acyclovir and Sarcoma--Kaposi

The current arsenal of antiviral agents available to the practitioner is expanding rapidly, such that by the time this article goes to press, new drugs may have already been added. Although the majority of approved drugs have been developed for use in only a few viral infections (eg, HIV, herpesviruses, and papillomavirus), discoveries made in the development of these drugs may lead to antiviral agents effective against other viruses. In addition, new uses for the currently available drugs are under evaluation. This review of antiviral agents discusses the treatments available for viral infections such as herpes simplex virus, varicella zoster virus, cytomegalovirus, human papillomavirus, chronic viral hepatitis, and others.

Topics: 2-Aminopurine; Acyclovir; Antiviral Agents; Chickenpox; Cytomegalovirus Infections; Famciclovir; Foscarnet; Guanine; Hepatitis B; Hepatitis C; Herpes Genitalis; Herpes Simplex; Herpesvirus 3, Human; Herpesvirus 8, Human; Humans; Papillomavirus Infections; Sarcoma, Kaposi; Skin Diseases, Viral; Valacyclovir; Valine

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

The skin is the largest and most visible organ of the body, and a perception of good health depends on its appearance as well as its function. As about 90% of HIV-infected patients develop cutaneous signs and symptoms, diagnosis and management are vital in recognising progression of HIV infection.

Topics: Acyclovir; Antifungal Agents; Antiviral Agents; Dermatomycoses; Drug Eruptions; HIV Infections; Humans; Ketoconazole; Sarcoma, Kaposi; Skin Diseases; Skin Diseases, Papulosquamous; Skin Neoplasms

To determine if use of antiherpes drugs protects against the development of AIDS-associated Kaposi's sarcoma (KS), data from 935 homosexual men with AIDS from the Multicenter AIDS Cohort Study were analyzed. In nested case-control analysis, neither acyclovir use for human immunodeficiency virus infection (odds ratio [OR], 0.84; 95% confidence interval [CI], 0.56-1.26; P = .39) nor acyclovir use for any indication (OR, 1.02; 95% CI, 0.76-1.38; P = .89) was associated with a reduced risk of KS as initial AIDS diagnosis. In longitudinal analysis, acyclovir was also not protective against developing KS as a late manifestation of AIDS (after initial non-KS AIDS diagnosis). Among men with cytomegalovirus disease, ganciclovir use (relative risk [RR], 0.56; 95% CI, 0.22-1.44; P = .23) and foscarnet use (RR, 0.40; 95% CI, 0.051-3.10; P = .38) were associated (although not significantly) with a reduced risk of KS. Thus, acyclovir use does not appear to reduce the risk of KS, but further study of other antiherpes drugs such as ganciclovir and foscarnet is warranted.

Topics: Acyclovir; AIDS-Related Opportunistic Infections; Antiviral Agents; Bisexuality; Case-Control Studies; Foscarnet; Ganciclovir; Herpesviridae Infections; Homosexuality, Male; Humans; Longitudinal Studies; Male; Risk; Sarcoma, Kaposi

With the recent identification of a new herpesvirus in patients with Kaposi's sarcoma (human herpesvirus-8 or Kaposi's sarcoma-associated herpesvirus), there have been several reports on the use of anti-herpesvirus therapy (foscarnet, ganciclovir and aciclovir) and risk of developing Kaposi's sarcoma. We therefore investigated the association between use of anti-herpesvirus drugs and Kaposi's sarcoma in a large unselected group of patients with AIDS.. We studied a group of HIV-positive patients at the Chelsea and Westminster Hospital, for whom details on all AIDS-defining diagnoses made during follow-up, treatment and regular CD4 counts were available. Cox proportional hazards models with time-dependant covariates were used to assess the association between treatment with aciclovir, foscarnet and ganciclovir and risk of Kaposi's sarcoma.. A total of 3688 patients have been followed up for a median period of 4.2 years, during which time 598 patients (16.2%) developed Kaposi's sarcoma. After adjustments for sex, exposure category, age, treatment with antiretrovirals or Pneumocystis carinii pneumonia prophylaxis, the development of AIDS-defining conditions (including separate adjustment for the development of cytomegalovirus and herpes simplex virus) and CD4 count, there was a decreased risk of developing Kaposi's sarcoma with foscarnet [relative hazard (RH), 0.38; 95% confidence interval (CI), 0.15-0.95; P = 0.038] and with ganciclovir (RH, 0.39; 95% CI, 0.19-0.84; P = 0.015), but not with aciclovir (RH, 1.10; 95% CI, 0.88-1.38; P = 0.40).. These results suggest that both foscarnet and ganciclovir may have some activity in preventing the occurrence of Kaposi's sarcoma, but that aciclovir has no benefit. Further studies of the effect of these drugs on the risk of Kaposi's sarcoma is warranted.

Topics: Acyclovir; Adolescent; Adult; Aged; Antiviral Agents; Disease Progression; Female; Follow-Up Studies; Foscarnet; Ganciclovir; HIV Infections; Humans; Male; Middle Aged; Proportional Hazards Models; Sarcoma, Kaposi

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Anti-Retroviral Agents; Antiviral Agents; Bronchial Neoplasms; Bronchoscopy; Cerebrospinal Fluid; Encephalitis, Varicella Zoster; Fatal Outcome; Herpesvirus 3, Human; Herpesvirus 8, Human; Humans; Male; Medication Adherence; Sarcoma, Kaposi; Spinal Puncture; Young Adult

Immune Reconstitution Inflammatory Syndromes (IRIS) are exaggerated pathological inflammatory reactions occurring after initiation of highly active antiretroviral therapy (HAART) due to exuberant immune responses to occult or apparent opportunistic infections or cancers. In view of paucity of studies from Nigeria, we report 3 cases of IRIS presenting as disseminated infections in HIV-1 infected patients initiating HAART. The first case was a previously healthy female who developed disseminated tuberculosis after 4 weeks of regular HAART. Her HAART regimen was continued and she improved after commencement of anti-tuberculosis drugs, with evidence of progressive increase in CD4 cell count. The second case was a HAART-experienced female who stopped her drugs for 4 months. Two months after recommencement of her previous HAART regimen, she developed features of disseminated herpes zoster infection, despite evidence of decrease in viral load by 95%. HAART was continued and she recovered completely after receiving valaciclovir tablets and antibiotics. The third patient was a female student who was commenced HAART on account of chronic cough and weight loss. Three months after regular HAART, she developed features of disseminated Kaposi's sarcoma involving the skin, oropharynx and lungs, despite evidence of 42% increase in CD4 cell count. Unfortunately, she rapidly deteriorated and died during the course of management. Clinicians should be alert to the possibility of IRIS in HIV-infected patients initiated or re-initiated on HAART. There is need for future prospective studies determining risk factors for IRIS in HIV-infected patients from Nigeria.

Topics: Acyclovir; Adult; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Antiviral Agents; CD4 Lymphocyte Count; Disease Susceptibility; Fatal Outcome; Female; Herpes Zoster; HIV Infections; HIV-1; Humans; Immune Reconstitution Inflammatory Syndrome; Nigeria; Respiratory Tract Neoplasms; Sarcoma, Kaposi; Skin Neoplasms; Tuberculosis, Miliary; Valacyclovir; Valine; Viral Load; Viremia; Young Adult

Studies were conducted to investigate changes in the extent of human herpesvirus 8 (HHV-8) shedding and diversity of HHV-8 strains in the mouth of a renal allograft recipient who developed cutaneous post-transplantation Kaposi's sarcoma.. Matched oral and blood samples were obtained from a Saudi Arabian renal allograft recipient from 3 days before to 38 weeks after transplantation, and from his kidney donor. Polymerase chain reaction (PCR) protocols to amplify selected HHV-8 sub-genomic regions were applied to detect and quantify HHV-8 DNA. Sequence diversity was determined by cloning the PCR products and subjecting them to denaturing gradient gel electrophoresis and to nucleotide sequencing.. Before transplantation, the recipient was seropositive for anti-HHV-8 immunoglobulin G, but the donor was seronegative; HHV-8 DNA could be detected in the recipient's blood, whole-mouth saliva (WMS) and buccal exfoliates, and the salivary viral load was estimated as 2.6 million genome-copies/ml. Post-transplantation, the recipient's salivary viral load initially increased to 4.1 million genome-copies/ml, and thereafter declined precipitously, coinciding with an increase in the dosage of valaciclovir given; HHV-8 DNA was detected most often in WMS compared with parotid saliva, and buccal and palatal exfoliates. Carriage of multiple HHV-8 strains was evident in blood and oral samples; whereas before transplantation strains belonging to genotypes A1 and A5 were observed, after transplantation genotype A5 strains became dominant and A2 strains emerged.. Immunosuppression and antiviral prophylaxis may interact to influence the spectrum of oral HHV-8 strains and the extent of post-transplantation HHV-8 shedding into the mouth.

Topics: Acyclovir; Adult; Antiviral Agents; Blood; Colonic Neoplasms; DNA, Viral; Genetic Variation; Herpesvirus 8, Human; Humans; Immunophenotyping; Immunosuppression Therapy; Kidney Transplantation; Leukocytes; Male; Molecular Sequence Data; Mouth Mucosa; Saliva; Sarcoma, Kaposi; Skin Neoplasms; Stomach Neoplasms; Valacyclovir; Valine; Viral Load; Virus Shedding

To evaluate the impact of antiretroviral and antiherpesvirus therapies on the incidence of KS and assess trends in incidence of Kaposi's sarcoma (KS) in a large multicenter HIV/AIDS surveillance system between 1990 and 1998.. Incidence was calculated per 100 person-years (py); the effects of therapies on risk for KS were calculated by using multivariate Poisson regression controlling for gender, race/ethnicity, age, HIV exposure mode, CD4+ cell count, and calendar year. Antiretroviral therapy was defined as monotherapy, dual therapy, or triple therapy (95% of triple therapy regimens contained a protease inhibitor). Acyclovir, ganciclovir, and foscarnet were the antiherpesvirus therapies evaluated.. There were 37,303 HIV-infected people in the study contributing 70,238 py. Those prescribed triple antiretroviral therapy had a 50% reduction in the incidence of KS (95% confidence interval, 20%-70%) compared with those who were not prescribed antiretroviral therapy and there was a reduction in risk for KS among persons prescribed foscarnet (p =.05). Overall, KS incidence declined an estimated 8.8% per year (observed incidence 4. 1 per 100 py in 1990 to 0.7 per 100 py in 1998; p <.001).. Incidence of KS is declining in this large U.S. population and may continue to decline as new, more effective antiretroviral agents are developed and used widely.

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Drug Therapy, Combination; Female; Foscarnet; Ganciclovir; HIV Infections; Homosexuality, Male; Humans; Incidence; Male; Middle Aged; Multicenter Studies as Topic; Retrospective Studies; Risk Factors; Sarcoma, Kaposi; Skin Neoplasms

There is no current curative treatment for HIV-related Kaposi's sarcoma. The identification of human herpesvirus-8 as a possible aetiological agent suggests potential efficacy of anti-viral agents. We report here on the complete histological remission of Kaposi's sarcoma following treatment with protease inhibitors, even in patients with limited virological response and persistence of HHV-8.

Topics: Acyclovir; Herpesvirus 8, Human; HIV Protease Inhibitors; Humans; Sarcoma, Kaposi; Valacyclovir; Valine

Using a cell line (termed BCBL-1) derived from a peripheral effusion (body cavity-based) lymphoma latently infected with Kaposi's sarcoma-associated herpesvirus (KSHV), we recently reported the successful induction of KSHV replication in culture (Renne, R., W. Zhong, B. Herndier, M. McGrath, N. Abbey, D. Kedes, and D. Ganem. 1996. Nat. Med. 2:342-346). Here we report the first use of this system for establishing the susceptibility of KSHV to available antiviral drugs. Latently infected BCBL-1 cells were induced to lytic replication with phorbol esters; such cells secrete large numbers of KSHV virions into the culture medium. We assayed the ability of the antivirals to block KSHV production, as measured by the release of encapsidated viral DNA. The results show that KSHV replication is insensitive to acyclovir (9-[(2-hydroxyethoxy)-methyl]guanine) (50% inhibitory concentration [IC50] = 60-80 microM), but sensitive to ganciclovir (9-[1,3-dihydroxy-2-propoxymethyl]guanine) (IC50 = 2.7-4 microM), foscarnet (trisodium phosphonoformate hexahydrate) (IC50 = 80-100 microM), and cidofovir (1-[(S)-3-hydroxy-2-(phosphonomethoxy)propyl]cytosine) (IC50 = 0.5-1 microM).

Topics: Acyclovir; Antiviral Agents; Cidofovir; Cytosine; DNA Probes; DNA, Viral; Foscarnet; Ganciclovir; Herpesvirus 8, Human; HIV Protease Inhibitors; Humans; Methylurea Compounds; Nucleic Acid Hybridization; Organophosphonates; Organophosphorus Compounds; Phorbol Esters; Pyridines; Sarcoma, Kaposi; Tumor Cells, Cultured; Valine; Virus Replication

Kaposi's sarcoma-associated herpesvirus (KSHV), or human herpesvirus 8, has been implicated as the causative agent of Kaposi's sarcoma. Retrospective studies show that the risk of development of Kaposi's sarcoma is significantly lower in AIDS patients who received ganciclovir or phosphonoformic acid (PFA) therapy. Therefore, in vitro antiviral drug sensitivity of KSHV was studied.. The KSHV genome is a latent episome in lymphoma cells such as the BCBL-1 cell line. Lytic KSHV DNA synthesis is induced by the phorbol ester 12-O-tetradecanoyl phorbol-13-acetate in BCBL-1 cells; this system was used to evaluate the effects of antiviral drugs on KSHV DNA synthesis.. Linear (lytic) KSHV DNA synthesis and virus secretion was inhibited in BCBL-1 cell cultures by cidofovir (median inhibitory concentration, 0.05 microM), ganciclovir (5.1 microM) and PFA (97 microM), and by aciclovir (75 microM). Prolonged incubation of BCBL-1 cells with antiviral drugs had no effect on episomal KSHV DNA synthesis.. The antiviral drug assay developed shows that KSHV is very sensitive to cidofovir, moderately sensitive to ganciclovir and PFA, and weakly sensitive to aciclovir. Therefore, low doses of cidofovir, or high doses of PFA or ganciclovir could suppress clinical reactivation of KSHV. Antiviral drugs did not inhibit episomal virus DNA synthesis, suggesting that the latent form of viral DNA is replicated by host DNA polymerases. Consequently, no benefit can be expected from antiviral drugs in KSHV-positive B-cell lymphomas or during latency.

Topics: Acyclovir; Antiviral Agents; Carcinogens; Cidofovir; Cytosine; DNA-Directed DNA Polymerase; DNA, Viral; Foscarnet; Ganciclovir; Herpesvirus 8, Human; Humans; Microbial Sensitivity Tests; Organophosphonates; Organophosphorus Compounds; Phorbol 12,13-Dibutyrate; Sarcoma, Kaposi; Thymidine; Tumor Cells, Cultured; Virus Latency

Topics: Acyclovir; AIDS-Related Opportunistic Infections; Antiviral Agents; Bias; Female; Follow-Up Studies; Foscarnet; Ganciclovir; HIV Seropositivity; Humans; Information Systems; Male; Proportional Hazards Models; Risk Factors; Sarcoma, Kaposi

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; AIDS-Related Opportunistic Infections; Female; Foscarnet; Ganciclovir; Herpesviridae Infections; Humans; Male; Retrospective Studies; Risk Factors; Sarcoma, Kaposi

The Second Human Retroviruses Conference covered many topics, including statistics on the viruses' prevalence in American society and some survey results on sexual behavior. Conference meetings were dominated by discussions on protease inhibitors and current clinical trial data on two inhibitors in particular, 3TC and ZDV. Evidence of a new herpes virus causing Kaposi's sarcoma (KS), and research on anti-KS agents, were discussed, including assessments concerning the struggle between the virus and the immune system, and arguments about using immune-based therapies versus attacking the virus directly. Of particular interest concerning immune-based therapy was the National Institute of Allergy and Infectious Diseases' (NIAID) interleukin-2 trial which is showing impressive results in affecting CD4+ counts, if CD4+ counts are not too low initially. Antiretroviral information centered on two investigations surrounding Parke-Davis' PD121871 and PD144975, which seem to prevent activation of latently-infected cells, and return activated cells to a quiescent state. Other conference topics covered acyclovir survival levels, the new therapies and renewed concerns about cytomegalovirus, planning an overall prophylactic strategy, the slow progress in developing a vaccine, and whether low-dose chemotherapy for lymphoma was as good as the standard dose.

Topics: Acyclovir; AIDS Vaccines; AIDS-Related Opportunistic Infections; Antineoplastic Agents; Antiviral Agents; CD4 Lymphocyte Count; Cytomegalovirus Retinitis; Herpesviridae; HIV Infections; Humans; Interleukin-2; Lamivudine; Lymphoma, Non-Hodgkin; Retroviridae; Sarcoma, Kaposi; Zalcitabine; Zidovudine

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Anti-Bacterial Agents; Antitrichomonal Agents; Female; Genital Neoplasms, Female; Gonorrhea; Humans; Lice Infestations; Lymphogranuloma Venereum; Lymphoma; Pregnancy; Pregnancy Complications, Infectious; Sarcoma, Kaposi; Sexually Transmitted Diseases; Syphilis

The number of AIDS patients is still increasing. In 30-50% of these patients ocular lesions occur, which are of diagnostic and prognostic significance. If the life-span of AIDS patients lengthens in the future, adequate treatment of the ocular conditions will become increasingly important. The two most important ocular manifestations AIDS are CMV-retinitis and Kaposi's sarcoma of the conjunctiva. DHPG, a new virustatic for human cytomegalovirus, appears promising as treatment for the severe CMV-retinitis, which leads rapidly to blindness. Two case histories illustrate the preliminary results obtained with DHPG treatment. Kaposi's sarcoma of the conjunctiva is relatively benign is AIDS and can be treated successfully by surgical excision, radiotherapy, cryotherapy or local injections of cytostatics.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Chemical Phenomena; Chemistry; Conjunctival Neoplasms; Cytomegalovirus Infections; Ganciclovir; Humans; Male; Middle Aged; Retinitis; Sarcoma, Kaposi