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Study Objective Genital herpes, which can be spread through oral sex, is an important target for microbicides. We examined episode-specific predictors of young women’s receptive oral sex and of microbicide surrogate use. Design Longitudinal study. Setting Participants were recruited to participate in a microbicide acceptability study from adolescent clinics and local colleges and through snowballing. Participants Young women (ages 14 to 21 y) who reported sexual contact on at least 1 weekly phone interview (n = 181) were included from the larger sample of 208 young women. Main Outcome Measures On weekly diary phone interviews, participants reported whether or not their last sexual contact included receptive oral sex and whether or not their last sexual contact included use of a microbicide surrogate. Results and Conclusions Participants reported a total of 1042 episodes of sexual contact of which 311 included receptive oral sex and 354 included microbicide surrogate use. Being older, having sex for the first time with a partner, and having given oral sex were associated with having received oral sex during a sexual episode. Being older, being African American, and having discussed the microbicide surrogate with their partner were associated with having used the microbicide surrogate use during a sexual episode. These results indicate that oral sex should be considered in the design of clinical trials. Future studies need to evaluate ways to promote consistent microbicide use in the context of receiving oral sex as well as those factors (eg, taste, pleasure) which may serve as a barrier.

Background Despite widespread use of acyclovir, infection with acyclovir-resistant herpes simplex virus type 2 (HSV-2) remains uncommon. To understand the frequency and clinical significance of acyclovir-resistant isolates, we evaluated the in vitro acyclovir sensitivities of sequential isolates from 34 immunocompetent women. Methods HSV-2-seropositive women collected daily samples of genital secretions while receiving acyclovir or placebo, each for 10 weeks. In vitro acyclovir sensitivity testing was performed using the dye uptake assay; isolates for which the concentration of acyclovir that inhibited cytopathic effect by 50% (EC50) was > or = 3 microg/mL were defined as resistant. Results A total of 351 isolates from 26 women were tested (median, 10 isolates/woman [range, 3-45 isolates/woman]). The median EC50 was 0.91 microg/mL. Overall, 7 isolates (1.7%) from 6 women had EC50 values > or = 3 microg/mL. None of the women was receiving acyclovir when the acyclovir-resistant isolates were detected. Acyclovir-sensitive and acyclovir-resistant isolates were detected in samples collected on the same day from separate anatomic sites in 3 women. The acyclovir-resistant isolates were transient, because acyclovir-sensitive isolates were obtained before and after the acyclovir-resistant isolates from 5 women were detected. Conclusions Among immunocompetent women, the finding of acyclovir-resistant HSV-2 isolates likely represents transient mucosal variants and does not predict treatment failure.

Changes in sexual practices have led to an increase in the incidence of genital herpes simplex virus type 1 (HSV-1) infections. Such infections affect an estimated 400 newborns each year, with serious consequences.To evaluate the use of a serodiagnostic test for HSV-1 to be used by pregnant women, and possibly their sexual partners, in preventing neonatal HSV-1 infections by identifying seronegative (at-risk) women.The number of cases of neonatal HSV-1 prevented by a test of a given sensitivity and specificity is estimated using two simple models parameterized with data from published sources.Used by women only, a 90%-specific test for HSV-1 could avert 71%-90% of the expected cases of infection among women using the test, requiring about 14,000 tests per case averted. This result depends linearly on the specificity of the test and does not depend on the sensitivity. Use by women and their partners results in more tests for the same benefit (about 24,000 tests per case averted if the test is 90% sensitive and 90% specific), because the only additional information provided by testing the partner of an at-risk woman is to determine that her partner may not be HSV-1 positive.The key feature of such a diagnostic test is its specificity; its use to identify at-risk women could provide public health benefits if the specificity exceeds 70%, but these benefits would increase dramatically for higher specificities. Use of such a test for couples is likely to be more costly and less effective than testing women only.

Reactivation of herpes simplex virus type 2 (HSV-2) occurs intermittently as perceived clinically and by viral culture. We performed a series of studies to evaluate the frequency and pattern of HSV-2 reactivation using both viral isolation and HSV PCR assay. Daily samples of genital secretions were obtained from 27 HSV-2 seropositive women; a subset of subjects obtained samples while receiving oral acyclovir 400 mg PO twice a day. HSV DNA was detected in genital swab specimens on 28% of 1,410 d compared with 8.1% of days by viral isolation. 11 of 20 women had HSV DNA detected on > 20% of days, 4 on > 50%, and 2 on > 75% of days; in contrast, none of the women shed on > 21% of days by viral isolation. The daily administration of oral acyclovir promptly reduced the frequency of HSV DNA detection by a median of 80%. Within 3-4 d of discontinuing daily acyclovir, HSV DNA again appeared in the genital area. HSV-2 shedding in the genital mucosa occurs much more frequently than previously appreciated. This frequent reactivation likely plays a role in the epidemic spread of genital herpes worldwide.

Twenty-one patients with postherpetic neuralgia of two- to 84-months duration participated in a double-blind, placebo-controlled study of oral acyclovir. Pain perception was assessed with the Melzack Pain Questionnaire at baseline and at two- to six-week intervals during the ensuing six months. Clinically significant pain reduction occurred in eight patients: four received acyclovir, and four received a placebo. Several treatment strategies have been advocated for relief of postherpetic neuralgia. Results of the present study demonstrate the need for a double-blind, placebo-controlled paradigm to substantiate the efficacy of new clinical approaches. The same caveat applies to the more common syndromes encountered in psychiatric practice.

Education and counseling constitute a substantial portion of management of patients with genital herpes. Innovative methods for education about genital herpes are needed.To test the ability of an interactive, computer-based program to educate patients about genital herpes.Persons seeking care at five urban offices were asked to participate. A knowledge test about genital herpes was administered before and after participation. Participants' satisfaction was assessed with a questionnaire.Four hundred thirty-five participants enrolled, and 428 completed the herpes knowledge test. Of six questions evaluated, a statistically significant increase in the proportion of correct answers was noted on five of six questions. Fifty-one percent of participants answered all the questions correctly after the program, compared with 39% before the program. Satisfaction with the program was very high.Innovative, computer-based programs can provide education and assist in the management of chronic sexually transmitted infections.

Orally administered acyclovir ameliorates the clinical course and decreases the duration of viral shedding in patients with first-episode genital herpes infections. We investigated in a randomized, double-blind, comparative trial whether a higher (4 g) than standard (1 g) daily dose of oral acyclovir results in greater clinical benefit and influences the time to first recurrence. A total of 139 patients with first-episode genital herpes were randomized to receive orally 4 or 1 g of acyclovir daily. A total of 52 subjects were excluded from the efficacy analysis because most had recurrent disease. Of 87 eligible subjects, 28 (32%) had primary herpes simplex virus type 1 (HSV-1) infections, 48 (55%) had primary HSV-2 infections, and 11 (13%) had nonprimary HSV-2 infections. We did not find any statistically significant differences in the duration of symptoms or viral shedding between the two dose groups, nor did the median time to first recurrence differ between the two groups. Initiation of therapy with either dose within the first 3 days of the appearance of symptoms shortened the duration of the first episode. Adverse gastrointestinal effects developed in 8% of subjects receiving the higher dose, whereas no adverse reactions were observed among those receiving the standard dose (P = 0.10). We conclude that, in comparison with standard therapy, higher-dose oral acyclovir does not result in additional clinical benefit or modify the time to first recurrence. The present study may have implications for the development and efficacy of congeners of acyclovir which provide higher levels in blood than the standard dose of acyclovir.

To assess safety, pharmacokinetics, and in-vivo virologic activity of five different combination regimens of zidovudine and didanosine compared with zidovudine alone in patients with human immunodeficiency virus type 1 (HIV-1) infection.Open-label, partially randomized, dose-ranging study.University-affiliated, medical center clinics.A total of 69 patients with HIV-1 infection, CD4+ cell counts fewer than 400 cells/mm3, and fewer than 121 days of previous zidovudine treatment.Fifty-five patients received combination therapy with zidovudine and didanosine, and 14 received zidovudine therapy alone (600 mg/d). Daily dosages in milligrams of zidovudine and didanosine, respectively, in the five combination groups were 150 and 90 mg, 300 and 334 mg, 600 and 334 mg, 300 and 500 mg, and 600 and 500 mg.CD4+ cell counts, HIV-1 RNA titers in plasma, and toxic effects.The combination regimens were associated with higher and more sustained increases in CD4+ cells than zidovudine alone, even after adjustment for initial CD4+ counts and previous zidovudine therapy (P0.001). The median increase in CD4+ cell counts was 166 cells/mm3 with combination therapy and 77 cells/mm3 with zidovudine alone (P = 0.001) and did not differ statistically among the five combination regimens. Human immunodeficiency virus type 1 RNA titers in plasma decreased in 15 (83%) of 18 combination-therapy recipients compared with 2 of 7 zidovudine-alone recipients (P = 0.017). No pharmacokinetic interactions were seen between zidovudine and didanosine. Toxicity rates were low among all treatment groups. A greater decrease in hemoglobin levels was seen with the regimen using zidovudine alone (-8 g/L) compared with combination regimens using the same zidovudine dose (-1.5 g/L, P = 0.03).Combination therapy with zidovudine and didanosine produced larger and more sustained increases in CD4+ cell counts, more frequent decreases in plasma HIV-1 RNA titers, and more stable hematologic status than zidovudine therapy alone. The effects of this combination on the progression of HIV disease merit further study, to provide information about clinical outcome, because this was a relatively small study based on surrogate markers of HIV-1 infection.

Objective: Education of patients with genital herpes about their disease is time consuming. To evaluate the effectiveness of an educational computer program, we developed a multimedia interactive presentation to teach patients about genital herpes. Such programs can supplement clinician visits for patients with genital herpes, or those at risk for HSV acquisition. Methods: Patients seeking care for genital herpes, or those at risk for HSV acquisition, were asked to participate in the program during routine clinic visits at 5 physician’s offices nationwide. A self-administered 7 item herpes knowledge questionnaire was given before and after participation. An additional questionnaire evaluating the satisfaction with the program was also self-administered at completion. Results: 428 patients were enrolled and completed the pre- and post-knowledge questionnaire and 332 patients completed the satisfaction survey. On the pre-test, 20.1% of patients answered all questions correctly, 65.4% answered correctly 4 to 6 questions, and 14.5% 3 or less. On the post-test, 32.9% of patients answered all questions correctly, 61.5% answered correctly 4 to 6 questions, and 5.6% 3 or less (P < .001 for pre- and post-test comparison). A positive change in knowledge between pre- and post-test was seen on 6 of 7 items (P < .001 for all 6). The overall satisfaction with the program was high: the mean rating was 6.2 on a scale 1 (poor) to 7 (excellent). Conclusion: Computer-based education programs about genital herpes may provide a useful adjunct to teaching in physician offices and result in knowledge gain about the disease, at least short-term. Such programs may assist in management of chronic sexually transmitted infections.

Therapy for recurrent genital herpes is difficult to evaluate because of the short duration of lesions and viral shedding. Very early treatment, however, can be begun by patients who experience prodromes before onset of lesions. We have found prodromes to occur in 73 percent of male and 84 percent of female patients; 57 percent of the men and 68 percent of the women experienced prodromes in at least three out of every four recurrent episodes. Variables that might affect results of such a patient-initiated study evaluating topical acyclovir included: application of the ointment (drug or placebo) without prodrome (10 percent); the possibility of a false prodrome (less than or equal to 10 percent); long intervals between experiencing a prodrome and ointment application (15 percent greater than 24 hours); the inability to sense a prodrome during sleep; lack of ointment application to the involved areas with initial or later lesions (approximately 15 percent); noncompliance of enrollees in returning for study evaluations (greater than or equal to 10 percent). Such variables will need to be considered when the code is broken in this multicenter study, as well as for patient-initiated studies with other formulations of acyclovir or with other drugs. Earlier negative studies with other agents given within two to three days of appearance of lesions might also require reevaluation with similar patient-initiated studies.

Meta-analysis of seroprevalence surveys shows that horizontal transmission of hepatitis B virus (ie, that occurring without apparent parenteral, sexual, or perinatal exposure) is common in areas endemic for the virus. It occurs especially in pre-adolescent children. In developed countries, where endemicity of hepatitis B virus is low, horizontal transmission (probably via saliva or open wounds) may occur in households with a persistent carrier, but it is less efficient a means of infection than is sexual or perinatal transmission. Horizontal transmission also seems possible in pre-school day-care centres in developed countries, despite the small numbers of carriers in such places.

A collaborative multicenter double-blind, placebo-controlled trial of intravenous acyclovir treatment of first-episode genital herpes was performed in order to substantiate previous findings on the efficacy and safety of this drug, to evaluate the influence of parenteral therapy on recurrence frequency, and to obtain further data on the natural history of genital herpes.Eighty-two patients with first episodes of genital herpes simplex virus (HSV) infection were randomly assigned in a double-blind fashion to treatment with intravenous acyclovir (5 mg/kg every eight hours) or placebo for five days. Before therapy, all lesions in the genital/perineal area and in extragenital sites were cultured. New lesions appearing in both areas after the onset of therapy were cultured separately. Lesions in all groups were cultured until completely healed. Sera were collected from all patients on entry to the study and on Day 21 to determine presence or absence of antibodies to HSV-1 and HSV-2. Time to healing, time to crusting, time to cessation of viral shedding, and appearance of new lesions during therapy were compared for each treatment group.Patients receiving acyclovir experienced a significant reduction in the median duration of pain (4.3 versus 4.8 days, p = 0.019), viral shedding (1.9 versus 8.4 days, p less than 0.001), and time to healing (8.4 versus 11.5 days, p = 0.02) compared with placebo recipients. These differences were largely attributable to the effect of therapy in the subset of patients with primary disease in whom acyclovir reduced the median duration of pain from 10.6 days to 4.2 days, the median duration of viral shedding from 17.1 days to 1.9 days, and the median time to healing from 14.2 days to 8.3 days. The rate of subsequent recurrence of genital herpes was not altered by acyclovir treatment: 24 of 32 acyclovir recipients (75 percent) experienced one or more recurrences during a mean follow-up of 14 months compared with 19 of 27 placebo recipients (70 percent). Among patients experiencing recurrences, the mean number of recurrences per month among acyclovir recipients was 0.25 compared with 0.19 for patients given placebo.This multicenter trial confirms the efficacy of intravenous acyclovir in the management of first-episode genital herpes, especially in patients with primary infection. However, therapy did not alter the frequency of recurrences.

Sixty-three immunocompromised patients with infections caused by herpes simplex virus were evaluated in a double-blind, placebo-controlled study of topical acyclovir therapy; 33 patients received acyclovir and 30 received the placebo. The two populations of patients were balanced in terms of age, race, sex, underlying disease, preceding chemotherapy, and site, size, and duration of lesions. Acyclovir recipients experienced an acceleration in the clearance of virus (P = .0006), the resolution of pain (P = .004), and the total healing of lesions (P = .038); median temporal differences between populations averaged six days for each of these three parameters. The surface area of herpetic lesions continued to enlarge in placebo recipients after entry into the trial; in contrast, lesion surface area decreased progressively during therapy in drug recipients. The speed of healing was influenced by lesion size. Patients with lesions of greater than or equal to 50 mm2 benefited most from therapy, particularly in terms of pain resolution and time to total healing (median differences between groups, eight days). Irrespective of underlying disease, sex, preceding chemotherapy, or age, acyclovir therapy was of clinical benefit. No adverse clinical or laboratory reactions were encountered.

Twenty-nine patients with first-episode rectal herpes simplex virus infection were enrolled in a double-blind trial of oral acyclovir, 400 mg five times daily, vs placebo treatment. Eighty percent of those receiving acyclovir compared with 25% of placebo recipients no longer had herpes simplex virus isolated from their rectal lesions three days after onset of therapy. The median duration of rectal lesions and viral excretion from rectal lesions (median, five and zero days, respectively) was significantly shorter in patients treated with acyclovir than in placebo-treated patients (14 and 11 days, respectively). Durations of local signs and symptoms of proctitis, such as rectal pain, discharge, and friability, were shorter in acyclovir recipients than in placebo recipients, but these differences were not statistically significant. Daily administration of 2 g of oral acyclovir for ten days alleviates some of the clinical signs of herpes simplex virus rectal infection.