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Neonatal herpes is a devastating disease, the most serious complication of genital herpes, one of the most common serious congenital or perinatal infections, and the most frequent complication of sexually transmitted infections among children. Nevertheless, neonatal herpes is not reportable to health authorities in most states. The potential for prevention has been enhanced by recent diagnostic and therapeutic advances, and the disease meets widely accepted criteria for reporting, including incidence rates that exceed those of comparable conditions, epidemiologic instability, disease severity, direct and indirect socioeconomic costs, concern by persons at risk, the potential for prevention by public health interventions, and the prospect that the resulting data would influence public health policy. The absence of national surveillance contributes to beliefs by healthcare providers and the public health community that genital and neonatal herpes are uncommon conditions that affect small segments of society, beliefs that directly interfere with prevention. Neonatal herpes should be a reportable condition.

Acyclovir therapy was compared to the acyclovir prodrug valacyclovir in pregnant women with a history of genital herpes simplex infection. Pharmacokinetic profiles were established after the 36th week of pregnancy, the onset of drug therapy. Ten women who took a daily dose of 1,000 mg of valacyclovir had higher concentrations of the drug in their blood than the ten women who received 1,200 mg of acyclovir. Overall, valacyclovir appeared to be non-toxic and was well tolerated.

Byline: Debora F. Kimberlin, Stephen Weller, Richard J. Whitley, William W. Andrews, John C. Hauth, Fred Lakeman, Gerri Miller Keywords: Acyclovir; genital herpes; herpes simplex virus; pharmacokinetics; pregnancy; valacyclovir Abstract: Objective: The objective was to obtain preliminary pharmacokinetic data for acyclovir from gravid women receiving herpes simplex virus suppressive therapy with the acyclovir prodrug valacyclovir. Study Design: In a prospective, double-blind trial, 20 women with a history of recurrent genital herpes simplex virus infection and positive herpes simplex virus 2 serologic results were randomly assigned at 36 weeks' gestation to receive oral valacyclovir (500 mg twice daily) or acyclovir (400 mg 3 times daily). Acyclovir pharmacokinetic profiles were obtained after the initial dose (36 weeks) and at steady state (38 weeks). Amniotic fluid samples were obtained during labor and simultaneous umbilical cord and maternal plasma samples were collected at delivery. Laboratory studies were performed to screen for laboratory evidence of toxicity in mothers and infants. Results: Peak acyclovir plasma concentrations (mean [+ or -] standard deviation) were higher in valacyclovir recipients than in acyclovir recipients after the initial dose (3.14 [+ or -] 0.7 [mu]g/mL vs 0.74 [+ or -] 0.6 [mu]g/mL, P < .0001) and at steady state (3.03 [+ or -] 1.0 [mu]g/mL vs 0.94 [+ or -] 0.7 [mu]g/mL, P < .001). The daily area under the curve values were higher in valacyclovir recipients than acyclovir recipients after the initial dose (17.8 [+ or -] 3.6 h * [mu]g/mLvs 7.71 [+ or -] 2.5 h * [mu]g/mL, P < .001) and at steady state (19.65 [+ or -] 6.4 h * [mu]g/mL versus 11.0 [+ or -] 4.5 h * [mu]g/mL, P = .009). There was no significant difference in drug elimination half-life or in time to peak concentration between valacyclovir and acyclovir recipients at either sampling interval. Acyclovir was concentrated in the amniotic fluid; however, there was no evidence of preferential fetal drug accumulation (mean maternal/umbilical vein plasma ratios at delivery were 1.7 for valacyclovir and 1.3 for acyclovir). Valacyclovir was well tolerated, and no significant laboratory or clinical evidence of toxicity was detected. Conclusion: In this phase I trial maternal valacyclovir therapy resulted in higher plasma acyclovir levels, with significantly higher peak concentrations and daily area under the curve values, than did acyclovir therapy. Additional trials are needed to further evaluate the safety and efficacy of suppressive valacyclovir therapy during late pregnancy. (Am J Obstet Gynecol 1998;179:846-51.) Author Affiliation: Birmingham, Alabama, and Research Triangle Park, North Carolina Article Note: (footnote) [star] From the Department of Obstetrics and Gynecology, University of Alabama at Birmingham,a and Glaxo-Wellcome, Inc.b , [star][star] Support provided in part by Glaxo Wellcome, Inc., a Reprint requests: Debora F. Kimberlin, MD, Department of Obstetrics and Gynecology, 618 S 20th St, Old Hillman Building Room 452, Birmingham, AL 35233-7333., aa 0002-9378/98 $5.00 + 0 6/6/92965

Objective: To provide recommendations for the treatment of acquired immunodeficiency syndrome-related cytomegalovirus (CMV) end-organ diseases, including retinitis, colitis, pneumonitis, and neurologic diseases. Participants: A 17-member panel of physicians with expertise in clinical and virological research and inpatient care in the field of CMV diseases. Evidence: Available clinical and virological study results. Recommendations are rated according to the quality and strength of available evidence. Recommendations were limited to the treatment of CMV diseases; prophylaxis recommendations are not included. Process: The panel was convened in February 1997 and met regularly through November 1997. Subgroups of the panel summarized and presented available information on specific topics to the full panel; recommendations and ratings were determined by group consensus. Conclusions: Although the epidemiological features of CMV diseases are changing in the setting of potent, combination antiretroviral therapy, continued attention must be paid to CMV diseases in patients infected with the human immunodeficiency virus to prevent irreversible end-organ dysfunction. The initial and maintenance treatment of CMV retinitis must be individualized based on the characteristics of the lesions, including location and extent, specific patient factors, and characteristics of available therapies among others. Management of relapse or refractory retinitis must be likewise individualized. Ophthalmologic screening for patients at high risk for retinitis or who have a prior diagnosis of extraretinal disease is recommended. Recommendations for gastrointestinal, pulmonary, and neurologic manifestations are included. Arch Intern Med. 1998;158:957-969

Objective: To determine the effect of acyclovir and prednisone treatment of herpes zoster on chronic pain and quality-of-life outcomes. Design: Randomized, double-blind, placebo-controlled study with a 2 x 2 factorial design. Setting: 15 university hospitals or affiliated clinics. Patients: 208 immunocompetent patients older than 50 years of age who had localized herpes zoster that developed less than 72 hours before study enrollment. Intervention: Acyclovir or a matched placebo was administered orally, 800 mg five times daily, for 21 days. Prednisone or a matched placebo was administered orally at 60 mg/d for the first 7 days, 30 mg/d for days 8 to 14, and 15 mg/d for days 15 to 21. The four treatments regimens given were acyclovir plus prednisone; acyclovir plus prednisone placebo; prednisone plus acyclovir placebo; and placebos for both acyclovir and prednisone. Measurements: Patients were monitored daily for the first 28 days for lesion healing, resolution of pain, return to usual activity, and return to uninterrupted sleep. Monitoring was then done monthly for 6 months. Patients documented analgesic requirements each day, and adverse events and laboratory abnormalities were recorded at each clinic visit. An intention-to-treat analysis was used. Results: Patients were randomly allocated to receive one of the four regimens. Demographic characteristics were similar for each group. Time to total crusting and healing was accelerated for patients receiving acyclovir plus prednisone compared with patients receiving two placebos; the risk ratios were 2.27 (95% Cl, 1.46 to 3.55) for total crusting and 2.07 (Cl, 1.26 to 3.38) for healing. Similarly, compared with the placebo group, patients receiving acyclovir plus prednisone had accelerated time to cessation of acute neuritis (risk ratio, 3.02 [Cl, 1.42 to 6.41]), time to return to uninterrupted sleep (risk ratio, 2.12 [Cl, 1.25 to 3.58]); time to return to usual daily activity (risk ratio, 3.22 [Cl, 1.92 to 5.40]); and time to cessation of analgesic therapy (risk ratio, 3.15 [Cl, 1.69 to 5.89]). In the acyclovir plus prednisone group, resolution of pain during the 6 months after disease onset did not statistically differ from that in the other groups. No important clinical or laboratory adverse events occurred in any group. Conclusions: In relatively healthy persons older than 50 years of age who have localized herpes zoster, combined acyclovir and prednisone therapy can improve quality of life., A combination of acyclovir and prednisone treatment appears to be effective in accelerating the recovery process in otherwise healthy patients with shingles. Two hundred eight patients with newly developed shingles flare-ups were randomly assigned to take either acyclovir plus prednisone, prednisone plus placebo, acyclovir plus placebo, or two placebos for 21 days. Patients taking both drugs experienced faster healing, a restoration of normal sleep and activity patterns and shorter periods of pain than the other groups.

Infection with human immunodeficiency virus type I (HIV-I) is characterized by the progressive deterioration of the immune and nervous systems and disorders of the blood, heart, lungs, kidneys, and gastrointestinal tract. The replication of HIV leads to high levels of the virus in the blood, and enhances the transmission and development of the disease. Studies show that HIV-I infects the CD4+ lymphocytes, a type of immune cell, in blood and brain cells derived from monocytes, a type of white blood cell. Increases in the number of infected cells and the quantity of viral DNA produced are associated with progression of HIV disease. HIV p24 antigen is a measure of HIV-1 replication and can be detected in the early stages of HIV disease and when there are low numbers of CD4+ cells. The presence of cell-free HIV in the blood (virus not associated with cells) is also a measure of HIV-1 replication and was shown to increase in relation to elevations in p24 antigen levels and disease progression. The relations between levels of cell-free HIV in the blood, patient age at diagnosis, number of CD4+ lymphocytes, indicators of HIV infection, clinical stage of disease, and response to antiviral agents were assessed in 68 adults and 9 children with HIV-I infection. Viremia, or the presence of cell-free HIV in the blood, had developed in 18 of 68 adults and 5 of 9 children. Among the adults, viremia was detected in none of the patients without symptoms; 4 of 34 patients with AIDS-related complex (ARC); and 14 of 15 patients with AIDS. Patients with CD4+ lymphocyte numbers greater than 400 per cubic millimeter had no viremia, whereas cell-free HIV was detected in the blood of 3 of 17 patients with CD4+ counts between 200 to 400 per cubic millimeter and 15 of 16 patients with less than 200 CD4+ lymphocytes per cubic millimeter. All children infected with HIV during pregnancy or childbirth developed viremia regardless of the number of CD4+ cells, duration of infection, or clinical stage. Viremia was less prevalent among children infected at an older age. The antiviral agent zidovudine was effective in decreasing the amount of cell-free HIV in eight patients. (Consumer Summary produced by Reliance Medical Information, Inc.)

Herpes simplex encephalitis (HSE) is an infection of the brain that is accurately diagnosed by clinical symptoms. While HSE has frequently been fatal in the past, safe and effective treatment now exists. Despite the relative ease of diagnosis and safety of treatment, it remains controversial whether there is a need to confirm the diagnosis of HSE by brain biopsy (taking a sample of brain tissue to test for the presence of HSE) before treatment is offered or initiated. Since 1972, the Collaborative Antiviral Study Group of the National Institute of Allergy and Infectious Diseases (NIAID) has evaluated patients with HSE. The value of brain biopsy for diagnosis has been established as one result of the group's work. It also became apparent that the use of brain biopsy allowed doctors to distinguish between HSE and other treatable conditions that may be similar to HSE. Using the results of the NIAID studies, data was analyzed mathematically to determine the value of brain biopsy in patients suspected of suffering from HSE. Patients under Strategy I had a brain biopsy and were treated with acyclovir (ACV; a recognized therapy for HSE). Under strategy II, patients were given ACV only. A mathematical model suggests that patients under strategy I will have a greater six-month survival rate than patients under Strategy II. The authors recommend that brain biopsy be the diagnostic approach of choice for most patients suspected of having HSE. (Consumer Summary produced by Reliance Medical Information, Inc.)

Antivirals stand now where penicillin stood in 1940-on the brink of widespread use, acceptance, and success. Our experts outline the uses and limitations of today's most important antiviral agents. Four [...]

Research by Balfour et al. concerning the effects of administering the anti-viral drug acyclovir to children with chickenpox was presented in the April 1990 issue of The Journal of Pediatrics. This editorial comments on, but does not cite, the Balfour study, which collected data rigorously and confirms the known history of chickenpox infection. Although enhanced healing was observed, the formation of new lesions and spread of the infection did not diminish among patients who were treated with acyclovir. Further data from a larger study must be evaluated before the indications for acyclovir therapy can be established for children with chickenpox. The real value and cost-benefit ratio of acyclovir treatment must also be assessed. In spite of the usually benign course of chickenpox, effective therapy is needed, and the Balfour study provides a first step in defining appropriate treatment. (Consumer Summary produced by Reliance Medical Information, Inc.)