Mindell Seidlin

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.

Heterosexual transmission of HIV in a cohort of couples in New York City

Objective:Since heterosexual transmission of HIV in the United States is occurring at an increasing rate, especially among black and Hispanic couples and those in which one member has a history of intravenous drug use, we sought to study the heterosexual transmission of HIV in couples. Design:Multiple logistic regression analysis of risks for HIV infection in female partners. Methods:We enrolled 158 non-intravenous drug user (IVDU) steady heterosexual partners of HIV-infected individuals (indexes) in this study. Of these, 93% were women, 54% were Hispanic whites, 23% were black and 65.6% were partners of IVDU. Results:In a multiple logistic regression analysis of risks for HIV infection in female partners, the strongest predictors of transmission were AIDS or AIDS-related complex (ARC) in the index [adjusted odds ratios (OR), 16.81; P< 0.001 and 12.53; P = 0.003, respectively], a history of anal intercourse (adjusted OR, 10.81; P< 0.001) and bleeding as a result of intercourse (adjusted OR, 4.90; P< 0.05). Female-to-male transmission was detected in seven out of 11 couples at risk. Ethnicity, number of episodes of vaginal intercourse, number of other sexual partners and history of sexually transmitted infections were not significantly associated with transmission to women. Conclusion:Our study demonstrates that health of the index, anal intercourse and bleeding as a result of intercourse are the major determinants of sexual transmission of HIV to women in couples.

Herpes Simplex Virus Infection: Biology, Treatment, and Prevention

Abstract Herpes simplex viruses cause common mucocutaneous infections, but many aspects of their epidemiology and transmission are incompletely defined. Although the incidence of oral herpes remain...

Oral Acyclovir to Suppress Recurring Herpes Simplex Virus Infections in Immunodeficient Patients

Thirty-two episodes of herpes simplex virus infection in four immunodeficient patients with frequent recurrences were successfully treated with oral acyclovir, one capsule five times a day for 5 days. In 23 of these episodes, the treatments were extended for 1 to 6 months using two to five capsules a day with the aim of suppressing expected recurrences. In these patients, who routinely had more than one recurrence per month before treatment, there were only six outbreaks during more than 60 patient-months of suppressive therapy. Infection always recurred after treatments were completed, but the time to recurrence was shorter after treatments with two acyclovir capsules per day than after treatments with five capsules per day (p less than 0.001).

Effect of oral acyclovir treatment on symptomatic and asymptomatic virus shedding in recurrent genital herpes

Twenty-six men and women with recurrent genital herpes maintained diaries of their symptoms and signs of infection and submitted 6,515 self-collected cultures during a one-year study of acyclovir therapy. As compared with periods before or after treatment, the mean rates of experiencing symptoms or lesions, and of shedding virus were significantly lower during treatment. Acyclovir treatment reduced the rate of symptomatic shedding from 95 positive cultures to six per 1,000 cultures, but the rate of asymptomatic shedding remained relatively constant, averaging eight per 1,000 cultures. Among the isolates of herpes simplex virus studied, there was no differences in sensitivity to acyclovir between strains recovered on or off therapy or during symptomatic or asymptomatic recurrences. The endonuclease cleavage profiles of asymptomatically shed viruses were essentially the same as those of the symptomatically shed viruses from the same individual. Chronic acyclovir therapy significantly reduced the symptoms and signs of recurrent genital herpes but did not eliminate virus shedding, nor, therefore, the possibility of disease transmission.

Relationship between Dideoxyinosine Exposure, CD4 Counts, and p24 Antigen Levels in Human Immunodeficiency Virus Infection: A Phase I Trial

OBJECTIVE To determine the relation between exposure to dideoxyinosine (ddl) and increased CD4 cell counts and suppression of serum p24 antigen in patients infected with the human immunodeficiency virus (HIV). DESIGN Open-label, phase I study. SETTING Two university hospitals. Patients were studied in both inpatient and outpatient settings. PATIENTS Of 36 HIV-infected patients enrolled, 18 had adequate pharmacokinetic information for analysis. INTERVENTION Dideoxyinosine was administered intravenously every 12 hours for 2 weeks. Patients were switched to oral administration at twice the intravenous dose. Pharmacokinetic profiles were obtained twice during each period. A 40-fold range of dose was examined. MEASUREMENTS CD4-positive T-lymphocyte counts and serum p24 antigen levels were determined. Plasma area under the ddl concentration-time curve was determined for a single dose and at steady state. RESULTS Increases in CD4-positive T-lymphocyte counts were independent of ddl exposure and were proportional to the starting CD4 count. Suppression of circulating p24 antigen was influenced by cumulative exposure to ddl and was statistically significant. CONCLUSIONS The CD4-positive T-lymphocyte count increased at low ddl concentrations or exposures; the extent of this increase was directly proportional to the patients CD4 count at the start of therapy. Suppression of p24 antigen was related to cumulative exposure to ddl. Therapeutic responses can probably be obtained with ddl, while minimizing long-term toxicity, using daily doses of 10 mg/kg body weight, or less.

Pancreatitis and pancreatic dysfunction in patients taking dideoxyinosine

Objective.To describe the incidence, clinical characteristics and dose relationship of dideoxyinosine (ddl)-associated pancreatitis. Design.Patients enrolled in a Phase I dose escalation trial of ddI [AIDS Clinical Trials Croup (ACTC) 0641 were evaluated tor signs and symptoms of pancreatic dysfunction. Setting.Two ACTG sites. Patients.Forty-four patients with AIDS or AIDS-related complex (ARC) and a CD4 cell count ≤400 x 106/I. Main outcome measures.Seven patients developed pancreatitis that lasted from 1 to 7 weeks and varied in severity from mild to life-threatening. Seven other patients had evidence of hyperamylasemia or hypertriglyceridemia. Six patients who developed pancreatitis were able to tolerate rechallenge with lower doses of ddl. Results.Development of pancreatitis correlated with cumulative dose of ddl but not with stage of disease or concomitant medications. Cumulative dose was not significantly associated with development of hyperamylasemia or hypertriglyceridemia in patients without clinical pancreatitis. Conclusions.The development of pancreatitis in AIDS or ARC patients receiving ddl varies in severity and time course and is associated with cumulative dose. Patients who develop pancreatitis may be able to tolerate therapy with a lower dose after resolution of their symptoms. Patients receiving ddl require careful monitoring for the development of this complication.

Double-blind comparison of weekend and daily regimens of oral acyclovir for suppression of recurrent genital herpes

The potential utility of intermittent regimens of oral acyclovir for suppression of recurrent genital herpes depends on how long the suppressive effect of the drug persists during pauses in treatment. To study this question, we admitted 38 patients in a double-blind controlled trial comparing the results of daily acyclovir treatment (200 mg t.i.d.) with treatment on weekend days only (400 mg t.i.d. on Saturday and Sunday) for suppression of recurrent genital herpes. Of the 35 patients completing the study, significantly more failures occurred in the weekend group (13/17) than in the daily group (3/18, P less than 0.001). Failures on the weekend regimen were more frequent as the week progressed (P = 0.005). The findings suggest a short-term persistence of suppression by acyclovir and hence that intermittent regimens with more closely spaced periods of treatment may be more effective than the regimen we studied. Most virus isolates studied, including all of those isolated from the patients during treatment, were sensitive to acyclovir.