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PubMed2000

Structural requirements for determining the substrate affinity of peptide transporters PEPT1 and PEPT2.

Peptide transporters PEPT1 and PEPT2 transport numerous compounds including small peptides, peptide-like drugs and nonpeptidic compounds such as valacyclovir. PEPT1 and PEPT2 show low and high affinity for most substrates, respectively, but beta-lactam antibiotics without an alpha-amino group are the only known substrates that prefer PEPT1 to PEPT2. The aim of this study was to compare the recognition and affinity of various substrates between rat PEPT1 and rat PEPT2, and to determine the structural requirements influencing the substrate affinity. [14C]Glycylsarcosine uptake by PEPT1- or PEPT2-expressing transfectant was inhibited by di- and tripeptides, but not by amino acids, tetrapeptides or most cyclic dipeptides. All dipeptides and tripeptides examined showed more potent inhibition of [14C]glycylsarcosine uptake via PEPT2 than via PEPT1, irrespective of their charge and structure. Modification of the alpha-amino group of dipeptides reduced their substrate affinity to both transporters, as compared to unmodified dipeptides, but these dipeptides still showed potent inhibitory effects on PEPT2. Among the nonpeptidic substrates tested, only the eight-amino-octanoic acid displayed stronger inhibition of [14C]glycylsarcosine uptake in PEPT1 than in PEPT2. These findings suggest that alpha- or beta-amino carbonyl function is the key structure responsible for the higher affinity for PEPT2 than for PEPT1.

Animals↗
PubMed1998

Esophageal Infections.

Infectious esophagitis is a common problem in immunocompromised patients that can result in prolonged discomfort and malnutrition. Common infectious causes of esophagitis can be confirmed by laboratory testing, but esophagoscopy is often necessary not only to visualize the esophageal mucosa but also to obtain diagnostic biopsies. Empiric, systemic antifungal or antiherpetic therapies are often prescribed prior to confirming an etiologic diagnosis in esophagitis. In some cases, however, endoscopy is needed to guide therapy. Systemic antifungal therapy is usually superior to topical therapy for Candida esophagitis, and the first choice of agent is generally fluconazole. Valacyclovir or famciclovir are the preferred first treatments for herpetic esophagitis because of their clinical efficacy and convenient dosing schedules. Thalidomide may be useful in the management of aphthous ulcerations of the mouth and esophagus in patients with HIV.

Journal Article↗
PubMed2000

Monitoring pregnancy outcomes after prenatal drug exposure through prospective pregnancy registries: a pharmaceutical company commitment.

OBJECTIVE: Glaxo Wellcome becomes aware of prenatal exposures to its medications as early as the clinical trial phase of development. An international process for monitoring prenatal exposure to all Glaxo Wellcome medicines has been developed. For specific products there are prospective pregnancy registries. STUDY DESIGN: The registries are observational, case-registration, and follow-up studies designed to detect evidence of teratogenicity associated with specific medications. After prenatal exposure to the registry medication, pregnancies are registered prospectively, through voluntary reports by health care providers. An advisory committee of independent scientists for each registry reviews data and advises in dissemination of information. Risk of birth defects, as defined by the Centers for Disease Control and Prevention, is compared with published risks both in women in the general population and in women with the underlying condition being treated, if available. RESULTS: The following data show results from the prospective first-trimester exposures registered since establishment of each registry. The published risk of birth defects in the general population range is 3% to 5%, and the risk in women with epilepsy is 6% to 9%. The proportions of outcomes with birth defects are as follows: in the Acyclovir (antiviral medication) Pregnancy Registry (1984-1998) (19/581), 3.3% (95% confidence interval, 2.0%-5.2%); in the Lamotrigine (monotherapy and polytherapy antiepileptic medication) Pregnancy Registry (1992-September 1998) (8/123), 6.5% (95% confidence interval, 3.1%-12.8%); in the Sumatriptan (migraine medication) Pregnancy Registry (1996-October 1998) (7/183), 3.8% (95% confidence interval, 1.7%-8.0%). The Valacyclovir, Bupropion, and Naratriptan registries have insufficient data for analysis. CONCLUSION: None of the registries has provided a risk estimate exceeding that expected in the disorder treated, and no pattern of defects has been observed. Whereas information from the larger registries is reassuring regarding risk, these studies cannot rule out possible small excess risks from use of these drugs in pregnancy. Data obtained through these registries are shared with the medical community as a supplement to animal toxicology studies to assist in weighing potential risks and benefits of treatment for individual patients. The success of the registries depends on the continued willingness of the obstetrics and gynecology community to notify the registries of prenatal exposures.

Abnormalities, Drug-Induced↗
PubMed2003

Functional expression and characterization of a sodium-dependent nucleoside transporter hCNT2 cloned from human duodenum.

We have cloned and functionally expressed a sodium-dependent human nucleoside transporter, hCNT2, from a CNS cancer cell line U251. Our cDNA clone of hCNT2 had the same predicted amino acid sequence as the previously cloned hCNT2 transporter. Of the several cell lines studied, the best hCNT2 transport function was obtained when transiently expressed in U251 cells. Na(+)-dependent uptake of [3H]inosine in U251 cells transiently expressing hCNT2 was 50-fold greater than that in non-transfected cells, and uptake in Na(+)-containing medium was approximately 30-fold higher than that at Na(+)-free condition. The hCNT2 displayed saturable uptake of [3H]inosine with K(m) of 12.8 microM and V(max) of 6.66 pmol/mg protein/5 min. Uptake of [3H]inosine was significantly inhibited by the purine nucleoside drugs dideoxyinosine and cladribine, but not by acyclic nucleosides including acyclovir, ganciclovir, and their prodrugs valacyclovir and valganciclovir. This indicates that the closed ribose ring is important for binding of nucleoside drugs to hCNT2. Among several pyrimidine nucleosides, hCNT2 favorably interacted with the uridine analogue floxuridine. Interestingly, we found that benzimidazole analogues, including maribavir, 5,6-dichloro-2-bromo-1-beta-D-ribofuranosylbenzimidazole (BDCRB), and 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB), were strong inhibitors of inosine transport, even though they have a significantly different heterocycle structure compared to a typical purine ring. As measured by GeneChip arrays, mRNA expression of hCNT2 in human duodenum was 15-fold greater than that of hCNT1 or hENT2. Further, the rCNT2 expression in rat duodenum was 20-fold higher than rCNT1, rENT1 or rENT2. This suggests that hCNT2 (and rCNT2) may have a significant role in uptake of nucleoside drugs from the intestine and is a potential transporter target for the development of nucleoside and nucleoside-mimetic drugs.

Animals↗
PubMedDate not supplied

Advances in the treatment of herpesvirus infection: the role of famciclovir.

Shingles (herpes zoster) is the result of reactivation of varicella-zoster virus after years of latency. The acute phase is self-limiting but is often associated with moderate-to-severe pain; postherpetic neuralgia is the most frequent and debilitating complication of shingles, occurring in 3.4 per 1000 individuals per year. In the case of genital herpes, herpes simplex virus can reactivate to cause recurrent episodes as often as several times a year, sometimes for the remainder of a person's life. Antiviral agents such as famciclovir, valacyclovir, and acyclovir can be used to shorten the course and decrease the severity of these diseases and may suppress the virus itself, thereby preventing future outbreaks of genital herpes. This article presents a brief synopsis of the etiology of herpes zoster and genital herpes and reviews 12 key studies that demonstrate the efficacy of famciclovir in the management of these two conditions.

2-Aminopurine↗
PubMed1999

New developments in the epidemiology, natural history and management of genital herpes.

The prevalence of genital herpes is increasing in several populations worldwide. Factors that may be contributing to this increase include greater numbers of sexual partners, the high frequency of asymptomatic infections, poor use of safe sexual practices, and possibly the decreased incidence of childhood oral herpes simplex virus infection. Transmission occurs via skin-to-skin or mucous membrane contact during periods of viral shedding when lesions are present but may also occur when the patient is unaware of the lesions or when lesions are not clinically apparent. This has important implications for strategies to prevent transmission of the disease. The introduction of the antiherpes agent, acyclovir, and more recently famciclovir and valacyclovir, facilitates the management of genital herpes. Treatment of first-episode genital herpes reduces the severity and duration of symptoms, time to lesion healing, and cessation of viral shedding. Episodic treatment of recurrences as they occur may be of benefit to some patients. Daily suppressive therapy significantly reduces the frequency of recurrences and asymptomatic viral shedding. Accordingly, patients who experience frequent or severe recurrences, those particularly troubled by their disease, and those who wish to reduce the frequency of asymptomatic infection generally prefer suppressive therapy. The possibility that suppressive therapy may have an impact on transmission of the disease is currently under investigation. Antiviral treatments have important implications for public health and may help reduce the psychological and psychosocial impact of genital herpes on individual patients.

Antiviral Agents↗
PubMed2000

Meeting future challenges in topical ocular drug delivery: development of an air-interfaced primary culture of rabbit conjunctival epithelial cells on a permeable support for drug transport studies.

The purpose of this study was to develop and characterize a functional air-interfaced primary culture of rabbit conjunctival epithelial cells grown on a permeable support for drug transport studies. Conjunctival epithelial cells from the pigmented rabbit were isolated, seeded at 1.2 x 10(6) cells cm(-2) on permeable Transwell filters, and cultured at the air interface using a modified PC-1 medium. Conjunctival epithelial cell layers showed a transepithelial resistance of 1.1+/-0.1 kOmega cm(2), a potential difference of 17.0+/-0.5 mV, and an equivalent short-circuit current (I(eq)) of 16.1+/-0.4 microA cm(-2). The I(eq) was reduced by 35% using 0.01 mM bumetanide, 66% using 0.1 mM ouabain, 46% using 2 mM barium chloride (all three in the basolateral fluid), and 63% using 0.3 mM NPAA in the apical fluid, consistent with active Cl(-)-secretion across the conjunctival epithelial barrier. Amiloride-sensitive Na(+) channels were absent. The permeability of the cell layers to polar solutes decreased with increased solute size, and the calculated equivalent pore size was about 8.0 nm. The Papp of beta-blockers varied with lipophilicity in a sigmoidal fashion. Uridine transport showed temperature sensitivity and directionality, favoring transport in the apical-to-basolateral direction. Apical L-carnosine uptake was reduced by 46% in the absence of an inwardly directed proton gradient, and lowering the temperature to 4 degrees C abolished direction-dependent L-carnosine uptake. Furthermore, uptake was inhibited by 73% using apical 10 mM glycyl sarcosine (a dipeptide transporter substrate) and by 60% using 1 mM L-valacyclovir (a dipeptide prodrug). In conclusion, a functional air-interfaced primary culture of rabbit conjunctival epithelial cell layers was established. This air-interfaced primary culture model may be useful for studying passive and active transport processes for ion and solute translocation in the mammalian conjunctival epithelial barrier in a defined experimental setting.

Adrenergic beta-Antagonists↗
PubMed1999

Acute varicella zoster with postherpetic hyperhidrosis as the initial presentation of HIV infection.

A 31-year-old man presented with acute pain in his left arm and hemorrhagic vesicles that followed his left 8th cervical nerve. A diagnosis of herpes zoster was made, and the patient was treated with valacyclovir. He refused testing for antibodies to HIV because he denied being at risk. Two months later he returned with postherpetic neuralgia and postherpetic hyperhidrosis in the distribution of the vesicles, which had since resolved. Serology for HIV at this visit was positive, and the patient admitted to having sexual relations with prostitutes. Six months later the patient was being treated with triple antiretroviral therapy, and all signs and symptoms of postherpetic zoster had resolved. This case report documents the need for HIV testing in patients with unusual presentations of herpes zoster even if they initially deny being at risk.

AIDS-Related Opportunistic Infections↗
PubMed1998

Monitoring pregnancy outcomes following prenatal drug exposure through prospective pregnancy registries and passive surveillance: a pharmaceutical company commitment.

Objectives: Glaxo Wellcome (G.W.) becomes aware of prenatal exposures to its medications from as early as the clinical trial phase of development. An international process for monitoring prenatal exposure to all G.W. medicines has been developed utilizing a passive surveillance system and, for specific products, pregnancy registries. Additionally, G.W. jointly sponsors the multi-company Antiretroviral and North American Antiepileptic Drug (AED) Pregnancy Registries.Study Design: The registries are observational, case-registration and follow-up studies designed to detect evidence of teratogenicity associated with specific medications. Pregnancies are registered prospectively following prenatal exposure to the registry medication. An advisory committee for each registry reviews data and assists in dissemination of information. Committee members include independent scientists with expertise in fields such as obstetrics, teratology, epidemiology, pediatrics, and the relevant therapeutic areas.Results: The following data are from the prospective first-trimester exposures in each registry. Through December 1996, the proportion of outcomes in the Acyclovir Pregnancy Registry with birth defects (n = 17/505) is 3.4% (95% CI 2.0%, 5.4%). Through March 1997, the proportion of outcomes in the Lamotrigine Pregnancy Registry with birth defects (n = 4/76) is 5.3% (95% CI 1.7%, 13.6%). Through April 1997, the proportion of outcomes in the Sumatriptan Pregnancy Registry with birth defects (n = 5/148) is 3.4% (95% CI 1.3%, 8.1%). The newer Valacyclovir and Bupropion Pregnancy Registries have insufficient data for analysis. None of the registries have provided a risk estimate exceeding that expected in the general population, and no pattern of defects has been observed.Conclusions: The outcomes accumulated to date represent a sample of insufficient size for reaching conclusions regarding the possible teratogenic risk of using these drugs in pregnancy. Data obtained through these registries are shared with the medical community as a supplement to animal toxicology studies and to assist in weighing potential risks and benefits of treatment for individual patients. The success of the registries depends on the continued willingness of the OB/GYN community to notify the registries of prenatal exposures.

Journal Article↗
PubMed2000

Recent advances in the therapy and prevention of CMV infections.

The introduction of highly active antiretroviral therapy (HAART) for HIV has had a major impact on the treatment of CMV disease in HIV-infected individuals. There is mounting evidence that in patients with CMV retinitis who have a sustained response to HAART, CMV maintenance treatment can be discontinued without relapse of retinitis. In HAART-naïve individuals with newly diagnosed CMV retinitis, the optimal timing for the initiation of HAART relative to the start of anti-CMV treatment is currently unknown. New local therapies for CMV retinitis (e.g. ganciclovir implant, the new antisense compound fomivirsen) provide treatment options in situations where high local drug delivery is warranted. A treatment algorithm for CMV disease in the HAART era is proposed. In the transplant setting, ganciclovir and foscarnet remain the major compounds used for treatment of CMV disease. In marrow and stem cell transplant recipients, CMV pneumonia still carries a high mortality. Ganciclovir in combination with CMV-specific immunoglobulin or regular intravenous IG remains the treatment of choice for CMV pneumonia; extended antiviral maintenance for several months is recommended in patients with continued immunosuppression. Preemptive treatment based on virologic markers (e.g. pp65 antigenemia, CMV DNA) has been very successful in reducing the incidence of early CMV disease in the transplant setting. The duration of preemptive treatment should be guided by the underlying immunosuppression and virologic markers. Late CMV disease is a challenge in marrow and stem cell transplant recipients, and occurs increasingly in highly immunosuppressed solid organ transplant recipients as well. Recent advances in prophylaxis strategies include oral ganciclovir for liver transplant recipients and valacyclovir for kidney transplant recipients.

AIDS-Related Opportunistic Infections↗
PubMed1998

5'-Amino acid esters of antiviral nucleosides, acyclovir, and AZT are absorbed by the intestinal PEPT1 peptide transporter.

PURPOSE: General use of nucleoside analogues in the treatment of viral infections and cancer is often limited by poor oral absorption. Valacyclovir, a water soluble amino acid ester prodrug of acyclovir has been reported to increase the oral bioavailability of acyclovir but its absorption mechanism is unknown. This study characterized the intestinal absorption mechanism of 5' -amino acid ester prodrugs of the antiviral drugs and examined the potential of amino acid esters as an effective strategy for improving oral drug absorption. METHODS: Acyclovir (ACV) and Zidovudine (AZT) were selected as the different sugar-modified nucleoside antiviral agents and synthesized to L-valyl esters of ACV and AZT (L-Val-ACV and L-Val-AZT), D-valyl ester of ACV (D-Val-ACV) and glycly ester of ACV (Gly-ACV). The intestinal absorption mechanism of these 5' -amino acid ester prodrugs was characterized in three different experimental systems; in situ rat perfusion model, CHO/hPEPT1 cells and Caco-2 cells. RESULTS: Testing 5' -amino acid ester prodrugs of acyclovir and AZT, we found that the prodrugs increased the intestinal permeability of the parent nucleoside analogue 3- to 10-fold. The dose- dependent permeation enhancement was selective for L-amino acid esters. Competitive inhibition studies in rats and in CHO cells transfected with the human peptide transporter, hPEPT1, demonstrated that membrane transport of the prodrugs was mediated predominantly by the PEPT1 H+/dipeptide cotransporter even though these prodrugs did not possess a peptide bond. Finally, transport studies in Caco-2 cells confirmed that the 5' - amino acid ester prodrugs enhanced the transcellular transport of the parent drug. CONCLUSIONS: This study demonstrates that L-amino acid-nucleoside chimeras can serve as prodrugs to enhance intestinal absorption via the PEPT1 transporter, providing a novel strategy for improving oral therapy of nucleoside drugs.

Acyclovir↗
PubMed2000

Varicella zoster meningoencephalitis following treatment for dermatomal zoster in an alloBMT patient.

Herpes zoster infections are frequently observed after allogeneic bone marrow transplantation (alloBMT). In the majority of cases, the infection is restricted to specific dermatomes and responds to oral acyclovir, without visceral dissemination. We report the case of a 40-year-old male who developed dermatomal herpetic infection 8 months post alloBMT. The herpetic rash responded well to treatment with high-dose oral acyclovir. However, within a week of cessation of therapy, the patient re-presented with dermatomal zoster and meningoencephalitis. Although the cutaneous lesions resolved with intravenous acyclovir, clinical features of meningoencephalitis persisted, along with evidence of varicella zoster virus (VZV) DNA in cerebrospinal fluid (CSF). A satisfactory response to treatment was observed only after the addition of intravenous foscarnet to acyclovir. Based on our experience with this patient, we suggest that in a subset of alloBMT recipients, late dermatomal herpes zoster infections may respond only partially to treatment with standard oral acyclovir. The use of oral acyclovir preparations with higher bioavailability (valacyclovir) or intravenous acyclovir early on may prevent the considerable morbidity associated with disseminated zoster infection. Bone Marrow Transplantation (2000) 26, 795-796.

Acyclovir↗
PubMed2000

Antimicrobial prophylaxis in dermatology.

Few circumstances in dermatology warrant antimicrobial prophylaxis. In cutaneous surgery postoperative infections are too infrequent and insufficiently severe to justify preventive antibiotics, except rarely. Petrolatum is as effective as, and cheaper than, topical antibiotic ointment to cover surgical wounds. In patients with numerous staphylococcal skin infections, oral clindamycin 150 mg every day for 3 months safely reduces further episodes. For recurrent cellulitis, oral penicillin or erythromycin 250 mg twice daily or monthly intramuscular benzathine penicillin decreases subsequent attacks. In patients with frequent episodes of genital or labial herpes simplex an antiviral agent such as valacyclovir 500 mg to 1 g every day is effective as a suppressant.

Anti-Bacterial Agents↗
PubMed2002

Clinical manifestations and treatment considerations of herpes simplex virus infection.

Herpes simplex viruses (HSV) types 1 and 2 cause infections manifesting as dermatologic, immunologic, and neurologic disorders. Some of the most important manifestations and complications of HSV infection are considered here in a neuroanatomic context. This discussion should aid in understanding the pathogenesis and, in some cases, diagnosis and management of associated HSV-related diseases. The sensory nervous system, rather than skin and mucous membranes, is the primary target of HSV infection. With the intention of extending the benefits of acyclovir, valacyclovir is now being explored in a number of HSV-related conditions. This review extends contemporary thinking about how new antiherpetic drugs might be put to greater therapeutic use in the future.

Antiviral Agents↗
PubMed1999

New therapies and prevention strategies for genital herpes.

Genital herpes is among the most prevalent sexually transmitted diseases. Optimal management of genital herpes includes accurate diagnosis, antiviral therapy, and counseling of patients about complications and transmission of herpes simplex virus (HSV). Antiviral therapy offers significant palliation, and the option of episodic or suppressive treatment should be offered to all patients with genital herpes. Valacyclovir and famciclovir are two newer antiviral agents that are effective and safe for the treatment of genital herpes. Prevention strategies for sexual and perinatal transmission of HSV have not been well defined. Availability of type-specific serological tests for HSV antibodies may assist in identifying persons at risk for acquiring or transmitting HSV infection. Further research is needed to define strategies to prevent the spread of this epidemic infection.

AIDS-Related Opportunistic Infections↗
PubMed2003

Phase I dose escalation clinical trial of adenovirus vector carrying osteocalcin promoter-driven herpes simplex virus thymidine kinase in localized and metastatic hormone-refractory prostate cancer.

Osteocalcin (OC), a major noncollagenous bone matrix protein, is expressed prevalently in prostate cancer epithelial cells, adjacent fibromuscular stromal cells, and osteoblasts in locally recurrent prostate cancer and prostate cancer bone metastasis [Matsubara, S., Wada, Y., Gardner, T.A., Egawa, M., Park, M.S., Hsieh, C.L., Zhau, H.E., Kao, C., Kamidono, S., Gillenwater, J.Y., and Chung, L.W. (2001). Cancer Res. 61, 6012-6019]. We constructed an adenovirus vector carrying osteocalcin promoter-driven herpes simplex virus thymidine kinase (Ad-OC-hsv-TK) to cotarget prostate cancer cells and their surrounding stromal cells. A phase I dose escalation clinical trial of the intralesional administration of Ad-OC-hsv-TK followed by oral valacyclovir was conducted at the University of Virginia (Charlottesville, VA) in 11 men with localized recurrent and metastatic hormone-refractory prostate cancer (2 local recurrent, 5 osseous metastasis, and 4 lymph node metastasis) in order to determine the usefulness of this vector for the palliation of androgen-independent prostate cancer metastasis. This is the first clinical trial in which therapeutic adenoviruses are injected directly into prostate cancer lymph node and bone metastasis. Results show that (1). all patients tolerated this therapy with no serious adverse events; (2). local cell death was observed in treated lesions in seven patients (63.6%) as assessed by TUNEL assay, and histomorphological change (mediation of fibrosis) was detected in all posttreated specimens; (3). one patient showed stabilization of the treated lesion for 317 days with no alternative therapy. Of the two patients who complained of tumor-associated symptoms before the treatment, one patient with bone pain had resolution of pain, although significant remission of treated lesions was not observed by image examination; (4). CD8-positive T cells were predominant compared with CD4-positive T cells, B cells (L26 positive), and natural killer cells (CD56 positive) in posttreated tissue specimens; (5). levels of HSV TK gene transduction correlated well with coxsackie-adenovirus receptor expression but less well with the titers of adenovirus injected; and (6). intrinsic OC expression and the efficiency of HSV TK gene transduction affected the levels of HSV TK protein expression in clinical specimens. Our data suggest that this form of gene therapy requires further development for the treatment of androgen-independent prostate cancer metastasis although histopathological and immunohistochemical evidence of apoptosis was observed in the specimens treated. Further studies including the development of viral delivery will enhance the efficacy of Ad-OC-hsv-TK.

Adenoviridae↗
PubMed2003

Nodular perianal herpes simplex with prominent plasma cell infiltration.

BACKGROUND: Nodules are exceptional manifestations of herpes simplex virus (HSV) infection in immunocompromised patients. Only two cases of nodular HSV-2 infection of the perianal region have been reported previously. GOAL: The case of a 46-year-old homosexual man with AIDS presenting with painful perianal nodules resembling squamous cell carcinoma is described. STUDY DESIGN: This case report presents details of the histologic findings and treatment regimen. RESULTS: Histologic examination showed the presence of rare multinucleated giant epithelial cells and a dense inflammatory infiltrate composed mostly of plasma cells. Polymerase chain reaction analysis was positive for HSV-2 and negative for HSV-1, cytomegalovirus, Epstein-Barr virus, and human herpesvirus types 6 and 7. After being treated ineffectively with oral acyclovir (4 g/d) for 15 days, the patient was treated with oral valacyclovir (6 g/d), resulting in marked improvement in 10 days and complete resolution after 2 months. CONCLUSIONS: In immunocompromised patients, HSV-2 infection may present with atypical clinical and histopathological features.

AIDS-Related Opportunistic Infections↗
PubMed2001

New developments in the management of cytomegalovirus infection and disease after renal transplantation.

The clinical management of cytomegalovirus infection and disease in renal transplant recipients has recently been significantly improved with the availability of data on prophylaxis with oral ganciclovir and valacyclovir. In addition, significant progress in early diagnosis and the quantitation of viral load has been achieved. The influence of novel immunosuppressants on the clinical course of cytomegalovirus infection has been clarified to some extent by recent clinical data. The identification of risk factors for cytomegalovirus disease beyond seroconstellation and immunosuppression is an ongoing process that might lead to a more targeted use of antiviral agents, given the risk of ganciclovir resistance. The understanding of the effects of cytomegalovirus on long-term graft outcome still needs to be deepened in order to design cytomegalovirus-specific interventions to improve graft survival.

Cytomegalovirus Infections↗