Herpes Simplex Virus Type 2 Treatment Research Articles

Computational and Theoretical Analysis of the Association Between Gender and HSV-2 Treatment Adherence.

Herpes simplex virus type 2 (HSV-2) is the most prevalent sexually transmitted infection in the world, despite the availability of effective anti-viral treatments. A mathematical model to explore the association between gender and HSV-2 treatment adherence is developed. Threshold parameters are determined and stabilities analyzed. Sensitivity analysis of the reproduction number and the numerical simulations suggest that treatment adherence for both females and males are equally important in keeping the reproduction as low as possible. The basic model is then extended to incorporate time-dependent intervention strategies. The Pontryagin's Maximum Principle is used to characterize the optimal level of the controls, and the resulting optimality system is solved numerically.

Incident HSV-2 Infections Are Common Among HIV-1-discordant Couples

The synergy between herpes simplex virus type 2 (HSV-2) and human immunodeficiency virus type 1 (HIV-1) is well known, but lack of knowledge about the epidemiology of HSV-2 acquisition in HIV-1-discordant couples hampers development of HSV-2 prevention interventions that could reduce HIV-1 transmission. HIV-1-discordant couples were enrolled in Nairobi, Kenya, and followed for up to 2 years. HSV-2 status was determined using HerpeSelect HSV-2 ELISA. Correlates of prevalence and incidence were assessed. RESULTS.: Of 469 HIV-1-discordant couples, at baseline, 353 (75.3%) were affected by HSV-2, of which 189 (53.5%) were concordantly HSV-2 seropositive and 164 (46.5%) were HSV-2-discordant. Prevalence was lowest among HIV-1-uninfected men (39.9%) compared to HIV-1-infected women (64.8%), HIV-1-infected men (66.7%), and HIV-1-uninfected women (68.5%). During follow-up, HSV-2 seroincidence was 14.9 per 100 person-years. Incidence was 1.6-fold higher among females compared to males (95% confidence interval [CI], 1.00-2.48) and 2.5-fold higher in HIV-1-infected compared to uninfected women (95% CI, 1.12-5.74). At least 30% of incident HSV-2 infections originated from an outside partner. The high HSV-2 prevalence and incidence in HIV-1-discordant couples in sub-Saharan Africa suggest HSV-2 treatment and prevention could be an effective targeted strategy to reduce HSV-2 and HIV-1 transmission in this high-risk population.

Effect of daily aciclovir on HIV disease progression in individuals in Rakai, Uganda, co-infected with HIV-1 and herpes simplex virus type 2: a randomised, double-blind placebo-controlled trial.

Daily suppression of herpes simplex virus type 2 (HSV-2) reduces plasma HIV-1 concentrations and modestly delayed HIV-1 disease progression in one clinical trial. We investigated the effect of daily suppressive aciclovir on HIV-1 disease progression in Rakai, Uganda. We did a single site, parallel, randomised, controlled trial of HIV-1, HSV-2 dually infected adults with CD4 cell counts of 300-400 cells per μL. We excluded individuals who had an AIDS-defining illness or active genital ulcer disease, and those that were taking antiretroviral therapy. Participants were randomly assigned (1:1) with computer-generated random numbers in blocks of four to receive either aciclovir 400 mg orally twice daily or placebo; participants were followed up for 24 months. All study staff and participants were masked to treatment, except for the two statisticians. The primary outcome was CD4 cell count less than 250 cells per μL or initiation of antiretroviral therapy for WHO stage 4 disease. Our intention-to-treat analysis used Cox proportional hazards models, adjusting for baseline log(10) viral load, CD4 cell count, sex, and age to assess the risk of disease progression. We also investigated the effect of suppressive HSV-2 treatment stratified by baseline HIV viral load with a Cox proportional hazards model. This trial is registered with ClinicalTrials.gov, number NCT00405821. 440 participants were randomly assigned, 220 to each group. 110 participants in the placebo group and 95 participants in the treatment group reached the primary endpoint (adjusted hazard ratio [HR] 0·75, 95% CI 0·58-0·99; p=0·040). 24 participants in the placebo group and 22 in the treatment group were censored, but all contributed data for the final analysis. In a subanalysis stratified by baseline HIV viral load, participants with a baseline viral load of 50,000 copies mL or more in the treatment group had a reduced HIV disease progression compared with those in the placebo group (0·62, 0·43-0·96; p=0·03). No significant difference in HIV disease progression existed between participants in the treatment group and those in the placebo group who had baseline HIV viral loads of less than 50,000 copies per mL (0·90, 0·54-1·5; p=0·688). No safety issues related to aciclovir treatment were identified. Aciclovir reduces the rate of disease progression, with the greatest effect in individuals with a high baseline viral load. Suppressive aciclovir might be warranted for individuals dually infected with HSV-2 and HIV-1 with viral loads of 50,000 copies per mL or more before initiation of antiretroviral treatment. National Institute of Allergy and Infectious Diseases, National Cancer Institute (National Institutes of Health, USA).

Getting research into policy - Herpes simplex virus type-2 (HSV-2) treatment and HIV infection: international guidelines formulation and the case of Ghana

BackgroundObservational epidemiological and biological data indicate clear synergies between Herpes simplex virus type 2 (HSV-2) and HIV, whereby HSV-2 enhances the potential for HIV acquisition or transmission. In 2001, the World Health Organization (WHO) launched a call for research into the possibilities of disrupting this cofactor effect through the use of antiherpetic therapy. A WHO Expert Meeting was convened in 2008 to review the research results. The results of the trials were mostly inconclusive or showed no impact. However, the WHO syndromic management treatment guidelines were modified to include acyclovir as first line therapy to treat genital ulcer disease on the basis of the high prevalence of HSV-2 in most settings, impact and cost-benefit of treatment on ulcer healing and quality of life among patients.MethodsThis paper examines the process through which the evidence related to HIV–HSV-2 interactions influenced policy at the international level and then the mechanism of international to national policy transfer, with Ghana as a case study. To better understand the context within which national policy change occurs, special attention was paid to the relationships between researchers and policy-makers as integral to the process of getting evidence into policy. Data from this study were then collected through interviews conducted with researchers, program managers and policy-makers working in sexual health/STI at the 2008 WHO Expert Meeting in Montreux, Switzerland, and in Accra, Ghana.ResultsThe major findings of this study indicate that investigations into HSV-2 as a cofactor of HIV generated the political will necessary to reform HSV-2 treatment policy. Playing a pivotal role at both the international level and within the Ghanaian policy context were ‘policy networks’ formed either formally (WHO) or informally (Ghana) around an issue area. These networks of professionals serve as the primary conduit of information between researchers and policy-makers. Donor influence was cited as the single strongest impetus and impediment to policy change nationally.ConclusionsPolicy networks may serve as the primary driving force of change in both international context and in the case of Ghana. Communication among researchers and policy-makers is critical for uptake of evidence and opportunities may exist to formalize policy networks and engage donors in a productive and ethical way.

Investing in the future: lessons learnt from communicating the results of HSV/ HIV intervention trials in South Africa

BackgroundCommunicating the results of randomised controlled trials may present challenges for researchers who have to work with communities and policy-makers to anticipate positive outcomes, while being aware that results may show no effect or harm.MethodsWe present a case study from the perspective of researchers in South Africa about the lessons learnt from communicating the results of four trials evaluating treatment for herpes simplex virus type 2 (HSV-2) as a new strategy for HIV prevention.ResultsWe show that contextual factors such as misunderstandings and mistrust played an important role in defining the communications response. Use of different approaches in combination was found to be most effective in building understanding, credibility and trust in the research process. During the communication process, researchers acted beyond their traditional role of neutral observers and became agents of social change. This change in role is in keeping with a global trend towards increased communication of research results and presents both opportunities and challenges for the conduct of future research.ConclusionsDespite disappointing trial results which showed no benefit of HSV-2 treatment for HIV prevention, important lessons were learnt about the value of the communication process in building trust between researchers, community members and policy-makers, and creating an enabling environment for future research partnerships.

Racial/Ethnic Disparities in Undiagnosed Infection With Herpes Simplex Virus Type 2

Herpes simplex virus type 2 (HSV-2) is a common sexually transmitted infection (STI) that is the main cause of genital herpes. Studies have found racial/ethnic disparities in HSV-2 prevalence, but there have been few studies of racial/ethnic differences in the proportion of infections that go without a genital herpes diagnosis. Data from 1396 HSV-2-seropositive participants of the National Health and Nutrition Examination Survey 1999-2004 were used to examine racial/ethnic differences in the odds of reporting being diagnosed previously with genital herpes. The proportion of participants who reported not being diagnosed previously with genital herpes was 85.5%. In adjusted analysis, non-Hispanic blacks had twice the odds of reporting being undiagnosed as non-Hispanic whites (adjusted odds ratio = 2.0, 95% CI = 1.37, 2.87). Being undiagnosed was also significantly associated with less than high school education, no prior STI history or HIV test, no current health insurance, and residence in the Midwest and South. The low proportion of genital herpes diagnosis among non-Hispanic blacks with HSV-2 is not accounted for by other sociodemographic factors or health insurance. Combined with the high prevalence of HSV-2, the low proportion of diagnosis in this population is more likely to contribute to ongoing HSV-2 transmission than among non-Hispanic whites or Mexican Americans. More research is needed to assess the role that lack of diagnosis plays in ongoing HSV-2 transmission, and whether targeted HSV-2 screening, counseling and treatment could be part of a more effective prevention strategy for non-Hispanic blacks.

Seroprevalence of Herpes Simplex Virus Type 2 and Characteristics Associated With Undiagnosed Infection: New York City, 2004

Herpes simplex virus type 2 (HSV-2) infection is associated with substantial morbidity and increased risk for human immunodeficiency virus acquisition. We describe HSV-2 seroprevalence in adult New Yorkers, and examine the relationship between select characteristics, infection, and diagnosis. HSV-2 seroprevalence and risk factors were measured using the 2004 New York City Health and Nutrition Examination Survey, a population-based cross-sectional survey of adults. HSV-2 seroprevalence and corresponding 95% confidence intervals were computed for select characteristics. Associations between proposed risk factors and HSV-2 infection and diagnosis were estimated using unadjusted and adjusted odds ratios. Nearly 28% of adults were infected with HSV-2; 88.4% of HSV-2 positive persons were undiagnosed. Black women had the highest seroprevalence (59.7%) of any sex or race/ethnicity group. Women, non-Hispanic blacks, and Hispanics (vs. non-Hispanic whites), and men who have sex with men were at greater odds of HSV-2 infection. Among HSV-2 infected individuals, non-Hispanic blacks (vs. non-Hispanic whites), uncircumcised men, and those with no routine place of care were less likely to be diagnosed. HSV-2 is highly prevalent and largely undiagnosed in New York City; seroprevalence varies by subgroup. Targeted HSV-2 screening, counseling and treatment may help reduce transmission of HSV-2 and human immunodeficiency virus.

Modelling the cost per ulcer treated of incorporating episodic treatment for HSV-2 into the syndromic algorithm for genital ulcer disease

Background:The proportion of genital ulcer disease (GUD) due to herpes simplex virus type-2 (HSV-2) has increased in sub-Saharan Africa. The most recent 2003 WHO syndromic GUD algorithm includes antiviral treatment...

HIV/AIDS: Management of Herpes Simplex Virus Type 2 Infection in HIV Type 1–Infected Persons

Human immunodeficiency virus type 1 (HIV-1)-infected persons have high rates of herpes simplex virus type 2 (HSV-2) infection, ranging from 50% to 90% in studies of HIV-infected populations from different parts of the world. Genital herpes in persons with HIV type 1 (HIV-1) infection is associated with more-severe and chronic lesions, as well as increased rates of asymptomatic genital shedding of HSV-2. Nucleoside analogues (acyclovir, valacyclovir, and famciclovir) decrease the frequency and severity of HSV-2 recurrences and asymptomatic HSV-2 reactivation and are effective, safe, well-tolerated drugs in patients with HIV-1 infection. These anti-HSV drugs may result in additional clinical and public health benefits for persons with HIV-1 and HSV-2 coinfection by decreasing HIV-1 levels in the blood and genital tract. Given these benefits, HIV-1-infected persons should be routinely tested for HSV-2 infection using type-specific serologic tests. Persons with HSV-2 infection should be offered HSV-2 education and treatment options. Studies to quantify the potential clinical and public health benefits of treating individuals who have HIV-1 and HSV-2 coinfection with anti-HSV therapy are underway.

Association between human immunodeficiency virus and herpes simplex virus type 2 seropositivity among male factory workers in Zimbabwe.

To determine the seroprevalence of herpes simplex virus type 2 (HSV-2), to identify correlates of infection, and to describe the correlation with human immunodeficiency virus (HIV) seropositivity, 224 HIV-negative and 191 HIV-positive male factory workers in Zimbabwe were screened for HSV-2-specific antibodies. HSV-2 seroprevalence was 35.7% among HIV-negative subjects and 82.7% among HIV-positive subjects. The weighted estimate of HSV-2 seroprevalence in this population is 44.6%. The correlation between HIV and HSV-2 remained significant after controlling for multiple sex partners, paying for sex, and history of sexually transmitted disease (adjusted odds ratio, 8.0; 95% confidence interval, 4.8-13.1). If the association between HSV-2 and HIV is causal, then the high seroprevalence of HIV and HSV-2 suggests that suppressive HSV-2 treatment should be considered as a strategy to reduce HIV transmission in this population. HSV-2 seroconversion may be a suitable surrogate end point to evaluate HIV prevention interventions.

Estimation of menstrual age.

<h3>Background:</h3> The proportion of genital ulcer disease (GUD) due to herpes simplex virus type-2 (HSV-2) has increased in sub-Saharan Africa. The most recent 2003 WHO syndromic GUD algorithm includes antiviral treatment for HSV-2 for anyone with “typical” symptoms/signs, and suggests that all GUD patients receive treatment for HSV-2 in settings where HSV-2 GUD aetiology is greater than 30%. The previous algorithm (1994) only targeted <i>Haemophilus ducreyi</i> (HD) and <i>Treponema pallidum</i> (TP). <h3>Methods:</h3> A static deterministic model was used to compare the cost per ulcer treated of using the 1994 and 2003 algorithms amongst individuals presenting with GUD, with sensitivity analyses for different economic and epidemiological scenarios. <h3>Results:</h3> Except when the proportion of ulcers due to HD/TP (defined as ulcer prevalence) is high (&gt;40%), and HSV-2 ulcer prevalence is low (&lt;30%), the 2003 algorithm should result in more patients receiving the correct treatment (correct drugs for the syndrome) than the 1994 algorithm, and it will cost less per ulcer treated if HSV-2 treatment costs less than US$2. Greatest impact in terms of ulcers treated is achieved with the 2003 algorithm if HSV-2 treatment is given to all GUD patients. The incremental and/or relative cost per ulcer treated of doing this, compared to only treating those with typical symptoms/signs, is reduced if the HSV-2 ulcer prevalence is high and/or the HSV-2 treatment cost or sensitivity of HSV-2 ulcer diagnosis (using symptoms/signs) is low. <h3>Conclusions:</h3> In certain scenarios, including HSV-2 treatment can increase the number of ulcers treated and reduce the cost per ulcer treated of GUD syndromic management.