Acyclovir halts progression of herpes zoster in immunocompromised patients

We conducted a placebo-controlled, double-blind study of acyclovir therapy for acute herpes zoster in immunocompromised patients. Of the 94 patients enrolled in the study, 52 had localized skin lesions at entry, and 42 had disseminated cutaneous zoster. A one-week course of intravenous acyclovir (1500 mg per square meter of body-surface area per day) halted progression of zoster in both groups, as determined by development or progression of cutaneous dissemination, development of visceral zoster, or proportion of cases deemed treatment failures. Significantly fewer patients treated with acyclovir within the first three days after the onset of exanthem had complications of zoster, as compared with patients treated with placebo (P = 0.02 by Fisher's exact test), but acyclovir also stopped progression of zoster in patients treated after three days of rash (P = 0.05 by Fisher's exact test). Acyclovir recipients with disseminated cutaneous zoster had a significantly accelerated rate of clearance of virus from vesicles, as compared with placebo recipients (P = 0.05 by the Breslow test).     

Treatment of varicella-zoster virus infection in severely immunocompromised patients. A randomized comparison of acyclovir and vidarabine

In a prospective, randomized trial, we compared intravenous acyclovir and vidarabine in the treatment of varicella-zoster virus infection in severely immunocompromised patients who presented within 72 hours of onset of the infection. Eleven patients were treated in each group. Cutaneous dissemination of infection occurred in none of the 10 acyclovir recipients and in 5 of the 10 vidarabine recipients who had presented with localized dermatomal disease (P = 0.016). As compared with vidarabine, acyclovir treatment shortened the median periods during which cultures were positive for the virus (four vs. seven days, P = 0.004) and new lesions formed (three vs. six days, P = 0.03). Acyclovir also shortened the median interval until the first decrease in pain (4 vs. 7 days, P = 0.005), the pustulation of all lesions (4 vs. 7 days, P = 0.0004), the crusting of all lesions (7 vs. 17 days, P = 0.0003), and the complete healing of lesions (17 vs. 28 days, P = 0.003). In addition, acyclovir reduced the incidence of fever (two vs. eight patients, P = 0.015). We conclude that acyclovir is better than vidarabine for the treatment of varicella-zoster infection in immunocompromised patients.     

Acyclovir prophylaxis of herpes-simplex-virus infections

We conducted a double-blind, placebo-controlled study of acyclovir prophylaxis against infection with herpes simplex virus (HSV) in 20 seropositive recipients of bone-marrow transplants. Acyclovir or placebo was administered for 18 days, starting three days before transplantation. Culture-positive HSV lesions developed during the study in seven of the 10 patients who received placebo. In contrast, no such lesions appeared in the 10 patients who received acyclovir (P congruent to 0.003). None of the patients had evidence of drug toxicity. Five of the patients treated with acyclovir had mild culture-positive HSV infections after cessation of the drug, and two additional patients shed virus without having lesions. Acyclovir appears to be a potent inhibitor of HSV replication. Although acyclovir does no appear to eradicate latent infection, it can provide effective prophylaxis against reactivated infections.     

Treatment of first episodes of genital herpes simplex virus infection with oral acyclovir. A randomized double-blind controlled trial in normal subjects

We performed a double-blind placebo-controlled trial of oral acyclovir in the treatment of first episodes of genital herpes simplex virus infections in 48 young adults (31 women and 17 men). Subjects were randomized to receive either placebo or acyclovir (200 mg per dose) five times daily for 10 days; they were examined on at least eight visits until healed and at monthly visits thereafter. Acyclovir treatment, as compared with placebo, significantly reduced virus shedding, new lesion formation after 48 hours, and the duration of genital lesions in both men and women. The total duration and severity of clinical symptoms (such as pain, adenopathy, dysuria, and malaise) were significantly reduced by acyclovir in both men and women by the third and fourth day, respectively (P less than or equal to 0.025), as compared with placebo. No toxicity was observed. Recurrence rates have so far been similar in placebo and acyclovir recipients. Oral acyclovir treatment of first-episode genital herpes simplex virus infections is clinically effective, but it does not seem to prevent virus latency or associated recurrent disease.     

A double-blind study of oral acyclovir for suppression of recurrences of genital herpes simplex virus infection

Patients with frequently recurring genital herpes were enrolled in a double-blind placebo-controlled trial comparing 200-mg acyclovir capsules, given five or two times daily, with placebo. Of 47 placebo recipients, 44 (94 per cent) had recurrences during the 120-day treatment period, compared with 13 (29 per cent) of 45 patients treated with acyclovir five times daily and 18 of 51 (35 per cent) treated with acyclovir twice daily (P less than 0.001 for each regimen compared with placebo). The median time to the first clinical recurrence was 18 days in placebo recipients, compared with over 120 days in both acyclovir-treated groups (P less than 0.001 for both groups compared with placebo). The mean monthly recurrence rate during the medication period was 0.86 in placebo recipients, compared with 0.13 in patients treated with acyclovir five times daily and 0.14 in patients treated with acyclovir twice daily (P less than 0.001 for both groups compared with placebo). While receiving therapy, 86 of 96 acyclovir-treated patients had over a 50 per cent reduction in their pretreatment recurrence rate. Breakthrough recurrences in acyclovir recipients were of shorter duration and associated with a lower frequency of viral shedding than recurrences in placebo recipients. After medication was discontinued, the subsequent recurrence rate returned to pretreatment frequencies. Daily oral acyclovir was well tolerated. We conclude that oral acyclovir given for four months markedly reduces but does not completely prevent recurrences of genital herpes and does not influence the long-term natural history of the disease.     

Acyclovir for prevention of cytomegalovirus infection and disease after allogeneic marrow transplantation

Patients undergoing allogeneic bone marrow transplantation who are seropositive for cytomegalovirus are vulnerable to serious cytomegalovirus infection, presumably because of reactivation of latent endogenous virus and severe immunosuppression. We administered intravenous acyclovir from 5 days before to 30 days after allogeneic marrow transplantation for hematologic neoplasms in an effort to prevent cytomegalovirus infection and disease in patients seropositive for cytomegalovirus before transplantation. Eighty-six patients seropositive for both cytomegalovirus and herpes simplex virus before transplantation received acyclovir, whereas 65 patients seropositive only for cytomegalovirus served as controls (acyclovir is the standard prophylactic agent against herpes simplex virus in this setting). The probability that cytomegalovirus infection would develop within the first 100 days after transplantation was 0.70 among acyclovir recipients and 0.87 among control patients at medians of 62 and 40 days after transplantation, respectively (P = 0.0001 by log-rank test). Invasive cytomegalovirus disease developed in 19 acyclovir recipients (22 percent) and 25 control patients (38 percent) (P = 0.008). Survival within the first 100 days after transplantation was better among acyclovir recipients (P = 0.002). Acyclovir prophylaxis was associated with a relative risk of 0.5 or less for the development of cytomegalovirus infection or disease or for death within the first 100 days after transplantation (P less than or equal to 0.04), in proportional-hazards regression analysis. We conclude that prophylaxis with intravenous acyclovir significantly reduced the risk of both cytomegalovirus infection and cytomegalovirus disease in seropositive patients after allogeneic bone marrow transplantation and that it was also associated with significantly improved survival.     

Acyclovir treatment for varicella does not lower gpI and IE-62 (p170) antibody responses to varicella-zoster virus in normal children.

The varicella-zoster virus (VZV) membrane glycoprotein gpI elicits a major immunoglobulin G antibody response after naturally acquired VZV infection; antibody to a nonglycosylated immediate-early protein, IE-62 (p170), represents a response to a nonmembrane VZV component. We evaluated antibody response to VZV gpI and IE-62 (p170) at 28 days and 1 year following infection in 34 children (ages 5 to 16 years) enrolled in a randomized placebo-controlled study of oral acyclovir for the treatment of varicella. All children were VZV antibody negative at enrollment, were previously healthy, and had laboratory-documented varicella. Compared with placebo recipients, acyclovir recipients had lower geometric mean titers by the fluorescent antibody to membrane antigen technique at 28 days (620 versus 836) but similar titers at 1 year (122 versus 122). All children had antibodies to gpI and IE-62 detectable by enzyme-linked immunosorbent assay at 28 days and 1 year. No difference in gpI at 28 days compared with 1 year was noted in acyclovir recipients. No difference in antibody to IE-62 (p170) was noted when acyclovir and placebo recipients were compared at either 28 days or 1 year. Antibody responses to gpI and IE were similar when children were stratified by age (5 to 6 years, 7 to 11 years, 12 to 16 years). A short course of oral acyclovir for the treatment of varicella did not affect antibody responses to gpI or IE-62 (p170) in healthy children at 28 days and 1 year following varicella.     

A trial of topical acyclovir in genital herpes simplex virus infections

Seventy-seven patients with first episodes of genital herpes and 111 with recurrent episodes were enrolled in a double-blind trial comparing topical acyclovir with a placebo (polyethylene glycol ointment). Among acyclovir-treated patients with first-episode primary genital herpes, the mean duration of viral shedding (4.1 days) and the time to complete crusting of lesions present at the initiation of therapy (7.1 days) were shorter than among placebo recipients (7.0 and 10.5 days, respectively) (P less than 0.05). Acyclovir-treated patients with recurrent herpes had a shorter duration of viral shedding than placebo recipients (0.95 vs. 1.90 days) (P = 0.03). Among the patients with recurrent herpes, acyclovir reduced the time to crusting of lesions in men but had no effect on the symptoms or healing times in women. Topical acyclovir shortens the duration of viral shedding and accelerates healing of some genital herpes simplex virus infections.     

A randomized, placebo-controlled trial of oral acyclovir for the prevention of cytomegalovirus disease in recipients of renal allografts

Cytomegalovirus is a major viral pathogen in patients who undergo renal transplantation, and cytomegalovirus disease is difficult to treat. We therefore conducted a randomized, placebo-controlled, double-blind trial of acyclovir for the prevention of cytomegalovirus disease in recipients of renal allografts from cadavers. Acyclovir was given orally in doses of 800 to 3200 mg per day, according to the patients' estimated level of renal function. Patients took the first dose of either acyclovir or placebo six hours before transplantation and continued to take the assigned medication for 12 weeks. Of 118 patients enrolled in the study, 104 completed at least 30 days on the study medication and were included in our analysis of the results. During the first year after transplantation, 4 of 53 patients (7.5 percent) in the acyclovir group had symptomatic cytomegalovirus disease, as compared with 15 of 51 (29 percent) in the placebo group (P = 0.002). There was a single case of cytomegalovirus pneumonia in the acyclovir group, as compared with nine in the placebo group. The greatest prophylactic benefit of acyclovir was observed among seronegative patients who had received a kidney from a seropositive donor; only one of six such patients in the acyclovir group had cytomegalovirus disease, as compared with all seven in the placebo group. Acyclovir decreased the incidence of documented cytomegalovirus infection (with or without symptomatic disease) to 36 percent from 61 percent among the patients who received the placebo (P = 0.011). Among the patients who received acyclovir, the rates of recovery of virus from the blood and urine were significantly reduced, but the rate of viral shedding from the pharynx was not significantly different from that in the placebo group. There were no differences between the groups in the frequency of adverse events or in the rate of survival of either grafts or patients. We conclude that the oral administration of acyclovir, beginning before the transplantation of a renal allograft from a cadaver, reduces the rate of cytomegalovirus infection and disease without affecting the survival rate of either grafts or patients.     

The effectiveness of the varicella vaccine in clinical practice

BACKGROUND: A live attenuated varicella vaccine was approved for use in the United States in March 1995 and is recommended for all susceptible persons 12 months of age or older. METHODS: To assess the effectiveness of the varicella vaccine, we conducted a case-control study with two controls per child with chickenpox, matched according to both age and pediatric practice. Children with potential cases of chickenpox were identified by active surveillance of pediatric practices in the New Haven, Connecticut, area. Research assistants visited the children on day 3, 4, or 5 of the illness, assessed the severity of the illness, and collected samples from lesions to test for varicella-zoster virus by polymerase chain reaction (PCR). RESULTS: From March 1997 through November 2000, data collection was completed for 330 potential cases, of which 243 (74 percent) were in children who had positive PCR tests for varicella-zoster virus. Of the 56 vaccinated children with chickenpox, 86 percent had mild disease, whereas only 48 percent of the 187 unvaccinated children with chickenpox had mild disease (P<0.001). Among the 202 children with PCR-confirmed varicella-zoster virus and their 389 matched controls, 23 percent of the children with chickenpox and 61 percent of the matched controls had received the vaccine (vaccine effectiveness, 85 percent; 95 percent confidence interval, 78 to 90 percent; P<0.001). Against moderately severe and severe disease the vaccine was 97 percent effective (95 percent confidence interval, 93 to 99 percent). The effectiveness of the vaccine was virtually unchanged (87 percent) after adjustment for potential confounders by means of conditional logistic regression. CONCLUSIONS: Varicella vaccine is highly effective as used in clinical practice.     

Persistence of immunity to varicella in children with leukemia immunized with live attenuated varicella vaccine

To determine the safety and efficacy of varicella vaccine, we studied 437 children in remission from leukemia who were immunized with live attenuated varicella virus. Three hundred one of the patients received two doses of vaccine and 136 received a single dose of vaccine from 1 of 10 lots from two manufacturers. The patients have been followed for an average of three years (range, one to six). Seroconversion occurred in 88 percent of the 437 children after the first dose of vaccine and in 98 percent after one or two doses. The proportions of patients who were seronegative after one, three, and five years were 20, 25, and 30 percent, respectively, with little change over time in the geometric mean titers of specific antibody (6.3, 6.5, and 5.7, respectively). Chickenpox has been documented in 36 vaccinated patients (8 percent) who had 3 to 640 vesicles (mean, 100), mild illness, and no complications. Of the 83 vaccinated patients exposed to varicella within their families, 11 had chickenpox; the attack rate was 14 percent (8 percent among seropositive patients, 29 percent among seronegative patients). There was no relation between the time since vaccination and either the attack rate or the severity of the breakthrough illness. Two doses of vaccine appeared to be no more effective than a single dose. Of the 372 patients receiving maintenance chemotherapy when immunized, 149 (40 percent) had a rash, which was treated with acyclovir in 16 children (4 percent) and became a severe febrile illness in 4. These reactions were not fatal and were all associated with vaccine lots, the use of which has since been discontinued. We conclude that in children in remission from leukemia, varicella vaccine is safe and induces an immunity to chickenpox that persists for more than three years.     

Oral brivudin vs. intravenous acyclovir in the treatment of herpes zoster in immunocompromised patients: A randomized double-blind trial

The efficacy of oral brivudin vs. intravenous acyclovir was compared in a randomized multicentered study under double-blind conditions using the double-dummy technique. Forty-eight patients with a herpes zoster rash less than 72 hours in duration were entered in the study. Brivudin was given as one 125-mg tablet every 6 hours. Acyclovir was infused over 1 hour at a dose of 10 mg/kg every 8 hours. Treatment was continued for 5 days. There was no significant difference between the treatment groups when analyzed in terms of new lesion formation, increase in the area of rash within the primary dermatome, cutaneous dissemination, and affection of mucous membranes or visceral organs. Both treatment regimes were also equally effective in the time to full crusting of lesions. Oral brivudin and intravenous acyclovir were well tolerated by most patients. There was no need to interrupt the treatment in any case. As effective as intravenous acyclovir in the treatment of herpes zoster, oral brivudin offers the potential for outpatient treatment of herpes zoster in immunocompromised patients. © 1995 Wiley-Liss, Inc.     

Suppression of frequently recurring genital herpes. A placebo-controlled double-blind trial of oral acyclovir

We studied 35 otherwise healthy adults with frequently recurring genital herpes (greater than or equal to 1 episode per month), in a double-blind trial comparing oral acyclovir with placebo capsules for suppression of recurrent infection. The patients were treated for 125 days unless herpes recurred. Among 32 evaluable patients, there were significantly fewer recurrences during acyclovir treatment (4 of 16) than during placebo treatment (16 of 16, P less than 0.001). The mean duration of therapy was significantly longer for patients receiving acyclovir than for those receiving placebo (114.9 vs. 24.8 days, P less than 0.001). Of 19 patients who had recurrences in the blind trial, only 2 had recurrences when given acyclovir in a second, open-study phase. All patients had recurrences after completing acyclovir treatment. The therapy was well tolerated, with minimal gastrointestinal upset and one hypersensitivity reaction. Studies of the viral isolates demonstrated that lesions developing in patients receiving acyclovir contained drug-resistant virus. Later recurrences in these patients were associated with drug-sensitive virus. We conclude that oral acyclovir suppresses genital herpes in patients with frequent recurrences, but the potential for problems with drug resistance and the long-term safety need to be more fully explored.     

Fatal varicella in steroid-dependent asthma

Disseminated varicella infection is a potentially life-threatening complication of chronic high-dose corticosteroid (CS) or immunosuppressive therapy. A review of the literature indicates that, with one possible exception, this complication has not occurred in a CS-dependent subject with asthma. We present in this article the clinical features and autopsy findings of a steroid-dependent subject with asthma who died of acute, disseminated varicella. A 16-year-old poorly compliant, steroid-dependent subject with asthma received two courses of high-dose intravenous methylprednisolone during a 3-week period, followed by a tapering schedule of oral prednisone. During this time, she was exposed to chickenpox. She subsequently developed a classic varicella rash, sever back pain, rapidly progressive hepatic failure, pneumonitis, and encephalopathy. Death ensued 3 days after the onset of the rash. Evidence of disseminated varicella infection was confirmed at autopsy. This case illustrates that a small number of subjects with severe asthma receiving high-dose CS need to be considered as a separate, high-risk group for developing disseminated varicella. We recommend that the immune status of these patients to varicella-zoster virus be assessed by a serum titer. If these patients are nonimmune, they would be candidates for varicella-zoster immune globulin on exposure, and for acyclovir therapy should varicella dissemination occur.     

Outbreaks of disease suspected of being due to human monkeypox virus infection in the Democratic Republic of Congo in 2001

Seven outbreaks of disease characterized by a pustular rash and suspected to have been caused by human monkeypox virus were investigated. The outbreaks occurred between February and August 2001 in the province of Equateur in the Democratic Republic of Congo. The outbreaks involved a total of 31 persons and caused five deaths. Specimens from 14 patients were available and were analyzed by electron microscopy, virus isolation, and PCR assays specific for monkeypox virus and varicella-zoster virus. We provide evidence that two outbreaks were indeed caused by monkeypox virus (16 cases, with four deaths), that in two outbreaks both monkeypox and varicella-zoster virus were involved (seven cases, with one death), and that two outbreaks were cases of chickenpox caused by infection with varicella-zoster virus (six cases, with no deaths). In one outbreak, no evidence for either monkeypox or chickenpox was found (two cases, with no deaths).     

Vidarabine versus acyclovir therapy in herpes simplex encephalitis

We randomly assigned 208 patients who underwent brain biopsy for presumptive herpes simplex encephalitis to receive either vidarabine (15 mg per kilogram of body weight per day) or acyclovir (30 mg per kilogram per day) for 10 days. Sixty-nine patients (33 percent) had biopsy-proved disease; 37 received vidarabine, and 32 acyclovir. The mortality in the vidarabine recipients was 54 percent, as compared with 28 percent in the acyclovir recipients (P = 0.008). Six-month mortality varied according to the Glasgow coma score at the onset of therapy. For scores of greater than 10, 7 to 10, and less than or equal to 6, mortality was 42, 46, and 67 percent in the patients treated with vidarabine, as compared with 0, 25, and 25 percent in those treated with acyclovir. A six-month morbidity assessment using an adapted scoring system revealed that 5 of 37 patients receiving vidarabine (14 percent) as compared with 12 of 32 receiving acyclovir (38 percent) were functioning normally (P = 0.021). Eight vidarabine-treated patients (22 percent) and three acyclovir-treated patients (9 percent) had moderate debility. Patients under 30 years of age and with a Glasgow coma score above 10 had the best outcome with acyclovir treatment. We conclude that acyclovir is currently the treatment of choice for biopsy-proved herpes simplex encephalitis.     

A randomized, controlled trial of vitamin A in children with severe measles

BACKGROUND. Measles kills about 2 million children annually, and there is no specific therapy for the disease. It has been suggested that vitamin A may be of benefit in the treatment of measles. METHODS. We conducted a randomized, double-blind trial involving 189 children who were hospitalized at a regional center in South Africa because of measles complicated by pneumonia, diarrhea, or croup. The children (median age, 10 months) were assigned to receive either vitamin A (total dose, 400,000 IU of retinyl palmitate, given orally; n = 92) or placebo (n = 97), beginning within five days of the onset of the rash. At base line, the characteristics of the two groups were similar. RESULTS. Although clinically apparent vitamin A deficiency is rare in this population, the children's serum retinol levels were markedly depressed (mean [+/- SEM], 0.405 +/- 0.021 mumols per liter [11.6 +/- 0.6 micrograms per deciliter]), and 92 percent of them had hyporetinemia (serum retinol level less than 0.7 mumols per liter [20 micrograms per deciliter]). Serum concentrations of retinol-binding protein (mean, 30.1 +/- 2.0 mg per liter) and albumin (mean, 33.4 +/- 0.5 g per liter) were also low. As compared with the placebo group, the children who received vitamin A recovered more rapidly from pneumonia (mean, 6.3 vs. 12.4 days, respectively; P less than 0.001) and diarrhea (mean, 5.6 vs. 8.5 days; P less than 0.001), had less croup (13 vs. 27 cases; P = 0.03), and spent fewer days in the hospital (mean, 10.6 vs. 14.8 days; P = 0.01). Of the 12 children who died, 10 were among those given placebo (P = 0.05). For the group treated with vitamin A, the risk of death or a major complication during the hospital stay was half that of the control group (relative risk, 0.51; 95 percent confidence interval, 0.35 to 0.74). CONCLUSIONS. Treatment with vitamin A reduces morbidity and mortality in measles, and all children with severe measles should be given vitamin A supplements, whether or not they are thought to have a nutritional deficiency.     

A controlled trial of ganciclovir to prevent cytomegalovirus disease after heart transplantation.

BACKGROUND. Because of the immunosuppression required, heart-transplant recipients frequently have complications caused by cytomegalovirus (CMV), including pneumonia, esophagitis, gastritis, and a syndrome of fever, hepatitis, and leukopenia. We undertook a controlled trial to evaluate the prophylactic administration of ganciclovir to prevent CMV-induced disease after heart transplantation. METHODS. This randomized, double-blind, placebo-controlled trial was conducted at four centers. Before randomization, the patients were stratified into two groups: those who were seropositive for CMV before transplantation and those who were seronegative but who received hearts from seropositive donors. Ganciclovir was given intravenously at a dose of 5 mg per kilogram of body weight every 12 hours from postoperative day 1 through day 14, then at a dose of 6 mg per kilogram each day for 5 days per week until day 28. RESULTS. Among the seropositive patients, CMV illness occurred during the first 120 days after heart transplantation in 26 of 56 patients given placebo (46 percent), as compared with 5 of 56 patients treated with ganciclovir (9 percent) (P less than 0.001). Among 37 seronegative patients, CMV illness was frequent in both groups (placebo, 29 percent; ganciclovir, 35 percent; P not significant). From day 15 through day 60, the patients who took ganciclovir had significantly fewer urine cultures positive for CMV, but by day 90 there was no difference. More of the ganciclovir-treated patients had serum creatinine concentrations greater than or equal to 221 mumol per liter (2.5 mg per deciliter) (18 percent vs. 4 percent in the placebo group), but those elevations were transient. CONCLUSIONS. The prophylactic administration of ganciclovir after heart transplantation is safe, and in CMV-seropositive patients it reduces the incidence of CMV-induced illness.     

Human leukocyte interferon for the treatment of varicella in children with cancer

Human leukocyte interferon was evaluated as a treatment for varicella in a randomized double-blind, placebo-controlled study carried out in two phases. A total of 44 children being treated for cancer were enrolled within 72 hours of the appearance of the exanthem. The mean number of days of new lesion formation was 3.8 +/- 1.89 (+/- S.D.) in the interferon recipients and 5.3 +/- 2.56 in the placebo recipients (P less than 0.05). Eighty-one per cent of the interferon recipients had had no new lesions for 24 hours by Day 7, as compared with 56 per cent of the placebo recipients (P less than 0.025). In the second, higher-dose phase of the study 92 per cent of the interferon recipients had had no new lesions for 24 hours by Day 6, as compared with 45 per cent of the placebo recipients (P less than 0.025). Three of 21 placebo recipients died of progressive varicella. Two of the 23 interferon recipients died two to three weeks after the onset of varicella; viral cultures were negative in one of these patients, and the second had recurrent viremia at the end of the treatment period. Among the survivors, treatment with interferon reduced the number of patients who had life-threatening dissemination (none of 21 vs. three of 18; P = 0.053). We conclude that interferon had an antiviral effect against varicella virus in immunocompromised patients.     

Vitreous pharmacokinetics and electroretinographic findings after intravitreal injection of acyclovir in rabbits

OBJECTIVES:

Acute retinal necrosis is a rapidly progressive and devastating viral retinitis caused by the herpesvirus family. Systemic acyclovir is the treatment of choice; however, the progression of retinal lesions ceases approximately 2 days after treatment initiation. An intravitreal injection of acyclovir may be used an adjuvant therapy during the first 2 days of treatment when systemically administered acyclovir has not reached therapeutic levels in the retina. The aims of this study were to determine the pharmacokinetic profile of acyclovir in the rabbit vitreous after intravitreal injection and the functional effects of acyclovir in the rabbit retina.

METHODS:

Acyclovir (Acyclovir; Bedford Laboratories, Bedford, OH, USA) 1 mg in 0.1 mL was injected into the right eye vitreous of 32 New Zealand white rabbits, and 0.1 mL sterile saline solution was injected into the left eye as a control. The animals were sacrificed after 2, 9, 14, or 28 days. The eyes were enucleated, and the vitreous was removed. The half-life of acyclovir was determined using high-performance liquid chromatography. Electroretinograms were recorded on days 2, 9, 14, and 28 in the eight animals that were sacrificed 28 days after injection according to a modified protocol of the International Society for Clinical Electrophysiology of Vision.

RESULTS:

Acyclovir rapidly decayed in the vitreous within the first two days after treatment and remained at low levels from day 9 onward. The eyes that were injected with acyclovir did not present any electroretinographic changes compared with the control eyes.

CONCLUSIONS:

The vitreous half-life of acyclovir is short, and the electrophysiological findings suggest that the intravitreal delivery of 1 mg acyclovir is safe and well tolerated by the rabbit retina.