Acyclovir is an agent used to treat infections caused by the herpes simplex virus (HSV). It is FDA-approved to treat genital herpes and HSV encephalitis. Non-FDA-approved indications are mucocutaneous HSV, herpes zoster (shingles), and varicella zoster (chickenpox). Acyclovir is the first-line treatment for HSV encephalitis. Currently, no other medications are indicated for treating this condition.
Despite the long-term use of acyclovir to treat HSV encephalitis, there has not been a systematic review regarding the efficacy of this disease/treatment combination. Current systematic reviews addressing its safety and efficacy are ongoing, with the primary outcome being the mortality rate. A secondary outcome measure is the quality of life.
HSV keratitis has been shown to respond to oral acyclovir and topical steroids in pediatric patients.
Stromal keratitis with ulceration caused by the herpes simplex virus can be a clinically difficult corneal infection to treat. Pisitpayat P. et al. examined the efficacy of intravenous acyclovir treatment in two patients. The diagnosis was confirmed by corneal scraping samples, which underwent polymerase chain reaction (PCR) analysis. One patient had herpes simplex virus-1, and the other had herpes simplex virus-2.
The patient with herpes simplex virus-1 corneal infection initially received treatment with oral acyclovir. However, the corneal infection worsened, and the patient was switched to intravenous acyclovir. The corneal infection gradually improved. The patient with herpes simplex virus-2 corneal infection received treatment with intravenous acyclovir. The corneal infection improved. However, the patient had an epithelial lesion that required additional treatment with 100% autologous serum until the lesion healed. Both patients received prophylactic treatment with oral acyclovir to prevent corneal reinfection.
In patients with human immunodeficiency virus (HIV), acyclovir is sometimes used to treat eczema herpeticum. It is also used to prevent infections of the skin, eyes, nose, and mouth. Eczema herpeticum is rare but rapidly progressive if untreated. Those with extensive involvement, systemic symptoms, or decreased oral intake should undergo admission for intravenous acyclovir treatment. Also, acyclovir treats oral hairy leukoplakia.
Acyclovir has been proven useful in treating myelopathy secondary to varicella-zoster infection. In a small case series, researching patients from 1994 to 2014 with laboratory-confirmed varicella-zoster virus (VZV) and MRI-confirmed myelopathy, marked improvement of symptoms was the outcome in most patients within two months.
Brachial plexus neuritis secondary to VZV infection and visceral disseminated VZV infection (characteristic features are abdominal and absence of skin lesions) has also responded to acyclovir, alleviating all symptoms.
In recipients of hematopoietic stem cell transplantation, herpes simplex virus and varicella-zoster reactivation may respond to treatment with acyclovir prophylaxis. Prophylactic use of acyclovir should also be considered in HSV-1 and HSV-2-seropositive organ recipients. Diseases from such viruses have decreased secondary to this intervention. However, a breakthrough infection may occur. Not surprisingly, HSV and VZV infection is not uncommon in patients that have discontinued acyclovir prophylaxis.
Another form of prophylactic acyclovir use is juvenile-onset recurrent respiratory papillomatosis. In a prospective observational study involving 21 patients, oral acyclovir was a postoperative adjuvant. It was shown to decrease the recurrence of papillomas and thus decrease the need for successive surgeries and associated operative risks.
VZV infections have many complications, including cerebellitis. Treating the source infection has also been shown to decrease the complication burden. A 2019 case report, for instance, describes a patient presenting with truncal ataxia. After intravenous acyclovir treatment, the patient was free of neurologic disability and cerebellitis.  Similarly, paresis secondary to dermatomal herpes zoster infections has been shown to respond to oral acyclovir; this is a rare complication of herpes zoster when the virus affects motor nerve fibers in addition to/instead of the dorsal root ganglion.