acyclovir and Leukoplakia--Hairy

Viral lesions of the mouth in patients with HIV infection are common and these diseases any be a marker for HIV and disease progression. We review the spectrum of oral viral manifestations and discuss treatment modalities. The most common Epstein-Barr virus (EBV)-induced disorder in HIV-infected patients is oral hairy leukoplakia. EBV-related oral B-cell and T-cell lymphoma in AIDS patients has been described repeatedly. Herpes virus type 1 and rarely type 2 may lead to painful and resistant oral ulcers, and systemic treatment with acyclovir, valaciclovir or famciclovir is indicated. In acyclovir-resistant cases foscarnet is the treatment of choice. In recent years it has been documented that Kaposi's sarcoma, which often affects oral mucosa, is probably induced by herpesvirus type 8. Cytomegalovirus was found in 53% of cases with herpesviridae-induced mucosal ulcers as the only ulcerogenic viral agent in AIDS patients. In severe cytomegalovirus infection treatment with ganciclovir is helpful. Viral warts induced by different HPV may occur in the mouth. Several physical treatment modalities are possible in the oral mucosa. In AIDS patients mollusca contagiosa may occur as large and atypical lesions in the face and lips and rarely in the oral cavity. Cryotherapy is a bloodless treatment in such patients.

Topics: 2-Aminopurine; Acyclovir; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Cytomegalovirus Infections; Disease Progression; Famciclovir; Foscarnet; Ganciclovir; Herpesviridae Infections; Herpesvirus 1, Human; Herpesvirus 2, Human; Herpesvirus 4, Human; Herpesvirus 8, Human; Humans; Leukoplakia, Hairy; Lymphoma, B-Cell; Lymphoma, T-Cell; Molluscum Contagiosum; Mouth Diseases; Mouth Neoplasms; Oral Ulcer; Prodrugs; Sarcoma, Kaposi; Stomatitis, Herpetic; Tumor Virus Infections; Valacyclovir; Valine; Virus Diseases; Warts

A case of a 9-year-old boy with AIDS and severe hairy leukoplakia on the tongue is reported. Clinically it appears as a bilateral whitish-grey, nonremovable lesion on the lateral margins of the tongue with characteristic vertical corrugations. The lesion failed to respond to topical and systemic antifungal treatment. In contrast, it completely disappeared after treatment with 600 mg acyclovir per day for 1 month. During the hairy leukoplakia development the CD4-lymphocytes count was 95/microL.

Topics: Acyclovir; AIDS-Related Opportunistic Infections; Child; Humans; Leukoplakia, Hairy; Male; Tongue Diseases

The aim of this study was to present a new topical treatment protocol for oral hairy leukoplakia (OHL), consisting of a 25% podophyllin resin with a 1% penciclovir cream (PP), and to compare this topical treatment protocol's efficacy with that of 2 other topical treatment protocols: a 25% podophyllin resin (P) and a 25% podophyllin resin with a 5% acyclovir cream (PA).. Forty-two human immunodeficiency virus-positive patients with 69 OHL lesions were randomly treated using P, PA, or PP (14 patients in each topical treatment protocol). Clinical healing was determined when the white plaque could no longer be seen in the primary location of the lesion. Topical treatment performance was evaluated by clinical healing within each week of topical treatment protocol as well as by the recurrence of the lesion. Statistical survival analysis was performed using a Cox proportional hazards model.. Approximately 55% of the patients presented with clinical healing of OHL within 7-8 weeks of each topical treatment protocol. After the sixth week, the PA treatment protocol presented a faster clinical healing rate of OHL. Recurrence was observed in 3 and 7 OHL lesions treated with P and PP treatment protocols, respectively.. The PP treatment protocol proved to be effective; however, the PA treatment protocol was more effective in the clinical healing rate for OHL than P and PP after the sixth week of treatment, and no recurrent OHL was observed in the PA treatment group.

Topics: Acyclovir; Administration, Topical; Adult; Antifungal Agents; Antineoplastic Agents, Phytogenic; Antiviral Agents; Candidiasis, Oral; Double-Blind Method; Female; Follow-Up Studies; Guanine; Heterosexuality; HIV Infections; HIV Seropositivity; Humans; Leukoplakia, Hairy; Male; Middle Aged; Neoplasm Recurrence, Local; Podophyllin; Proportional Hazards Models; Remission Induction; Time Factors; Tongue Neoplasms; Treatment Outcome; Young Adult

The objective of this study was to assess the efficiency of topical applications of podophyllin resin (25%) (P) versus podophyllin resin (25%) together with acyclovir cream (5%) (PA) in the treatment of oral hairy leukoplakia (OHL) in accordance with the following criteria: (1) number of applications necessary for the total clinical resolution of OHL; (2) correlation between the decrease of lesion size and the number of applications; (3) total clinical resolution of OHL; and (4) clinical reevaluation 12 months after the end of treatment.. Forty-six OHLs were treated with P (P group) or with PA (PA group). Applications were performed weekly. Student t, Fisher exact, and Pearson correlation tests were used for statistical analysis.. All 24 lesions from the PA group presented total clinical resolution while 4 lesions from the P group did not. The P group required up to 25 applications performed weekly while the PA group required up to 18. Observed was a negative significant association between the size of the lesions and the number of applications performed weekly in the PA group.. The present study demonstrated the following: (1) P and PA topical treatments presented a similar average number of applications performed weekly; (2) both groups showed the same clinical response at 12 months post-therapy; and (3) PA presented a 100% clinical resolution and a continuous decrease in OHL size over the course of weekly applications.

Topics: Acyclovir; Administration, Topical; Adult; Antiviral Agents; Drug Therapy, Combination; HIV Infections; Humans; Keratolytic Agents; Leukoplakia, Hairy; Middle Aged; Podophyllin

Epstein-Barr virus (EBV) replicates productively in oral hairy leukoplakia (HLP). One characteristic of human immunodeficiency virus (HIV)-associated HLP is a decreased oral epithelial Langerhans cell count. This prospective study tested the hypothesis that oral epithelial EBV replication decreases oral Langerhans cell counts. EBV replication in HLP was highly correlated with decreased oral Langerhans cell counts. Inhibition of EBV replication restored oral Langerhans cell counts to normal control levels, and the return of EBV replication after treatment resulted in a recurrent decline in oral Langerhans cell counts. Decreased oral Langerhans cell counts occurred independently of HIV infection, as demonstrated in HLP of otherwise healthy HIV-seronegative individuals. These results support the tested hypothesis and suggest that EBV manipulates and evades the mucosal immune response in oral epithelial infection. This novel EBV strategy for eliminating oral Langerhans cells may facilitate the persistence of oral epithelial EBV and may contribute to the pathogenesis of HLP.

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; Cell Count; Herpesvirus 4, Human; HIV Infections; Humans; Langerhans Cells; Leukoplakia, Hairy; Male; Middle Aged; Mouth; Valacyclovir; Valine; Virus Replication

Nineteen cases of human immunodeficiency virus (HIV)-associated oral hairy leukoplakia (HLP) and Epstein-Barr virus (EBV) replication were treated with high-dose oral valacyclovir to inhibit productive EBV replication. The clinical, histopathological, and molecular viral responses to treatment were assessed in surgical biopsy specimens obtained before, during, and after treatment. In the majority of treated cases, HLP was resolved, and EBV replication was terminated. In many cases, the initial response to inhibition of replication was a persistent, nonproductive, EBV infection of the oral mucosa, characterized by limited expression of replicative EBV genes, especially BZLF1. In some cases, productive EBV replication recurred after discontinuation of treatment with valacyclovir. In a few treated cases, treatment failed, and productive EBV replication persisted, possibly because of the evolution of acyclovir-resistant EBV. In summary, safe treatment of HLP and of EBV replication, with valacyclovir, provides new insight into the mechanisms of EBV persistence in oral mucosa.

Topics: Acyclovir; Adolescent; Adult; Aged; Antiviral Agents; Drug Resistance, Viral; Herpesvirus 4, Human; HIV Infections; Humans; Leukoplakia, Hairy; Middle Aged; Mouth Mucosa; Treatment Outcome; Valacyclovir; Valine; Viral Proteins; Virus Replication

This prospective study examined the persistence and transition of Epstein-Barr virus (EBV) in human immunodeficiency virus (HIV)-seropositive subjects with and without oral hairy leukoplakia, a replicative EBV-associated epithelial disease. The intrahost molecular epidemiology of EBV infection was characterized in subjects treated with valacyclovir to suppress EBV replication. Tongue epithelial tissues of HIV-seropositive subjects were found to support not only EBV replication but also persistent, nonproductive EBV infection. EBV appeared to enter the tongue from the blood reservoir of infection and, possibly, from exogenous sources as well. EBV transition from the blood to the tongue appeared to occur even during valacyclovir-mediated suppression of EBV replication, suggesting EBV entry into tongue epithelial tissue as a cell-associated latent infection. In conclusion, these results describe the persistence and transition of EBV as a dynamic interaction between the blood and epithelial reservoirs of EBV infection and suggest a role for entry, persistence, and reactivation of oral epithelial EBV in the pathogenesis of oral hairy leukoplakia.

Topics: Acyclovir; Adult; Amino Acid Sequence; Antiviral Agents; DNA, Viral; Epithelium; Genotype; Herpesvirus 4, Human; HIV Infections; Humans; Leukocytes, Mononuclear; Leukoplakia, Hairy; Male; Middle Aged; Molecular Epidemiology; Molecular Sequence Data; Prospective Studies; Sequence Analysis, DNA; Tongue; Valacyclovir; Valine; Virus Activation; Virus Latency; Virus Replication

This retrospective study examined expression of Epstein-Barr virus (EBV) latent genes in oral epithelium from human immunodeficiency virus-seropositive subjects, to identify genes associated with the pathogenesis of oral hairy leukoplakia (HLP). Transcription of EBV latent genes was detected in tissues with productive EBV replication and, also, in normal oral epithelial tissues without EBV replication. Expression of the EBV EBNA-2 open-reading frame in oral epithelium was identified as an important cofactor associated with the pathogenesis of HLP. In vitro experiments suggested that a recombinant variant of the EBNA-2 gene may play a role in the pathogenesis of HLP, through modulation of EBNA-2 protein function.

Topics: Acyclovir; Biopsy; Epithelium; Epstein-Barr Virus Nuclear Antigens; Gene Expression Regulation, Viral; Genes, Viral; Herpesvirus 4, Human; HIV Infections; Humans; Leukoplakia, Hairy; Mouth Mucosa; Retrospective Studies; RNA, Messenger; RNA, Viral; Transcription, Genetic; Valacyclovir; Valine; Viral Matrix Proteins; Viral Proteins; Virus Replication

The features of oral hairy leukoplakia (OHL) have been widely reported in the literature. However, no studies have described this lesion in the Australian setting. This study retrospectively examines, with respect to specific clinical factors, the prevalence of OHL in a South Australian HIV-infected population.. Clinical data were collected from the records of 197 HIV-infected patients who had attended the Adelaide Dental Hospital between January 1986 and February 1995. Data were analysed using the chi-square test.. The prevalence of OHL in South Australian HIV-infected patients was 45.2 per cent. The study found the presence of OHL was not related to CD4+ T-lymphocyte count or AIDS-defining illness nor did the length of time a patient had been infected with HIV relate to the presence of OHL. An association was observed between a reduced prevalence of OHL in patients who were taking antiviral medication.. The prevalence of OHL in South Australia is comparable with results of other studies. This study supports the notion that OHL is not an indicator of immunosuppression in South Australian HIV-infected patients. Further longitudinal studies are required to ascertain the relationship of OHL to HIV disease progression.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Aged; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Antiviral Agents; CD4 Lymphocyte Count; Chi-Square Distribution; Female; HIV Infections; Humans; Leukoplakia, Hairy; Male; Middle Aged; Prevalence; Retrospective Studies; South Australia; Time Factors; Zidovudine

Productive Epstein-Barr virus (EBV) replication characterizes hairy leukoplakia, an oral epithelial lesion typically occurring in individuals infected with human immunodeficiency virus (HIV). Serial tongue biopsy specimens were obtained from HIV-infected subjects before, during, and after valacyclovir treatment. EBV replication was detected by Southern hybridization to linear terminal EBV genome fragments, reverse-transcriptase polymerase chain reaction amplification of EBV replicative gene transcripts, immunohistochemical detection of EBV replicative protein, and in situ hybridization to EBV DNA. EBV replication was detected in both hairy leukoplakia and normal tongue tissues. Valacyclovir treatment completely abrogated EBV replication in vivo, resulting in resolution of hairy leukoplakia when it was present. EBV replication returned in normal tongue epithelial cells after valacyclovir treatment. These data suggest that normal oral epithelium supports persistent EBV infection in individuals infected with HIV and that productive EBV replication is necessary but not sufficient for the pathogenesis of oral hairy leukoplakia.

Topics: Acyclovir; Antiviral Agents; Biopsy; DNA-Binding Proteins; Epithelial Cells; Epstein-Barr Virus Infections; Herpesvirus 4, Human; HIV Infections; Humans; Leukoplakia, Hairy; Tongue; Trans-Activators; Valacyclovir; Valine; Viral Proteins; Virus Replication