Herpes simplex, with AIDS

In advanced AIDS, MM is usually associated with opportunistic infections such as CMV (Said et al. 1991 RouUet et al. 1994 Kolson and Gonzalez-Scarano 2001) or is secondary to lymphoma (Fuller et al. 1993). Despite a role for other herpes viruses in AIDS-associated myelitis, no substantive evidence has been published in support of a role for other vimses in the development of HIV-associated MM, including herpes simplex 1 or 2, varicella zoster, or Epstein Barr vims (Kolson and Gonzalez-Scarano 2001). MM can occur secondary to hepatitis B and C viruses, which are common co-infections of HIV-infected patients, particularly when there is an associated cryoglobulinemia (Taillan et al. 1993 Caniatti et al. 1996). Rarely... 

Miguelez M, Correa-Nazco VJ et al (1999) [Lumbosacral polyradiculomyelitis caused by herpes simplex virus (HSV) in a patient with AIDS]. An Med Interna 16(8) 417 19 MiUer RJ, Meucci O (1999) AIDS and the brain is there a chemokine connection Trends Neurosd 22(10) 471-479... 

Acyclovir [9-(2-hydroxyethoxymethyl)guanine] (ACV) is clinically useful in the treatment of infections caused by several members of the herpes virus (e.g., herpes simplex, varicella zoster and Epstein-Barr virus [2,38,39]). An enzyme coded for by the virus phosphorylates ACV to a monophosphate intermediate. This species in turn undergoes further phosphorylation to a triphosphate with the aid of normal cell enzymes. Then, ACV triphosphate inhibits the herpes virus DNA... 

A 40-year-old female with a history of AIDS develops a herpes simplex keratitis of the eye. Which of the following antiviral agents should be administered in this case ... 

The topical ophthalmic antiviral preparations appear to interfere with viral reproduction by altering DNA synthesis. Trifluridine is effective treatment for herpes simplex infections of the conjunctiva and cornea. Ganciclovir is indicated for use in immunocompromised patients with cytomegalovirus (CMV) retinitis and for prevention of CMV retinitis in transplant patients. Foscarnet is indicated for use only in AIDS patients with CMV retinitis. 

Antiviral Efficacy and Clinical Use. Foscarnet (Fos-cavir) is primarily given to treat CMV retinitis in patients with AIDS.6,24 This agent may also help control other infections in patients with a compromised immune system, including serious cytomegaloviral infections (pneumonia, gastrointestinal infections) and some herpesvirus infections (herpes simplex, varicella-zoster). 

Foscarnet represents a diphosphate analogue. Incorporation of nucleotide into a DNA strand entails cleavage of a diphosphate residue. Foscarnet inhibits DNA polymerase by interacting with its binding site for the diphosphate group. Indications systemic therapy in severe cytomegaly infections in AIDS patients local therapy of herpes simplex infections. 

Aciclovir-resistant herpes simplex virus has been reported in patients with AIDS foscamet (see p. 262) has been used in these cases. 

Valaciclovir is highly active against Herpes simplex and Herpes zoster. It is also effective in suppressing recurrent episodes of genital herpes (1). Prophylactic administration of high doses of valaciclovir to prevent CMV disease was effective in patients with AIDS and in liver transplant recipients (2,3). 

The trisodium salt of phosphonofonnic acid (PFA), called Foscamet, is an effective antiviral agent with potential application in acquired immunodeficiency syndrome (AIDS) therapy. PFA inhibits replication of HIV-I in the laboratory and reduces viremia in patients with AIDS. It also inhibits DNA polymerase from cytomcgalovims (CMV), herpes simplex virus (HSV), and other DNA vimses and thus has been useful in the treatment of secondary viral infections in AIDS patients. Because PFA bears a stmctural resemblance to pyrophosphate, it can be viewed as a product analogue as opposed to a substrate analogue. 

Gateley A, Gander RM, Johnson PC, et al. Herpes simplex virus type 2 meningoencephalitis resistant to acyclovir in a patient with AIDS. J Infect Dis 1990 161 711-715. 

Herpes simplex viruses (HSV) types 1 and 2 cause significant morbidity in patients with AIDS. Seropositivity for HSV is widespread among adults with AIDS, and clinical disease usually is the result of reactivation of latent virus. The manifestations of HSV disease observed in persons with AIDS include orolabial, genital, and anorectal mucocutaneous disease esophagitis and less commonly, encephalitis. Ulcerative HSV lesions present for longer than 1 month in an individual with laboratory evidence for HIV infection or no other apparent cause for immunodeficiency are considered an AIDS-defining condition. 

Foscamet is an antiviral agent that inhibits replication of all known herpes viruses, including cytomegalovirus (CMV), herpes simplex virus types 1 and 2 (HSV-1, HSV-2), human herpes virus 6 (HHV-6), Epstein-Barr virus (EBV) and varicella-zoster virus (VZV). It is indicated in the treatment of CMV retinitis in patients with AIDS treatment of acyclovir-resistant mucocutaneous HSV infections in immunocompromised patients and as combination therapy with ganciclovir for patients who have relapsed after monotherapy with either drug. 

Uric acid nephrolithiasis calcium renal stones Malignant mesothelioma Status epilepticus Herpes simplex encephalitis Neurosyphilis Status epilepticus Cognitive dysfunction Malignant non-Hodgkin s lymphomas Treatment of PCP associated with AIDS Acanthamoeba keratitis Peripheral arterial occlusive disease Congenital or acquired protein C deficiency Respiratory distress syndrome associated with prematurity... 

Adenine itself was successfully incorporated into a number of pharmaceuticals, Adefovir dipivoxil, also known as bis-POM PMEA, with trade names Preveon and Hepsera, is used for the treatment of hepatitis B and herpes simplex virus infection. It is an orally administered nucleotide analog as a reverse transcriptase inhibitor (NRTI). Reverse transcriptase is an enzyme crucial to viral production. A second NRXI that contains adenine is Tenofovir disoproxil fumarate (TDF), which has been used in the treatment of HIV/AIDS and hepatitis B. TDF is a prodrug of tenofovir (also known as PMPA) designed to improve absorption and cell permeability of the active moiety under the trade name Viread. Both adefovir dipivoxil and TDF are marketed by Gilead Sciences. 

An amino-analogue of idoxuridine known as Aid Urd (4-12) may have clinical potential, because of its very unusual biochemistry. This substance (5-iodo-5 -amino-2, 5 -dideoxyuridine) is activated to its cytostatic triphosphate by the kinase of herpes virus, but not by kinases in uninfected human, murine, or simian cells. It inhibited herpes simplex infection with no sign of toxicity to the host. However, when a mammalian cell was infected with herpes virus, the drug was incorporated into the DNA of both host and virus (Chen, Ward, and Prusoff, 1976). This incorporation will not matter, provided that all infected cells die, and the replication of the virus is halted. Acycloguanosine, recently developed, is 3000 times more toxic to herpes simplex virus than to mammalian cells. This substance, 9-(2-hydroxyethoxymethyl)guanine, zovirax , is phosphorylated by virus-specified thymidine kinase and the product is highly lethal to the virus (only). Healthy human cells carry out little of this phosphorylation, and are unharmed by the product, hence the phenomenal selectivity (Elion et aLy 1977) and its clinical usefulness. 

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