PubMed Health⌕ Search

PubMed · 10193689

Fomivirsen.

Abstract

Fomivirsen (ISIS 2922) is an antisense oligonucleotide which specifically inhibits replication of human cytomegalovirus. It achieves this by binding to complementary sequences on messenger RNA transcribed from the major immediate-early transcriptional unit of the virus. It is being developed for the treatment of cytomegalovirus retinitis. Mean maximum retinal concentrations of fomivirsen occurred approximately 2 days after a single intravitreal injection in monkeys. The elimination half-life of fomivirsen (after a single 115 microg dose) in monkey retina was 78 hours. Fomivirsen, administered as an intravitreal injection, significantly delayed progression of cytomegalovirus retinitis in patients with AIDS in preliminary clinical trials. In 18 patients with newly diagnosed, unilateral, peripheral cytomegalovirus retinitis treated with fomivirsen 165 microg once weekly for 3 weeks, then 165 microg every second week, the median time to disease progression was significantly longer than in 10 patients in whom fomivirsen treatment was deferred until early disease progression (71 vs 14 days). In patients with advanced, refractory, sight-threatening disease, treatment with fomivirsen 330 microg once weekly for 3 weeks and then 330 microg every 2 weeks (n = 34) or 330 microg on days 1 and 15 and then monthly (n = 20) significantly delayed disease progression. The interpolated median time to disease progression was 90 days in both treatment groups. The most common adverse events reported in clinical trials of fomivirsen were increased intraocular pressure and mild to moderate intraocular inflammation. These events were generally transient or reversible with topical steroid treatment.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

C M Perry, J A Balfour. 1999. Fomivirsen.. https://doi.org/10.2165/00003495-199957030-00010

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

Modeling changes in CD4-positive T-lymphocyte counts after the start of highly active antiretroviral therapy and the relation with risk of opportunistic infections: the Aquitaine Cohort, 1996-1997.

After initiation of a treatment for human immunodeficiency virus type 1 infection containing a protease inhibitor, immune restoration associated with increases in CD4-positive (CD4+) T lymphocyte count may be delayed. In a sample of patients who had been prescribed protease inhibitors for the first time, the authors tested to see whether there was a minimal duration of CD4+ cell count increase before the increase had an impact on the occurrence of opportunistic infections. The evolution (difference between time t and baseline) of CD4+ cell count was modeled using a mixed effects linear model. Changes in CD4+ count estimated by this model were then included as time-dependent covariates in a proportional hazards model. Finally, the authors tested for the existence of a CD4+ change x time interaction. The authors used a sample of 553 French patients first prescribed protease inhibitors in 1996 and followed for a median of 16 months. During the first 120 days, there was no association between CD4+ change and the rate of opportunistic infections. After 120 days, each 50-cell/mm3 increase in CD4+ count was associated with a 60% (95% confidence interval: 45, 72) reduction in the incidence of opportunistic infections. These results, based on modeling of CD4+ cell response, at least indirectly reinforce the concept of a delayed but possible immune recovery with the use of protease inhibitors. The findings support the potential for interruption of certain types of prophylaxis against opportunistic infections under reasonable conditions of duration of antiretroviral therapy and sustained CD4+ cell response.

AIDS-Related Opportunistic Infections↗

A review of efficacy studies of 6-month short-course therapy for tuberculosis among patients infected with human immunodeficiency virus: differences in study outcomes.

Six-month regimens that include rifampin for the treatment of tuberculosis in patients without human immunodeficiency virus (HIV) infection are recommended because of low percentage of relapses. Whether a similar duration of therapy should be used to treat tuberculosis in HIV-infected patients is unclear. Six studies of patients with HIV-infection and 3 of patients without HIV infection were reviewed and compared. The studies differed in terms of design, eligibility criteria, site of disease, frequency of dosing, dose administration methods, and outcome definitions. Among HIV-infected patients, the following percentages were found: cure, 59.4%--97.1%; treatment success, 34.0%--100%; effective treatment, 29.4%--88.2%; and relapse, 0%--10%. In those without HIV infection, percentages were as follows: cure, 62.3%--88.0%; treatment success, 91.2%--98.8%; effective treatment, 70.6%--83.8%; and relapse, 0%--3.4%. Although the rate of relapse appeared to be higher in some studies of HIV-infected patients with tuberculosis, this review demonstrates the limitation in the use of relapse as the exclusive outcome of interest when comparing studies.

AIDS-Related Opportunistic Infections↗

Augmentation of apoptosis and interferon-gamma production at sites of active Mycobacterium tuberculosis infection in human tuberculosis.

Pleural tuberculosis (TB) was employed as a model to study T cell apoptosis at sites of active Mycobacterium tuberculosis (MTB) infection in human immunodeficiency virus (HIV)-coinfected (HIV/TB) patients and patients infected with TB alone. Apoptosis in blood and in pleural fluid mononuclear cells and cytokine immunoreactivities in plasma and in pleural fluid were evaluated. T cells were expanded at the site of MTB infection, irrespective of HIV status. Apoptosis of CD4 and non-CD4 T cells in the pleural space occurred in both HIV/TB and TB. Interferon (IFN)-gamma levels were increased in pleural fluid, compared with plasma. Spontaneous apoptosis correlated with specific loss of MTB-reactive, IFN-gamma-producing pleural T cells. Immunoreactivities of molecules potentially involved in apoptosis, such as tumor necrosis factor-alpha, Fas-ligand, and Fas, were increased in pleural fluid, compared with plasma. These data suggest that continued exposure of immunoreactive cells to MTB at sites of infection may initiate a vicious cycle in which immune activation and loss of antigen-responsive T cells occur concomitantly, thus favoring persistence of MTB infection.

AIDS-Related Opportunistic Infections↗