Valaciclovir versus aciclovir for herpes simplex virus infection in                HIV-infected individuals: two randomized trials

Conant, Marcus A.; Schacker, Timothy W.; Murphy, Robert L.; Gold, Jonathan W. M.; Crutchfield, Lila; Crooks, R. J.

doi:10.1258/0956462021924550

Cited by 102 publications

(58 citation statements)

References 23 publications

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“…Antiviral therapy also resulted in lower (arithmetic) genome copy numbers of HSV-1 and EBV (data not shown) and significantly fewer adults who shed EBV at consecutive appointments compared with placebo (P ϭ 0.03). These findings are consistent with the observed effects of acyclovir and valacyclovir on HSV and EBV replication (4,16,18,54,77,87) and clearly demonstrate that the antiviral benefit extended a few days after administration.…”

Section: Discussionsupporting

confidence: 89%

Effect of Prophylactic Valacyclovir on the Presence of Human Herpesvirus DNA in Saliva of Healthy Individuals after Dental Treatment

Miller¹,

Avdiushko²,

Danaher³

et al. 2005

J Clin Microbiol

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Human herpesviruses (HHVs) are ubiquitous pathogens that intermittently reactivate from latency. Transmission is believed to be facilitated by their frequent appearance in saliva. This study sought to understand the factors that influence the appearance of these viruses in saliva by examining the prevalence, pattern, and quantity of all eight HHVs in saliva of immunocompetent adults with a history of recurrent oral herpes simplex virus (HSV) infections following dental treatment and antiviral therapy. Valacyclovir or matched placebo was given (2 g twice on the day of treatment and 1 g twice the following day) to 125 patients in a randomized, double-blind controlled trial. Saliva, collected on the day of dental treatment and 3 and 7 days later, was analyzed using real-time quantitative PCR. At all visits, HHVs coinfected saliva. Over the course of the week, the DNAs of HHV-6 and HHV-7 were detected significantly more often (97% to 99% of patients) than Epstein-Barr virus (EBV; 64.8%), HSV-1 (13.0%), HHV-8 (3.2%), cytomegalovirus (2.4%), HSV-2 (0%), and varicella-zoster virus (0%), irrespective of drug treatment (P < 0.002). Mean genome copy numbers were highest for HSV-1 and HHV-6. Dental treatment did not influence asymptomatic viral shedding patterns. However, valacyclovir treatment resulted in significantly fewer patients shedding EBV at both postoperative visits compared with placebo (P < 0.008). These results suggest that HHVs are simultaneously present in the saliva of healthy adults at levels that could facilitate transmission, and valacyclovir therapy decreases the prevalence of EBV in saliva but has little effect on HHV-6 and HHV-7.Herpesviruses are ubiquitous pathogens that infect many animal species, including humans. Eight distinct members of the human Herpesviridae family have been identified. They include herpes simplex virus type 1 (HSV-1), HSV-2, varicellazoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus 6 (HHV-6), HHV-7, and HHV-8 (Kaposi's sarcoma herpesvirus [KSHV]) (62, 81). These large DNA viruses each express more than 70 genes that specify a number of proteins and enzymes that can cause destruction of infected cells during the lytic infection (12,63). Following the initial lytic infection, HHVs establish a latent state in a diverse group of cells that ensures survival of the viral genome throughout the life of the host. Periodic reactivation and viral recrudescence (i.e., appearance with or without clinical symptoms) occur after stress and alterations in immune surveillance. Frank immunosuppression is associated with more severe disease and complications (e.g., encephalitis, pneumonia, hepatitis, and various forms of cancer) (2,7,13,14,40,53,57,60,67,68,78,83,84).Over 95% of the adult population are infected with HHVs (28,39,70,71,86). Infections occur following intimate contact with virus-laden secretions and in some case by fomites (e.g., nurseries, day care centers) (22,72). Saliva harbors most of the HHVs and appears to be an important mode for viru...

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Section: Discussionsupporting

confidence: 89%

Effect of Prophylactic Valacyclovir on the Presence of Human Herpesvirus DNA in Saliva of Healthy Individuals after Dental Treatment

Miller¹,

Avdiushko²,

Danaher³

et al. 2005

J Clin Microbiol

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“…The potential clinical benefit of ACV or the prodrug version valacyclovir in treating HIV/HSV-2 co-infection has been tested in large clinical trials (35)(36)(37). HIV co-infection with HSV-2 can exacerbate disease progression (38,39).…”

Section: Discussionmentioning

confidence: 99%

Mechanisms Associated with HIV-1 Resistance to Acyclovir by the V75I Mutation in Reverse Transcriptase

Tchesnokov

Obikhod

Massud

et al. 2009

Journal of Biological Chemistry

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It has recently been demonstrated that the anti-herpetic drug acyclovir (ACV) also displays antiviral activity against the human immunodeficiency virus type 1 (HIV-1). The triphosphate form of ACV is accepted by HIV-1 reverse transcriptase (RT), and subsequent incorporation leads to classical chain termination. Like all approved nucleoside analogue RT inhibitors (NRTIs), the selective pressure of ACV is associated with the emergence of resistance. The V75I mutation in HIV-1 RT appears to be dominant in this regard. By itself, this mutation is usually not associated with resistance to currently approved NRTIs. Here we studied the underlying biochemical mechanism. We demonstrate that V75I is also selected under the selective pressure of a monophosphorylated prodrug that was designed to bypass the bottleneck in drug activation to the triphosphate form (ACV-TP). Pre-steady-state kinetics reveal that V75I discriminates against the inhibitor at the level of catalysis, whereas binding of the inhibitor remains largely unaffected. The incorporated ACV-monophosphate (ACV-MP) is vulnerable to excision in the presence of the pyrophosphate donor ATP. V75I compromises binding of the next nucleotide that can otherwise provide a certain degree of protection from excision. Collectively, the results of this study suggest that ACV is sensitive to two different resistance pathways, which warrants further investigation regarding the detailed resistance profile of ACV. Such studies will be crucial in assessing the potential clinical utility of ACV and its derivatives in combination with established NRTIs.

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“…Resistance is a high possibility in HIV+ patients. Antiviral treatment has been shown to be efective in HIV+ patients as well [59,60]. However, antiviral treatment has not been found to be efective in preventing the transmission of HIV or HSV to the possible partner [61,62].…”

Section: Hsv Management In Hiv-positive Patientsmentioning

confidence: 99%

Genital Herpes

Emre¹,

Akkus²

2017

Fundamentals of Sexually Transmitted Infections

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Genital herpes simplex virus (HSV) infections are among the most commonly seen sexually transmited infections in the world. Genital herpes is a serious health problem because the infection continues through life with remissions and relapses, it causes recurring painful ulcers, and there is no known cure for it. The real prevalence of the genital herpes infection is unknown due to asymptomatic cases. The majority of infected individuals are not aware of the infection due to short duration of symptoms and signs or its asymptomatic nature. The clinical presentation of genital herpes shows certain differences in terms of the primary atack following the irst encounter with the virus and recurrent atacks. There is a strong relationship between HSV-2 positivity and human immunodeiciency virus (HIV). A serious complication of genital herpes in the mother during pregnancy, neonatal herpes, has a mortality risk of 60% if not treated. Antiviral therapy is safe and efective, for both episodic treatment and chronic suppression of HSV. Epidemiology, clinical presentation, laboratory, and treatment options of genital herpes are summarized in this chapter.

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Valaciclovir versus aciclovir for herpes simplex virus infection in HIV-infected individuals: two randomized trials

Cited by 102 publications

References 23 publications

Effect of Prophylactic Valacyclovir on the Presence of Human Herpesvirus DNA in Saliva of Healthy Individuals after Dental Treatment

Effect of Prophylactic Valacyclovir on the Presence of Human Herpesvirus DNA in Saliva of Healthy Individuals after Dental Treatment

Mechanisms Associated with HIV-1 Resistance to Acyclovir by the V75I Mutation in Reverse Transcriptase

Genital Herpes

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