Biomedical subjects

Lawrence Corey

Publications and source records attributed to Lawrence Corey.

At least 19 recordsLinked to original sources

PubMed2007

Phase 2 study of an HIV-1 canarypox vaccine (vCP1452) alone and in combination with rgp120: negative results fail to trigger a phase 3 correlates trial.

BACKGROUND: A goal of T-cell HIV vaccines is to define the correlation between a vaccine-induced immune response and protection from HIV infection. We conducted a phase 2 trial to determine if a canarypox vaccine candidate (vCP1452) administered with rgp120 subunit protein would "qualify" for a trial to define a correlate of efficacy. METHODS: A total of 330 healthy volunteers were enrolled into 4 groups: 120 received vCP1452 alone (0, 1, 3, and 6 months), 120 received vCP1452 with 2 different regimens of rgp120 coadministration, and 90 received placebo. HIV-specific antibody responses were measured by enzyme-linked immunoassay (ELISA) and neutralizing activity. T-cell responses were measured by chromium release and interferon-gamma (IFNgamma) enzyme-linked immunospot (ELISpot) assay. RESULTS: Significant neutralizing antibody responses to the HIV MN strain were detected in all vaccine groups, with net responses ranging from 57% (95% confidence interval [CI]: 40% to 71%) to 94% (95% CI: 85% to 99%). Net cumulative HIV-specific CD8 IFNgamma ELISpot assay responses were 13% (95% CI: -1% to 26%) for recipients of vCP1452 alone and 16% (95% CI: 2% to 29%) for recipients of vCP1452 plus rgp120. CONCLUSIONS: Overall, the HIV-specific CD8 cytotoxic T lymphocyte (CTL) response was not sufficient to qualify the regimen for a subsequent trial designed to detect an immune correlate of protection requiring a minimum CD8 CTL frequency of 30%.

AIDS Vaccines↗

PubMed2006

Frequent and asymptomatic oropharyngeal shedding of human herpesvirus 8 among immunocompetent men.

BACKGROUND: Little is known about the clinical and virologic manifestations of human herpesvirus (HHV)-8 infection in immunocompetent persons in the absence of malignancy. METHODS: A total of 46 human immunodeficiency virus-negative, HHV-8-seropositive men collected saliva daily, and 25 recorded 15 common symptoms daily (gastrointestinal, constitutional, and oropharyngeal) and absences from work or school. Quantitative polymerase chain reaction measured HHV-8 DNA in saliva. RESULTS: Some 44 (96%) of 46 men reported having sex with men (MSM). Of the 44 MSM, 27 (61%) had HHV-8 detected in saliva on > or = 1 day; heterosexual men also shed HHV-8. In analyses restricted to MSM, HHV-8 DNA was detected on 636 (22%) of 2897 days. Among MSM with HHV-8 detected in saliva, the median rate was 20% (range, 1%-100%), with 30% shedding on > 50% of days, and the median quantity was 4.5 log10 copies/mL (range, 2.0-7.3 log10 copies/mL). The quantity of HHV-8 shed was lower in nonwhites (P<.001) and younger participants (P=.03). The frequency of HHV-8 detection and quantity were correlated (r=0.62; P<.001). Symptoms were reported on 10 (9%) of 114 days when HHV-8 was present, compared with 78 (9%) of 830 days without (odds ratio, 0.93 [95% confidence interval, 0.30-2.88]; P=.9). CONCLUSIONS: HHV-8 is detected frequently and intermittently in the saliva of chronically infected immunocompetent MSM, but this infection is asymptomatic.

Adult↗

PubMed2006

Oral herpes simplex virus type 2 reactivation in HIV-positive and -negative men.

BACKGROUND: Previous studies using viral cultures rarely reported herpes simplex virus type 2 (HSV-2) isolation from the mouth. We sought to characterize oral HSV-2 shedding as detected by HSV DNA polymerase chain reaction among HSV-2-seropositive men. METHODS: Participants collected daily swabs from oral and anogenital areas for HSV detection with a quantitative polymerase chain reaction assay. RESULTS: A total of 109 HSV-2-seropositive men (59 of whom were human immunodeficiency virus [HIV] negative, and 50 of whom were HIV positive) were sampled for a median of 64 consecutive days. Forty-four (40.4%) had HSV-2 detected from oral swabs on at least 1 day. Oral HSV-2 was detected on 148 (2.3%) of 6,422 days, genital HSV-2 was detected on 1,110 (17%) of 6,505 days, oral HSV-1 was detected on 220 (5.5%) of 4,018 days, and genital HSV-1 was detected on 88 (2.2%) of 4,073 days. Oral HSV-2 shedding was never associated with an oral lesion, but it was often concurrent with genital HSV-2 shedding. Both oral and genital HSV-2 were detected on 90 (61%) of 148 days with oral HSV-2 shedding. Oral HSV-2 shedding occurred on 90 (8.2%) of 1,110 days with genital HSV-2 shedding, versus 58 (1.1%) of 5,316 days without genital HSV-2 shedding (P<.001). The HIV-positive men shed HSV-2 orally more frequently than did the HIV-negative men (odds ratio, 2.7 [95% confidence interval, 1.1-7.1]). CONCLUSIONS: Oral HSV-2 reactivation was common (especially among HIV-positive men), was always asymptomatic, and often occurred on days of genital HSV-2 reactivation.

Adult↗

PubMed2006

HIV vaccines: new frontiers in vaccine development.

A human immunodeficiency virus (HIV) vaccine is the most promising and feasible strategy to prevent the events during acute infection that simultaneously set the course of the epidemic in the community and the course of the disease for the individual. Because safety concerns limit the use of live, attenuated HIV and inactivated HIV, a variety of alternate approaches is being investigated. Traditional antibody-mediated approaches using recombinant HIV envelope proteins have shown no efficacy in 2 phase III trials. Current HIV vaccine trials are focusing primarily on cytotoxic T lymphocyte-mediated products that use viral vectors, either alone or as boosts to DNA plasmids that contain viral genes. The most immunogenic of these products appear to be the recombinant adenovirus vector vaccines, 2 of which are now in advanced clinical development.

AIDS Vaccines↗

PubMed2006

Peptide selection for human immunodeficiency virus type 1 CTL-based vaccine evaluation.

Dozens of human immunodeficiency virus-type 1 (HIV-1) vaccine candidates specifically designed to elicit cytotoxic T-lymphocyte (CTL) responses have entered the pipeline of clinical trials. Evaluating the immunogenicity and potential efficacy of these HIV-1 vaccine candidates is challenging in the face of the extensive viral genetic diversity of circulating strains. Standardized peptide reagents to define the magnitude and potential breadth of the T-cell response, especially to circulating strains of HIV-1, are needed. For this purpose we developed a biometric approach based on T-cell recognition pattern for defining standardized reagents. Circulating strains in the Los Alamos database were evaluated and standardized algorithms to define all potential T-cell epitopes (PTEs) were generated. While many unique PTEs could be identified, a finite number based upon prevalence of circulating strains in the database, which we define as vaccine-important PTEs (VIPs), were used to select a common standardized panel of HIV-1 peptides for CTL-based vaccine evaluation. The usability of PTE peptide set was manifested by detection of Nef-specific CTL responses in HIV-1 subtype B infections.

AIDS Vaccines↗

PubMed2006

Abacavir hypersensitivity reaction in primary HIV infection.

OBJECTIVE: To evaluate risk factors associated with the abacavir hypersensitivity reaction during primary HIV infection (PHI). DESIGN: Acute HIV Infection and Early Disease Research Program protocol (AIEDRP) AI-02-001 provided antiretroviral therapy including abacavir. This retrospective analysis evaluated variables potentially associated with hypersensitivity in the cohort enrolled in AI-02-001 at the University of Washington Primary Infection Clinic. METHODS: Cases of suspected hypersensitivity were identified prospectively and reviewed retrospectively using a standardized case definition. Controls were the remaining cohort without hypersensitivity. Univariate analyses were performed by linear logistic regression. RESULTS: Nine (18%) of 50 individuals treated with abacavir developed suspected hypersensitivity. Two of nine cases and no controls were HLA-B5701 positive. When antiretroviral medications were started, cases had lower mean CD8 T-cell percentage and plasma HIV RNA value. After 2 weeks on abacavir, cases had a lower mean HIV RNA value and a trend towards greater decrease in RNA. Cases began abacavir a median of 103 days after HIV acquisition compared to 48 days for controls. There was no significant in vitro abacavir-specific lymphoproliferation or IFN-gamma production in peripheral blood mononuclear cells from individuals following the suspected hypersensitivity reaction. CONCLUSIONS: Abacavir use during PHI may be associated with increased risk of hypersensitivity. As in chronic infection, HLA-B5701 is associated with the abacavir hypersensitivity reaction in PHI. Although levels of CD8 T cells and HIV RNA may be risk factors for hypersensitivity, the observed association may be due to correlation with HLA-B5701. The interesting temporal association of hypersensitivity with initiation of abacavir later in PHI merits future investigation.

Adult↗

PubMed2006

Airflow decline after myeloablative allogeneic hematopoietic cell transplantation: the role of community respiratory viruses.

We conducted a 12-year retrospective study to determine the effects that the community respiratory-virus species and the localization of respiratory-tract virus infection have on severe airflow decline, a serious and fatal complication occurring after hematopoietic cell transplantation (HCT). Of 132 HCT recipients with respiratory-tract virus infection during the initial 100 days after HCT, 50 (38%) developed airflow decline < or =1 year after HCT. Lower-respiratory-tract infection with parainfluenza (odds ratio [OR], 17.9 [95% confidence interval {CI}, 2.0-160]; P=.01) and respiratory syncytial virus (OR, 3.6 [95% CI, 1.0-13]; P=.05) independently increased the risk of development of airflow decline < or =1 year after HCT. The airflow decline was immediately detectable after infection and was strongest for lower-respiratory-tract infection with parainfluenza virus; it stabilized during the months after the respiratory-tract virus infection, but, at < or =1 year after HCT, the initial lung function was not restored. Thus, community respiratory virus-associated airflow decline seems to be specific to viral species and infection localization.

Adult↗

PubMed2006

Lower genitourinary tract sources of seminal HIV.

OBJECTIVE: To investigate genital tract sources of HIV-1, we conducted extensive genitourinary sampling of 23 seropositive men without urethritis who shed HIV in their seminal plasma. DESIGN: Semen was collected, then samples were obtained for HIV RNA in blood plasma, urethral fluid, pre-prostate massage fluid/urine (PMF/U) and post-PMF/U, and expressed prostatic secretions. Systematic transrectal ultrasound-guided prostate biopsies obtained from multiple prostate areas were evaluated for HIV RNA and DNA. RESULTS: Seminal HIV RNA levels correlated with HIV RNA levels in urethral fluid and post-PMF/U and with prostate biopsies HIV DNA, but not with expressed prostatic secretions HIV RNA. However, only the HIV RNA level in post-PMF/U independently predicted that in semen (2.77-fold change in semen for each 10-fold change in post-PMF/U; 95% confidence interval, 1.0-7.7) accounting for one third of the seminal HIV RNA level variation, irrespective of adjustment for antiretroviral therapy. CONCLUSIONS: These data indicate that distal genitourinary sources other than the prostate appear to be the major source of seminal HIV in men without clinical urethritis or prostatitis. Because the HIV RNA level in blood plasma is not reliable as an independent clinical predictor of virus levels in seminal plasma, these findings also extend the concept that the male genital tract is a distinct virological compartment from blood.

Adult↗

PubMed2006

Immunostimulation by induced expression of NKG2D and its MIC ligands in HTLV-1-associated neurologic disease.

The NKG2D receptor costimulates effector/memory CD8 T cells and is normally absent on CD4 T cells but can be induced by T cell antigen receptor complex stimulation and interleukin-15 (IL-15). Among its ligands are the human major histocompatibility complex class I-related MICA and MICB, which have a restricted tissue distribution but are frequently associated with malignancies and some microbial infections. Moreover, aberrant expression of MIC may promote autoimmune disease progression. Human T cell lymphotropic virus type I (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic inflammatory disease of the central nervous system that resembles multiple sclerosis. Disease progression involves production of IL-15 and its receptor through transactivation by the viral Tax regulator protein, an activated immune response state, and local cytokine production and T cell fratricide by Tax-specific cytotoxic T lymphocytes (CTL). This study shows that as with CD8 T cells, substantial proportions of HAM/TSP patient CD4 T cells are positive for NKG2D and that large numbers of T cells from both subsets express MIC, which can be transactivated by Tax independent of nuclear factor kappaB. Engagement of MIC by NKG2D promotes spontaneous HAM/TSP T cell proliferation and, apparently, CTL activities against HTLV-1-infected T cells. These results reveal a viral strategy that may exploit immune stimulatory mechanisms to negotiate a balance between promotion and limitation of infected host T cell expansions.

CD4-Positive T-Lymphocytes↗

PubMed2006

Brief communication: fatal human metapneumovirus infection in stem-cell transplant recipients.

BACKGROUND: Human metapneumovirus (hMPV), a recently discovered respiratory virus, is associated with clinical disease in young and elderly persons. OBJECTIVE: To determine the importance of hMPV in hematopoietic stem-cell transplant recipients. DESIGN: Retrospective survey of patients with consecutive residual bronchoalveolar lavage (BAL) samples. SETTING: Referral cancer center. PATIENTS: Hematopoietic stem-cell transplant recipients who underwent BAL because of lower respiratory tract disease. MEASUREMENTS: Bronchoalveolar lavage specimens were assayed by quantitative real-time polymerase chain reaction methods. RESULTS: Human metapneumovirus was detected in BAL specimens from 5 of 163 patients (3.0%). Persistent viral infection was noted in 3 patients with several samples, and hMPV was detected in 1 of 2 lung specimens tested. Infected patients became symptomatic within the first 40 days after transplantation. Initial symptoms included fever, cough, nasal congestion, and sore throat. Clinical findings included respiratory failure, pulmonary hemorrhage, and culture-negative septic shock. Four of 5 patients died with acute respiratory failure. LIMITATIONS: This retrospective study did not evaluate asymptomatic patients or those with mild disease. CONCLUSION: Human metapneumovirus infection in the lower respiratory tract is associated with respiratory failure in immunocompromised adults who were previously considered to have "idiopathic pneumonia." The infection may result in fulminant respiratory decompensation and shock after transplantation.

Adrenal Cortex Hormones↗

PubMed2006

High serum hepatitis C virus (HCV) RNA load predicts the presence of HCV RNA in saliva from individuals with chronic and acute HCV infection.

The detection of hepatitis C virus (HCV) in saliva was studied. Twenty-three subjects with chronic HCV infection and 1 subject with acute HCV infection were enrolled in a 21-day study. Roche COBAS Amplicor and Bayer VERSANT HCV RNA qualitative assays were used. For the 23 subjects with chronic HCV infection, 72% of 474 saliva samples were positive (or were imputed to be positive) for HCV RNA. Serum HCV RNA load predicted the detection of HCV RNA in saliva (odds ratio of 378.7 [95% confidence interval, 18.9-9996.6] for each additional log10 value). This association was also observed in 1 subject with acute HCV infection. Thus, our data demonstrate that salivary HCV RNA detection was associated with serum HCV RNA load in individuals who were chronically or acutely infected with HCV.

Acute Disease↗

PubMed2006

Repeat-region polymorphisms in the gene for the dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin-related molecule: effects on HIV-1 susceptibility.

In 1716 individuals--801 human immunodeficiency virus (HIV)-1-seropositive individuals, 217 high-risk HIV-1-seronegative individuals, and 698 general HIV-1-seronegative individuals--from a Seattle cohort and a Multicenter AIDS Cohort Study cohort, the association between HIV-1 susceptibility and repeat-region polymorphisms in the gene for the dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin-related molecule (DC-SIGNR) was investigated; 16 genotypes were found in the DC-SIGNR repeat region. The DC-SIGNR homozygous 7/7 repeat was found to be associated with an increased risk of HIV-1 infection (17.5% in high-risk HIV-1-seronegative individuals vs. 28.5% in HIV-1-seropositive individuals; P=.0015), whereas the DC-SIGNR heterozygous 7/5 repeat tended to be correlated with resistance to HIV-1 infection (35.5% in high-risk HIV-1-seronegative individuals vs. 27.6% in HIV-1-seropositive individuals; P=.0291). These findings suggest that DC-SIGNR polymorphisms may influence susceptibility to HIV-1.

Cell Adhesion Molecules↗

PubMed2006

CD4+ T cell receptor repertoire perturbations in HIV-1 infection: association with plasma viremia and disease progression.

CD4+ T cell depletion and dysfunction are the hallmark of HIV-1 disease. Our primary objectives were to define the diversity of the CD4+ T cell receptor Vbeta (TCRBV) repertoire in subjects with HIV-1 infection by CDR3 (complementarity-determining region) length spectratyping and to determine the correlates of CD4+ repertoire perturbation and its restoration with virus suppression. During primary HIV-1 infection, the proportion of perturbed CD4+ TCRBV subfamilies was significantly greater compared to HIV-1 seronegative subjects (median 48% vs. 10%, P = 0.0159). During chronic infection, the extent of repertoire perturbation was significantly associated with higher levels of plasma viremia (Spearman Correlation coefficient, R = 0.65, P = 0.049) and disease progression. Restoration of the repertoire with antiretroviral therapy was variable despite adequate virologic suppression. We speculate that the use of immunomodulators as an adjunct to antiretroviral drugs may enhance immune reconstitution in persons with suboptimal increases in CD4+ T cell counts despite adequate virus suppression.

Anti-Retroviral Agents↗

PubMed2006

Human herpesvirus 8 infection among adolescents in the REACH cohort.

OBJECTIVE: Human herpesvirus 8 (HHV-8) infection is common among children in areas where Kaposi sarcoma is endemic. Human herpesvirus 8 is uncommon in children but prevalent in adults at risk for human immunodeficiency virus (HIV) infection in the United States, including men who have sex with men (MSM) and women who engage in high-risk sexual behavior. We examined the prevalence and predictors of HHV-8 infection among adolescents with or at high risk for acquiring HIV infection. DESIGN: Cross-sectional analysis. SETTING: National study of HIV infection among adolescents in primary care. PARTICIPANTS: A total of 537 young adults practicing high-risk sexual behavior, of which 403 were women and 134 were men; among the 134 men, 75% were MSM. INTERVENTIONS: Detailed questionnaires and testing for serum antibodies to HHV-8. OUTCOME MEASURE: Detection of serum antibodies to HHV-8. RESULTS: Sixty (11.2%) of 537 young adults were HHV-8 seropositive, including 20 MSM (19.6%), 2 male heterosexuals (6.5%), and 27 female heterosexuals (8.2%). The prevalence of HHV-8 in HIV-positive MSM (17/74 [23.0%]) was twice as high as that in HIV-negative MSM (3/28 [10.7%]) (P = .18), but no characteristic predicted HHV-8 infection among MSM. In multivariate analysis, history of gonorrhea (odds ratio [OR], 2.8; 95% confidence interval [CI], 1.4-5.7; P<.01), history of having sex with women (OR, 2.4; 95% CI, 1.1-5.3; P = .03), and African American race (OR, 3.4; 95% CI, 1.1-10.0; P = .03) were associated with HHV-8 infection among women. CONCLUSIONS: Human herpesvirus 8 is common among US adolescents practicing high-risk sexual behaviors. Sexual identity, race, and sexual behavior may influence the risk of infection with HHV-8 in women.

Adolescent↗

PubMed2006

Maternal herpes simplex virus antibody avidity and risk of neonatal herpes.

OBJECTIVE: The objective of the study was to assess whether herpes simplex virus antibody avidity is associated with risk of transmission of herpes simplex virus to the neonate. STUDY DESIGN: We developed a novel herpes simplex virus type 1 avidity test based on the commercially available Focus HerpeSelect-1 enzyme-linked immunosorbent assay kit using sera from nonpregnant subjects with genital herpes simplex virus-1 infection. We used this test, and the previously developed herpes simplex virus type 2 avidity test, to compare maternal herpes simplex virus-1 and herpes simplex virus-2 antibody avidity in women who transmitted herpes simplex virus to the neonate and women who had herpes simplex virus isolated from genital secretions at delivery but who did not transmit herpes simplex virus to their infants. RESULTS: Among nonpregnant subjects with genital herpes simplex virus-1 infection whose sera were used to develop the herpes simplex virus-1 avidity test, a significant relationship between herpes simplex virus-1 antibody avidity and time since herpes simplex virus-1 acquisition was observed (P < .001, mixed-effects model), with median avidity values increasing over time after primary infection. Among pregnant, herpes simplex virus-1, or herpes simplex virus-2 seropositive women, 4 of 8 women (50%) with avidity 40 or greater transmitted herpes simplex virus to the neonate, compared with only 12 of 97 (12%) of women with avidity greater than 40 (P = .02). CONCLUSIONS: Herpes simplex virus-1 antibody avidity increased over time after genital herpes simplex virus-1 acquisition, as has been previously observed for herpes simplex virus-2. Among women with herpes simplex virus antibody at delivery, low antibody avidity was associated with herpes simplex virus transmission to the neonate and may be a useful marker for recent seroconversion.

Adult↗

PubMed2006

Polymerase chain reaction diagnosis of primary human herpesvirus-6 infection in the acute care setting.

OBJECTIVE: To evaluate the potential utility of identifying primary human herpesvirus (HHV)-6 infection in an emergency department setting by determining the frequency of HHV-6 viremia, diagnostic testing, and empiric treatment of serious bacterial infection (SBI) in HHV-6 viremic children, and concurrent SBI and HHV-6 viremia. STUDY DESIGN: Children under age 2 years and who had a blood specimen taken for evaluation of fever were tested for HHV-6 by polymerase chain reaction (PCR). HHV-6 viremia was defined as detection of HHV-6 DNA in acute plasma. RESULTS: A total of 32 of the 181 subjects (18%) had HHV-6 viremia. Children with HHV-6 viremia frequently underwent procedures for diagnosis and empiric treatment of SBI: 60% had bladder catheterizations, 6% had lumbar punctures, 47% had radiographs, 32% received empiric antibiotics, and 34% were hospitalized. Four of the 32 children with HHV-6 viremia (12.5%) were diagnosed with SBI, although none had a positive culture of blood or cerebrospinal fluid. CONCLUSIONS: Rapid diagnosis of HHV-6 viremia may not serve to adequately differentiate infants with and without SBI in acute care settings. Although no children with HHV-6 viremia had bacteremia or meningitis, it appears that additional criteria are needed to increase the specificity of HHV-6 PCR testing before withholding evaluation for SBI.

Bacterial Infections↗

PubMed2006

Isolation of herpes simplex virus from the genital tract during symptomatic recurrence on the buttocks.

OBJECTIVE: To estimate the frequency of isolation of herpes simplex virus (HSV) from the genital tract when recurrent herpes lesions were present on the buttocks. METHODS: Data were extracted from a prospectively observed cohort attending a research clinic for genital herpes infections between 1975 and 2001. All patients with a documented herpes lesion on the buttocks, upper thigh or gluteal cleft ("buttock recurrence") and concomitant viral cultures from genital sites including the perianal region were eligible. RESULTS: We reviewed records of 237 subjects, 151 women and 86 men, with a total of 572 buttock recurrences. Of the 1,592 days with genital culture information during a buttock recurrence, participants had concurrent genital lesions on 311 (20%, 95% confidence interval [CI] 14-27%) of these days. Overall, HSV was isolated from the genital region on 12% (95% CI 8-17%) of days during a buttock recurrence. In the absence of genital lesions, HSV was isolated from the genital area on 7% (95% CI 4%-11%) of days during a buttock recurrence and, among women, from the vulvar or cervical sites on 1% of days. CONCLUSION: Viral shedding of herpes simplex virus from the genital area is a relatively common occurrence during a buttock recurrence of genital herpes, even without concurrent genital lesions, reflecting perhaps reactivation from concomitant regions of the sacral neural ganglia. Patients with buttock herpes recurrences should be instructed about the risk of genital shedding during such recurrences. LEVEL OF EVIDENCE: II-2.

Adolescent↗

PubMed2006

Comparative efficacy of famciclovir and valacyclovir for suppression of recurrent genital herpes and viral shedding.

BACKGROUND: 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. OBJECTIVES: To compare the clinical and virologic effects of famciclovir and valacyclovir administered as daily suppressive therapy for persons with genital herpes. STUDY DESIGN: 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. RESULTS: 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). CONCLUSION: 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.

2-Aminopurine↗