Acyclovir resistant infection, with AIDS

Infection owing to resistant HSV is rare in immunocompetent persons in immunocompromised hosts, resistant HSV isolates can cause extensive mucocutaneous disease and, rarely, meningoencephalitis, pneumonitis, or visceral disease. Resistant HSV can be recovered from 6% to 17% of immunocompromised patients receiving acyclovir treatment. Recurrences after acyclovir cessation usually are due to sensitive virus but may be due to acyclovir-resistant virus in AIDS patients. In patients with progressive disease, intravenous foscarnet therapy is effective, but vidarabine is not. 

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. 

Immunocompromised patients are at greatest risk for severe and recurrent HSV infections. Acyclovir, valacyclovir, and famciclovir have been used to prevent reactivation of infection in patients seropositive for HSV who undergo transplantation procedures or induction chemotherapy for acute leukemia. Immunocompromised individuals, such as patients with AIDS, who fail treatment or prophylaxis with recommended antiviral doses frequently demonstrate improved response with higher doses. If resistance is suspected or confirmed with recommended first-line antivirals, foscarnet is usually effective. However, its use is associated with a greater risk of serious... 

Acyclovir-resistant HSV has been isolated from patients with AIDS. The primary mechanism of resistance appears to be a deficiency in viral thymidine kinase. Strategies that have been employed for management of severe acyclovir-resistant HSV infections include increasing the dose of acyclovir, discontinuing acyclovir, and use of an alternative antiviral agent. Vidarabine and foscarnet, because they do not require phosphorylation by thymidine kinase, are examples of potential alternative agents. A randomized comparison of foscarnet and vidarabine indicated that foscarnet is more effective and associated with fewer adverse reactions than vidarabine. ... 

Zoster usually begins as radicular pain followed by localized erythematous rash and characteristic vesicles. Zoster usually remains confined to a limited number of dermatomes, but complications such as widespread cutaneous involvement and disseminated visceral zoster may occur. As in the treatment of HSV infections, acyclovir is the drug of choice for VZV infections. While an oral acyclovir regimen of 4 g/day is effective for the treatment of zoster in immunocompetent adults, the drug has not been fuUy evaluated in immunocompromised patients such as those with AIDS. For practical reasons, oral acyclovir, famciclovir, or valacyclovir is often used for localized zoster. However, careful monitoring for signs of progression of zoster is essential. AIDS patients with disseminated cutaneous or visceral zoster should receive treatment with intravenous acyclovir in doses of 30 mg/kg per day for at least 7 days or until all lesions are crusted. Acyclovir-resistant VZV infections have been reported in patients with AIDS." ... 

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. 

Clinical uses and toxicity The drug is used for prophylaxis and treatment of cytomegalovirus (CMV) infections (including CMV retinitis) and has activity against ganciclovir-resistant strains of this virus (Table 49-1). Foscarnet inhibits herpes DNA polymerase in acyclovir-resistant strains that are thymidine kinase-deficient and may suppress such resistant herpetic infections in patients with AIDS. Adverse effects include nephrotoxicity (30% incidence) with disturbances in electrolyte balance (especially hypocalcemia), genitourinary ulceration, and CNS effects (headache, hallucinations, seizures). 

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