Diagnosis and Management of Genital Herpes: Key Questions and Review of the Evidence for the 2021 Centers for Disease Control and Prevention Sexually Transmitted Infections Treatment Guidelines

Johnston, Christine

doi:10.1093/cid/ciab1056

Cited by 13 publications

(19 citation statements)

References 75 publications

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“…Считается, что ГГ преимущественно возникает после заражения ВПГ-2, однако за последние десятилетия число случаев ГГ, вызванных ВПГ-1, увеличилось, особенно в промышленно разви-тых странах [1 -2]. Вирус может присутствовать в половых путях бессимптомно, что приводит к передаче половым партнёрам или новорождённым, если он присутствует в половых путях во время родов [3]. Инфицирование ВПГ-2 утраивает риск заражения вирусом иммунодефицита человека (ВИЧ) при незащищённом половом контакте [4].…”

Section: Introductionunclassified

Antimicrobial peptides for treatment of patients with herpes virus-associated chronic prostatitis

2023

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Introduction. Genital herpes is a chronic sexually transmitted infection characterised by recurrent self-limiting genital ulcers caused by herpes simplex virus type 1 (HSV-1) or type 2 (HSV-2) and can be associated with chronic prostatitis (CP).Objective. To determine the efficacy of cytokines-antimicrobial peptides complex in therapy of patients with herpes virus-associated chronic prostatitis.Materials & methods. The pilot, open, prospective, non-comparative study included 23 patients who were followed up for CP for a mean of 9.7 ± 4.2 years. All were diagnosed with abacterial CP / chronic pelvic pain syndrome (CPPS) with signs of inflammation and detection of HSV DNA in urethral swabs by polymerase chain reaction (PCR). Prescribed therapy: Tab. Valaciclovir 500 mg b.i.d. p.o. for 10 days, Tab. Ketoprofen 100 mg q.d. for 5 days, Supp. Superlymph 10 IU q.d. p.r. q.h.s. for 20 days. The results were evaluated at the end of therapy, 3 and 6 months after its completion.Results. At the end of therapy, the leukocytes count in prostate secretion decreased by almost five times and remained stable throughout the entire follow-up period. The total symptom scale score at the end of therapy decreased from 22.96 ± 6.01 to 6.61 ± 3.71 points (p < 0.05). There was also a change in the perception of pain on a visual analog scale. If, before the start of treatment, 14 patients (60.9%) assessed the pain intensity as “severe” and only two (8.7%) had “weak” pain intensity, then after the end of therapy, none of the patients had severe pain, 21 (91.3%) patients noted "mild" pain and in 2 patients (8.7%) the intensity of pain was regarded as "average". Quality of life improved from baseline 8.23 ± 1.91 points to 2.43 ± 1.41 points immediately after completion of therapy (p < 0.05). Three months after therapy, patients assessed the quality of life as 2.43 ± 1.41 points, and six months later, as 2.81 ± 1.21 points. During the first three months, one patient experienced a HPV-relapse; one more — within the next three months. These patients underwent a second course according to a similar scheme. None of the patients reported significant side effects on any component of the therapeutic complex.Conclusion. In abacterial CP/CPPS, a herpes infection should be identified. Being neurotropic, HSV can cause / exacerbate the pain characteristic of CP/CPPS. In case of persistent pain, HSV infection should be excluded. In the treatment of patients with herpes virus-associated abacterial CP, Supp. Superlymph showed good immediate and long-term results.

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Section: Introductionunclassified

Antimicrobial peptides for treatment of patients with herpes virus-associated chronic prostatitis

2023

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“…Despite the oral bioavailability advantages of valacyclovir, intravenous acyclovir continues to be used in pediatric and neonatal populations due to their increased risk of severe disease (Abdalla et al, 2020;Harris and Holmes, 2017;Poole and Kimberlin, 2018). Intravenous acyclovir is also administered for adult patients with symptoms of serious HSV disease such as hepatitis, meningitis, or encephalitis (Johnston, 2022). The intravenous administration is advantageous for rapidly increasing systemic acyclovir concentrations, and after severe symptoms have subsided, patients transition to oral suppressive therapy.…”

Section: Introductionmentioning

confidence: 99%

Cell and Tissue Specific Metabolism of Nucleoside and Nucleotide Drugs: Case Studies and Implications for Precision Medicine

2022

Drug Metab Dispos

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Many clinically used antiviral drugs are nucleoside or nucleotide analogue drugs, which have a unique mechanism of action that requires intracellular phosphorylation. This dependence on intracellular activation presents novel challenges for the discovery and development of nucleoside/nucleotide analogue drugs. Contrary to many small molecule drug development programs that rely on plasma pharmacokinetics and systemic exposures, the precise mechanisms that result in efficacious intracellular nucleoside triphosphate concentrations must be understood in the process of nucleoside/nucleotide drug development. The importance is highlighted here, using the following as case studies: the herpes treatment acyclovir, the cytomegalovirus therapy ganciclovir, and human immunodeficiency virus (HIV) treatments based on tenofovir, which are also in use for HIV prophylaxis. For each drug, the specificity of metabolism that results in its activation in different cells or tissues is discussed, and the implications explored. Acyclovir's dependence on a viral enzyme for activation provides selective pressure for resistance mutations.Ganciclovir is also dependent on a viral enzyme for activation, and suicide gene therapy capitalizes on that for a novel oncology treatment. The tissue of most relevance for tenofovir activation depends on its use as treatment or as prophylaxis, and the pharmacogenomics and drug-drug interactions in those tissues must be considered. Finally, differential metabolism of different tenofovir prodrugs and its effects on toxicity risk are explored. Taken together, these examples highlight the importance of understanding tissue specific metabolism for optimal use of nucleoside/nucleotide drugs in the clinic.

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“…2 Furthermore, epidemiological evidence strongly shows that individuals with HSV-2 infection have a three-fold higher risk of acquiring an HIV infection. 1 To date, no vaccine is available for the prevention of this lifelong highly prevalent STI. Oral nucleoside analogs such as acyclovir, valacyclovir, or famciclovir are the only approved therapies for the management of GH that target the HSV DNA polymerase.…”

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confidence: 99%

“…Oral nucleoside analogs such as acyclovir, valacyclovir, or famciclovir are the only approved therapies for the management of GH that target the HSV DNA polymerase. 1,3 However, the emergence of drug-resistant strains to nucleoside analogs and side effects associated with oral nucleoside analogs necessitates the development of new therapies for GH. 3 BX795 is a weakly basic monoaminopyrimidine derivative that was previously explored for cancer therapy.…”

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confidence: 99%

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Oral Self-Nanoemulsifying System Containing Ionic Liquid of BX795 Is Effective against Genital HSV-2 Infection in Mice

Sutar,

Singh,

Dhoble

et al. 2023

ACS Infect. Dis.

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BX795 is an emerging drug candidate that has shown a lot of promise as a next-generation non-nucleoside antiviral agent for the topical treatment of herpes simplex virus type-1 (HSV-1) and herpes simplex virus type-2 (HSV-2) infections. Our studies indicated that BX795 has limited oral bioavailability, which could be attributed to its low and pH-dependent solubility. Lipidbased formulations such as self-nanoemulsifying systems (SNESs) can improve the solubility and oral bioavailability of BX795, but the poor lipid solubility of BX795 further limits the development of SNES. To improve the loading of BX795 into SNES, we evaluated the ability of various bulky and biocompatible anions to transform BX795 into an ionic liquid (IL) with higher lipid solubility. Our studies showed that sodium lauryl sulfate and docusate sodium were able to transform BX795 into IL. Compared to pure BX795, the developed BX795 ILs showed differential in vitro cytocompatibility to HeLa cells but exhibited similar in vitro antiviral activity against HSV-2. Interestingly, BX795 docusate (BX795-Doc), an IL of BX795 with ∼135-fold higher lipid solubility than pure BX795, could be successfully incorporated into an SNES, and the developed BX795-Doc-SNES could readily form nanoemulsions of size ≤200 nm irrespective of the pH of the buffer used for dilution. Our in vitro studies showed that BX795-Doc-SNES retained the inherent antiviral activity against HSV-2 and showed similar in vitro cytocompatibility, indicating the availability of BX795 from the SNES in vitro. Finally, orally delivered SNES containing BX795-Doc showed a significant reduction in HSV-2 infection in mice compared to the untreated control. Thus, the transformation of BX795 into IL and the subsequent incorporation of the BX795 IL into the SNES are an effective strategy to improve oral therapy of genital herpes infection.

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Diagnosis and Management of Genital Herpes: Key Questions and Review of the Evidence for the 2021 Centers for Disease Control and Prevention Sexually Transmitted Infections Treatment Guidelines

Cited by 13 publications

References 75 publications

Antimicrobial peptides for treatment of patients with herpes virus-associated chronic prostatitis

Antimicrobial peptides for treatment of patients with herpes virus-associated chronic prostatitis

Cell and Tissue Specific Metabolism of Nucleoside and Nucleotide Drugs: Case Studies and Implications for Precision Medicine

Oral Self-Nanoemulsifying System Containing Ionic Liquid of BX795 Is Effective against Genital HSV-2 Infection in Mice

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