Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A meta-analysis of 8 randomized trials (1792 patients, 2947 patient-years of follow-up) showed that acyclovir (> or = 3200 mg/day) offered a significant survival benefit (P = .006 by log-rank test) in human immunodeficiency virus (HIV) infection. The treatment effect did not vary significantly in patient subgroups of different CD4 cell counts, hemoglobin levels, age, race, and sex, and with or without AIDS diagnosis. Acyclovir treatment (hazard ratio, 0.78; 95% confidence interval [CI], 0.65-0.93), higher CD4 cell count (P < .001), higher hemoglobin level (P < .001), and younger age (P < .001) reduced the hazard of mortality. Acyclovir decreased herpes simplex virus infections (odds ratio [OR], 0.28; 95% CI, 0.21-0.37) and varicella-zoster virus infections (OR, 0.29; 95% CI, 0.13-0.63) but not cytomegalovirus disease or mortality from lymphoma or Kaposi's sarcoma. A survival advantage was seen specifically in studies with high incidence of clinical herpesvirus infections (> or = 25% per year). Given the wide confidence intervals, the small effect in low-risk patients, and recent changes in HIV therapeutics, the results should be interpreted cautiously, but the meta-analysis supports the importance of pathogenetic interactions between herpesviruses and HIV.
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PMID:Clinical efficacy of high-dose acyclovir in patients with human immunodeficiency virus infection: a meta-analysis of randomized individual patient data. 969 14

The rates of herpes simplex virus (HSV) infection are rising, the highest prevalence being in the group infected with the human immunodeficiency virus (HIV). We review the relation between these 2 infections. The presence of genital ulcers increases the transmission of HIV, and the presence of HIV adversely affects the natural history of HSV infection. The detection and treatment of sexually transmitted diseases such as genital herpes actually decrease the rates of HIV infection in groups studied. The treatment of HSV in persons with HIV is challenging because the incidence of immunosuppression increases. Acyclovir resistance is more common in this group, but acyclovir use may prolong survival in some HIV-seropositive patients. Further studies are needed to determine whether persons with HIV disease should routinely be given HSV-specific therapy.
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PMID:Relation between herpes simplex viruses and human immunodeficiency virus infections. 1056 40

The most common therapies against human herpes virus (HSV-1) and human immunodeficiency virus (HIV-1) infectivity are based on the administration of nucleoside analogues. Acyclovir (ACV) is the drug of choice against HSV-1 infection, while the acyclic nucleoside phosphonate analogue PMPA has shown marked anti-HIV activity in a phase I and II clinical studies. As monocyte-derived macrophages are assumed to be important as reservoirs of both HSV-1 and HIV-1 infection, new approaches able to inhibit replication of both viruses in macrophages should be welcome. ACVpPMPA, a new heterodinucleotide consisting of both an antiherpetic and an antiretroviral drug bound by a phosphate bridge, was synthesized and encapsulated into autologous erythrocytes modified to increase their phagocytosis by human macrophages. ACVpPMPA-loaded erythrocytes provided an effective in vitro protection against both HSV-1 and HIV-1 replication in human macrophages.
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PMID:A new acyclic heterodinucleotide active against human immunodeficiency virus and herpes simplex virus. 1097 67

During the period of profound combined immunodeficiency after bone marrow or peripheral blood stem cell transplantation (SCT), patients are at increased risk for serious viral disease. Recent advances in rapid diagnostic methods and the introduction of potent antiviral compounds have made it possible to establish efficient management strategies for several herpesviruses. Acyclovir, valaciclovir, and famciclovir are widely used for the treatment of herpes simplex virus or varicella zoster virus disease. Intravenous ganciclovir, foscarnet, and cidofovir are available for prevention or therapy of cytomegalovirus disease, and oral valganciclovir could become a valuable alternative to intravenous treatment if shown to be effective and safe after SCT. Preliminary data on pleconaril for therapy of picornaviral disease are promising. Future investigations may help to clarify the role of the neuraminidase inhibitors zanamivir and oseltamivir in the management of influenza in SCT recipients. The emergence of viruses resistant to antiviral drugs is of concern, and alternative treatment strategies need to be defined.
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PMID:Challenges and options in the management of viral infections after stem cell transplantation. 1190 84

Herpes simplex virus (HSV) infections are very common in the general population and among immunocompromised patients. Acyclovir (ACV) is an effective treatment which is widely used. We deemed it essential to conduct a wide and coordinated survey of the emergence of ACV-resistant HSV strains. We have formed a network of 15 virology laboratories which have isolated and identified, between May 1999 and April 2002, HSV type 1 (HSV-1) and HSV-2 strains among hospitalized subjects. The sensitivity of each isolate to ACV was evaluated by a colorimetric test (C. Danve, F. Morfin, D. Thouvenot, and M. Aymard, J. Virol. Methods 105:207-217, 2002). During this study, 3900 isolated strains among 3357 patients were collected; 55% of the patients were immunocompetent. Only six immunocompetent patients excreted ACV-resistant HSV strains (0.32%), including one female patient not treated with ACV who was infected primary by an ACV-resistant strain. Among the 54 immunocompromised patients from whom ACV-resistant HSV strains were isolated (3.5%), the bone marrow transplantation patients showed the highest prevalence of resistance (10.9%), whereas among patients infected by human immunodeficiency virus, the prevalence was 4.2%. In 38% of the cases, the patients who excreted the ACV-resistant strains were treated with foscarnet (PFA), and 61% of them developed resistance to PFA. The collection of a large number of isolates enabled an evaluation of the prevalence of resistance of HSV strains to antiviral drugs to be made. This prevalence has remained stable over the last 10 years, as much among immunocompetent patients as among immunocompromised patients.
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PMID:Surveillance network for herpes simplex virus resistance to antiviral drugs: 3-year follow-up. 1471 60

A 37-year-old man with a three-year history of Acquired Immunodeficiency Syndrome was admitted with impaired consciousness, seizures and fever. He was on highly active antiretroviral therapy and on neurotoxoplasmosis secondary prophylaxis. Laboratory exams from two months before showed a CD4 cell count of 37/microL and a viral load of 230,000 copies/mL. Three months before admission he developed herpetic skin rash in the right trunk and acyclovir was added to his treatment regimen. On physical exam he was drowsy and had motor and sensory aphasia. The patient had elevated protein levels and normal pressure in the cerebrospinal fluid (CSF). Contrast enhanced computed tomography scan of the brain showed a hypodense lesion in the left parietal lobe, with poorly defined margins and no contrast enhancement. The magnetic resonance scan (MRI) showed multiple hyperintensities in T2-weighted image in white and grey matters and hypointense products of hemorrhage in both hemispheres and in the cerebellum. He was empirically treated with intravenous acyclovir and prednisone. Viral DNA of Varicella-zoster virus (VZV) was detected in the CSF by means of polymerase chain reaction (PCR) analysis. Acyclovir was continued for 10 days and the patient became well, with improvement of aphasia. We present a case of VZV encephalitis, confirmed by nested PCR, in a patient with suggestive MRI findings, who succeeded with treatment. VZV encephalitis is a rare opportunistic infection, occurring in 0.1 to 4% of AIDS patients with neurological disease; it is related to severe immunodeficiency and has a high mortality.
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PMID:Varicella-zoster virus encephalitis in an AIDS patient. 1547 58

The antiviral drug acyclovir is a guanosine nucleoside analog that potently inhibits herpes simplex virus (HSV) replication. Acyclovir treatment in patients coinfected with HSV and human immunodeficiency virus (HIV) has been observed to alter disease course and decrease HIV viral load, a finding that has been attributed to indirect effects of HSV suppression on HIV replication. Based on this hypothesis, several clinical studies have recently investigated the use of acyclovir for treatment of patients coinfected with HSV and HIV or for prophylaxis against HIV transmission. In this report, we use a single round HIV infectivity assay to show that acyclovir directly inhibits HIV infection with an IC50 of approximately 5 microm. The target of acyclovir in HIV-infected cells is validated as HIV reverse transcriptase (RT) by the emergence of the RT variant V75I under the selective pressure of acyclovir. The V75I mutation is part of the multidrug resistance pathway that enhances viral resistance to many of the best RT inhibitors approved for the treatment of HIV. Biochemical analyses demonstrate that acyclovir triphosphate is a chain terminator substrate for HIV RT and can compete with dGTP for incorporation into DNA. Although acyclovir may prove a useful lead for development of new HIV treatments, the selection of resistant mutants raises a cautionary note to the use of acyclovir monotherapy in patients coinfected with HSV and HIV.
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PMID:The antiherpetic drug acyclovir inhibits HIV replication and selects the V75I reverse transcriptase multidrug resistance mutation. 1881 98

Herpes simplex virus type 2 (HSV2) infection is a major source of morbidity in human immunodeficiency virus (HIV)-infected patients, since reactivations - whether symptomatic or asymptomatic - are associated with increased HIV viral load and viral shedding. Acyclovir, valacyclovir and famcyclovir are indicated for the treatment of HSV2 in HIV patients. This class of drugs has been shown to enhance survival in HIV-infected individuals. However, with the emergence of drug-resistant strains of HSV2, the rates of resistance among HIV patients are almost ten-fold those in immunocompetent individuals, comparing 0.6% to 6%. These HSV2 infections tend to be more severe and to recur. More ominously, disease progression of HIV is promoted by concurrent infection with HSV2. Intravenous foscarnet and cidofovir may be used for acyclovir-resistant HSV; however, resistance to these drugs has been documented. Newer therapies such as the toll-like receptor agonist imiquimod and immunomodulating dipeptides offer promise for the treatment of HSV2 in HIV-infected individuals.
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PMID:Drug-resistant herpes simplex virus in HIV infected patients. 1911 Nov 44

Management of genital herpes is complex. Apart from using the standard antivirals, an ideal management protocol also needs to address various aspects of the disease, including the psychological morbidity. Oral acyclovir, valacyclovir or famciclovir are recommended for routine use. Long-term suppressive therapy is effective in reducing the number of recurrences and the risk of transmission to others. Severe or disseminated disease may require intravenous therapy. Resistant cases are managed with foscarnet or cidofovir. Genital herpes in human immunodeficiency virus-infected individuals usually needs a longer duration of antiviral therapy along with continuation of highly active anti retroviral therapy (HAART). Genital herpes in late pregnancy increases the risk of neonatal herpes. Antiviral therapy and/or cesarean delivery are indicated depending on the clinical circumstance. Acyclovir appears to be safe in pregnancy. But, there is limited data regarding the use of valacyclovir and famciclovir in pregnancy. Neonatal herpes requires a higher dose of acyclovir given intravenously for a longer duration. Management of the sex partner, counseling and prevention advice are equally important in appropriate management of genital herpes. Vaccines till date have been marginally effective. Helicase-primase inhibitors, needle-free mucosal vaccine and a new microbicide product named VivaGel may become promising treatment options in the future.
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PMID:Newer trends in the management of genital herpes. 1991 35

Acyclovir suppressive therapy (400 mg twice daily) reduces herpes simplex virus (HSV) type 2-associated genital ulcer disease and lesional HSV shedding. In an international trial of acyclovir for suppression of HSV type 2 to prevent human immunodeficiency virus (HIV) acquisition (HIV Prevention Trials Network 039), acyclovir had a smaller effect on the frequency of genital ulcer disease as well as a smaller effect on the frequency and quantity of lesional HSV DNA in African women and Peruvian men, compared with its effects in men in the United States. The observed regional variation in the clinical and virologic efficacy of acyclovir for HSV suppression warrants further evaluation of determinants of responses to acyclovir. (ClinicalTrials.gov identifier: NCT00076232.).
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PMID:Clinical and virologic efficacy of herpes simplex virus type 2 suppression by acyclovir in a multicontinent clinical trial. 2021 74


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