 25 publications

Randomized study of valacyclovir as prophylaxis against cytomegalovirus reactivation in recipients of allogeneic bone marrow transplants

Randomized study of valacyclovir as prophylaxis against cytomegalovirus reactivation in recipients of allogeneic bone marrow transplants

Cytomegalovirus reactivation following allogeneic stem cell transplantation is associated with the presence of dysfunctional antigen-specific CD8+ T cells

Valacyclovir for the prevention of cytomegalovirus infection after allogeneic stem cell transplantation: a single institution retrospective cohort analysis

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