Recurrence and resistance patterns of herpes simplex virus following cessation of > or = 6 years of chronic suppression with acyclovir. Acyclovir Study Group.

Questions have arisen regarding the clinical outcome and the possible selection of resistant virus when patients with genital herpes discontinue prolonged chronic acyclovir; 239 immunocompetent patients with a history of frequently recurring genital herpes who stopped successful suppressive therapy after 6 years were studied. Of the patients, 85.8% had at least one recurrence and 75% had at least two recurrences in the subsequent year (median time to first and second recurrence, 68 and 180 days, respectively). Herpes simplex virus isolates recovered from these patients had a median acyclovir sensitivity of 0.79 micrograms/mL and 4 (3.5%) were resistant (> or = 3 micrograms/mL). These values are comparable to those of pretherapy isolates and to reported values of isolates from acyclovir-naive patients. Also, paired pre- and posttherapy isolates from 13 patients showed no trend toward development of resistance. Thus, even after 6 years of acyclovir suppression, most patients continue to have recurrences, but the selection of resistant virus has not been observed.

Long-term suppression of recurrent genital herpes with acyclovir. A 5-year benchmark. Acyclovir Study Group.

BACKGROUND AND DESIGN: This multicenter trial (19 sites) was initiated in 1984 in more than 1100 immunocompetent individuals with a history of frequently recurring genital herpes (mean, > or = 12 episodes per year). The first year of this suppressive therapy trial was placebo controlled, with acyclovir being provided for episodic treatment in both groups. Thereafter, patients were treated with open-label acyclovir suppressive therapy on a long-term basis (400 mg twice daily) to continue to assess its long-term safety and efficacy. Complete data are available on 389 of the 430 patients who began the fifth year of the study. RESULTS: Patients were seen quarterly for review of diaries and clinical laboratory evaluations. The percentage of patients recurrence free for any 3-month quarter of the fifth year ranged from 86% to 90%. The mean annual number of recurrences per patient declined from 1.7 during the first year to 0.8 during the fifth year of suppressive therapy. The frequency of false prodromes has also decreased over time. More than 20% of the patients receiving suppressive therapy for 5 years have been recurrence free the entire time. The duration of herpetic outbreaks during suppressive therapy has not changed. CONCLUSION: This study extends the safety and efficacy profile of oral acyclovir in the suppression of genital herpes to 5 years. The majority of the patients were recurrence free on an annual basis during suppressive therapy. Therapy was well tolerated. Acyclovir usage was not associated with serious side effects or cumulative toxicity.

Continuous five-year treatment of patients with frequently recurring genital herpes simplex virus infection with acyclovir.

This study presents data relative to the efficacy and safety following the continuous use of oral acyclovir in the treatment of genital herpes over a 5-year period. In this study, 1,146 patients (53% males; 47% females) were originally enrolled. These included patients with a history of frequently recurring genital herpes (mean > 12 episodes per year). During the first year, patients were randomized between those receiving 400 mg of acyclovir twice daily and an equal number receiving placebo. Additionally, acyclovir was utilized for episodic treatment (ES) in both groups. Thereafter, patients received open-label acyclovir suppressive therapy for the remainder of the study period. Complete data are available on 389 patients who completed the fifth year of therapy. All the participants who completed the fifty year of the study had completed either 4 or 5 years of daily suppressive acyclovir therapy. During the first year, a significant decrease in the frequency of recurrences in patients receiving continuous acyclovir (SS) was noted as compared to the placebo group (1.7 vs. 12.5 recurrences; P < 0.0001). From year one to the end of year three, a progressive decrease in the frequency of recurrences was noted in both groups. Yet, those patients who had received SS for the full 3 years had significantly fewer recurrences than those who had received ES in the first year (P = 0.05). During years four and five, the decrease in frequency of recurrences between the ES and SS groups was not significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of zidovudine on serum human immunodeficiency virus core antigen levels. Results from a placebo-controlled trial.

We assessed the effect of antiviral therapy on serum human immunodeficiency virus core antigen (HIV-Ag) levels in patients enrolled in the phase II trial on zidovudine for acquired immunodeficiency syndrome (AIDS) and AIDS-related complex. Human immunodeficiency virus core antigen was detected in 45% of subjects at entry (59% with AIDS and 37% of patients with AIDS-related complex). Median HIV-Ag levels in zidovudine-treated subjects fell from 111 pg/mL at entry to 46 pg/mL at four weeks, while levels in placebo recipients did not change significantly. Decline in HIV-Ag in zidovudine recipients was sustained through 16 weeks of treatment and was significantly different from the placebo group. Anti-p24 antibody levels did not change in either group. We conclude that in patients with HIV-antigenemia changes in HIV-Ag level are an important marker of anti-retroviral activity.

Hematopoietic neoplasias of the RFM/Un mouse contain somatic re-integration of the restriction endogenous ecotropic provirus.

We have examined the spleen DNA of individual mice of the RFM/Un strain for evidence of re-integration of the endogenous ecotropic provirus in radiation-induced and spontaneous neoplasms. The ecotropic env specific probe detects only a single 19 kb EcoRI or a single 7.0 kb HindIII fragment in all DNA preparations from normal tissues of RFM mice, corresponding to the endogenous provirus. Additional DNA restriction fragments containing the ecotropic virus (eco) specific sequence, corresponding to somatically acquired provirus, are detected in two out of five spleen DNA samples from animals with myeloid leukemia and one of three with thymic lymphoma. In addition somatically acquired eco-specific fragments are also detected in greater than 85% of DNA samples from reticulum cell sarcomas, a late occurring spontaneous hematopoietic neoplasm in this mouse strain. These results are consistent with a 'promoter/enhancer insertion' model of leukemogenesis involving the endogenous ecotropic provirus and are of particular interest since the RFM/Un mouse possesses a locus that restricts exogenous infection of cells by the endogenous virus.