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L Corey

Publications and source records attributed to L Corey.

At least 37 records · Page 2Linked to original sources
PubMed2001

CD8 CTL from genital herpes simplex lesions: recognition of viral tegument and immediate early proteins and lysis of infected cutaneous cells.

HSV-2 causes chronic infections. CD8 CTL may play several protective roles, and stimulation of a CD8 response is a rational element of vaccine design for this pathogen. The viral Ags recognized by CD8 T cells are largely unknown. It has been hypothesized that HSV inhibition of TAP may favor recognition of virion input proteins or viral immediate early proteins. We tested this prediction using HSV-specific CD8 CTL clones obtained from genital HSV-2 lesions. Drug and replication block experiments were consistent with specificity for the above-named classes of viral proteins. Fine specificity was determined by expression cloning using molecular libraries of viral DNA, and peptide epitopes recognized at nanomolar concentrations were identified. Three of four clones recognized the viral tegument proteins encoded by genes UL47 and UL49. These proteins are transferred into the cytoplasm on virus entry. Processing of the tegument Ag-derived epitopes was TAP dependent. The tegument-specific CTL were able to lyse HLA class I-appropriate fibroblasts after short times of infection. Lysis of keratinocytes required longer infection and pretreatment with IFN-gamma. Another clone recognized an immediate early protein, ICP0. Lymphocytes specific for these lesion-defined epitopes could be reactivated from the PBMC of additional subjects. These data are consistent with an influence of HSV immune evasion genes upon the selection of proteins recognized by CD8 CTL in lesions. Tegument proteins, identified for the first time as Ags recognized by HSV-specific CD8 CTL, are rational candidate vaccine compounds.

ATP-Binding Cassette Transporters↗
PubMed2001

QS-21 promotes an adjuvant effect allowing for reduced antigen dose during HIV-1 envelope subunit immunization in humans.

Three separate studies were undertaken in HIV-1 uninfected persons to determine if the adjuvant QS-21 improves the magnitude or kinetics of immune responses induced by recombinant soluble gp120 HIV-1(MN) protein (rsgp120) immunization. The QS-21 was administered at two doses (50 and 100 microg), either alone or in combination with aluminum hydroxide (600 microg). At the highest doses of rsgp120 (100, 300, and 600 microg), QS-21 exerted no significant effect on either binding or neutralizing antibody titers. Antibody binding and neutralizing responses fell dramatically when rsgp120, formulated with alum alone, was given at low doses (3 and 30 microg). In contrast, antibody responses similar in titer to those in the high dose antigen groups were induced with the low dose rsgp120 formulated with QS-21. In addition, the lymphocyte proliferation and delayed type hypersensitivity skin testing were superior in the QS-21 recipients compared with the alum recipients at the low antigen doses. Moderate to severe pain was observed in majority of the volunteers receiving QS-21 formulations, and vasovagal episodes and hypertension were not infrequent. Thus, the use of QS-21 may provide a means to reduce the dose of a soluble protein immunogen.

AIDS Vaccines↗
PubMed2001

Rising pp65 antigenemia during preemptive anticytomegalovirus therapy after allogeneic hematopoietic stem cell transplantation: risk factors, correlation with DNA load, and outcomes.

To determine the risk factors and outcomes associated with rising cytomegalovirus (CMV) antigenemia levels during preemptive therapy among stem cell allograft recipients, 119 patients with CMV antigenemia were studied. Patients were prospectively monitored for CMV antigenemia weekly; those with positive findings on antigenemia tests were treated with intravenous ganciclovir (5 mg/kg twice daily for 1 week, followed by 5 mg/kg per day for 5-6 d/wk). While on therapy, 47 of 119 (39%) patients demonstrated increases that were 2 or more times greater than their baseline values, whereas 33 of 119 (28%) patients demonstrated increases that were 5 or more times greater. Rising antigenemia was confirmed by polymerase chain reaction for CMV DNA. Multivariate analysis identified corticosteroids as the primary risk factor for increasing antigenemia: for increases greater than or equal to twice the baseline, 1 to 2 mg/kg steroids was associated with an odds ratio (OR) of 4.0. For increases greater than or equal to 2 mg/kg steroids, the OR was 10.1. CMV isolates obtained at the time of rising antigenemia were susceptible to ganciclovir, indicating that resistance was not a major factor. Overall, rising antigenemia levels were not correlated with CMV disease. All 4 patients in whom CMV disease developed during therapy, however, had rising antigenemia levels. Among the 47 patients with antigenemia increases greater than or equal to twice the baseline, 15 were re-induced with antivirals, whereas 32 continued to receive maintenance therapy. All 4 patients in whom CMV disease developed during therapy received maintenance therapy, and 3 died with CMV disease. Thus, host factors such as the receipt of corticosteroids explain increasing viral load during the early phase of preemptive therapy. Continued induction dosing or re-induction may protect against early breakthrough CMV disease and CMV-related death among patients with rising antigenemia on preemptive therapy. (Blood. 2001;97:867-874)

Adolescent↗
PubMed2001

Productive infection of T cells in lymphoid tissues during primary and early human immunodeficiency virus infection.

Current models suggest that during human immunodeficiency virus type 1 (HIV-1) transmission virions are selected that use the CCR5 chemokine receptor on macrophages and/or dendritic cells. A gradual evolution to CXCR4 chemokine receptor use causes a shift in the proportion of productively infected cells to the CD4 cell population. Productively infected cells during acute and early infection in lymphoid tissue were assessed, as well as the impact of productive infection on the T cell population in 21 persons who had biopsies performed on days 2-280 after symptoms of acute HIV-1 seroconversion. Even in the earliest stages of infection, most productively infected cells were T lymphocytes. There were sufficient infected cells in lymphoid tissue (LT) to account for virus production and virus load in plasma. Despite the relatively high frequency of productively infected cells in LT, the impact on the size of the T cell population in LT at this stage was minor.

CD4-Positive T-Lymphocytes↗
PubMed2001

Virological, clinical, and ophthalmologic features of cytomegalovirus retinitis after hematopoietic stem cell transplantation.

We identified 10 patients who developed cytomegalovirus (CMV) retinitis after HSCT during a 14-year period. The median day of diagnosis of CMV retinitis after transplantation was day 251 (range, days 106--365). CMV retinitis was associated with CMV serostatus of donor or recipient (P=0.01), CMV reactivation before day 100 (P=0.007), delayed lymphocyte engraftment (P<0.05), and chronic graft versus host disease (GVHD; P<0.001). In allogeneic recipients of HSCT who were alive at day 100 after transplantation and had chronic clinical extensive GVHD, the incidence of GVHD was 1.4% (8 of 577). Five of 10 patients had other manifestation of CMV disease before retinitis occurred (4 with gastrointestinal disease and 1 with interstitial pneumonia; median time, 70 days before onset of CMV retinitis; range, 58--279 days), and 4 others had CMV excretion. CMV retinitis was bilateral in 4 patients; 9 of 10 patients had ocular symptoms (i.e., decreased vision and floaters). Six of 7 patients responded well to ganciclovir or foscarnet systemic treatment, 1 improved only after switching to cidofovir, and 1 patient who received a transplant in 1983 did not respond to acyclovir treatment. In conclusion, CMV retinitis is an uncommon late complication after HSCT that occurs mainly in seropositive allograft recipients with previous CMV reactivation and chronic GVHD, and with delayed engraftment of lymphocytes.

Adult↗
PubMed2001

Inhibition of apoptosis by primary isolates of herpes simplex virus.

HSV-1 inhibits apoptosis of the infected cell, presumably to increase viral yield. Weaker anti-apoptotic activity was previously reported in laboratory-adapted HSV-2, but not in two low-passage clinical HSV-2 isolates, suggesting that the anti-apoptotic effect might result from adaptation to laboratory growth. We therefore assembled a large panel of clinical strains of HSV-1 and HSV-2. Clinical and laboratory strains of HSV-1 strongly inhibited apoptosis of Jurkat cells, as determined by morphologic change or caspase activation, while clinical HSV-2 strains showed no inhibitory activity in Jurkat cells. These findings suggest fundamental differences between HSV-1 and HSV-2 in their manipulation of host cell apoptosis.

Animals↗
PubMed2001

Seroepidemiology of human herpesvirus 8 among young men who have sex with men.

BACKGROUND: The modes of transmission of human herpesvirus 8 (HHV-8) remain unclear. GOAL: To study HHV-8 seroprevalence and risk factors among young men. STUDY DESIGN: The Young Men's Survey was a multisite cross-sectional HIV seroprevalence and behavioral risk survey of men aged 15 to 22 years who attended public venues frequented by young men who have sex with men (MSM). Blood specimens were tested for HHV-8 by using an immunofluorescence assay at a 1:40 dilution among 488 participants in Seattle-King County, WA. RESULTS: Total HHV-8 seroprevalence was 6% among MSM and 5% among men who have sex only with women (MSW). In multivariate analysis, unprotected receptive anal sex during the past 6 months, injection drug use, and cytomegalovirus infection were associated with HHV-8 seropositivity in MSM. CONCLUSION: The HHV-8 seroprevalence among these young MSM was similar to the HHV-8 seroprevalence among young MSW, but lower than seroprevalence estimates in earlier studies of older MSM. The association of MSM between HHV-8 infection and unprotected receptive anal sex supports previous findings that HHV-8 is sexually transmitted. Although CMV infection and injection drug use may be markers for unsafe sexual practices, it is also possible that these are independent risk factors for acquiring HHV-8.

Adolescent↗
PubMed2001

Activation of Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) lytic replication by human cytomegalovirus.

The majority of Kaposi's sarcoma-associated herpesvirus (KSHV)-infected cells identified in vivo contain latent KSHV, with lytic replication in only a few percent of cells, as is the case for the cells of Kaposi's sarcoma (KS) lesions. Factors that influence KSHV latent or lytic replication are not well defined. Because persons with KS are often immunosuppressed and susceptible to many infectious agents, including human cytomegalovirus (HCMV), we have investigated the potential for HCMV to influence the replication of KSHV. Important to this work was the construction of a recombinant KSHV, rKSHV.152, expressing the green fluorescent protein (GFP) and neo (conferring resistance to G418). The expression of GFP was a marker of KSHV infection in cells of both epithelial and endothelial origin. The rKSHV.152 virus was used to establish cells, including human fibroblasts (HF), containing only latent KSHV, as demonstrated by latency-associated nuclear antigen expression and Gardella gel analysis. HCMV infection of KSHV latently infected HF activated KSHV lytic replication with the production of infectious KSHV. Dual-color immunofluorescence detected both the KSHV lytic open reading frame 59 protein and the HCMV glycoprotein B in coinfected cells, and UV-inactivated HCMV did not activate the production of infectious KSHV-GFP. In addition, HCMV coinfection increased the production of KSHV from endothelial cells and activated lytic cycle gene expression in keratinocytes. These data demonstrate that HCMV can activate KSHV lytic replication and suggest that HCMV could influence KSHV pathogenesis.

Cytomegalovirus↗
PubMed2001

Role for HLA class II molecules in HIV-1 suppression and cellular immunity following antiretroviral treatment.

HIV-1-infected patients treated early with combination antiretrovirals respond favorably, but not all maintain viral suppression and improved HIV-specific Th function. To understand if genetic factors contribute to this variation, we prospectively evaluated over 18 months 21 early-treated patients stratified by alleles of class II haplotypes. All seven subjects with the DRB1*13-DQB1*06 haplotype, but only 21% of other subjects, maintained virus suppression at every posttreatment measurement. Following HIV-1 p24 antigen stimulation, PBMCs from patients with this haplotype demonstrated higher mean lymphoproliferation and IFN-gamma secretion than did cells from patients with other haplotypes. Two DRB1*13-restricted Gag epitope regions were identified, a promiscuous one that bound its putative restriction element with nanomolar affinity, and another that mapped to a highly conserved region. These findings suggest that class II molecules, particularly the DRB1*13 haplotype, have an important impact on virologic and immunologic responses. The advantage of the haplotype may relate to selection of key HIV-1 Th1 epitopes in highly conserved regions with avid binding to class II molecules. Eliciting responses to the promiscuous epitope region may be beneficial in vaccine strategies.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Safety and efficacy of high-dose intravenous acyclovir in the management of neonatal herpes simplex virus infections.

OBJECTIVE: The objective of this investigation was to establish the safety of high-dose (HD) acyclovir for the treatment of neonatal herpes simplex virus (HSV) disease. In addition, an estimate of therapeutic efficacy was sought, both with respect to mortality and to morbidity. Virologic efficacy of HD acyclovir was also assessed. PARTICIPANTS: Infants who were </=28 days old and whose disease was considered to be caused by HSV were enrolled in this study. Patients with central nervous system (CNS; N = 28) or disseminated (N = 41) HSV infection were offered participation in the trial. A small number of patients with HSV disease limited to the skin, eyes, or mouth (SEM; N = 10) or whose disease was clinically consistent with HSV but who did not have virologic confirmation of infection (N = 9) also were enrolled on a compassionate basis. Only patients with virologically confirmed HSV disease were included in efficacy analyses. All enrolled patients were included in safety analyses. METHODS: The study was an open-label evaluation of intravenous acyclovir at dosages higher than the 30 mg/kg/d standard dosage approved by the US Food and Drug Administration. The first 16 patients enrolled received intermediate-dose (ID) acyclovir (45 mg/kg/d), and the next 72 patients received HD acyclovir (60 mg/kg/d). Acyclovir was administered in 3 divided daily doses for 21 days. Neonates were assessed prospectively throughout treatment and at scheduled follow-up visits for the first 4 years of life. Data were compared with those of a previous National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group trial in which patients received standard-dose (SD) acyclovir for 10 days and in which identical methods (with the exception of acyclovir dosage and duration of therapy) were used. RESULTS: Six (21%) of 29 HD acyclovir recipients whose HSV disease remained localized to the SEM or CNS experienced neutropenia. One of the 6 had an absolute neutrophil count <500/mm(3), and 5 patients had an absolute neutrophil count (ANC) between 500/mm(3) and 1000/mm(3). In all 6 cases, the ANC recovered during continuation of acyclovir at the same dosage or after completion of acyclovir therapy, and there were no apparent adverse sequelae of the transient neutropenia. No other drug-related adverse events were reported among ID or HD recipients, and no other laboratory aberrations could be correlated specifically with antiviral therapy. The survival rate for the patients with disseminated HSV disease treated with HD acyclovir was significantly higher than for those in the previous study treated with SD acyclovir, with an odds ratio (OR) of 3.3 (95% confidence interval [CI]: 1.4-7.9). For patients with CNS disease, however, survival rates were similar for the HD and SD groups. To assess the effect of HD acyclovir on survival for the entire population with neonatal HSV disease, the Cox proportional hazards regression analysis was performed with stratification for disease category (CNS versus disseminated). In performing this analysis, differences in mortality for each disease category were weighted to allow statistical comparison of the treatment dosage groups (HD, ID, and SD). This analysis indicated that the survival rate for patients treated with HD acyclovir was statistically significantly higher than for patients treated with SD acyclovir (OR: 3.3; 95% CI: 1.5-7.3). Recipients of HD acyclovir had a borderline significant decrease in morbidity compared with SD recipients, after stratification for the extent of disease (SEM vs CNS vs disseminated) and controlling for the potential confounding factors of HSV type (HSV-1 vs. HSV-2), prematurity, and disease severity (seizures). Patients treated with HD acyclovir were 6.6 times (adjusted OR; 95% CI: 0.8-113.6) as likely to be developmentally normal at 12 months of age as patients treated with SD therapy. CONCLUSION: These data support the use of a 21-day course of HD (60 mg/kg/d) intravenous acyclovir to treat neonatal CNS and disseminated HSV disease. Throughout the course of HD acyclovir therapy, serial ANC determination should be made at least twice weekly. Decreasing the acyclovir dosage or administering granulocyte colony-stimulating factor should be considered if the ANC remains below 500/mm(3) for a prolonged period.

Acyclovir↗
PubMed2000

Cytomegalovirus (CMV) DNA load in plasma for the diagnosis of CMV disease before engraftment in hematopoietic stem-cell transplant recipients.

Among hematopoietic stem-cell transplant (HSCT) recipients, cytomegalovirus (CMV) disease before engraftment is rare but often fatal, and cell-based diagnostic tests have low sensitivity in this clinical setting. We used the quantitative real-time polymerase chain reaction (PCR) assay to test for CMV DNA in plasma samples from 15 HSCT recipients who developed CMV disease before engraftment and from 33 matched control patients. CMV DNA was detected in plasma in 14 (93.3%) of the 15 patients who had CMV disease before engraftment, compared with 5 (15.2%) of 33 control patients (P<.001). CMV DNA was detected a median of 13 days before the onset of CMV disease (range, 0-35 days). The maximum CMV virus load in plasma was >1 log(10) higher among case patients than among control patients (median, 1700 [range, 50 to 5.5x107] vs. <50 [range, <50-350] CMV DNA copies/mL plasma, respectively; P<.001). Quantitative PCR for CMV DNA in plasma appears to be useful for the identification of HSCT recipients at risk for CMV disease before engraftment.

Adolescent↗
PubMed2000

Immunization with recombinant canarypox vectors expressing membrane-anchored glycoprotein 120 followed by glycoprotein 160 boosting fails to generate antibodies that neutralize R5 primary isolates of human immunodeficiency virus type 1.

Antibodies generated by candidate HIV-1 vaccines in a phase I clinical trial were assessed for neutralizing activity with a panel of eight well-characterized, genetically diverse clade B primary isolates having an R5 phenotype. The vaccines consisted of one of three different recombinant canarypox vectors expressing membrane-anchored HIV-1(MN)gp120 (ALVAC vCP205, vCP1433, and vCP1452) followed by boosting with a soluble gp160 hybrid consisting of MNgp120 and the majority of gp41 from strain IIIB. Serum samples from a subset of volunteers in each arm of the trial, containing moderate to high titers of neutralizing antibodies to HIV-1 MN, were analyzed. Competition assays with peptides revealed that the majority of neutralizing activity was specific for the MN-V3 loop. Despite MN-specific neutralization titers that sometimes exceeded 1:500, no neutralization of primary isolates was detected and, in some cases, mild infection enhancement was observed. In addition, little or no neutralization of the HIV-1 IIIB heterologous T cell line-adapted strain of virus was detected. These results reinforce the notion that monovalent HIV-1 ENV is a poor immunogen for generating cross-reactive neutralizing antibodies.

AIDS Vaccines↗
PubMed2000

Mucosal shedding of human herpesvirus 8 in men.

BACKGROUND: Epidemiologic studies suggest that human herpesvirus 8 (HHV-8) is sexually transmitted among men who have sex with men; however, the mode of transmission is unclear. METHODS: To evaluate the patterns of shedding of HHV-8, we obtained mucosal-secretion samples from a cohort of HHV-8-seropositive men who had sex with men and had no clinical evidence of Kaposi's sarcoma. Quantitative polymerase-chain-reaction (PCR) assays, in situ PCR assays, and in situ RNA hybridization were used to identify potential sources of infectious HHV-8. RESULTS: We detected HHV-8 in at least one mucosal sample from 30 of 50 men who were seropositive for HHV-8 (60 percent). Overall, HHV-8 was detected in 30 percent of oropharyngeal samples, as compared with 1 percent of anal and genital samples (P<0.001). In 39 percent of the HHV-8-seropositive men, HHV-8 was detected in saliva on more than 35 percent of the consecutive days on which samples were obtained. The median log titer of HHV-8 from the oral cavity was approximately 2.5 times as high as the titer at all other sites. In situ hybridization studies indicated that HHV-8 DNA and messenger RNA were present in oral epithelial cells. Among 92 men who had sex with men and who were seronegative for the human immunodeficiency virus (HIV), a history of sex with a partner who had Kaposi's sarcoma, deep kissing with an HIV-positive partner, and the use of amyl nitrite capsules ("poppers") or inhaled nitrites were independent risk factors for infection with HHV-8. CONCLUSIONS: Oral exposure to infectious saliva is a potential risk factor for the acquisition of HHV-8 among men who have sex with men. Hence, currently recommended safer sex practices may not protect against HHV-8 infection.

Anal Canal↗
PubMed2000

Chlamydia pneumoniae, herpes simplex virus type 1, and cytomegalovirus and incident myocardial infarction and coronary heart disease death in older adults : the Cardiovascular Health Study.

BACKGROUND: Whether serological evidence of prior infection with Chlamydia pneumoniae, herpes simplex virus type 1 (HSV-1), and cytomegalovirus (CMV) is associated with myocardial infarction (MI) and coronary heart disease (CHD) death remains a source of controversy. METHODS AND RESULTS: We conducted a nested case-control study among participants in the Cardiovascular Health Study, a cohort study of persons aged >/=65 years. Cases experienced an incident MI and CHD death (n=213). Control subjects were matched to cases by age, sex, clinic, year of enrollment, and month of blood draw (n=405). Serum was analyzed for IgG antibodies to C pneumoniae, HSV-1, and CMV. After adjustment for other risk factors, the risk of MI and CHD death was associated with the presence of IgG antibodies to HSV-1 (odds ratio [OR] 2.0, 95% CI 1.1 to 3.6) but was not associated with the presence of IgG antibodies to either C pneumoniae (OR 1.1, 95% CI 0.7 to 1.8) or CMV (OR 1.2, 95% CI 0.7 to 1.9). Although there was little association with low to moderate C pneumoniae antibody titers (</=1:512), high-titer (1:1024) C pneumoniae antibody was associated with an increased risk (OR 2.2, 95% CI 1.1 to 4.4). CONCLUSIONS: Among older adults, the presence of IgG antibodies to HSV-1 was associated with a 2-fold increase in the risk of incident MI and CHD death. For C pneumoniae, only high-titer IgG antibodies were associated with an increased risk of MI and CHD death. The presence of IgG antibodies to CMV was not associated with risk among the elderly.

Adult↗
PubMed2000

Prolonged fluconazole prophylaxis is associated with persistent protection against candidiasis-related death in allogeneic marrow transplant recipients: long-term follow-up of a randomized, placebo-controlled trial.

Two randomized, placebo-controlled trials previously showed that fluconazole (400 mg/d) administered prophylactically decreases the incidence of candidiasis in blood and marrow transplant (BMT) recipients. However, there exists conflicting data regarding the optimal duration of fluconazole administration, specifically whether prophylaxis through acute graft-versus-host disease (GVHD) results in improved survival in allograft recipients. Reported here are the results of long-term follow-up and a detailed analysis of invasive candidiasis and candidiasis-related death in 300 patients who received fluconazole (400 mg/d) or placebo for 75 days after BMT at the Fred Hutchinson Cancer Research Center. Patients in both treatment arms were compared for survival, causes of death, and the incidence of invasive fungal infections early (less than 110 days) and late (more than 110 days) after BMT. After 8 years of follow-up, survival is significantly better in fluconazole recipients compared with placebo recipients (68 of 152 vs 41 of 148, P =.0001). The overall incidence of invasive candidiasis was increased in patients who received placebo compared with fluconazole (30 of 148 vs 4 of 152, P <.001). More patients who received placebo died with candidiasis early (13 of 148 vs 1 of 152, P =.001) and late (8 of 96 vs 1 of 121, P =.0068) after BMT. The incidence of severe GVHD involving the gut was higher in patients who did not receive fluconazole (20 of 143 vs 8 of 145, P =.02), and fewer patients who received fluconazole died with this complication. Thus, administration of fluconazole (400 mg/d) for 75 days after BMT appears to be associated with decreased gut GVHD, a persistent protection against disseminated candidal infections and candidiasis-related death, resulting in an overall survival benefit in allogeneic BMT recipients.

Adult↗
PubMed2000

Emergence of ganciclovir-resistant cytomegalovirus disease among recipients of solid-organ transplants.

BACKGROUND: Concerns have been raised about emergence of ganciclovir resistance as a result of the advent of both routine oral ganciclovir prophylaxis and highly potent immunosuppression. We retrospectively assessed the occurrence of ganciclovir-resistant cytomegalovirus disease among transplant recipients who had received oral ganciclovir prophylaxis and highly potent immunosuppression. METHODS: We studied 240 recipients of liver, kidney, or pancreas transplants. Antiviral susceptibility testing of blood cytomegaloviral isolates was done when patients failed to respond to intravenous ganciclovir treatment for symptomatic cytomegalovirus infection. Portions of the UL97 gene associated with ganciclovir resistance were sequenced in cytomegalovirus isolates with phenotypic resistance to ganciclovir. FINDINGS: Ganciclovir-resistant cytomegalovirus disease developed in five (7%) of 67 seronegative recipients of cytomegalovirus-seropositive organs (D+/R-) compared with none of 173 seropositive recipients (p=0.002). Among the 25 (10.4%) patients who developed cytomegalovirus disease within 1 year after transplantation, five had ganciclovir-resistant cytomegalovirus disease. Among D+/R-transplant recipients, ganciclovir-resistant cytomegalovirus disease was more common among the group receiving the most potent immunosuppression--ie, recipients of kidney and pancreas or pancreas alone (four of 19) compared with all other transplant recipients (one of 48, p=0.02). Ganciclovir-resistant cytomegalovirus disease was diagnosed at a median of 10 months after transplantation (range 7-12) after lengthened exposure to ganciclovir, was associated with previously described mutations of the UL97 gene, and led to serious clinical complications. INTERPRETATION: Ganciclovir-resistant cytomegalovirus is an important cause of late morbidity among D+/R- transplant recipients who have had lengthened exposure to ganciclovir and have received highly potent immunosuppression. Strategies to reduce this complication, especially among D+/R- patients, are warranted.

Adult↗