Days Of Antiviral Therapy Research Articles

Adequate antiviral treatment lowers overall complications of cytomegalovirus colitis among inpatients with inflammatory bowel diseases

BackgroundCytomegalovirus (CMV) colitis significantly complicates the course of inflammatory bowel disease (IBD), frequently leading to severe flare-ups and poor outcomes. The role of antiviral therapy in hospitalized IBD patients with CMV colitis is currently under debate. This retrospective analysis seeks to clarify the influence of antiviral treatment on these patients.MethodsWe retrospectively reviewed IBD patients diagnosed with CMV colitis via immunohistochemistry staining from colonic biopsies at a major tertiary center from January 2000 to May 2021. The study focused on patient demographics, clinical features, risk factors, prognostic indicators, and antiviral treatment outcomes.ResultsAmong 118 inpatients, 42 had CMV colitis. Risk factors included hypoalbuminemia and antibiotic use. IBD patients with CMV colitis receiving < 14 days of antiviral therapy had higher complication (72% vs. 43%, p = 0.028) and surgery rates (56% vs. 26%, p = 0.017) compared to those without CMV. Adequate antiviral therapy (≥ 14 days) significantly reduced complications in the CMV group (29% vs. 72%, p = 0.006), especially in Crohn’s disease (20% vs. 100%, p = 0.015). Independent predictors of IBD-related complications were CMV colitis (Odds Ratio [OR] 3.532, 90% Confidence Interval [CI] 1.012–12.331, p = 0.048), biological treatment failure (OR 4.953, 95% CI 1.91-12.842, p = 0.001), and adequate antiviral therapy (OR 0.108, 95% CI 0.023–0.512, p = 0.005).ConclusionCMV colitis and a history of biological treatment failure increase complication risks in IBD patients. Adequate antiviral therapy significantly mitigates these risks, highlighting its importance in managing IBD patients with CMV colitis.

Epidemiology of cytomegalovirus antiviral resistance testing for solid organ and bone marrow transplant patients from 2011 - 2019.

CMV reactivation post-transplantation is common, with need for prompt identification of patients most at-risk for CMV antiviral drug resistance (AVDR). This study describes CMV AVDR frequencies, antiviral prescribing practices, and AVDR risk factors in patients from 2011 to 2019 in British Columbia, Canada. Retrospective review of demographics, transplant type, viral loads, antiviral exposure duration, and 12-month mortality was conducted for all patients with samples submitted for CMV AVDR testing from 2011 to 2019. Genotyping of AVDR mutations occurred at the national reference laboratory. Mann-Whitney U, T-test or Fisher's exact tests examined differences between patients with and without AVDR. Fifty-three plasma and three tissue/fluid specimens successfully underwent CMV AVDR testing; of these samples, 27/56 (48%) had AVDR mutations detected. The commonest AVDR mutations were at UL97 loci A594 (20%), H596 (12%) and L595 (12%). Mutations occurred more frequently in requests from solid organ than hematopoietic stem cell transplant patients (58% vs. 27%, p=0.05). Previous resistance testing was a significant risk factor for AVDR (p<0.001). Patients with AVDR had approximately 51 more days of antiviral therapy (p=0.007) and took 9 days longer to clear viremia (p=0.23). The median turnaround time from sample send-out to reporting was nine days. However, empiric use of second-line antivirals occurred in most cases (39/53, 74%) before results were available. Laboratories should strive to provide timely CMV AVDR testing for transplant patients, to minimize unnecessary exposure to second-line antiviral agents. The findings of this study may help guide clinicians when selecting empiric antiviral therapy.

Changes in PD-1- and CTLA-4-bearing blood lymphocytes in ICU COVID-19 patients treated with Favipiravir/Kaletra or Dexamethasone/Remdesivir: a pilot study.

COVID-19, caused by SARS-CoV-2, requires new approaches to control the disease. Programmed cell death protein (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) play important roles in T-cell exhaustion in severe COVID-19. This study evaluated the frequency of whole blood lymphocytes expressing PD-1 and CTLA-4 in COVID-19 patients upon admission to the intensive care unit (ICU) (i.e., severe) or infection ward (i.e., moderate) and after 7 days of antiviral therapy. COVID-19 patients were treated with either favipiravir or Kaletra (FK group, 11 severe and 11 moderate) or dexamethasone plus remdesivir (DR group, 7 severe and 10 moderate) for 7 days in a pilot study. Eight healthy control subjects were also enrolled. The frequency of PD-1+ and CTLA-4+ lymphocytes in whole blood was evaluated by flow cytometry. Patients on DR therapy had shorter hospital stays than those on FK therapy. The frequency of PD-1+ lymphocytes in the FK group at baseline differed between COVID-19 patients and healthy controls, while the frequency of both PD-1+ and CTLA-4+ cells increased significantly 7 days of FK therapy. The response was similar in both moderate and severe patients. In contrast,the frequency of PD-1+ and CTLA-4+ lymphocytes varied significantly between patients and healthy controls before DR treatment. DR therapy enhanced PD-1+ but not the CTLA-4+ frequency of these cells after 7 days. We show that the frequency of PD-1 and CTAL-4-bearing lymphocytes during hospitalization was increased in Iranian ICU COVID-19 patients who received FK treatment, but that the frequency of CTLA-4+ cells was higher at baseline and did not increase in patients who received DR. The effectiveness of DR treatment may reflect differences in T-cell activation or exhaustion status, particularly in CTLA-4-expressing cells.

Herpes simplex keratitis following Smart Pulse Technology assisted transepithelial photorefractive keratectomy: a case report

BackgroundHerpes simplex keratitis (HSK) is a rare and sight-threatening complication following refractive surgery. SmartSurfACE surgery is the result of combining transepithelial photorefractive keratectomy (trans-PRK) with Smart Pulse Technology (SPT) to diminish surface irregularities of the residual stromal bed after surgery with less pain, faster re-epithelialization, and better postoperative visual acuity. In this article, we report the first case of HSK following SmartSurf ACE without history of herpetic eye disease.Case presentationA 21-year-old woman underwent bilateral SmartSurfACE without history of clinical herpetic infection, active eye disease, or systemic disease. Mild superficial punctate keratitis occurred on the tenth postoperative day. The condition was not improved by ophthalmic drugs of anti-inflammation or epithelial healings. Dendritic corneal ulcer appeared within one month, which is the commonly recognized clinical manifestation of herpes simplex keratitis. The patient was managed with topical and systemic antiviral agents. After nine days of antiviral therapy, the lesion healed up, remaining mild stromal scarring in both eyes ultimately.ConclusionHerpes simplex keratitis is a rare but sight-threatening complication following refractive surgery. For the ocular irritation symptoms of postoperative patients, we should consider the possibility of HSK and give timely treatment.

Dual infection of the brain, varicella zoster and tuberculosis in an immunocompetent adult: A rare scenario

The spectrum of central nervous system diseases caused by mycobacterium tuberculosis (TB) and herpes virus is broad and overlapping, ranging from self-limiting meningitis to life-threatening encephalitis. In a country like India where TB is a common infection of the brain, antitubercular therapy finds itself as frontline empirical therapy in appropriate clinical scenarios. In this case report, we describe a challenging case of a middle-aged immunocompetent male whose cerebrospinal fluid came positive for herpes zoster which aided us in diagnosing viral meningoencephalitis. However, later on, when the patient deteriorated in spite of 21 days of antiviral therapy, repeat brain imaging revealed another pathology, which was TB. We wish to highlight the fact that both these pathogens can mimic each other in clinical presentation and investigations can be misleading. One should always keep them as early differentials in appropriate clinical scenarios so as not to squander crucial time in treatment.

Predictors of the efficiency of short-term interferon-containing therapy using direct-acting antiviral drugs in patients with chronic hepatitis C virus genotype 1

To identify predictors for the high efficiency of short-term interferon-containing antiviral therapy (AVT) using direct-acting antivirals (DAAs) in patients with chronic hepatitis C (CHC) virus (HCV) type 1 (CHC-1). A total of 2,798 case histories of patients aged 18 to 60 years who received AVT using peginterferon, ribavirin in combination with DAAs for CHC-1, which was stopped at 10 to 14 weeks, were selected from the archives of the healthcare facilities of the Moscow Region. The inclusion criteria were aviremia achieved when AVT was discontinued; therapy using the dose recommended in compliance with the international standards; and adherence during treatment. The analysis included 179 case histories, including 158 cases of discontinuation of triple AVT using a protease inhibitor (telaprevir) and 22 cases of that of quadruple treatment (QT) with asunaprevir and daclatasvir. There were two main factors predicting a high probability of achieving a sustained virological response (SVR) in patients with HCV-1 during short-term triple AVT: viremia at 28 days of AVT, which was registered by a highly sensitive polymerase chain reaction (PCR) assay (its analytical sensitivity was 12 IU/ml), and the genotype CC of interleukin-28B (IL-28B) rs12979860. With a combination of these two factors, recovery was observed in 100% of cases. SVR was observed in all cases of QT discontinuation, regardless of the stage of fibrosis and the subtype of CHC genotype. However, the resulting sample was unrepresentative. Triple AVT using a protease inhibitor may be reduced in patients with CHC-1 and the CC allelic variant in IL-28B if viremia is achieved at 28 days of AVT, as evidenced by highly sensitive PCR assay. Short-term QT needs further investigation.

Factors associated with HBV virological breakthrough.

Little is known about non-adherence to HBV therapy. This study aimed to investigate the relationship between self-reported missed days of antiviral therapy and HBV virological breakthrough and factors associated with virological breakthrough. A cross-sectional survey of 211 HBV patients receiving oral antiviral therapies was undertaken at three tertiary hospitals in Sydney, Australia. Associations between 0 to >6 missed days in the last 30 days and virological breakthrough (defined as >10-fold rise in serum HBV DNA above nadir or after achieving virological response in the last 12 months) were examined. Logistic regression analyses determined the number of missed days most strongly associated with virological breakthrough and the associated factors. We report odds ratios (ORs) and relative risks (RRs). Of the 204, 32 participants (15.6%) had quantifiable HBV DNA levels (>20 IU/ml); 15 (46.8%) of them experienced virological breakthrough. Participants reported never missing medication (n=130, 63.7%) or missing 1 day (n=23, 11.3%), >1 day (n=23, 11.3%), 2-6 days (n=15, 7.3%) and >6 days (n=13, 6.4%). The most discriminating definition of non-adherence was missing >1 day of medication (RR=8.3; OR=10.2, 95% CI 3.1, 33.8, receiver operating characteristic curve 0.76). Factors independently associated with virological breakthrough included non-adherence (OR=9.0, 95% CI 2.5, 31.9) diagnosed with HBV ≤14 years (OR=5.3, 95% CI 1.0, 26.2) and age ≤47 years (OR=5.4, 95% CI 1.1, 26.9). Results provide an evidence-based definition of non-adherence to inform clinical practice and provide a basis for key patient education messages. Closer monitoring of groups at risk of viral breakthrough is required.

Host immunological response and factors associated with clinical outcome in patients with the novel influenza A H7N9 infection

In March 2013, an influenza outbreak caused by the novel avian-origin H7N9 influenza A virus emerged in eastern China and had caused 43 fatalities by 31 July 2013, although the basis for disease pathogenesis still remains unclear. To assess the immunological and viral factors associated with disease severity, viral RNA and inflammatory cytokines were quantified for 18 H7N9 patients in Shanghai, China. Detailed clinical information was collected and clinical laboratory investigations were performed for all patients. H7N9 infection is characterized by high pharyngeal virus load and frequent detection of viral RNA in blood. High pharyngeal virus load persisted through the first 10 days of antiviral therapy in fatal cases. Genetic characterization of the H7N9 virus revealed an Arg292Lys mutation in the neuraminidase gene associated with oseltamivir-resistance. Pronounced lymphopenia and high chemokine and cytokine levels were observed in H7N9-infected patients, particularly in those where disease was fatal. Serum levels of interleukin-6 (IL-6), IL-8 and macrophage inflammatory protein-1β in our subjects also correlated positively with pharyngeal virus load. Lymphocyte counts <0.5 × 109 cells/L, and serum IL-6 >97 pg/mL, IL-8 >40 pg/mL and C-reactive protein >90 mg/L were identified as being connected with adverse clinical outcome through univariate logistic analysis. Significant survival differences were also observed between patients with serum C-reactive protein <90 mg/L or creatinine <90 µmol/L and those with higher levels. Our data demonstrated that high viral load, and the resulting intense inflammatory responses, played an important role in H7N9 pathogenesis. Though immunomodulatory treatment has potential benefits, the focus of clinical management should be on preventing the intense cytokine response by early diagnosis and effective antiviral treatment.

Virological Clearance Rate of High-Dose Oseltamivir or Triple-Combination Antiviral Therapy in Complicated 2009 Pandemic Influenza A (H1N1) Infection

The 2009 pandemic influenza A (H1N1) was a considerable public health concern worldwide. Significant morbidity and mortality were observed in complicated cases, despite the early administration of neuramidase inhibitors. The limitations of neuramidase inhibitor monotherapy have renewed interest in combination antiviral therapy or higher-dose oseltamivir therapy. Herein, we report our clinical experience and virological outcomes with high-dose oseltamivir or combination antiviral therapy in seriously complicated 2009 pandemic influenza A (H1N1) infection. Eight patients were treated with high-dose oseltamivir (150 mg twice a day), and 6 patients were treated with triple combination antiviral drugs (150 mg oseltamivir twice a day, 100 mg amantadine twice a day, and 300 mg ribavirin three times a day). Nine of 14 patients (64%) developed acute respiratory distress syndrome and 6 (43%) required mechanical ventilation. Viral clearance was obtained in 9 of 12 patients (75%) after 5 days of antiviral therapy. Two patients died within 5 days of antiviral therapy. The overall mortality rate was 29% (4/14).

Standard-dose and high-dose daily antiviral therapy for short episodes of genital HSV-2 reactivation: three randomised, open-label, cross-over trials

Skin and mucosal herpes simplex virus type 2 (HSV-2) shedding predominantly occurs in short subclinical episodes. We assessed whether standard-dose or high-dose antiviral therapy reduces the frequency of such shedding.HSV-2-seropositive, HIV-seronegative people were enrolled at the University of Washington Virology Research Clinic (WA, USA). We did three separate but complementary open-label cross-over studies comparing no medication with aciclovir 400 mg twice daily (standard-dose aciclovir), valaciclovir 500 mg daily (standard-dose valaciclovir) with aciclovir 800 mg three times daily (high-dose aciclovir), and standard-dose valaciclovir with valaciclovir 1 g three times daily (high-dose valaciclovir). The allocation sequence was generated by a random number generator. Study drugs were supplied in identical, numbered, sealed boxes. Study periods lasted 4-7 weeks, separated by 1 week wash-out. Participants collected genital swabs four times daily for quantitative HSV DNA PCR. Clinical data were masked from laboratory personnel. The primary endpoint was within-person comparison of shedding rate in each study group. Analysis was per protocol. The trials are registered at ClinicalTrials.gov (NCT00362297, NCT00723229, NCT01346475).Of 113 participants randomised, 90 were eligible for analysis of the primary endpoint. Participants collected 23 605 swabs; 1272 (5·4%) were HSV-positive. The frequency of HSV shedding was significantly higher in the no medication group (n=384, 18·1% of swabs) than in the standard-dose aciclovir group (25, 1·2%; incidence rate ratio [IRR] 0·05, 95% CI 0·03-0·08). High-dose aciclovir was associated with less shedding than standard-dose valaciclovir (198 [4·2%] vs 209 [4·5%]; IRR 0·79, 95% CI 0·63-1·00). Shedding was less frequent in the high-dose valaciclovir group than in the standard-dose valaciclovir group (164 [3·3%] vs 292 [5·8%]; 0·54, 0·44-0·66). The number of episodes per person-year did not differ significantly for standard-dose valaciclovir (22·6) versus high-dose aciclovir (20·2; p=0·54), and standard-dose valaciclovir (14·9) versus high-dose valaciclovir (16·5; p=0·34), but did for no medication (28·7) and standard-dose aciclovir (10·0; p=0·001). Median episode duration was longer for no medication than for standard-dose aciclovir (13 h vs 7 h; p=0·01) and for standard-dose valaciclovir than for high-dose valaciclovir (10 h vs 7 h; p=0·03), but did not differ significantly between standard-dose valaciclovir and high-dose aciclovir (8 h vs 8 h; p=0·23). Likewise, maximum log(10) copies of HSV detected per mL was higher for no medication than for standard dose aciclovir (3·3 vs 2·9; p=0·02), and for standard-dose valaciclovir than for high-dose valaciclovir (2·5 vs 3·0; p=0·001), but no significant difference was recorded for standard-dose valaciclovir versus high-dose aciclovir (2·7 vs 2·8; p=0·66). 80% of episodes were subclinical in all study groups. Except for a higher frequency of headaches with high-dose valaciclovir (n=13, 30%) than with other regimens, all regimens were well tolerated.Short bursts of subclinical genital HSV reactivation are frequent, even during high-dose antiherpes therapy, and probably account for continued transmission of HSV during suppressive antiviral therapy. More potent antiviral therapy is needed to eliminate HSV transmission.NIH. Valaciclovir was provided for trial 3 for free by GlaxoSmithKline.

Lung ultrasound imaging of H1N1 influenza

We describe the case of a 8 year-old child with acute respiratory distress syndrome (ARDS) during H1N1 swine flu. Lung ultrasound performed at the time of admission showed a typical ARDS ultrasound pattern, with multiple sonographic signs of interstitial oedema (also known as B-lines or ultrasound lung comets), and diffuse bilateral sub-pleural lung consolidations. After five days of anti-viral therapy, lung ultrasound showed a reduction of the dimension of consolidations, not clearly visible at chest X-ray, helping in the management of the patient.

Prospective comparison of PCR-based vs late mRNA-based preemptive antiviral therapy for HCMV infection in patients after allo-SCT

Human CMV (HCMV)-directed preemptive therapy has helped to improve the outcome following allo-SCT. In this study, we evaluated the safety and efficacy of a late mRNA-based (NucliSens CMV pp67) anti-HCMV treatment strategy. A prospective randomized multicenter pilot trial was performed comparing PCR-based, with late mRNA-based preemptive HCMV-directed antiviral therapy in patients after allo-SCT. In all, 133 patients were randomized in three different centers at the time of transplant, 130 of whom are evaluable. Viral screening was performed weekly. Antiviral therapy was initiated at the second consecutive positive PCR result, or at the first detection of late mRNA. The therapy was stopped if clearance of HCMV DNA or late mRNA was demonstrated after 14 days of antiviral therapy. If HCMV infection persisted, antiviral therapy was continued in a reduced dose. The median duration of antiviral therapy during the first treatment episode was 28 days for PCR-, and 19 days for mRNA-screened patients (P<0.02). However, the overall duration of antiviral therapy, as well as the incidence of HCMV disease and the OS at day 100 after transplantation was comparable between the two study groups. We conclude that late mRNA-based anti-HCMV therapy may show comparable safety and efficacy with PCR-based therapy in patients after allo-SCT.

Immune Reconstitution and Immune Correlates of Clinical Outcome IN Acute LEUKEMIA PATIENTS Treated with Haploidentical STEM CELL TRANSPLANTATION.

Abstract 46The broader application of haploidentical stem cell transplantation (haplo-HCT), is limited by the delayed immune reconstitution (IR) secondary to the procedures for GvHD prophylaxis. This ultimately results in a high-rate of infectious complications and non-relapse mortality. We dynamically analyzed immunoreconstitution (IR) in patients undergoing haplo-HCT for acute leukemias enrolled in two different phase I-II clinical trials aimed at improving IR. In the first trial (TK007), 28 patients (out of 50 enrolled) received suicide-gene transduced donor T cells at day +42 after a T-cell depleted graft, in the absence of post-transplant immunosuppression. In the second trial (TrRaMM), 40 patients received an unmanipulated graft and a rapamycin-based GvHD prophylaxis. T-cell immune reconstitution was more rapid in TrRaMM than in TK007 patients, with a threshold of CD3 cells>100/μl reached at days +30 and +90, respectively. In both trials IR was mainly composed of Th1/Tc1 lymphocytes with an inverted CD4/CD8 ratio. While in TrRaMM patients we observed an early expansion of naïve and central memory T cells, producing high amounts of IL-2, in TK patients IR was mainly composed of activated effectors. Furthermore, in TrRaMM patients we detected high levels of CD4+CD25+CD127- T regulatory cells (up to 15% of circulating T lymphocytes) that persisted after rapamycin withdrawal, and was significantly superior to that observed in TK patients and in healthy controls. Interestingly, in contrast to the different kinetics of T-cell reconstitution, no differences were observed in time required to gain protective levels of CMV-specific T cells, as shown by ψIFN ELISPOT analysis. Protective frequencies of CMV-specific lymphocytes were observed 3 months after HCT in both groups, a time-point that in TrRaMM patients corresponds to the average time of rapamycin withdrawal. In both trials the number of circulating CMV-specific T cells was inversely correlated to the number and severity of subsequent CMV reactivations and days of antiviral therapy. GvHD was diagnosed in 16 TrRaMM patients (40%) and in 10 TK patients (35% of patients who received TK cells). Severity of GvHD was different in the two cohort of patients with 5 TrRaMM patients (12,5%) and only 2 TK patients (7%) with grade III-IV GvHD. Of interest, in the TrRaMM group CMV-specific immunity was significantly hampered by the immunosuppressive treatment required to treat GvHD. On the contrary, in the TK group, the administration of ganciclovir was able to activate the suicide machinery and control GvHD without impairing viral-specific T-cell immunocompetence. These results matched with the kinetics of CMV reactivations. We observed that while in TrRaMM patients 80% of viral reactivations occurred after the immunosuppressive therapy, in TK patients no significant differences could be assessed before and after therapy. IFN-ψ ELISPOT might thus be a relevant and predictive test to guide patient-specific clinical monitoring and antiviral treatment. Overall, these results show that early immune reconstitution can be promoted in haplo-HCT by different strategies associated with a wide range of alloreactive potential. The risks and benefits associated with alloreactivity should guide the therapeutic choice tuned on patient disease status and co-morbidities. Disclosures:Bordignon:Molmed Spa: Employment.

Persistence of HIV-1 receptor–positive cells after HSV-2 reactivation is a potential mechanism for increased HIV-1 acquisition

To explore the mechanism behind the association between HSV-2 and HIV-1 acquisition, we performed in situ analysis of the cellular infiltrate from sequential biopsies of HSV-2 lesions on and off antiviral therapy. CD4+ and CD8+ T cells, and a mixed population of plasmacytoid and myeloid dendritic cells (DCs), including cells expressing DC-SIGN, persisted at sites of HSV-2 reactivation for months after healing, even in the context of daily antiviral therapy. The CD4+ T cells that persisted reacted to HSV-2 antigen, were enriched for CCR5 expression, and were also contiguous to DCs expressing CD123 or DC-SIGN. Ex vivo infection with a CCR5-tropic strain of HIV-1 revealed increased concentrations of integrated HIV-1 DNA in cells derived from healed genital lesion biopsies as compared to control skin biopsies. The persistence and enrichment of HIV-receptor-positive inflammatory cells in the genitalia help explain the failure of anti-HSV-2 therapy to reduce HIV acquisition.

Prophylaxis Followed by Preemptive Therapy Versus Preemptive Therapy for Prevention of Human Cytomegalovirus Disease in Pediatric Patients Undergoing Liver Transplantation

Twenty-one pediatric liver transplant recipients were enrolled in a study comparing prophylaxis followed by preemptive therapy (10 patients) versus preemptive therapy alone (11 patients) for prevention of human cytomegalovirus (HCMV) disease. In the prophylaxis arm, patients were treated with ganciclovir for 30 days, then preemptive therapy was initiated with virologic monitoring for pp65 antigenemia. In the preemptive therapy arm, patients were treated on reaching 100,000 DNA copies/mL whole blood. An interim analysis showed that, although numbers of both infected and treated patients were comparable in the two arms, the median number of total days of antiviral therapy per patient (30 vs. 18, P<0.01) was significantly higher in the prophylaxis arm. No case of HCMV disease occurred in either arm. Therefore, the trial was interrupted and prophylaxis replaced with preemptive therapy alone. In parallel, the development of T-cell-mediated immune response was found to be comparable in both arms.

Comparative Efficacy of Famciclovir and Valacyclovir for Suppression of Recurrent Genital Herpes and Viral Shedding

Daily antiviral therapy with famciclovir and valacyclovir has been shown to be effective in reducing both symptomatic and asymptomatic reactivation of herpes simplex virus type 2 (HSV-2) when compared to placebo. However, few comparative studies between the 2 antivirals have been performed. To compare the clinical and virologic effects of famciclovir and valacyclovir administered as daily suppressive therapy for persons with genital herpes. Two randomized, double-blind, placebo-controlled studies comparing daily famciclovir 250 mg bid with valacyclovir 500 mg qd were performed. Study 1 randomized 320 participants and compared the clinical effect of the drugs given for 16 weeks, and study 2 enrolled 70 HSV-2 seropositive subjects and compared the virologic effect of the drugs given for 10 weeks. In study 1, the time to first recurrence was similar in famciclovir and valacyclovir recipients, hazard ratio (HR) 1.17 (95% CI, 0.78-1.76), but time to first virologically confirmed recurrence was shorter among famciclovir recipients, HR = 2.15 (95% CI, 1.00-4.60). In study 2, HSV was detected on 3.2% of days among famciclovir recipients and 1.3% of days among valacyclovir recipients, relative risk 2.33 (95% CI, 1.18-4.89). Valacyclovir appear to be somewhat better than famciclovir for suppression of genital herpes and associated shedding. Further comparative trials of antiviral drugs for various indications should be performed as acyclovir and penciclovir appear to have different ability to abrogate HSV reactivation.

Targeting virological core groups: a new paradigm for controlling herpes simplex virus type 2 epidemics.

Classic modeling of sexually transmitted diseases has focused on modeling behavioral heterogeneity and designing epidemic control strategies targeted at behavioral core groups. We analyzed a new mathematical model of herpes simplex virus type 2 (HSV-2) epidemics that includes virological core groups (i.e., groups of individuals with high rates of viral reactivation) and suggest a new paradigm for epidemic control. We used our model, in conjunction with virological data, to determine the potential role of virological core groups in contributing to transmission and the effect that daily antiviral therapy (DAT) could have on reducing transmission if virological core groups were targeted. We estimated that a virological core group (11% of infected individuals) can cause a disproportionately large percentage (44%) of new infections and that a median of only 6.4 person-years of DAT would be necessary to prevent 1 HSV-2 infection. We determined that relatively few individuals would need to receive DAT to substantially reduce the incidence of HSV-2 infection. Identifying and targeting individuals in the virological core group could be an effective and practical public health strategy for reducing transmission. Treating individuals who are high-frequency viral shedders should be evaluated as a strategy for reducing HSV-2 transmission.

Once-Daily Valacyclovir to Reduce the Risk of Transmission of Genital Herpes

Corey, Lawrence; Wald, Anna; Sacks, Stephen L.; Tyring, Stephen K.; Warren, Terri; Douglas, John M. Jr.; Paavonen, Jorma; Morrow, R. Ashley; Beutner, Karl R.; Stratchounsky, Leonid S.; Mertz, Gregory; Keene, Oliver N.; Watson, Helen A.; Tait, Dereck; Vargas-Cortes, Mauricio for the Valacyclovir HSV Transmission Study Group

Daily Antiviral Therapy Reduces Transmission of Genital HSV

In patients who are infected with genital herpes simplex virus (HSV), daily antiviral therapy limits the frequency of symptomatic episodes and