Modestly protective cytomegalovirus vaccination of young children effectively prevents congenital infection at the population level.

A vaccine to prevent congenital cytomegalovirus infection (cCMV) is a public health priority. cCMV results from maternal primary or non-primary CMV infection (reinfection, or reactivation of chronic infection) during pregnancy. Young children are a major source of transmission to pregnant women because they shed CMV at high viral loads for prolonged periods. CMV vaccines evaluated in clinical trials so far have demonstrated only approximately 50% efficacy against maternal primary infection. None of these have been approved, as higher levels of vaccine efficacy are assumed to be required to substantially reduce cCMV prevalence. Here, we designed a mathematical model to capture the relationship between viral shedding by young children and maternal CMV infections during pregnancy. Using this model, we were able to quantify the impact of CMV post-infection immunity on protecting against reinfection and viral shedding. There was a 36% reduction in the risk of infection to a seropositive person with post-infection immunity (reinfection) versus a seronegative person without this immunity (primary infection), given the same exposure. Viral shedding following reinfection was only 34% the quantity of that following primary infection. Our model also predicted that a vaccine that confers the equivalent of post-infection immunity, when given to young children, would markedly reduce both CMV transmission to pregnant women and the prevalence of cCMV. Thus, we predict that existing vaccine candidates that have been shown to be only modestly protective may in fact be highly effective at preventing cCMV by interrupting child-to-mother transmission.

A scoping review of non-specific predictors, moderators, and mediators of family-based treatment for adolescent anorexia and bulimia nervosa: a summary of the current research findings.

PURPOSE: This scoping review presents an up-to-date synthesis of the current evidence base for non-specific predictors, moderators, and mediators of family-based treatment (FBT) for adolescent anorexia and bulimia nervosa. METHODS: We identify ways in which end-of-treatment outcomes have been shown to differ based upon baseline clinical features and person-specific factors and explore psychological mechanisms that may explain differences in treatment response. We draw from this evidence base to outline recommendations for clinical practice, as well as directions for future clinical eating disorder research. RESULTS: Noted findings from review include that early response in weight gain and parental criticism may be particularly influential in treatment for anorexia nervosa. Further, for adolescents with either anorexia or bulimia nervosa, eating-related obsessionality may be a key intervention target to improve outcomes. CONCLUSION: In addition to highlighting a need for attention to specific patient- and caregiver-level factors that impact treatment response, recommendations for research and clinical practice include testing whether certain targeted treatments (e.g., exposure-based approaches) may be suitable within the context of FBT for eating disorders. LEVEL OF EVIDENCE: Level I: Evidence obtained from: at least one properly designed randomized controlled trials; experimental studies.

Examining the dynamics of Epstein-Barr virus shedding in the tonsils and the impact of HIV-1 coinfection on daily saliva viral loads.

Epstein-Barr virus (EBV) is transmitted by saliva and is a major cause of cancer, particularly in people living with HIV/AIDS. Here, we describe the frequency and quantity of EBV detection in the saliva of Ugandan adults with and without HIV-1 infection and use these data to develop a novel mathematical model of EBV infection in the tonsils. Eligible cohort participants were not taking antiviral medications, and those with HIV-1 infection had a CD4 count >200 cells/mm3. Over a 4-week period, participants provided daily oral swabs that we analysed for the presence and quantity of EBV. Compared with HIV-1 uninfected participants, HIV-1 coinfected participants had an increased risk of EBV detection in their saliva (IRR = 1.27, 95% CI = 1.10-1.47) and higher viral loads in positive samples. We used these data to develop a stochastic, mechanistic mathematical model that describes the dynamics of EBV, infected cells, and immune response within the tonsillar epithelium to analyse potential factors that may cause EBV infection to be more severe in HIV-1 coinfected participants. The model, fit using Approximate Bayesian Computation, showed high fidelity to daily oral shedding data and matched key summary statistics. When evaluating how model parameters differed among participants with and without HIV-1 coinfection, results suggest HIV-1 coinfected individuals have higher rates of B cell reactivation, which can seed new infection in the tonsils and lower rates of an EBV-specific immune response. Subsequently, both these traits may explain higher and more frequent EBV detection in the saliva of HIV-1 coinfected individuals.

Joubert syndrome diagnosed renally late.

Joubert syndrome is a genetically heterogeneous multisystem disorder typically diagnosed in childhood. Nephronophthisis is the most common renal pathology in Joubert syndrome, and renal failure usually occurs in childhood or in young adults. We report a 61-year-old female diagnosed with AHI1-related oculorenal Joubert syndrome, who presented initially with decline in renal function in her 50s. Our report describes exceptionally late presentation of renal disease in Joubert syndrome and highlights the importance of continued renal function monitoring in older adults with Joubert syndrome.

Real-world Outcomes With Rituximab-based Therapy for Posttransplant Lymphoproliferative Disease Arising After Solid Organ Transplant.

BACKGROUND: Optimal upfront therapy for posttransplant lymphoproliferative disease (PTLD) arising after solid organ transplant remains contentious. Rituximab monotherapy (R-Mono) in unselected patients has shown a lack of durable remissions. Cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP)-based chemotherapy confers improved response rates, although concerns exist about toxicity. METHODS: This multicenter retrospective study reports outcomes for adults with biopsy-proven B-cell PTLD treated initially with R-Mono or Rituximab plus CHOP (R-CHOP). Selection of therapy was made according to physician preference. RESULTS: Among 101 patients, 41 received R-Mono and 60 had R-CHOP. Most (93%) had undergone renal or liver transplantation. R-CHOP showed a trend toward improved complete (53% versus 71%; P = 0.066) and overall (75% versus 90%; P = 0.054) response rates. In the R-Mono group, 13 of 41 (32%) subsequently received chemotherapy, while 25 of 41 (61%) remained progression-free without further therapy. With median follow-up of 47 months, overall survival (OS) was similar for R-Mono and R-CHOP, with 3-year OS of 71% and 63%, respectively (P = 0.722). Non-PTLD mortality was 3 of 41 (7%) and 4 of 60 (7%) within 12 months of R-Mono or R-CHOP, respectively. The International Prognostic Index was statistically significant, with low- (0-2 points) and high-risk (≥3 points) groups exhibiting 3-year OS of 78% and 54%, respectively (P = 0.0003). In low-risk PTLD, outcomes were similar between therapies. However, in high-risk disease R-Mono conferred an inferior complete response rate (21% versus 68%; P = 0.006), albeit with no impact on survival. CONCLUSIONS: Our data support R-Mono as initial therapy for PTLD arising after renal or liver transplantation. However, upfront R-CHOP may benefit selected high-risk cases in whom rapid attainment of response is desirable.

Collapsing Glomerulopathy Affecting Native and Transplant Kidneys in Individuals with COVID-19.

Since the emergency of novel coronavirus COVID-19 (SARS-CoV-2) in December 2019, infections have spread rapidly across the world. The reported incidence of acute kidney injury (AKI) in the context of COVID-19 is variable, and its mechanism is not well understood. Data are emerging about possible mechanisms of AKI including virus-induced cytopathic effect and cytokine storm-induced injury. To date, there have been few reports of kidney biopsy findings in the context of AKI in COVID-19 infection. This article describes 2 cases of collapsing glomerulopathy, 1 in a native kidney and, for the first time, 1 in a kidney transplant. Both individuals were black, and both presented without significant respiratory compromise. Indeed, the 2 patients we describe remained systemically well for the majority of their inpatient stay, which would support the hypothesis that for these patients, AKI was caused by a cytopathic viral effect, rather than that of a cytokine storm or acute tubular necrosis caused by prolonged hypovolaemia or the effect of medication known to exacerbate AKI. Here, we report 2 cases of AKI with collapsing glomerulopathy in COVID-19, one of which is in a kidney transplant recipient, not previously described elsewhere.

Correction to: Interventions to Reduce Adverse Drug Event-Related Outcomes in Older Adults: A Systematic Review and Meta-analysis.

Unfortunately, the co-author name was incorrectly published as ' 'Lamona'' instead of ' 'Lamorna'' in the original article.

Interventions to Reduce Adverse Drug Event-Related Outcomes in Older Adults: A Systematic Review and Meta-analysis.

BACKGROUND: Many studies focus on interventions that reduce the processes that lead to adverse drug events (ADEs), such as inappropriate or high-risk prescribing, without assessing whether they result in a reduction in ADEs or associated adverse health outcomes. OBJECTIVES: Our objective was to systematically review interventions to reduce the incidence of ADEs measured by health outcomes in older patients in primary care settings. METHODS: The review included randomised controlled trials, controlled clinical trials, controlled before and after studies, interrupted time series studies and cohort studies conducted in the community care setting. Older patients (aged ≥ 65 years) receiving medical treatment in primary care were included. Interventions were aimed at reducing adverse health outcomes associated with ADEs in older patients. Risk of bias was assessed using the Cochrane Collaboration's tool. Outcomes were measured by reductions in hospitalisation, emergency department (ED) visits, mortality and improvements in quality of life (QoL), mental health and physical function. Fixed and random-effects models were used to calculate pooled effect estimates comparing interventions and control groups for the outcomes, where feasible. RESULTS: The literature search identified 1566 abstracts, seven of which were included in the systematic review. The interventions for reducing ADEs included prescription or medication reviews by a pharmacist (n = 4), primary care physician (n = 1) or research team (n = 1), and an educational intervention (n = 1) for nursing staff to improve the recognition of potentially harmful medications and corresponding ADEs. Meta-analysis found no statistically significant benefit from any interventions on hospitalisation, ED visits, mortality, QoL or mental health and physical function. CONCLUSIONS: No significant benefit was gained from any of the interventions in terms of the outcomes considered. New approaches are required to reduce ADEs in older adults.

Patterns of Religiosity, Death Anxiety, and Hope in a Population of Community-Dwelling Palliative Care Patients in New Zealand-What Gives Hope If Religion Can't?

This study examines the prevalence of religiosity, death anxiety, and hope in a sample of New Zealand community hospice patients in the last 6 months of life. It explores the factors triggering distress or hope and examines whether religiosity is protective against death anxiety for this population. Early studies showed religious faith helps relieve death anxiety, but later work suggests this may only be the case in societies which are generally religious. Very little research has been conducted on this topic in New Zealand, from which recent censuses indicate is an increasingly secular country. If religion is not an important source of hope for dying, it is important to explore what factors do help relieve existential anxiety and to consider their clinical relevance. This study confirmed that organized religion was not a major support factor. Yet several people who declared themselves nonreligious scored highly for intrinsic religiosity and were among the most hopeful participants. This could suggest that spirituality may be more relevant than organized religion in relieving existential distress. The main source of hope for most participants was joyful memories and meaningful relationships. Fear of being a burden and of causing family suffering were the most significant causes of distress. Systematic spiritual assessment for all patients, not just those with a declared religious faith, a biography service, and psychotherapy, may all have a role in managing death anxiety at the end of life. Further work with larger and more diverse populations would be needed to confirm these findings.

The association between medication non-adherence and adverse health outcomes in ageing populations: A systematic review and meta-analysis.

AIMS: The aim of this systematic review and meta-analysis was to synthesise the evidence relating to medication non-adherence and its association with health outcomes in people aged ≥50 years. METHODS: Seven databases were searched up to February 2019 for observational studies that measured medication (non-)adherence as a predictor of the following health outcomes in adults aged ≥50 years: healthcare utilisation (hospitalisation, emergency department visits, outpatient visits and general practitioner visits), mortality, adverse clinical events and quality of life. Screening and quality assessment using validated criteria were completed by 2 reviewers independently. Random effects models were used to generate pooled estimates of association using adjusted study results. The full methodological approach was published on PROSPERO (ID: CRD42017077264). RESULTS: Sixty-six studies were identified for qualitative synthesis, with 11 of these studies eligible for meta-analyses. A meta-analysis including 3 studies measuring medication non-adherence in adults aged ≥55 years showed a significant association with all-cause hospitalisation (adjusted odds ratio 1.17, 95% confidence interval [CI] 1.12, 1.21). A meta-analysis including 2 studies showed that medication non-adherence was not significantly associated with an emergency department visit (adjusted odds ratio 1.05, 95% CI 0.90, 1.22). Good adherence was associated with a 21% reduction in long-term mortality risk in comparison to medication non-adherence (adjusted hazard ratio 0.79, 95% CI 0.63, 0.98). CONCLUSION: Medication non-adherence may be significantly associated with all-cause hospitalisation and mortality in older people. Medication adherence should be monitored and addressed in this cohort to minimise hospitalisation, improve clinical outcomes and reduce healthcare costs.

Population pharmacokinetics of total and unbound concentrations of intravenous posaconazole in adult critically ill patients.

BACKGROUND: The population pharmacokinetics of total and unbound posaconazole following intravenous administration has not yet been described for the critically ill patient population. The aim of this work was, therefore, to describe the total and unbound population pharmacokinetics of intravenous posaconazole in critically ill patients and identify optimal dosing regimens. METHODS: This was a prospective observational population pharmacokinetic study in critically ill adult patients with presumed/confirmed invasive fungal infection. A single dose of 300 mg posaconazole was administered intravenously as an add-on to standard antifungal therapy, and serial plasma samples were collected over 48 h. Total and unbound posaconazole concentrations, measured by chromatographic method, were used to develop a population pharmacokinetic model and perform dosing simulations in R using Pmetrics. RESULTS: From eight patients, 93 pairs of total and unbound concentrations were measured. A two-compartment linear model with capacity-limited plasma protein binding best described the concentration-time data. Albumin and body mass index (BMI) were included as covariates in the final model. Mean (SD) parameter estimates for the volume of the central compartment (V) and the elimination rate constant were 72 (43) L and 42.1 (23.7) h-1, respectively. Dosing simulations showed that high BMI was associated with a reduced probability of achieving target total and unbound posaconazole concentrations. Low serum albumin concentration was associated with a reduced probability of attaining target total but not unbound posaconazole concentrations. CONCLUSIONS: An important clinical message of this study is that critically ill patients with increased BMI may require larger than approved loading doses of intravenous posaconazole when considering currently recommended dosing targets. Variability in plasma albumin concentration appears unlikely to affect dosing requirements when the assessment is based on unbound concentrations. Where available, therapeutic drug monitoring of unbound concentrations may be useful.

Impact of drug burden index on adverse health outcomes in Irish community-dwelling older people: a cohort study.

BACKGROUND: The Drug Burden Index (DBI) quantifies exposure to medications with anticholinergic and/or sedative effects. A consensus list of DBI medications available in Ireland was recently developed for use as a DBI tool. The aim of this study was to validate this DBI tool by examining the association of DBI score with important health outcomes in Irish community-dwelling older people. METHODS: This was a cohort study using data from The Irish Longitudinal Study on Ageing (TILDA) with linked pharmacy claims data. Individuals aged ≥65 years participating in TILDA and enrolled in the General Medical Services scheme were eligible for inclusion. DBI score was determined by applying the DBI tool to participants' medication dispensing data in the year prior to outcome assessment. DBI score was recoded into a categorical variable [none (0), low (> 0 and < 1), and high (≥1)]. Outcome measures included any Activities of Daily Living (ADL) impairment, any Instrumental Activities of Daily Living (IADL) impairment, any self-reported fall in the previous 12 months, any frailty criterion met (Fried Phenotype measure), quality of life (QoL) score (CASP-19 [Control Autonomy Self-realisation Pleasure] measure), and healthcare utilisation (any hospital admission and any emergency department (ED) visit) in the previous 12 months. Statistical analyses included multivariate logistic and linear regression models controlling for potential confounders. RESULTS: 61.3% (n = 1946) of participants received at least one DBI prescription in the year before their outcome assessment. High DBI exposure (DBI score ≥ 1) vs none was significantly associated with impaired function (ADL impairment adjusted OR 1.89, 95% CI 1.25, 2.88; IADL impairment adjusted OR 2.97, 95% CI 1.91, 4.61), self-reported falls (adjusted OR 1.50, 95%CI 1.03, 2.18), frailty (adjusted OR 1.74, 95% CI 1.14, 2.67), and reduced QoL (ß = - 1.84, 95%CI -3.14, - 0.54). There was no significant association between DBI exposure and healthcare utilisation. CONCLUSIONS: The findings validate the use of the DBI tool for predicting risk of functional impairment, falls, frailty and reduced QoL in older people in Ireland, and may be extended to other European countries. Integration of this tool into routine practice may be an appropriate step forward to improve outcomes in older people.

Identifying Adverse Drug Events in Older Community-Dwelling Patients.

PURPOSE: To evaluate a patient-report instrument for identifying adverse drug events (ADEs) in older populations with multimorbidity in the community setting. METHODS: This was a retrospective cohort study of 859 community-dwelling patients aged ≥70 years treated at 15 primary care practices. Patients were asked if they had experienced any of a list of 74 symptoms classified by physiologic system in the previous 6 months and if (1) they believed the symptom to be related to their medication, (2) the symptom had bothered them, (3) they had discussed it with their family physician, and (4) they required hospital care due to the symptom. Self-reported symptoms were independently reviewed by 2 clinicians who determined the likelihood that the symptom was an ADE. Family physician medical records were also reviewed for any report of an ADE. RESULTS: The ADE instrument had an accuracy of 75% (95% CI, 77%-79%), a sensitivity of 29% (95% CI, 27%-31%), and a specificity of 93% (95% CI, 92%-94%). Older people who reported a symptom had an increased likelihood of an ADE (positive likelihood ratio [LR+]: 4.22; 95% CI, 3.78-4.72). Antithrombotic agents were the drugs most commonly associated with ADEs. Patients were most bothered by muscle pain or weakness (75%), dizziness or lightheadedness (61%), cough (53%), and unsteadiness while standing (52%). On average, patients reported 39% of ADEs to their physician. Twenty-six (3%) patients attended a hospital outpatient clinic, and 32 (4%) attended an emergency department due to ADEs. CONCLUSION: Older community-dwelling patients were often not correct in recognizing ADEs. The ADE instrument demonstrated good predictive value and could be used to differentiate between symptoms of ADEs and chronic disease in the community setting.

REbeL peer education: A model of a voluntary, after-school program for eating disorder prevention.

Dissonance-based eating disorder prevention leads to decreases in risk factors for these disorders. Although controlled trials have demonstrated that targeted, manualized programs reduce eating disorder risk, concerns regarding implementation and dissemination remain. A primary concern is the difficulty in adapting programs for a high school setting for populations at highest risk: adolescents. This paper describes the REbeL Peer Education model and assesses the initial pilot trials of the intervention. The program is novel in that it utilizes a voluntary, self-selection model that is sustainable in a high school setting, and focuses on empowerment and effective cognitive dissonance based prevention activities. High school peer-educators self-selected into the semi-manualized dissonance based intervention. Group activities were peer led, designed to critique the thin ideal, and designed to empower macro (school and larger community wide) changes in the pilot trial (N=47) assess the effectiveness and feasibility of the intervention. Results of the initial pilot study revealed preliminary support for the feasibility of the program, increases in feelings of empowerment, and decreases in eating disorder cognitions and behaviors with moderate to large effect sizes. Feedback from participants indicated that the intervention was enjoyable, educational, and empowering. This study is the first to adapt dissonance-based prevention models to a semi-manualized, peer-led, prevention program integrated into high school settings.

Young adults with chronic kidney disease: An exploration of their relationships and support networks.

BACKGROUND: Young people with chronic kidney disease (CKD) have a number of key issues and life changes to manage while also possibly transitioning into adult care. During this time, the nature of their support networks including, social, romantic, family and health care relationships, is changing. OBJECTIVE: To explore these young people's experience and perceptions of their past, current and future relationships and support networks. DESIGN: Qualitative study. PARTICIPANTS AND METHODS: Fourteen young adults (8 male, 6 female, aged 18-26 years) with CKD Stages 3-5 participated. Semi-structured interviews were conducted in order to explore the relationships (friends, family and partners) of young adults with CKD at two UK NHS hospitals. These were transcribed and thematically analysed. RESULTS: There were four themes identified. 'Disclosure-To tell or not to tell?' identified the challenges young adults face when disclosing their condition to friends and prospective partners. 'Managing support networks' showed that participants appreciated support from other young adults with CKD but also desired just 'being normal' with their friends. While family support is still significant and much appreciated, some young adults also found it harder to develop their independence. 'Relationship strains and carer needs' highlights the impact of CKD on all relationships. Participants were also aware of the needs of their 'carers'. In 'Happy ever after?' young adults expressed concerns about meeting a partner and having children. CONCLUSIONS: Young adults with CKD need support in helping them manage new and existing relationships, at a time where relationships are taking on different forms and significance. Moreover, support needs for young adults extend beyond the patient, to those who support them; support services need to reflect this.

Anticholinergic and sedative drug burden in community-dwelling older people: a national database study.

OBJECTIVES: The Drug Burden Index (DBI) tool quantifies individual exposure to anticholinergic and sedative medications. The DBI has been internationally validated against adverse health outcomes in older people. DBI exposure has not been reported in the Irish older population. This study aimed to: (1) develop a list of drugs with clinically significant anticholinergic and/or sedative effects (DBI medications) relevant to Ireland; (2) examine, using the DBI formula, the prevalence of exposure to DBI medications in Irish older people and (3) explore patient factors associated DBI exposure. DESIGN: A cross-sectional national pharmacy claims database study. SETTING: Community setting using the General Medical Services (GMS) scheme pharmacy claims database maintained by the Health Service Executive Primary Care Reimbursement Services. PARTICIPANTS: Irish older individuals (aged ≥65 years) enrolled in the GMS scheme and dispensed at least one prescription item in 2016 (n=428 516). MAIN OUTCOME MEASURES: Prevalence of exposure to DBI medications and patient factors associated with DBI exposure. RESULTS: 282 874 (66%) of the GMS population aged ≥65 years were exposed to at least one DBI medication in 2016. Prevalence of exposure to DBI medications was significantly higher in females than males (females 71.6% vs males 58.7%, adjusted OR 1.65, 95% CI 1.63 to 1.68). Prevalence of DBI exposure increased progressively with the number of chronic drugs used, rising from 42.7% of those prescribed 0-4 chronic drugs to 95.4% of those on ≥12 chronic drugs (adjusted OR 27.8, 95% CI 26.7 to 29.0). The most frequently used DBI medications were codeine/paracetamol combination products (20.1% of patients), tramadol (11.5%), zopiclone (9.5%), zolpidem (8.5%), pregabalin (7.9%) and alprazolam (7.8%). CONCLUSIONS: The majority of older people in Ireland are exposed to medications with anticholinergic and/or sedative effects, particularly females and those with multiple comorbidities. The high use of low-dose codeine/paracetamol combination products, Z-drugs and benzodiazepines, suggests there are opportunities for deprescribing.

Using bivariate latent basis growth curve analysis to better understand treatment outcome in youth with anorexia nervosa.

OBJECTIVE: This study explored the relation between eating-related obsessionality and weight restoration utilizing bivariate latent basis growth curve modelling. Eating-related obsessionality is a moderator of treatment outcome for adolescents with anorexia nervosa (AN). This study examined the degree to which the rate of change in eating-related obsessionality was associated with the rate of change in weight over time in family-based treatment (FBT) and individual therapy for AN. METHOD: Data were drawn from a 2-site randomized controlled trial that compared FBT and adolescent focused therapy for AN. Bivariate latent basis growth curves were used to examine the differences of the relations between trajectories of body weight and symptoms associated with eating and weight obsessionality. RESULTS: In the FBT group, the slope of eating-related obsessionality scores and the slope of weight were significantly (negatively) correlated. This finding indicates that a decrease in overall eating-relating obsessionality is significantly associated with an increase in weight for individuals who received FBT. However, there was no relation between change in obsessionality scores and change in weight in the adolescent focused therapy group. DISCUSSION: Results suggest that FBT has a specific impact on both weight gain and obsessive compulsive behaviour that is distinct from individual therapy.

Effects of spatiotemporal HSV-2 lesion dynamics and antiviral treatment on the risk of HIV-1 acquisition.

Patients with Herpes Simplex Virus-2 (HSV-2) infection face a significantly higher risk of contracting HIV-1. This is thought to be due to herpetic lesions serving as entry points for HIV-1 and tissue-resident CD4+ T cell counts increasing during HSV-2 lesional events. We have created a stochastic and spatial mathematical model describing the dynamics of HSV-2 infection and immune response in the genital mucosa. Using our model, we first study the dynamics of a developing HSV-2 lesion. We then use our model to quantify the risk of infection with HIV-1 following sexual exposure in HSV-2 positive women. Untreated, we find that HSV-2 infected women are up to 8.6 times more likely to acquire HIV-1 than healthy patients. However, when including the effects of the HSV-2 antiviral drug, pritelivir, the risk of HIV-1 infection is predicted to decrease by up to 35%, depending on drug dosage. We estimate the relative importance of decreased tissue damage versus decreased CD4+ cell presence in determining the effectiveness of pritelivir in reducing HIV-1 infection. Our results suggest that clinical trials should be performed to evaluate the effectiveness of pritelivir or similar agents in preventing HIV-1 infection in HSV-2 positive women.