valacyclovir and HIV-Infections

valacyclovir has been researched along with HIV-Infections* in 57 studies

Reviews

7 review(s) available for valacyclovir and HIV-Infections

ArticleYear
Inflammatory pseudotumor associated with HSV infection of rectal vascular endothelium in a patient with HIV: a case report and literature review.
    BMC infectious diseases, 2020, Mar-19, Volume: 20, Issue:1

    Herpes simplex virus (HSV) typically infects oral or anogenital squamous epithelium and causes blisters and ulcerations. Here we reported an unusual case of HSV induced exuberant rectal inflammatory pseudotumor with vascular endothelial involvement.. A 52-year old man with HIV presented with abdominal pain, rectal drainage and constipation. Proctoscopy and CT scans revealed an 8 × 5 × 4 cm circumferential, mid-lower rectal mass that was concerning for malignancy. PET-CT showed mild to moderate FDG uptake of the rectal mass. Repeated biopsies showed exuberant lymphoplasmacytic inflammation with rich eosinophils and necrosis in the submucosa and scattered single or multi-nucleated viral inclusions in vascular endothelial cells that were positive for HSV by immunostains. There was no evidence of malignancy on histology or by immunostains. The patient started valacyclovir for three weeks and symptoms resolved after the antiviral therapy. Follow-up CT and sigmoidoscopy with biopsy revealed no rectal mass or drainable collection.. HSV may present as proctitis with exuberant inflammatory response and mass-like lesion, and damages vascular endothelial cells in patients with HIV. The HSV-associated mass-like lesion can be effectively treated by 3-week valacyclovir.

    Topics: Antiviral Agents; Endothelial Cells; Endothelium, Vascular; Follow-Up Studies; Granuloma, Plasma Cell; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; HIV Infections; Humans; Male; Middle Aged; Positron Emission Tomography Computed Tomography; Proctitis; Rectum; Treatment Outcome; Valacyclovir

2020
Fifty Years in Search of Selective Antiviral Drugs.
    Journal of medicinal chemistry, 2019, 08-22, Volume: 62, Issue:16

    Fifty years of research (1968-2018) toward the identification of selective antiviral drugs have been primarily focused on antiviral compounds active against DNA viruses (HSV, VZV, CMV, HBV) and retroviruses (HIV). For the treatment of HSV infections the aminoacyl esters of acyclovir were designed, and valacyclovir became the successor of acyclovir in the treatment of HSV and VZV infections. BVDU (brivudin) still stands out as the most potent among the marketed compounds for the treatment of VZV infections (i.e., herpes zoster). In the treatment of HIV infections 10 tenofovir-based drug combinations have been marketed, and tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF) have also proved effective in the treatment of HBV infections. As a spin-off of our anti-HIV research, a CXCR4 antagonist AMD-3100 was found to be therapeutically useful as a stem cell mobilizer, and has since 10 years been approved for the treatment of some hematological malignancies.

    Topics: Acyclovir; Antiviral Agents; DNA Virus Infections; DNA Viruses; HIV; HIV Infections; Humans; Molecular Structure; Tenofovir; Valacyclovir

2019
Antiviral drugs for viruses other than human immunodeficiency virus.
    Mayo Clinic proceedings, 2011, Volume: 86, Issue:10

    Most viral diseases, with the exception of those caused by human immunodeficiency virus, are self-limited illnesses that do not require specific antiviral therapy. The currently available antiviral drugs target 3 main groups of viruses: herpes, hepatitis, and influenza viruses. With the exception of the antisense molecule fomivirsen, all antiherpes drugs inhibit viral replication by serving as competitive substrates for viral DNA polymerase. Drugs for the treatment of influenza inhibit the ion channel M(2) protein or the enzyme neuraminidase. Combination therapy with Interferon-α and ribavirin remains the backbone treatment for chronic hepatitis C; the addition of serine protease inhibitors improves the treatment outcome of patients infected with hepatitis C virus genotype 1. Chronic hepatitis B can be treated with interferon or a combination of nucleos(t)ide analogues. Notably, almost all the nucleos(t) ide analogues for the treatment of chronic hepatitis B possess anti-human immunodeficiency virus properties, and they inhibit replication of hepatitis B virus by serving as competitive substrates for its DNA polymerase. Some antiviral drugs possess multiple potential clinical applications, such as ribavirin for the treatment of chronic hepatitis C and respiratory syncytial virus and cidofovir for the treatment of cytomegalovirus and other DNA viruses. Drug resistance is an emerging threat to the clinical utility of antiviral drugs. The major mechanisms for drug resistance are mutations in the viral DNA polymerase gene or in genes that encode for the viral kinases required for the activation of certain drugs such as acyclovir and ganciclovir. Widespread antiviral resistance has limited the clinical utility of M(2) inhibitors for the prevention and treatment of influenza infections. This article provides an overview of clinically available antiviral drugs for the primary care physician, with a special focus on pharmacology, clinical uses, and adverse effects.

    Topics: Acyclovir; Adenine; Amantadine; Antiviral Agents; Comorbidity; Drug Therapy, Combination; Foscarnet; Ganciclovir; Guanine; Hepatitis; Hepatitis B, Chronic; Hepatitis C; Herpesviridae Infections; HIV Infections; Humans; Influenza, Human; Interferons; Lamivudine; Nucleosides; Oligopeptides; Organophosphonates; Oseltamivir; Proline; Protease Inhibitors; Pyrimidinones; Ribavirin; Telbivudine; Thymidine; Valacyclovir; Valganciclovir; Valine; Virus Replication; Zanamivir

2011
Recent developments in the management of herpes simplex virus infection in HIV-infected persons.
    Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2004, Nov-01, Volume: 39 Suppl 5

    Topics: Acyclovir; Antiviral Agents; Herpes Genitalis; Herpesvirus 2, Human; HIV; HIV Infections; Humans; Secondary Prevention; Valacyclovir; Valine

2004
Challenges in genital herpes simplex virus management.
    The Journal of infectious diseases, 2002, Oct-15, Volume: 186 Suppl 1

    Development of serologic assays to detect antibodies to herpes simplex virus (HSV) glycoproteins (g)G1 and (g)G2 has allowed accurate definition of the seroprevalence of HSV-2 worldwide. Studies from all continents indicate epidemic proportions of HSV-2 infection. In the United States, 1 in 5 sexually active adults is infected. In Africa and the Caribbean, HSV prevalence is higher. Since the development of the acyclic nucleoside derivatives acyclovir, famciclovir, and valacyclovir, treatment of mucocutaneous HSV is a practice of everyday medical care. Yet, despite effective drugs, there is widespread discontent by clients and providers about care of patients with genital herpes. Much of this relates to transmission complexities and the varied natural history of the infection. However, over time, most patients adjust to their disease and the medical and psychosocial complications. Recent studies show condoms reduce transmission, providing an important tool for counseling the patient with newly diagnosed genital herpes.

    Topics: 2-Aminopurine; Acyclovir; Antibodies, Viral; Antiviral Agents; Condoms; Counseling; Famciclovir; Female; Global Health; Herpes Genitalis; Herpesvirus 2, Human; HIV Infections; Humans; Male; Patient Education as Topic; Prevalence; Seroepidemiologic Studies; Valacyclovir; Valine; Virus Activation

2002
Valacyclovir for herpes simplex virus infection: long-term safety and sustained efficacy after 20 years' experience with acyclovir.
    The Journal of infectious diseases, 2002, Oct-15, Volume: 186 Suppl 1

    An extensive clinical trial program combined with 5 years' postmarketing experience with valacyclovir provides evidence of favorable safety and efficacy in herpes simplex virus (HSV) management. Valacyclovir enhances acyclovir bioavailability compared with orally administered acyclovir. Long-term use of acyclovir for up to 10 years for HSV suppression is effective and well tolerated. Acyclovir is also approved for use in children, is available in some countries over the counter in cream formulation for herpes labialis, and has been monitored in over 1000 pregnancies. Safety monitoring data from clinical trials of valacyclovir, involving over 3000 immunocompetent and immunocompromised persons receiving long-term therapy for HSV suppression, were analyzed. Safety profiles of valacyclovir (

    Topics: Acyclovir; Administration, Oral; Administration, Topical; Adult; Antiviral Agents; Child; Clinical Trials as Topic; Drug Resistance, Viral; Female; Herpes Genitalis; Herpes Labialis; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; HIV Infections; Humans; Immunocompetence; Immunocompromised Host; Pregnancy; Pregnancy Complications, Infectious; Prodrugs; Valacyclovir; Valine

2002
Progress in meeting today's demands in genital herpes: an overview of current management.
    The Journal of infectious diseases, 2002, Oct-15, Volume: 186 Suppl 1

    Treatment of genital herpes requires accurate diagnosis, patient support, and effective treatment. Diagnosis is usually straightforward for classic presentations characterized by vesicular lesions but can be challenging for atypical presentations, which are more common. Diagnosis of asymptomatic infection requires access to molecular technology or type-specific serologic assays. Misconceptions about herpes simplex infection are common and patient education is essential. Patient concerns extend beyond disease frequency and severity-the psychological impact should not be underestimated. Antiviral therapy is relevant at all stages of infection. Acyclovir, valacyclovir, and famciclovir are effective and well tolerated for genital herpes treatment. Continuous suppressive therapy controls all symptoms of recurrent disease and helps to relieve disease complications. The prodrugs valacyclovir and famciclovir offer easier, less-frequent dosing than required for acyclovir. Valacyclovir achieves effective suppression when taken once a day. Interventions to prevent genital herpes transmission and to control the global problem are urgently required.

    Topics: 2-Aminopurine; Acute Disease; Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antibodies, Viral; Antiviral Agents; Chronic Disease; Clinical Trials as Topic; Dose-Response Relationship, Drug; Famciclovir; Herpes Genitalis; Herpesvirus 1, Human; Herpesvirus 2, Human; HIV Infections; Humans; Immunocompetence; Patient Education as Topic; Prodrugs; Secondary Prevention; Treatment Outcome; Valacyclovir; Valine

2002

Trials

27 trial(s) available for valacyclovir and HIV-Infections

ArticleYear
Effect of valaciclovir on CD4 count decline in untreated HIV: an international randomized controlled trial.
    The Journal of antimicrobial chemotherapy, 2019, 02-01, Volume: 74, Issue:2

    To determine the impact of valaciclovir on HIV disease progression in treatment-naive HIV-positive adults.. In this fully blind, multicentre, 1:1 randomized placebo-controlled trial, treatment-naive HIV-1-positive adults with CD4 counts 400-900 cells/mm3 and not meeting contemporaneous recommendations for combination ART (cART) were randomized to valaciclovir 500 mg or placebo twice daily, and followed quarterly until having two consecutive CD4 counts ≤350 cells/mm3 or initiating cART for any reason. The primary analysis compared the rate of CD4 count decline by study arm after adjusting for baseline CD4 count and viral load (VL). Secondary analyses compared the rate of CD4 percentage decline, HIV VL, herpes simplex virus (HSV) recurrences and drug-related adverse events. The trial closed after release of the START trial results in August 2015.. We enrolled 198 participants in Canada, Brazil, Argentina and the UK. Median (IQR) age was 35 (30-43) years. Baseline CD4 count was 592 (491-694) cells/mm3 and VL was 4.04 (3.5-4.5) log10 copies/mL. Over 276 person-years of follow-up, CD4 counts declined by 49 cells/mm3/year in the valaciclovir arm versus 58 cells/mm3/year in the placebo arm (P = 0.65). No differences were seen in the rate of change in CD4 percentage (-1.2%/year versus -1.7%/year, P = 0.34). VL was 0.27 log10 copies/mL lower in valaciclovir participants overall (P<0.001). Placebo participants had more HSV recurrences (62 versus 21/100 person-years, P < 0.0001) but similar rates of grade ≥2 drug-related adverse events.. Unlike prior trials using aciclovir, we found that valaciclovir did not slow CD4 count decline in cART-untreated adults, although power was limited due to premature study discontinuation. Valaciclovir modestly lowered HIV VL.

    Topics: Adult; Anti-HIV Agents; Argentina; Brazil; Canada; CD4 Lymphocyte Count; Disease Progression; Female; HIV Infections; HIV Seropositivity; Humans; Internationality; Male; Middle Aged; Treatment Outcome; United Kingdom; Valacyclovir; Viral Load

2019
Herpes Simplex Virus Suppressive Therapy in Herpes Simplex Virus-2/Human Immunodeficiency Virus-1 Coinfected Women Is Associated With Reduced Systemic CXCL10 But Not Genital Cytokines.
    Sexually transmitted diseases, 2016, Volume: 43, Issue:12

    Herpes simplex virus type-2 (HSV-2) may heighten immune activation and increase human immunodeficiency virus 1 (HIV-1) replication, resulting in greater infectivity and faster HIV-1 disease progression. An 18-week randomized, placebo-controlled crossover trial of 500 mg valacyclovir twice daily in 20 antiretroviral-naive women coinfected with HSV-2 and HIV-1 was conducted and HSV-2 suppression was found to significantly reduce both HSV-2 and HIV-1 viral loads both systemically and the endocervical compartment.. To determine the effect of HSV-2 suppression on systemic and genital mucosal inflammation, plasma specimens, and endocervical swabs were collected weekly from volunteers in the trial and cryopreserved. Plasma was assessed for concentrations of 31 cytokines and chemokines; endocervical fluid was eluted from swabs and assayed for 14 cytokines and chemokines.. Valacyclovir significantly reduced plasma CXCL10 but did not significantly alter other cytokine concentrations in either compartment.. These data suggest genital tract inflammation in women persists despite HSV-2 suppression, supporting the lack of effect on transmission seen in large scale efficacy trials. Alternative therapies are needed to reduce persistent mucosal inflammation that may enhance transmission of HSV-2 and HIV-1.

    Topics: Acyclovir; Adult; Antiviral Agents; Chemokine CXCL10; Coinfection; Cross-Over Studies; Cytokines; Female; Herpes Genitalis; Herpesvirus 2, Human; HIV Infections; HIV-1; Humans; Middle Aged; Reproductive Tract Infections; Valacyclovir; Valine; Viral Load; Young Adult

2016
The effect of valacyclovir on HIV and HSV-2 in HIV-infected persons on antiretroviral therapy with previously unrecognised HSV-2.
    International journal of STD & AIDS, 2015, Volume: 26, Issue:8

    In the absence of antiretroviral therapy, valacyclovir may reduce HIV viral load and increase CD4+ T-lymphocyte count. We sought to evaluate the impact of valacyclovir on HIV and HSV-2 in co-infected patients receiving antiretroviral therapy with previously unrecognised HSV-2 infection. A prospective, randomised-controlled, 24-week trial of valacyclovir 1000 mg was performed. Mean CD4+ T-lymphocyte count at 24 weeks compared to baseline CD4+ T-lymphocyte count was the primary outcome. HIV viral load suppression, HSV-2 outbreaks and asymptomatic HSV-2 shedding were secondary outcomes. Participants were randomised to valacyclovir (N = 66) or placebo (N = 35). Study completion was 64%. There was no change in 24 weeks compared to baseline CD4+ T-lymphocyte count in either group (valacyclovir p = 0.91, placebo p = 0.59) or the proportion with HIV viral load suppression (valacyclovir p = 0.75, placebo p = 1.0). Genital HSV and asymptomatic HSV-2 shedding were rare. Valacyclovir had no effect on CD4+ T-lymphocyte count or HIV viral load in this population. Valacyclovir may reduce clinical outbreaks and asymptomatic HSV-2 shedding, but the rarity of these events, along with its lack of benefit on HIV, does not support its use in this clinical setting.

    Topics: Acyclovir; Adult; Antiviral Agents; CD4 Lymphocyte Count; Coinfection; DNA, Viral; Double-Blind Method; Enzyme-Linked Immunosorbent Assay; Female; Herpes Genitalis; Herpesvirus 2, Human; HIV Infections; HIV-1; Humans; Male; Middle Aged; Pilot Projects; Prospective Studies; RNA, Viral; Treatment Outcome; Valacyclovir; Valine; Viral Load

2015
Valacyclovir Decreases Plasma HIV-1 RNA in HSV-2 Seronegative Individuals: A Randomized Placebo-Controlled Crossover Trial.
    Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2015, Jun-01, Volume: 60, Issue:11

    Acyclovir (ACV), a highly specific anti-herpetic drug, acts as a DNA chain terminator for several human herpesviruses (HHVs), including HHV-2 (HSV-2), a common human immunodeficiency virus (HIV)-1 co-pathogen. Several trials demonstrated that HSV-2 suppressive therapy using ACV or its prodrug valacyclovir (valACV) reduced plasma HIV-1 viral load (VL) in HIV-1/HSV-2 coinfected persons, and this was proposed to be due to a decrease in generalized immune activation. Recently, however, we found that ACV directly suppresses HIV-1 ex vivo in tissues free of HSV-2 but endogenously coinfected with other HHVs. Here, we asked whether valACV suppresses VL in HIV-1 infected HSV-2-seronegative persons.. Eighteen HIV-1 infected HSV-2-seronegative individuals were randomly assigned in a double blind placebo-controlled, crossover trial. Eligible participants had CD4 cell counts of ≥500 cells/µL and were not taking antiretroviral therapy. Subjects in group A received 12 weeks of valACV 500 mg given twice daily by mouth followed by 2 weeks of a no treatment washout and then 12 weeks of placebo; subjects in group B received 12 weeks of placebo followed by 2 weeks of no treatment washout and then 12 weeks of valACV 500 mg twice daily.. HIV-1 VL in plasma of patients treated with valACV 500 mg twice daily for 12 weeks was reduced on average by 0.37 log10 copies/mL.. These data indicate that the effects of valACV on HIV-1 replication are not related to the suppression of HSV-2-mediated inflammation and are consistent with a direct effect of ACV on HIV-1 replication.

    Topics: Acyclovir; Adult; Anti-HIV Agents; Cross-Over Studies; Female; HIV Infections; HIV-1; Humans; Male; Placebos; Plasma; RNA, Viral; Valacyclovir; Valine; Viral Load; Virus Replication; Young Adult

2015
High-dose valacyclovir decreases plasma HIV-1 RNA more than standard-dose acyclovir in persons coinfected with HIV-1 and HSV-2: a randomized crossover trial.
    Journal of acquired immune deficiency syndromes (1999), 2013, Jun-01, Volume: 63, Issue:2

    Standard doses of herpes simplex virus (HSV) suppressive therapy reduce plasma HIV-1 RNA levels (0.25-0.53 log10 copies per milliliter) among HIV-1/HSV-2 coinfected persons. Postulated mechanisms for this effect include direct inhibition of HIV-1 by acyclovir or indirect reduction by decreasing HSV-associated inflammation. We hypothesized that high-dose valacyclovir would further reduce plasma HIV-1 RNA and that the effect would be mediated by greater suppression of HSV shedding.. Thirty-four participants with HIV-1 and HSV-2 not on antiretroviral therapy were enrolled into a randomized, open-label crossover trial of valacyclovir 1000 mg twice daily or acyclovir 400 mg twice daily for 12 weeks, followed by a 2-week washout, and then the alternate treatment arm for 12 weeks. HSV DNA was measured from daily self-collected genital swabs for the initial 4 weeks of each arm, and HIV-1 RNA was quantified from weekly plasma samples.. Twenty-eight participants provided plasma samples and genital swabs on both acyclovir and valacyclovir. The genital HSV-2 shedding rate was the same on valacyclovir and acyclovir [7.8% vs. 8.2% of days; relative risk: 0.95; 95% confidence interval (CI): 0.66 to 1.37; P = 0.78]. Plasma HIV-1 RNA was 0.27 log10 copies per milliliter lower on valacyclovir compared with acyclovir (95% CI: -0.41 to -0.14 log10 copies per milliliter; P < 0.001); this was unchanged after adjustment for genital HSV-2 shedding.. High-dose valacyclovir reduces plasma HIV-1 RNA levels more than standard-dose acyclovir in HIV-1/HSV-2-seropositive persons not receiving antiretroviral therapy. The incremental reduction in plasma HIV-1 RNA achieved is not mediated by greater genital HSV-2 suppression.

    Topics: Acyclovir; Adult; Antiviral Agents; Coinfection; Cross-Over Studies; Cytomegalovirus; DNA, Viral; Female; Herpes Genitalis; Herpesvirus 2, Human; HIV Infections; HIV-1; Humans; Male; Middle Aged; Patient Compliance; RNA, Viral; Valacyclovir; Valine; Viral Load; Virus Shedding

2013
A randomized controlled pilot trial of valacyclovir for attenuating inflammation and immune activation in HIV/herpes simplex virus 2-coinfected adults on suppressive antiretroviral therapy.
    Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2013, Volume: 57, Issue:9

    Human immunodeficiency virus (HIV) is associated with increased systemic inflammation and immune activation that persist despite suppressive antiretroviral therapy (ART). Herpes simplex virus type 2 (HSV-2) is a common coinfection that may contribute to this inflammation.. Sixty HIV type 1 (HIV-1)/HSV-2-coinfected adults on suppressive ART were randomized 1:1:1 to 12 weeks of placebo, low-dose valacyclovir (500 mg twice daily), or high-dose valacyclovir (1 g twice daily) in this 18-week trial. Co-primary outcome measures were the percentage of activated (CD38(+)HLA-DR(+)) CD8 T cells in blood, and highly sensitive C-reactive protein, interleukin 6, and soluble intercellular adhesion molecule 1 in plasma. Secondary outcomes included additional immune, inflammatory cytokine, and endothelial activation markers. The impact of valacyclovir (both groups combined) on each outcome was estimated using treatment × time interaction terms in generalized estimating equation regression models.. Participants were mostly white (75%) men who have sex with men (80%). Median age was 51 (interquartile range [IQR], 47-56) years, median duration of HIV infection was 15 (IQR, 8-21) years, median CD4 count at enrollment was 520 (IQR, 392-719) cells/µL, and median nadir CD4 count was 142 (IQR, 42-240) cells/µL. Valacyclovir was not associated with significant changes in any primary or secondary immunological outcomes in bivariate or multivariable models. Medication adherence was 97% by self-report, 96% by pill count, and 84% by urine monitoring. Eight patients had adverse events deemed possibly related to the study drug (5 placebo, 1 low-dose, 2 high-dose), and 6 patients reported at least 1 HSV outbreak (3 placebo, 3 low-dose, 0 high-dose).. Valacyclovir did not decrease systemic immune activation or inflammatory biomarkers in HIV-1/HSV-2-coinfected adults on suppressive ART.. NCT01176409.

    Topics: Acyclovir; Adult; Anti-Retroviral Agents; Antiviral Agents; C-Reactive Protein; CD8-Positive T-Lymphocytes; Coinfection; Female; Herpes Genitalis; Herpesvirus 2, Human; HIV Infections; HIV-1; Humans; Immune Reconstitution Inflammatory Syndrome; Intercellular Adhesion Molecule-1; Interleukin-6; Lymphocyte Subsets; Male; Middle Aged; Placebos; Treatment Outcome; Valacyclovir; Valine

2013
Short communication: T cell activation in HIV-1/herpes simplex virus-2-coinfected Kenyan women receiving valacyclovir.
    AIDS research and human retroviruses, 2013, Volume: 29, Issue:1

    Herpes simplex virus-2 (HSV-2) suppression with acyclovir or valacyclovir reduces HIV-1 viral RNA levels; one hypothesis is that HSV-2 suppression reduces immune activation. We measured T cell immune activation markers among women participating in a randomized placebo-controlled trial of valacyclovir to reduce HIV-1 RNA levels among pregnant women. Although valacyclovir was associated with lower HIV-1 RNA levels, the distribution of both CD4(+) and CD8(+) CD38(+)HLA-DR(+) T cells was not different among women taking valacyclovir when compared to women taking placebo. Further study is needed to understand the mechanism of HIV-1 RNA reduction following herpes suppression among those coinfected with HIV-1 and HSV-2.

    Topics: Acyclovir; Adult; Antiviral Agents; Coinfection; Double-Blind Method; Female; Herpes Simplex; Herpesvirus 2, Human; HIV Infections; HIV-1; Humans; Kenya; Lymphocyte Activation; Pregnancy; Pregnancy Complications, Infectious; Simplexvirus; T-Lymphocytes; Valacyclovir; Valine; Young Adult

2013
Valacyclovir suppressive therapy reduces plasma and breast milk HIV-1 RNA levels during pregnancy and postpartum: a randomized trial.
    The Journal of infectious diseases, 2012, Feb-01, Volume: 205, Issue:3

    The effect of herpes simplex virus type 2 (HSV-2) suppression on human immunodeficiency virus type 1 (HIV-1) RNA in the context of prevention of mother-to-child transmission (PMTCT) interventions is unknown.. Between April 2008 and August 2010, we conducted a randomized, double-blind trial of twice daily 500 mg valacyclovir or placebo beginning at 34 weeks gestation in 148 HIV-1/HSV-2 coinfected pregnant Kenyan women ineligible for highly active antiretroviral therapy (CD4 > 250 cells/mm(3)). Women received zidovudine and single dose nevirapine for PMTCT and were followed until 12 months postpartum.. Mean baseline plasma HIV-1 RNA was 3.88 log(10) copies/mL. Mean plasma HIV-1 was lower during pregnancy (-.56 log(10) copies/mL; 95% confidence interval [CI], -.77 to -.34) and after 6 weeks postpartum (-.51 log(10) copies/mL; 95% CI, -.73 to -.30) in the valacyclovir arm than the placebo arm. Valacyclovir reduced breast milk HIV-1 RNA detection at 6 and 14 weeks postpartum compared with placebo (30% lower, P = .04; 46% lower, P = .01, respectively), but not after 14 weeks. Cervical HIV-1 RNA detection was similar between arms (P = .91).. Valacyclovir significantly decreased early breast milk and plasma HIV-1 RNA among women receiving PMTCT.. NCT00530777.

    Topics: Acyclovir; Adolescent; Adult; Anti-HIV Agents; Double-Blind Method; Female; HIV Infections; HIV-1; Humans; Infectious Disease Transmission, Vertical; Kenya; Milk, Human; Nevirapine; Placebos; Plasma; Postpartum Period; Pregnancy; Pregnancy Complications, Infectious; RNA, Viral; Treatment Outcome; Valacyclovir; Valine; Viral Load; Young Adult; Zidovudine

2012
Infant safety during and after maternal valacyclovir therapy in conjunction with antiretroviral HIV-1 prophylaxis in a randomized clinical trial.
    PloS one, 2012, Volume: 7, Issue:4

    Maternal administration of the acyclovir prodrug valacyclovir is compatible with pregnancy and breastfeeding. However, the safety profile of prolonged infant and maternal exposure to acyclovir in the context of antiretrovirals (ARVs) for prevention of mother-to-child HIV-1 transmission (PMTCT) has not been described.. Pregnant Kenyan women co-infected with HIV-1/HSV-2 with CD4 counts > 250 cells/mm(3) were enrolled at 34 weeks gestation and randomized to twice daily 500 mg valacyclovir or placebo until 12 months postpartum. Women received zidovudine from 28 weeks gestation and single dose nevirapine was given to women and infants at the time of delivery for PMTCT. Infant blood was collected at 6 weeks for creatinine and ALT. Breast milk specimens were collected at 2 weeks postpartum from 71 women in the valacyclovir arm; acyclovir levels were determined for a random sample of 44 (62%) specimens. Fisher's Exact and Wilcoxon rank-sum tests were used for analysis.. One hundred forty-eight women were randomized and 146 mother-infant pairs were followed postpartum. PMTCT ARVs were administered to 98% of infants and all mothers. Valacyclovir was not associated with infant or maternal toxicities or adverse events, and no congenital malformations were observed. Infant creatinine levels were all normal (< 0.83 mg/dl) and median creatinine (median 0.50 mg/dl) and infant growth did not differ between study arms. Acyclovir was detected in 35 (80%) of 44 breast milk samples collected at 2 weeks postpartum. Median and maximum acyclovir levels were 2.62 and 10.15 mg/ml, respectively (interquartile range 0.6-4.19).. Exposure to PMTCT ARVs and acyclovir after maternal administration of valacyclovir during pregnancy and postpartum to women co-infected with HIV-1/HSV-2 was not associated with an increase in infant or maternal toxicities or adverse events.. ClinicalTrials.gov NCT00530777.

    Topics: Acyclovir; Adult; Anti-HIV Agents; Coinfection; Drug-Related Side Effects and Adverse Reactions; Female; Herpesvirus 2, Human; HIV Infections; HIV-1; Humans; Infant; Infant, Newborn; Infectious Disease Transmission, Vertical; Milk, Human; Mothers; Postpartum Period; Pregnancy; Prenatal Exposure Delayed Effects; Time Factors; Valacyclovir; Valine; Young Adult

2012
Effects of valacyclovir on markers of disease progression in postpartum women co-infected with HIV-1 and herpes simplex virus-2.
    PloS one, 2012, Volume: 7, Issue:6

    Herpes simplex virus type 2 (HSV-2) suppression has been shown to reduce HIV-1 disease progression in non-pregnant women and men, but effects on pregnant and postpartum women have not been described.. We analyzed data from a cohort of Kenyan women participating in a randomized clinical trial of HSV-2 suppression. Pregnant HIV-1-seropositive, HSV-2-seropositive women who were not eligible for antiretroviral therapy (WHO stage 1-2, CD4>250 cells/µl) were randomized to either 500 mg valacyclovir or placebo twice daily from 34 weeks gestation through 12 months postpartum. Women received zidovudine and single-dose nevirapine for prevention of mother-to-child HIV-1 transmission. HIV-1 progression markers, including CD4 count and plasma HIV-1 RNA levels, were measured serially. Multivariate linear regression was used to compare progression markers between study arms.. Of 148 women randomized, 136 (92%) completed 12 months of postpartum follow-up. While adjusted mean CD4 count at 12 months (565 cells/µl placebo arm, 638 cells/µl valacyclovir arm) increased from antenatal levels in both arms, the mean CD4 count increase was 73 cells/µl higher in the valacyclovir arm than placebo arm (p = 0.03). Mean increase in CD4 count was 154 cells/µl in the valacyclovir arm, almost double the increase of 78 cells/µl in the placebo arm. At 12 months, adjusted HIV-1 RNA levels in the placebo arm increased by 0.66 log(10) copies/ml from baseline, and increased by only 0.21 log(10) copies/ml in the valacyclovir arm (0.40 log(10) copies/ml difference, p = 0.001).. Women randomized to valacyclovir suppressive therapy during pregnancy and postpartum had greater increases in CD4 counts and smaller increases in plasma HIV-1 RNA levels than women in the placebo arm. Valacyclovir suppression during pregnancy and breastfeeding may improve outcomes and delay antiretroviral therapy for HIV-1/HSV-2 co-infected women.

    Topics: Acyclovir; Antiviral Agents; Biomarkers; CD4 Antigens; Disease Progression; Female; Herpes Genitalis; Herpesvirus 2, Human; HIV Infections; HIV-1; Humans; Kenya; Linear Models; Nevirapine; Postpartum Period; Pregnancy; RNA, Viral; Valacyclovir; Valine; Zidovudine

2012
High-dose valacyclovir HSV-2 suppression results in greater reduction in plasma HIV-1 levels compared with standard dose acyclovir among HIV-1/HSV-2 coinfected persons: a randomized, crossover trial.
    The Journal of infectious diseases, 2011, Dec-15, Volume: 204, Issue:12

    Standard-dose HSV-2 suppressive therapy (acyclovir 400 mg twice daily) reduces plasma HIV-1 levels by 0.25-0.50 log(10) copies/mL. It is not known if higher doses might further suppress HIV-1 levels.. We enrolled 32 HIV-1/HSV-2 dually infected Kenyan individuals who were not on antiretroviral therapy (ART) into a randomized, crossover trial of 2 dosing regimens of HSV-2 suppression: valacyclovir 1.5 g vs acyclovir 400 mg, both twice daily for 12 weeks, then a 2-week washout, and then the alternative for 12 weeks. Weekly plasma HIV-1 RNA quantity was measured (ClinicalTrials.gov number NCT01026454).. Mean plasma HIV-1 levels were significantly lower on valacyclovir compared with acyclovir: 2.94 vs 3.56 log(10) copies/mL, an average difference of 0.62 log(10) copies/mL (95% confidence interval [CI]: -0.68, -0.55; P < .001), a 76% decrease. Valacyclovir resulted in a 1.23 log(10) copies/mL decrease compared with baseline HIV-1 levels without HSV-2 suppression. Adherence was similar (99.4% of dispensed study tablets taken), and high-dose valacyclovir was well tolerated.. High-dose valacyclovir reduced plasma HIV-1 viral levels by 0.62 log(10) copies/mL compared with standard-dose acyclovir. The potential for higher-dose HSV-2 suppressive therapy to slow HIV-1 disease progression and reduce HIV-1 infectiousness among HIV-1/HSV-2 coinfected persons not yet eligible for ART warrants further evaluation.

    Topics: Acyclovir; Adult; Antiviral Agents; Coinfection; Cross-Over Studies; Female; Herpes Genitalis; Herpesvirus 2, Human; HIV Infections; HIV-1; Humans; Male; Middle Aged; RNA, Viral; Valacyclovir; Valine; Viral Load; Young Adult

2011
Can herpes simplex virus type 2 suppression slow HIV disease progression: a study protocol for the VALacyclovir In Delaying Antiretroviral Treatment Entry (VALIDATE) trial.
    Trials, 2010, Nov-24, Volume: 11

    Although highly active antiretroviral therapy (HAART) has dramatically decreased HIV-related morbidity and mortality, the associated costs, toxicities, and resistance risks make the potential delay of HAART initiation an attractive goal. Suppression of herpes simplex virus type 2 (HSV-2) may be a novel strategy for achieving this goal because HSV-2 is associated with clinically significant increases in HIV viral load, the primary driver of HIV disease progression.. The VALacyclovir In Delaying Antiretroviral Treatment Entry (VALIDATE) trial is a multicentre, randomized, fully blinded, clinical trial of twice daily valacyclovir 500 mg versus placebo for delaying the need for initiating HAART among HIV-1, HSV-2 co-infected HAART-naïve adults. 480 participants from Canada, Brazil and Argentina will undergo quarterly clinical follow-up until reaching the composite primary endpoint of having a CD4+ T-cell count ≤ 350 cells/mm(3) or initiation of HAART for any reason, whichever occurs first. The primary analysis will use a proportional hazards model, stratified by site, to estimate the relative risk of progression to this endpoint associated with valacyclovir. Secondary analyses will compare the rates of change in CD4 count, median log10 HIV viral load, drug-related adverse events, frequency of HSV reactivations, rate of acyclovir-resistant HSV, and quality of life between study arms.. Although HIV treatment guidelines continue to evolve, with some authorities recommending earlier HAART among asymptomatic individuals, the potential delay of HAART remains a clinically relevant goal for many. If shown to be of benefit, implementation of the VALIDATE intervention will require careful consideration of both individual patient-level and public health implications.. Current Controlled Trials ISRCTN66756285. ClinicalTrials.gov NCT00860977.

    Topics: Acyclovir; Antiviral Agents; Clinical Protocols; Disease Progression; Herpesvirus 2, Human; HIV Infections; HIV-1; Humans; Valacyclovir; Valine; Viral Load

2010
HSV suppression reduces seminal HIV-1 levels in HIV-1/HSV-2 co-infected men who have sex with men.
    AIDS (London, England), 2009, Feb-20, Volume: 23, Issue:4

    Suppressive herpes simplex virus (HSV) therapy can decrease plasma, cervical, and rectal HIV-1 levels in HIV-1/HSV-2 co-infected persons. We evaluated the effect of HSV-2 suppression on seminal HIV-1 levels.. Twenty antiretroviral therapy (ART)-naive HIV-1/HSV-2 men who have sex with men (MSM) in Lima, Peru, with CD4 >200 cells/microl randomly received valacyclovir 500 mg twice daily or placebo for 8 weeks, then the alternative regimen for 8 weeks after a 2-week washout. Peripheral blood and semen specimens were collected weekly. Anogenital swab specimens for HSV DNA were self-collected daily and during clinic visits.. HIV-1 RNA was quantified in seminal and blood plasma by TaqMan real-time polymerase chain reaction (RT-PCR) or Roche Amplicor Monitor assays. HSV and seminal cytomegalovirus (CMV) were quantified by RT-PCR. Linear mixed models examined differences within participants by treatment arm.. Median CD4 cell count of participants was 424 cells/microl. HIV-1 was detected in 71% of 231 semen specimens. HSV was detected from 29 and 4.4% of swabs on placebo and valacyclovir, respectively (P < 0.001). Valacyclovir significantly reduced the proportion of days with detectable seminal HIV-1 (63% during valacyclovir vs. 78% during placebo; P = 0.04). Seminal HIV-1 quantity was 0.25 log10 copies/ml lower [95% confidence interval (CI) -0.40 to -0.10; P = 0.001] during the valacyclovir arm compared with placebo, a 44% reduction. CD4 cell count (P = 0.32) and seminal cellular CMV quantity (P = 0.68) did not predict seminal plasma HIV-1 level.. Suppressive valacyclovir reduced seminal HIV-1 levels in HIV-1/HSV-2 co-infected MSM not receiving ART. The significance of this finding will be evaluated in a trial with HIV-1 transmission as the outcome.

    Topics: Acyclovir; Adult; Antiviral Agents; CD4 Lymphocyte Count; Cross-Over Studies; Double-Blind Method; Herpes Genitalis; Herpesvirus 2, Human; HIV Infections; HIV-1; Homosexuality, Male; Humans; Male; Middle Aged; RNA, Viral; Semen; Valacyclovir; Valine; Viral Load; Young Adult

2009
Herpes simplex virus (HSV)-suppressive therapy decreases plasma and genital HIV-1 levels in HSV-2/HIV-1 coinfected women: a randomized, placebo-controlled, cross-over trial.
    The Journal of infectious diseases, 2008, Dec-15, Volume: 198, Issue:12

    A randomized cross-over trial of herpes simplex virus type 2 (HSV-2)-suppressive therapy (valacyclovir, 500 mg twice daily, or placebo for 8 weeks, a 2-week washout period, then the alternative therapy for 8 weeks) was conducted among 20 Peruvian women coinfected with HSV-2 and human immunodeficiency virus type 1 (HIV-1) who were not on antiretroviral therapy. Plasma samples (obtained weekly) and endocervical swab specimens (obtained thrice weekly) were collected for HIV-1 RNA polymerase chain reaction. Plasma HIV-1 level was significantly lower during the valacyclovir arm, compared with the placebo arm (-0.26 log10 copies/mL, a 45% decrease [P < .001]), as was cervical HIV-1 level (-0.35 log10 copies/swab, a 55% decrease [P < .001]). Suppressive HSV-2 therapy has the potential to reduce HIV-1 infectiousness and slow HIV-1 disease progression.

    Topics: Acyclovir; Adult; Antiviral Agents; Cross-Over Studies; Female; Herpes Simplex; Herpesvirus 2, Human; HIV Infections; HIV-1; Humans; Middle Aged; Valacyclovir; Valine; Virus Replication

2008
Reduction of HIV-1 RNA levels with therapy to suppress herpes simplex virus.
    The New England journal of medicine, 2007, Feb-22, Volume: 356, Issue:8

    Epidemiologic data suggest that infection with herpes simplex virus type 2 (HSV-2) is associated with increased genital shedding of human immunodeficiency virus type 1 (HIV-1) RNA and HIV-1 transmissibility.. We conducted a randomized, double-blind, placebo-controlled trial of HSV suppressive therapy with valacyclovir (at a dose of 500 mg twice daily) in Burkina Faso among women who were seropositive for HIV-1 and HSV-2; all were ineligible for highly active antiretroviral therapy. The patients were followed for 24 weeks (12 weeks before and 12 weeks after randomization). Regression models were used to assess the effect of valacyclovir on the presence and quantity of genital and plasma HIV-1 RNA and genital HSV-2 DNA during treatment, adjusting for baseline values, and to evaluate the effect over time.. A total of 140 women were randomly assigned to treatment groups; 136 were included in the analyses. At enrollment, the median CD4 cell count was 446 cells per cubic millimeter, and the mean plasma viral load was 4.44 log10 copies per milliliter. With the use of summary-measures analysis, valacyclovir therapy was found to be associated with a significant decrease in the frequency of genital HIV-1 RNA (odds ratio, 0.41; 95% confidence interval [CI], 0.21 to 0.80) and in the mean quantity of the virus (log(10) copies per milliliter, -0.29; 95% CI, -0.44 to -0.15). However, there was no significant decrease in detection of HIV (risk ratio, 0.93; 95% CI, 0.81 to 1.07). HSV suppressive therapy also reduced the mean plasma HIV-1 RNA level by 0.53 log(10) copy per milliliter (95% CI, -0.72 to -0.35). Repeated-measures analysis showed that these effects became significantly stronger during the 3 months of follow-up.. HSV suppressive therapy significantly reduces genital and plasma HIV-1 RNA levels in dually infected women. This finding may have important implications for HIV control. (ClinicalTrials.gov number, NCT00158509 [ClinicalTrials.gov].).

    Topics: Acyclovir; Adolescent; Adult; Antiviral Agents; Cervix Uteri; Female; Herpes Genitalis; Herpesvirus 2, Human; HIV Infections; HIV-1; Humans; RNA, Viral; Valacyclovir; Valine; Viral Load; Virus Replication; Virus Shedding

2007
Herpes simplex virus (HSV) suppression with valacyclovir reduces rectal and blood plasma HIV-1 levels in HIV-1/HSV-2-seropositive men: a randomized, double-blind, placebo-controlled crossover trial.
    The Journal of infectious diseases, 2007, Nov-15, Volume: 196, Issue:10

    Herpes simplex virus type 2 (HSV-2) infection is common among human immunodeficiency virus (HIV)-infected persons, and HSV reactivation increases plasma and genital HIV-1 levels. We studied HIV-1 levels during HSV suppression in coinfected persons in a placebo-controlled crossover trial.. Twenty antiretroviral therapy (ART)-naive HIV-1/HSV-2-seropositive men who have sex with men in Lima, Peru, with CD4 cell counts >200 cells/ microL were randomized to receive either valacyclovir at 500 mg twice daily or placebo for 8 weeks, after which they underwent a 2-week washout period and then received the alternative regimen for 8 weeks. Specimens included daily anogenital swabs (for HSV DNA polymerase chain reaction [PCR]), thrice weekly rectal mucosal secretions (for HIV-1 RNA and HSV DNA PCR) obtained by anoscopy, and weekly plasma (for HIV-1 RNA PCR). Outcomes were rectal and plasma HIV-1 RNA levels by treatment arm.. HIV-1 was detected in 73% of 844 rectal and 99% of 288 plasma specimens. HSV was detected in 29% and 4% of mucocutaneous specimens obtained during placebo and valacyclovir administration, respectively (P<.001). Valacyclovir resulted in a 0.16 (95% confidence interval [CI], 0.07-0.25; P=.0008; 33% decrease) log(10) copies/mL lower mean within-subject rectal HIV-1 level and a 0.33 (95% CI, 0.23-0.42; P<.0001; 53% decrease) log(10) copies/mL lower plasma HIV-1 level, compared with values for placebo.. Valacyclovir significantly reduces rectal and plasma HIV-1 levels in HIV-1/HSV-2-coinfected men. HSV suppression may provide clinical benefits to persons not receiving highly active ART as well as public health benefits.

    Topics: Acyclovir; Administration, Oral; Adult; Antiviral Agents; Cross-Over Studies; DNA, Viral; Double-Blind Method; Herpes Simplex; Herpesvirus 2, Human; HIV Infections; HIV-1; Homosexuality, Male; Humans; Male; Polymerase Chain Reaction; Rectum; RNA, Viral; Treatment Outcome; Valacyclovir; Valine; Viral Load

2007
Impact of suppressive herpes therapy on genital HIV-1 RNA among women taking antiretroviral therapy: a randomized controlled trial.
    AIDS (London, England), 2006, Nov-28, Volume: 20, Issue:18

    To demonstrate a causal relationship between herpes simplex virus 2 (HSV-2) and increased genital HIV-1-RNA shedding in women on HAART.. A randomized, double-blind, placebo-controlled trial of herpes-suppressive therapy (valacyclovir 500 mg twice a day) in HIV-1/HSV-2-infected women taking HAART in Burkina Faso.. Participants were followed for a total of 12 biweekly visits before and after randomization. The presence and frequency of genital and plasma HIV-1 RNA, and of genital HSV-2 were assessed using summary measures, adjusting for baseline values. Random effect linear regression models were used to assess the impact of treatment on genital and plasma viral loads among visits with detectable virus.. Sixty women were enrolled into the trial. Their median CD4 lymphocyte count was 228 cells/mul, and 83% had undetectable plasma HIV-1 RNA at baseline. Valacyclovir reduced the proportion of visits with detectable genital HSV-2 DNA [odds ratio (OR) 0.37, 95% confidence interval (CI) 0.13, 1.05], but had no significant impact on the frequency (OR 0.90, 95% CI 0.31, 2.62) or quantity (reduction of 0.33 log copies/ml, 95% CI -0.81, 0.16) of genital HIV-1 RNA. However, according to pre-defined secondary analyses restricted to women who shed HIV-1 at least once in the baseline phase, valacyclovir reduced both the proportion of visits with detectable HIV-1 shedding (OR 0.27, 95% CI 0.07, 0.99) and the quantity of genital HIV-1 RNA during these visits (-0.71 log10 copies/ml, 95% CI -1.27, -0.14).. HSV-2 facilitates residual genital HIV-1 replication among dually infected women taking HAART despite HIV-1 suppression at the systemic level.

    Topics: Acyclovir; Adult; Antiretroviral Therapy, Highly Active; Antiviral Agents; DNA, Viral; Double-Blind Method; Female; Genitalia, Female; Herpes Genitalis; HIV Infections; HIV-1; Humans; Middle Aged; RNA, Viral; Ulcer; Valacyclovir; Valine; Viral Load

2006
Effect of Epstein-Barr virus replication on Langerhans cells in pathogenesis of oral hairy leukoplakia.
    The Journal of infectious diseases, 2004, May-01, Volume: 189, Issue:9

    Epstein-Barr virus (EBV) replicates productively in oral hairy leukoplakia (HLP). One characteristic of human immunodeficiency virus (HIV)-associated HLP is a decreased oral epithelial Langerhans cell count. This prospective study tested the hypothesis that oral epithelial EBV replication decreases oral Langerhans cell counts. EBV replication in HLP was highly correlated with decreased oral Langerhans cell counts. Inhibition of EBV replication restored oral Langerhans cell counts to normal control levels, and the return of EBV replication after treatment resulted in a recurrent decline in oral Langerhans cell counts. Decreased oral Langerhans cell counts occurred independently of HIV infection, as demonstrated in HLP of otherwise healthy HIV-seronegative individuals. These results support the tested hypothesis and suggest that EBV manipulates and evades the mucosal immune response in oral epithelial infection. This novel EBV strategy for eliminating oral Langerhans cells may facilitate the persistence of oral epithelial EBV and may contribute to the pathogenesis of HLP.

    Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; Cell Count; Herpesvirus 4, Human; HIV Infections; Humans; Langerhans Cells; Leukoplakia, Hairy; Male; Middle Aged; Mouth; Valacyclovir; Valine; Virus Replication

2004
Efficacy and safety of valacyclovir for the suppression and episodic treatment of herpes simplex virus in patients with HIV.
    Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2004, Nov-01, Volume: 39 Suppl 5

    Three randomized controlled trials of valacyclovir for the management of recurrences of genital herpes in HIV-infected persons were conducted between 1991 and 2002. One study evaluated episodic therapy for the treatment of genital herpes, and 2 studies evaluated continuous suppressive therapy. Valacyclovir at 1000 mg twice daily for 5 days was comparable to acyclovir at 200 mg 5 times daily in accelerating healing of a single episode of genital herpes (hazard ratio, 1.0; 95% confidence interval [CI], 0.8-1.2; P=.89). Valacyclovir at 500 mg twice daily was effective in preventing or delaying recurrences of genital herpes compared with placebo (hazard ratio, 0.20; 95% CI, 0.13-0.30; P<.001) and with valacyclovir at 1000 mg once daily (hazard ratio, 0.56; 95% CI, 0.40-0.80; P=.001), in 6-month and 48-week studies, respectively. The safety profile of valacyclovir was similar to that of acyclovir. Valacyclovir is well tolerated, safe, and effective for the treatment and suppression of recurrent genital herpes in human immunodeficiency virus-infected persons.

    Topics: Acyclovir; Administration, Oral; Adult; Aged; Antiretroviral Therapy, Highly Active; Antiviral Agents; CD4 Lymphocyte Count; Double-Blind Method; Drug Administration Schedule; Female; Herpes Genitalis; HIV Infections; Humans; Male; Middle Aged; Prodrugs; Secondary Prevention; Valacyclovir; Valine

2004
Epstein-Barr virus replication in oral hairy leukoplakia: response, persistence, and resistance to treatment with valacyclovir.
    The Journal of infectious diseases, 2003, Sep-15, Volume: 188, Issue:6

    Nineteen cases of human immunodeficiency virus (HIV)-associated oral hairy leukoplakia (HLP) and Epstein-Barr virus (EBV) replication were treated with high-dose oral valacyclovir to inhibit productive EBV replication. The clinical, histopathological, and molecular viral responses to treatment were assessed in surgical biopsy specimens obtained before, during, and after treatment. In the majority of treated cases, HLP was resolved, and EBV replication was terminated. In many cases, the initial response to inhibition of replication was a persistent, nonproductive, EBV infection of the oral mucosa, characterized by limited expression of replicative EBV genes, especially BZLF1. In some cases, productive EBV replication recurred after discontinuation of treatment with valacyclovir. In a few treated cases, treatment failed, and productive EBV replication persisted, possibly because of the evolution of acyclovir-resistant EBV. In summary, safe treatment of HLP and of EBV replication, with valacyclovir, provides new insight into the mechanisms of EBV persistence in oral mucosa.

    Topics: Acyclovir; Adolescent; Adult; Aged; Antiviral Agents; Drug Resistance, Viral; Herpesvirus 4, Human; HIV Infections; Humans; Leukoplakia, Hairy; Middle Aged; Mouth Mucosa; Treatment Outcome; Valacyclovir; Valine; Viral Proteins; Virus Replication

2003
Health-related quality of life predicts survival, cytomegalovirus disease, and study retention in clinical trial participants with advanced HIV disease.
    Journal of clinical epidemiology, 2003, Volume: 56, Issue:9

    We tested whether health related quality of life (HRQOL) predicts mortality, development of active cytomegalovirus (CMV) disease, and study retention. We studied 957 patients with CD4 counts <100 cells/mm(3) in AIDS Clinical Trials Group Protocol 204, a randomized, double-blind trial comparing three prophylactic regimens against CMV end-organ disease. The MOS-HIV, a brief HRQOL questionnaire, generated physical health summary (PHS) and mental health summary (MHS) scores. We used Cox proportional hazards to predict events by baseline HRQOL, adjusted for treatment, demographics, and CD4. Each point increase in baseline PHS decreased the risk of death by 4%, CMV by 2%, and dropout by 2%. Each point increase in baseline MHS decreased the risk of death by 4% and study dropout by 1%. In conclusion, self-rated physical and mental health demonstrated predictive validity for survival, CMV end-organ disease, and retention in advanced HIV patients. The results show the clinical importance of HRQOL and may facilitate interpretation by clinicians.

    Topics: Acute Disease; Acyclovir; Adult; Age Factors; Anti-HIV Agents; Cytomegalovirus Infections; Double-Blind Method; Health Status; HIV Infections; Humans; Middle Aged; Patient Dropouts; Predictive Value of Tests; Proportional Hazards Models; Psychiatric Status Rating Scales; Quality of Life; Racial Groups; Sex Factors; Survival Rate; Valacyclovir; Valine

2003
Valacyclovir for the suppression of recurrent genital herpes in human immunodeficiency virus-infected subjects.
    The Journal of infectious diseases, 2003, Oct-01, Volume: 188, Issue:7

    To determine the efficacy and safety of valacyclovir (500 mg twice daily) for the suppression of recurrent genital herpes simplex virus infections in human immunodeficiency virus (HIV)-infected subjects, a randomized, double-blind, placebo-controlled, multicenter international trial was conducted. A total of 293 HIV-seropositive subjects receiving antiretroviral therapy were enrolled. The proportion of subjects who did not have a recurrence of genital herpes at 6 months was 65% among valacyclovir recipients versus 26% among placebo recipients (relative risk, 2.5; 95% confidence interval, 1.8-3.5). The time to first genital herpes recurrence was significantly shorter in the placebo group (median, 59 days) than in the valacyclovir group (median, >180 days). Valacyclovir was well tolerated; the incidence of adverse events for the 2 treatment groups was similar when the duration of treatment was considered. There were no episodes of thrombotic microangiopathy. Valacyclovir was safe and effective for the suppression of recurrent genital herpes infection in HIV-infected individuals.

    Topics: Acyclovir; Adult; Antiviral Agents; Female; Herpes Genitalis; HIV Infections; HIV-1; Humans; Male; Middle Aged; Proportional Hazards Models; Secondary Prevention; Simplexvirus; Valacyclovir; Valine

2003
Valaciclovir versus aciclovir for herpes simplex virus infection in HIV-infected individuals: two randomized trials.
    International journal of STD & AIDS, 2002, Volume: 13, Issue:1

    Our objective was to evaluate valaciclovir for anogenital herpes in HIV-infected individuals using 2 controlled trials conducted before highly active antiretroviral therapy (HAART) was used. In Study 1, 1062 patients (CD4+ > or = 100 cells/mm(3)) received suppressive valaciclovir or aciclovir for one year and were assessed monthly. In Study 2, 467 patients were treated episodically for > or =5 days with valaciclovir or aciclovir and evaluated daily. Valaciclovir was as effective as aciclovir for suppression and episodic treatment of herpes. Hazard ratios [95% confidence interval (CI)] for time to recurrence for valaciclovir 500 mg twice daily and 1000 mg once daily vs aciclovir were 0.73[0.50, 1.06], P=0.10, and 1.31[0.94, 1.82], P=0.11. Valaciclovir 500 mg twice daily was superior to 1000 mg once daily, P=0.001. Valaciclovir 1000 mg twice daily was comparable to aciclovir on herpes episode duration (hazard ratio 0.92[0.75, 1.14]). Adverse events were similar among treatments. In conclusion, valaciclovir is a safe, effective, convenient alternative to aciclovir for HSV infection in HIV-infected individuals.

    Topics: Acyclovir; Adult; Aged; AIDS-Related Opportunistic Infections; Antiviral Agents; Confidence Intervals; Double-Blind Method; Drug Administration Schedule; Female; Herpes Genitalis; HIV Infections; Humans; Male; Middle Aged; Recurrence; Simplexvirus; Treatment Outcome; Valacyclovir; Valine

2002
Cytomegalovirus (CMV) polymerase chain reaction profiles in individuals with advanced human immunodeficiency virus infection: relationship to CMV disease.
    The Journal of infectious diseases, 2002, Jun-15, Volume: 185, Issue:12

    Cytomegalovirus (CMV) disease is a common complication of patients with advanced human immunodeficiency virus infection. The aim of the present study, based on a case-cohort design, was to determine the predictive value of follow-up and baseline qualitative plasma CMV polymerase chain reaction (PCR) values for CMV end-organ disease in 378 patients (158 who progressed to CMV end-organ disease and 220 who did not develop CMV disease). These patients are part of the full AIDS Clinical Trials Group 204 multinational study (1227 patients), a randomized, controlled trial that compared the effects of valacyclovir with those of acyclovir for CMV disease prevention. Baseline PCR positivity was a significant risk factor for CMV disease progression (relative risk [RR], 1.81; 95% confidence interval [CI], 1.09-3.00). In multivariate analyses, time-updated PCR positivity was strongly associated with progression to CMV end-organ disease (RR, 4.42; 95% CI, 2.87-6.81). Change in cumulative PCR status was informative for the risk of subsequent CMV disease.

    Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Case-Control Studies; Cytomegalovirus; Cytomegalovirus Infections; HIV Infections; Humans; Male; Multivariate Analysis; Polymerase Chain Reaction; Predictive Value of Tests; Risk Factors; Valacyclovir; Valine

2002
Quantitative effects of valacyclovir on the replication of cytomegalovirus (CMV) in persons with advanced human immunodeficiency virus disease: baseline CMV load dictates time to disease and survival. The AIDS Clinical Trials Group 204/Glaxo Wellcome 123-
    The Journal of infectious diseases, 1999, Volume: 180, Issue:3

    Virus load is a major risk factor for disease in many human viral infections, especially human immunodeficiency virus (HIV) disease. The effect of cytomegalovirus (CMV) load on disease progression and the influence of antiviral chemotherapy on surrogate markers of replication was investigated in 310 patients with advanced HIV disease in a randomized controlled trial that compared the effects of valacyclovir with those of acyclovir. Sequential blood and urine samples were analyzed by polymerase chain reaction (PCR), for human CMV (HCMV) DNA. In multivariate analyses, elevated virus load in both blood and urine at baseline was associated with increased risk of HCMV disease (relative hazard, 1.49 and 1.44 per log increase, respectively). Elevated virus load in blood at baseline was also associated with a significantly shorter survival time (log rank, P=. 0001). In time-updated analyses, valacyclovir significantly suppressed the virus load in subjects who were PCR positive at baseline (in blood or urine), when compared with the combined acyclovir arms.

    Topics: Acyclovir; AIDS-Related Opportunistic Infections; Analysis of Variance; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Disease-Free Survival; HIV Infections; Humans; Multivariate Analysis; Polymerase Chain Reaction; Prodrugs; Risk Factors; Survival Rate; Time Factors; Valacyclovir; Valine; Virus Replication

1999
Manifestations resembling thrombotic microangiopathy in patients with advanced human immunodeficiency virus (HIV) disease in a cytomegalovirus prophylaxis trial (ACTG 204).
    Medicine, 1997, Volume: 76, Issue:5

    Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; Cytomegalovirus Infections; Double-Blind Method; Hemolytic-Uremic Syndrome; HIV Infections; Humans; Male; Middle Aged; Prodrugs; Prospective Studies; Purpura, Thrombotic Thrombocytopenic; Risk Factors; Valacyclovir; Valine

1997
Phase I trial of valaciclovir, the L-valyl ester of acyclovir, in patients with advanced human immunodeficiency virus disease.
    Antimicrobial agents and chemotherapy, 1994, Volume: 38, Issue:7

    Valaciclovir, the L-valyl ester of acyclovir, is rapidly and extensively converted in humans to acyclovir after oral administration by first-pass metabolism. A phase I study was conducted in two cohorts of volunteers with advanced human immunodeficiency virus (HIV) disease (absolute CD4 lymphocyte count of < 150 cells per microliters) who received oral valaciclovir at dosages of 1,000 or 2,000 mg four times daily for 30 days. All patients were clinically stable without any changes in underlying HIV-related medications for > or = 6 weeks prior to entry in study; these medications were continued throughout the study. Multiple-dose administration of valaciclovir showed a generally favorable safety profile. Nausea, vomiting, diarrhea, and abdominal pain each were reported in < or = 31% of the patients; of these symptoms, only one episode of diarrhea was considered causally related to valaciclovir exposure. Four patients developed neutropenia (two at each dose level) which was not clinically significant. There were no renal or neurologic adverse events. Valaciclovir was rapidly absorbed and converted to acyclovir, with plasma valaciclovir levels generally undetectable or levels of < or = 0.4 microgram/ml. After 3 h postdosing, valaciclovir was not detectable in plasma. Acyclovir was measurable in plasma as early as 15 min following valaciclovir dosing, and plasma concentrations of acyclovir greatly exceeded those of valaciclovir. The mean values for the maximum concentration of drug in plasma, time to maximum concentration of drug in plasma, area under the concentration-time curve from 0 h to infinity, and apparent half-life of acyclovir obtained after single- and multiple-dose valaciclovir administration in HIV-infected patients were similar to those reported in normal healthy volunteers. The time to maximum concentration in serum and half-life of acyclovir after valaciclovir administration were approximately 2 and 3 h, respectively, which were similar to those reported after oral administration of acyclovir itself. The mean trough and peak acyclovir concentrations and the daily area under the concentration-time curve acyclovir values at steady state were 2.5 and 8.4 micrograms/ml and 120 h micrograms/ml, respectively, after a dosage of 2,000 mg of valaciclovir four times daily. These values were approximately fivefold greater than those achieved with high dosages of oral acyclovir (800 mg, five times daily) and were not affected by continued use of medicatio

    Topics: Acyclovir; Adult; Antiviral Agents; Chromatography, High Pressure Liquid; Female; Half-Life; Hemoglobins; HIV Antibodies; HIV Infections; Humans; Male; Middle Aged; Valacyclovir; Valine

1994

Other Studies

23 other study(ies) available for valacyclovir and HIV-Infections

ArticleYear
An HIV-infected patient with acute retinal necrosis as immune reconstitution inflammatory syndrome due to varicella-zoster virus.
    AIDS (London, England), 2020, 04-01, Volume: 34, Issue:5

    Topics: Acyclovir; Administration, Intravenous; Adult; Cataract Extraction; Combined Modality Therapy; Ganciclovir; Herpesvirus 3, Human; HIV Infections; Humans; Immune Reconstitution Inflammatory Syndrome; Intravitreal Injections; Lens Implantation, Intraocular; Male; Polymerase Chain Reaction; Prednisolone; Retinal Detachment; Retinal Necrosis Syndrome, Acute; Treatment Outcome; Valacyclovir

2020
Modeling HIV disease progression and transmission at population-level: The potential impact of modifying disease progression in HIV treatment programs.
    Epidemics, 2018, Volume: 23

    Mathematical models that incorporate HIV disease progression dynamics can estimate the potential impact of strategies that delay HIV disease progression and reduce infectiousness for persons not on antiretroviral therapy (ART). Suppressive treatment of HIV-positive persons co-infected with herpes simplex virus-2 (HSV-2) with valacyclovir, an HSV-2 antiviral, can lower HIV viral load, but the impact of partially-suppressive valacyclovir relative to fully-suppressive ART on population HIV transmission has not been estimated.. We modeled HIV disease progression as a function of changes in viral load and CD4 count over time among ART naïve persons. The disease progression Markov model was nested within a dynamic model of HIV transmission at population level. We assumed that valacyclovir reduced HIV viral load by 1.23 log copies/μL, and that persons treated with valacyclovir initiated ART more rapidly when their CD4 fell below 500 due to retention in HIV care. We estimated the potential impact of valacyclovir on onward transmission of HIV in three scenarios of different ART and valacyclovir population coverage.. The average duration of HIV infection was 9.5 years. The duration of disease before reaching CD4 200cells/μL was 2.53 years longer for females than males. Relative to a baseline of ART initiation at CD4≤500cells/μL, the valacyclovir scenario resulted in 167,000 fewer HIV infections over ten years, with an incremental cost-effectiveness ratio (ICER) of $5276 per HIV infection averted. A Test and Treat scenario with 70% ART coverage and no valacyclovir resulted in 350,000 fewer HIV infections at an ICER of $2822 and $812 per HIV infection averted and QALY gained, respectively.. Even when compared with valacyclovir suppression, a drug that reduces HIV viral load, universal treatment for HIV is the optimal strategy for averting new infections and increasing public health benefit. Universal HIV treatment would most effectively and efficiently reduce the HIV burden.

    Topics: Adult; Africa South of the Sahara; Antiviral Agents; Cost-Benefit Analysis; Disease Progression; Female; Follow-Up Studies; HIV Infections; Humans; Male; Markov Chains; Valacyclovir; Viral Load

2018
Chronic penile ulcer as the first manifestation of HIV infection.
    BMJ case reports, 2017, Aug-07, Volume: 2017

    Topics: Acyclovir; Anti-HIV Agents; Antiviral Agents; Chronic Disease; HIV Infections; HIV-1; Humans; Male; Penile Diseases; Skin Ulcer; Valacyclovir; Valine; Young Adult

2017
Recalcitrant hypertrophic herpes genitalis in HIV-infected patient successfully treated with topical imiquimod.
    Dermatologic therapy, 2017, Volume: 30, Issue:3

    Herpes Simplex Virus type 2 is the primary cause of genital ulceration worldwide. The presence of atypical features like deep ulcerations, hypertrophic, or pseudotumoural lesions or unusual location can be a marker for co-infection with HIV. These immunocompromised patients are usually resistant to the conventional antiviral treatment. We present a case of an HIV-infected patient with hypertrophic herpes genitalis, refractory to conventional oral antiviral therapy, who was successfully treated with a combination of oral valcyclovir and topical application of 5% imiquimod.

    Topics: Acyclovir; Adjuvants, Immunologic; Administration, Topical; Aminoquinolines; Antiviral Agents; Drug Therapy, Combination; Herpes Genitalis; HIV Infections; Humans; Hypertrophy; Imiquimod; Immunocompromised Host; Male; Middle Aged; Valacyclovir; Valine

2017
Use of agent-based simulations to design and interpret HIV clinical trials.
    Computers in biology and medicine, 2014, Volume: 50

    In this study, we illustrate the utility of an agent-based simulation to inform a trial design and how this supports outcome interpretation of randomized controlled trials (RCTs). We developed agent-based Monte Carlo models to simulate existing landmark HIV RCTs, such as the Partners in Prevention HSV/HIV Transmission Study. We simulated a variation of this study using valacyclovir therapy as the intervention, and we used a male circumcision RCT based on the Rakai Male Circumcision Trial. Our results indicate that a small fraction (20%) of the simulated Partners in Prevention HSV/HIV Transmission Study realizations rejected the null hypothesis, which was no effect from the intervention. Our results also suggest that an RCT designed to evaluate the effectiveness of a more potent drug regimen for HSV-2 suppression (valacyclovir therapy) is more likely to identify the efficacy of the intervention. For the male circumcision RCT simulation, the greater biological effect of the male circumcision yielded a major fraction (81%) of RCT realizations' that rejects the null hypothesis, which was no effect from the intervention. Our study highlights how agent-based simulations synthesize individual variation in the epidemiological context of the RCT. This methodology will be particularly useful for designing RCTs aimed at evaluating combination prevention interventions in community-based RCTs, wherein an intervention׳s effectiveness is challenging to predict.

    Topics: Acyclovir; Anti-HIV Agents; Circumcision, Male; Clinical Trials as Topic; Computer Simulation; Herpes Genitalis; Herpesvirus 2, Human; HIV Infections; Humans; Male; Models, Theoretical; Monte Carlo Method; Research Design; Treatment Outcome; Valacyclovir; Valine

2014
Acne keloidalis nuchae on herpes zoster scar in an HIV patient: isotopic response or not?
    Giornale italiano di dermatologia e venereologia : organo ufficiale, Societa italiana di dermatologia e sifilografia, 2012, Volume: 147, Issue:2

    Topics: Acne Keloid; Acyclovir; Adult; Anti-HIV Agents; Antiviral Agents; Azithromycin; Black People; Cicatrix; Disease Susceptibility; Hair Follicle; Herpes Zoster; HIV Infections; Humans; Male; Neck; Sebaceous Glands; Triamcinolone Acetonide; Valacyclovir; Valine

2012
Response to valacyclovir in an HIV-infected girl with Epstein Barr infection.
    Indian pediatrics, 2012, Volume: 49, Issue:5

    Response of EBV infection to valacyclovir in HIV infected children has not been reported earlier. An 8 years old HIV infected girl with undetectable viral load and normal CD4 count on regular antiretroviral therapy presented with persistent fever, lymphadenopathy and pancytopenia due to Epstein Barr virus (EBV). The child responded to valacyclovir.

    Topics: Acyclovir; Alkynes; Antiretroviral Therapy, Highly Active; Antiviral Agents; Benzoxazines; Child; Cyclopropanes; Epstein-Barr Virus Infections; Female; HIV Infections; Humans; Lamivudine; Valacyclovir; Valine; Zidovudine

2012
Herpes simplex virus type 2 suppressive therapy with acyclovir or valacyclovir does not select for specific HIV-1 resistance in HIV-1/HSV-2 dually infected persons.
    The Journal of infectious diseases, 2011, Jan-01, Volume: 203, Issue:1

    Recent in vitro studies suggest that acyclovir may directly inhibit HIV-1 replication and can select for a specific HIV-1 reverse transcriptase mutation (V75I) with concomitant loss of an anti-HIV-1 effect. We tested for HIV-1 genotypic resistance at reverse transcriptase codon 75 in plasma from 168 HIV-1-infected persons from Botswana, Kenya, Peru, and the United States taking daily acyclovir or valacyclovir for between 8 weeks and 24 months. No V75I cases were detected (95% confidence interval, 0%-2.2%). These prospective in vivo studies suggest that standard-dose acyclovir or valacyclovir does not select for HIV-1 resistance.

    Topics: Acyclovir; Adult; Amino Acid Substitution; Antiviral Agents; Botswana; Drug Resistance, Viral; Female; Herpes Genitalis; Herpesvirus 2, Human; HIV Infections; HIV Reverse Transcriptase; HIV-1; Humans; Kenya; Male; Middle Aged; Molecular Sequence Data; Mutation, Missense; Peru; Point Mutation; Prospective Studies; Selection, Genetic; Sequence Analysis, DNA; United States; Valacyclovir; Valine

2011
Time to refocus on HSV interventions for HIV prevention?
    The Journal of infectious diseases, 2011, Dec-15, Volume: 204, Issue:12

    Topics: Acyclovir; Antiviral Agents; Female; Herpes Genitalis; Herpes Simplex; Herpesvirus 2, Human; HIV Infections; HIV-1; Humans; Male; RNA, Viral; Valacyclovir; Valine

2011
Disseminated infections due to Immune Reconstitution Inflammatory Syndrome after highly active antiretroviral therapy--report of 3 cases from Nigeria.
    The Pan African medical journal, 2011, Volume: 9

    Immune Reconstitution Inflammatory Syndromes (IRIS) are exaggerated pathological inflammatory reactions occurring after initiation of highly active antiretroviral therapy (HAART) due to exuberant immune responses to occult or apparent opportunistic infections or cancers. In view of paucity of studies from Nigeria, we report 3 cases of IRIS presenting as disseminated infections in HIV-1 infected patients initiating HAART. The first case was a previously healthy female who developed disseminated tuberculosis after 4 weeks of regular HAART. Her HAART regimen was continued and she improved after commencement of anti-tuberculosis drugs, with evidence of progressive increase in CD4 cell count. The second case was a HAART-experienced female who stopped her drugs for 4 months. Two months after recommencement of her previous HAART regimen, she developed features of disseminated herpes zoster infection, despite evidence of decrease in viral load by 95%. HAART was continued and she recovered completely after receiving valaciclovir tablets and antibiotics. The third patient was a female student who was commenced HAART on account of chronic cough and weight loss. Three months after regular HAART, she developed features of disseminated Kaposi's sarcoma involving the skin, oropharynx and lungs, despite evidence of 42% increase in CD4 cell count. Unfortunately, she rapidly deteriorated and died during the course of management. Clinicians should be alert to the possibility of IRIS in HIV-infected patients initiated or re-initiated on HAART. There is need for future prospective studies determining risk factors for IRIS in HIV-infected patients from Nigeria.

    Topics: Acyclovir; Adult; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Antiviral Agents; CD4 Lymphocyte Count; Disease Susceptibility; Fatal Outcome; Female; Herpes Zoster; HIV Infections; HIV-1; Humans; Immune Reconstitution Inflammatory Syndrome; Nigeria; Respiratory Tract Neoplasms; Sarcoma, Kaposi; Skin Neoplasms; Tuberculosis, Miliary; Valacyclovir; Valine; Viral Load; Viremia; Young Adult

2011
A missed point in deciphering the viral synergy between herpes simplex virus and HIV.
    The Lancet. Infectious diseases, 2009, Volume: 9, Issue:9

    Topics: Acyclovir; Antiviral Agents; Herpes Simplex; Herpesvirus 2, Human; HIV Infections; HIV-1; Humans; Valacyclovir; Valine

2009
An unusual vulval lesion in an HIV-infected woman.
    International journal of STD & AIDS, 2007, Volume: 18, Issue:3

    This is the case of a black African woman who presented with three distinct episodes of herpes simplex virus (HSV) infection unresponsive to first-line therapy. Clinical and virological resistance to aciclovir therapy was demonstrated, and although the first two episodes manifested as the deep ulceration often associated with HIV/HSV coinfection, the third was an atypical hypertrophic lesion. This is despite her CD4 count being persistently above 300 and there being no previous diagnosis of AIDS.

    Topics: Acyclovir; Adolescent; Anti-Retroviral Agents; Drug Resistance, Viral; Female; Herpes Simplex; HIV; HIV Infections; Humans; Pregnancy; Simplexvirus; Valacyclovir; Valine; Vulvar Diseases

2007
Herpes treatment may limit HIV transmission and progression.
    The Lancet. Infectious diseases, 2007, Volume: 7, Issue:4

    Topics: Acyclovir; Antiviral Agents; Disease Progression; Disease Transmission, Infectious; Female; Genitalia, Female; Herpes Simplex; HIV Infections; HIV-1; Humans; RNA, Viral; Time Factors; Valacyclovir; Valine; Viral Load

2007
HSV therapy and HIV-1 reduction.
    The New England journal of medicine, 2007, May-31, Volume: 356, Issue:22

    Topics: Acyclovir; Antiviral Agents; Drug Resistance, Viral; Herpes Simplex; Herpesvirus 2, Human; HIV Infections; HIV-1; Humans; RNA, Viral; Valacyclovir; Valine; Viral Load

2007
HSV therapy and HIV-1 reduction.
    The New England journal of medicine, 2007, May-31, Volume: 356, Issue:22

    Topics: Acyclovir; Antiviral Agents; Herpes Simplex; HIV Infections; HIV-1; Humans; RNA, Viral; Valacyclovir; Valine; Viral Load; Virus Replication

2007
Use of antiviral drugs to prevent herpesvirus transmission.
    The New England journal of medicine, 2004, Jan-01, Volume: 350, Issue:1

    Topics: Acyclovir; Antiviral Agents; Disease Transmission, Infectious; Female; Herpes Genitalis; Herpesvirus 2, Human; HIV Infections; HIV-1; Humans; Male; Valacyclovir; Valine

2004
Persistence and transition of Epstein-Barr virus genotypes in the pathogenesis of oral hairy leukoplakia.
    The Journal of infectious diseases, 2004, Jul-15, Volume: 190, Issue:2

    This prospective study examined the persistence and transition of Epstein-Barr virus (EBV) in human immunodeficiency virus (HIV)-seropositive subjects with and without oral hairy leukoplakia, a replicative EBV-associated epithelial disease. The intrahost molecular epidemiology of EBV infection was characterized in subjects treated with valacyclovir to suppress EBV replication. Tongue epithelial tissues of HIV-seropositive subjects were found to support not only EBV replication but also persistent, nonproductive EBV infection. EBV appeared to enter the tongue from the blood reservoir of infection and, possibly, from exogenous sources as well. EBV transition from the blood to the tongue appeared to occur even during valacyclovir-mediated suppression of EBV replication, suggesting EBV entry into tongue epithelial tissue as a cell-associated latent infection. In conclusion, these results describe the persistence and transition of EBV as a dynamic interaction between the blood and epithelial reservoirs of EBV infection and suggest a role for entry, persistence, and reactivation of oral epithelial EBV in the pathogenesis of oral hairy leukoplakia.

    Topics: Acyclovir; Adult; Amino Acid Sequence; Antiviral Agents; DNA, Viral; Epithelium; Genotype; Herpesvirus 4, Human; HIV Infections; Humans; Leukocytes, Mononuclear; Leukoplakia, Hairy; Male; Middle Aged; Molecular Epidemiology; Molecular Sequence Data; Prospective Studies; Sequence Analysis, DNA; Tongue; Valacyclovir; Valine; Virus Activation; Virus Latency; Virus Replication

2004
Expression of Epstein-Barr virus latent genes in oral epithelium: determinants of the pathogenesis of oral hairy leukoplakia.
    The Journal of infectious diseases, 2004, Jul-15, Volume: 190, Issue:2

    This retrospective study examined expression of Epstein-Barr virus (EBV) latent genes in oral epithelium from human immunodeficiency virus-seropositive subjects, to identify genes associated with the pathogenesis of oral hairy leukoplakia (HLP). Transcription of EBV latent genes was detected in tissues with productive EBV replication and, also, in normal oral epithelial tissues without EBV replication. Expression of the EBV EBNA-2 open-reading frame in oral epithelium was identified as an important cofactor associated with the pathogenesis of HLP. In vitro experiments suggested that a recombinant variant of the EBNA-2 gene may play a role in the pathogenesis of HLP, through modulation of EBNA-2 protein function.

    Topics: Acyclovir; Biopsy; Epithelium; Epstein-Barr Virus Nuclear Antigens; Gene Expression Regulation, Viral; Genes, Viral; Herpesvirus 4, Human; HIV Infections; Humans; Leukoplakia, Hairy; Mouth Mucosa; Retrospective Studies; RNA, Messenger; RNA, Viral; Transcription, Genetic; Valacyclovir; Valine; Viral Matrix Proteins; Viral Proteins; Virus Replication

2004
Microbiology. Domino effects from battles against microbes.
    Science (New York, N.Y.), 2002, Oct-11, Volume: 298, Issue:5592

    Topics: Acyclovir; Adult; Antiviral Agents; Chickenpox; Chickenpox Vaccine; Controlled Clinical Trials as Topic; Female; Herpes Genitalis; Herpes Zoster; HIV Infections; Humans; Infant; Influenza Vaccines; Influenza, Human; Male; Public Health; Vaccination; Valacyclovir; Valine

2002
Persistent productive Epstein-Barr virus replication in normal epithelial cells in vivo.
    The Journal of infectious diseases, 2001, Dec-15, Volume: 184, Issue:12

    Productive Epstein-Barr virus (EBV) replication characterizes hairy leukoplakia, an oral epithelial lesion typically occurring in individuals infected with human immunodeficiency virus (HIV). Serial tongue biopsy specimens were obtained from HIV-infected subjects before, during, and after valacyclovir treatment. EBV replication was detected by Southern hybridization to linear terminal EBV genome fragments, reverse-transcriptase polymerase chain reaction amplification of EBV replicative gene transcripts, immunohistochemical detection of EBV replicative protein, and in situ hybridization to EBV DNA. EBV replication was detected in both hairy leukoplakia and normal tongue tissues. Valacyclovir treatment completely abrogated EBV replication in vivo, resulting in resolution of hairy leukoplakia when it was present. EBV replication returned in normal tongue epithelial cells after valacyclovir treatment. These data suggest that normal oral epithelium supports persistent EBV infection in individuals infected with HIV and that productive EBV replication is necessary but not sufficient for the pathogenesis of oral hairy leukoplakia.

    Topics: Acyclovir; Antiviral Agents; Biopsy; DNA-Binding Proteins; Epithelial Cells; Epstein-Barr Virus Infections; Herpesvirus 4, Human; HIV Infections; Humans; Leukoplakia, Hairy; Tongue; Trans-Activators; Valacyclovir; Valine; Viral Proteins; Virus Replication

2001
Drugs for non-HIV viral infections.
    The Medical letter on drugs and therapeutics, 1999, Dec-03, Volume: 41, Issue:1067

    Topics: 2-Aminopurine; Acetamides; Acyclovir; Aged; Amantadine; Animals; Anti-HIV Agents; Antiviral Agents; Child; Child, Preschool; Dose-Response Relationship, Drug; Drug Resistance, Microbial; Enzyme Inhibitors; Famciclovir; Ganciclovir; Guanidines; Guanine; Herpes Simplex; Herpes Zoster; History, 18th Century; HIV Infections; Humans; Injections, Intravenous; Interferon-alpha; Lamivudine; Neuraminidase; Oseltamivir; Pyrans; Rats; Ribavirin; Sialic Acids; Teratogens; Valacyclovir; Valine; Zanamivir

1999
The status of CMV viral load testing.
    AIDS clinical care, 1996, Volume: 8, Issue:10

    Studies reveal that using PCR to measure CMV viral load is a promising source of information on the prophylactic value of using oral ganciclovir and valaciclovir. One study showed the greatest effect of valaciclovir treatment in patients who were PCR viremic at baseline. This shows a preemptive effect in aborting the development of CMV disease. Another study demonstrated that CMV PCR could be used prospectively to follow patients with constitutional symptoms and low CD4 counts (less than 50) in order to detect early development of asymptomatic CMV retinitis. The continued refinement of this technology and its ultimate commercial availability promise to revolutionize the management of CMV disease in advanced stage HIV infection.

    Topics: Acyclovir; Administration, Oral; Antiviral Agents; CD4 Lymphocyte Count; Cytomegalovirus; Cytomegalovirus Infections; Ganciclovir; HIV Infections; Humans; Polymerase Chain Reaction; Prospective Studies; Valacyclovir; Valine; Viral Load; Viremia

1996
CTG studies yield results. AIDS Clinical Trials Group.
    NIAID AIDS agenda, 1995,Spring

    NIAID's AIDS Clinical Trials Group (ACTG) has completed several studies and their findings are reported. Findings from two studies, ACTG 081, involving three therapies for pneumonia prevention, and ACTG 981, examining fluconazole for preventing fungal infections, are reported in The New England Journal of Medicine (March 16, 1995). Other studies reviewed include ACTG 152, using AZT alone and in combination in children, and ACTG 204, examining the effectiveness of valacyclovir and two different doses of acyclovir in preventing cytomegalovirus end stage-organ disease and survival extension.

    Topics: Acyclovir; Child; Clinical Trials as Topic; Cytomegalovirus Infections; Didanosine; Drug Therapy, Combination; Fluconazole; HIV Infections; Humans; Mycoses; Pneumonia, Pneumocystis; Valacyclovir; Valine; Zidovudine

1995