What are the symptoms that can be mistaken for genital herpes. How to differentiate between herpes and other skin conditions. When should you seek medical advice for herpes-like symptoms. What are the most effective methods for diagnosing genital herpes.

Understanding Herpes Simplex Virus: Types and Transmission

The Herpes Simplex Virus (HSV) is a common infection that often goes unrecognized due to its ability to mimic other conditions. There are two primary types of HSV:

• HSV-1: Typically associated with oral herpes, causing cold sores or fever blisters around the mouth and nose
• HSV-2: Commonly linked to genital herpes, resulting in sores or blisters in the genital area

Transmission of HSV occurs through skin-to-skin contact, including kissing and sexual activity. It’s important to note that HSV-1 can also cause genital herpes through oral sex if the person performing it has an active oral infection.

Asymptomatic Nature of Herpes

Surprisingly, only one in three people infected with herpes will exhibit noticeable symptoms. This means that many individuals may unknowingly carry and transmit the virus. When symptoms do appear, they can often be mistaken for other conditions, leading to confusion and potential misdiagnosis.

Conditions Commonly Mistaken for Genital Herpes

Several health issues can present symptoms similar to genital herpes, making accurate diagnosis crucial. Some of these conditions include:

1. Other sexually transmitted infections (STIs) like syphilis or genital warts (HPV)
2. Irritation caused by shaving
3. Ingrown hairs
4. Bacterial vaginosis (BV)
5. Pimples or acne in the genital area
6. Yeast infections
7. Hemorrhoids
8. Insect bites

Distinguishing Features of Herpes Symptoms

While herpes symptoms can vary, they typically include:

• Clusters of small, painful blisters
• Itching or tingling sensation before outbreak
• Flu-like symptoms during initial outbreak
• Recurrent outbreaks in the same area

Importance of Accurate Diagnosis for Herpes-Like Symptoms

Given the similarity between herpes symptoms and other conditions, proper diagnosis is essential. The only way to confirm whether you have herpes is through testing. Options for diagnosis include:

• Swab tests of active lesions
• Blood tests to detect HSV antibodies
• Visual examination by a healthcare professional

Early diagnosis can help manage symptoms, reduce transmission risk, and provide peace of mind.

Prevention and Management of Herpes Transmission

While herpes is a lifelong condition, there are ways to minimize transmission risk:

• Abstain from sexual contact during active outbreaks
• Use condoms consistently, although they don’t provide complete protection
• Communicate openly with sexual partners about STI status
• Consider daily antiviral medication to reduce outbreaks and transmission risk

The Role of Stress in Herpes Outbreaks

Stress is a known trigger for herpes outbreaks. Managing stress through relaxation techniques, adequate sleep, and a healthy lifestyle can help reduce the frequency and severity of outbreaks.

Seeking Professional Help: When to Consult a Healthcare Provider

If you notice any unusual symptoms in your genital area, it’s crucial to seek medical advice. A healthcare provider can:

• Perform a physical examination
• Order appropriate tests
• Provide an accurate diagnosis
• Recommend suitable treatment options

Remember, early intervention can lead to better management of symptoms and reduced risk of complications.

Treatment Options for Genital Herpes

While there is no cure for herpes, several treatment options can help manage symptoms and reduce outbreak frequency:

• Antiviral medications (e.g., acyclovir, valacyclovir)
• Topical creams for pain relief
• Over-the-counter pain relievers
• Warm baths to soothe affected areas

Your healthcare provider can help determine the best treatment plan based on your individual needs and the severity of your symptoms.

Living with Genital Herpes: Emotional and Psychological Aspects

A diagnosis of genital herpes can be emotionally challenging. It’s important to remember that:

• Herpes is a common condition affecting millions of people worldwide
• With proper management, most people with herpes lead normal, healthy lives
• Support groups and counseling services are available for those struggling with their diagnosis

Open communication with partners and healthcare providers can help alleviate anxiety and promote better overall well-being.

Advances in Herpes Research: Future Treatment Possibilities

Ongoing research in the field of herpes treatment offers hope for improved management and potential cures:

• Development of more effective antiviral medications
• Exploration of gene editing techniques to target the herpes virus
• Investigation of therapeutic vaccines to boost immune response
• Studies on novel drug delivery methods for better symptom control

While these advancements are promising, it’s important to focus on current best practices for managing herpes and preventing transmission.

The Importance of Continued Research and Education

As our understanding of herpes and other STIs evolves, ongoing education and awareness campaigns play a crucial role in:

• Reducing stigma associated with herpes and other STIs
• Promoting regular testing and early diagnosis
• Encouraging open discussions about sexual health
• Improving overall public health outcomes

By staying informed and proactive about sexual health, individuals can make better decisions and contribute to a healthier society.

Conclusion: Empowerment Through Knowledge and Action

While the symptoms of genital herpes can be mistaken for various other conditions, understanding the key differences and seeking proper medical advice is crucial. Remember:

• Many conditions can mimic herpes symptoms
• Only a healthcare professional can provide an accurate diagnosis
• Early detection and treatment can significantly improve quality of life
• With proper management, individuals with herpes can lead fulfilling lives

By staying informed, practicing safe sex, and maintaining open communication with healthcare providers and partners, you can take control of your sexual health and well-being.

Whether you’re concerned about potential herpes symptoms or simply want to stay informed about sexual health, remember that knowledge is power. Regular check-ups, open discussions, and a proactive approach to health can make a significant difference in managing herpes and other STIs.

As research continues to advance our understanding of herpes and potential treatments, it’s important to stay updated on the latest developments. Your healthcare provider can be an excellent resource for current information and personalized advice.

Ultimately, while a herpes diagnosis can be challenging, it doesn’t define you. With the right support, information, and treatment, you can continue to live a healthy, fulfilling life. Remember, millions of people worldwide manage herpes successfully every day, and with proper care and attention, you can too.

What can be mistaken for Herpes?

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Noticing a sign of Herpes can be worrying, but don’t panic. It is easy to mistake Herpes for something else. Here, we explain the other potential causes for Herpes-like symptoms and how to find out if it is Herpes, or not.

The Herpes Simplex Virus, also known as Herpes, is often misunderstood yet an extremely common infection. The symptoms of Herpes usually form as sores and blisters in the oral and/or genital area, depending on which type of Herpes it is. However, it is not always easy to differentiate the symptoms from other health or skin conditions.

The basics

Firstly, let’s understand the two most common types of
Herpes:

• Oral Herpes (HSV-1). This appears around the
  lips and nose or inside the mouth, commonly known as ‘cold sores’ or ‘fever
  blisters’
• Genital
  Herpes (HSV-2). This appears as sores or blisters in the genital area.

Often, people with Herpes will not show any symptoms. In
fact, only 1 in 3 people will have symptoms, whilst the majority will have
either mild symptoms or none. Therefore, it is highly likely that a person may
not even be aware that they have the virus.

If someone
is infected with Herpes, they can spread the virus to another person through skin
to skin contact, including kissing and sex. HSV-2 can be passed to a partner
through oral sex, if the person performing oral sex is infected with HSV-1.

When the virus is passed from one person to another, this most often occurs when either person has active sores or blisters. So, if you have visible symptoms, you should always refrain from sexual contact. However, Herpes can also be passed when symptoms are not present. Using condoms can help to prevent spreading or catching Herpes, but since condoms do not cover the entire genital area, they are not 100% effective.

What else can resemble Herpes?

Herpes
symptoms can be mistaken for many other things, including:

• A different STI which causes visible lesions, such as Syphilis or genital warts (HPV)
• Irritation caused by shaving
• Ingrown hairs
• Bacterial vaginosis (BV)
• Pimples
• Yeast infections
• Haemorrhoids
• Bug bites.

How to be sure whether it is Herpes or not

If you have noticed symptoms that are concerning you, getting
tested is the only way to be sure whether it is Herpes or not. You can choose
to book an appointment at one of our nationwide clinics or test at
home with one of our convenient home test
kits.

If you do have symptoms, a simple swab test can
provide you with the peace of mind you need. Alternatively, why not consider
our Blemish Screen? This swab test will detect Syphilis, Herpes and HPV, so you
can be sure which (if any) is causing your symptoms. This is available as a home test
kit, or you can book in at one of our clinics. Find out
more here.

With our convenient Photo Consultation service, you can send a photo of your lesion(s) to our expert doctor who will review your photograph and recommend the next steps based on your symptoms. If you feel unsure about which test or screen to book, this is the perfect option for you.

If you do not have symptoms but would like to find out
whether you have the Herpes virus, a simple blood test will tell
you this.

Read more about Herpes on our website.

Sources

[1] Health.com

[2] Everyday
Health

Genital Herpes Treatment | Everyday Health

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How to treat genital herpes on the genitals

04/28/2022

What is genital herpes,

how to find out that it is he

Genital herpes is a chronic viral infection that can be caused by herpes simplex viruses type I and II. Previously thought to be an infectious disease
is caused only by the second type of virus, and the “cold” on the lips is the antics of the type 1 virus, but oral sex has changed our lives. Recently, the proportion of cases of genital herpes caused by HSV type I has been increasing, which is especially noticeable among MSM and young women. Genital herpes caused by type II HSV is characterized by a more severe course and frequent relapses.

Transmission of the virus occurs through sexual contact with all types of sex, as well as contact with saliva, semen and other body fluids containing the virus.

In most people with no symptoms or with mild clinical manifestations, the diagnosis of genital herpes may not be established. Mild symptoms may go unnoticed or be mistaken for other skin conditions (pimples or ingrown hairs). This is not cool, because if a person does not know that he has herpes, he does not follow enough preventive measures so as not to transmit the virus to his sexual partner.

With symptomatic genital herpes, one or more blisters/vesicles usually appear in the genital area. The blisters burst and leave painful sores that may take a week or more to heal. Flu-like symptoms, such as fever, body aches, or swollen lymph nodes, may accompany or precede the rash.

Disease diagnosis

The diagnosis is established clinically – in the presence of characteristic changes on the lips, wings of the nose or genitals – but requires confirmation by PCR (detection of the genetic material of the virus in the fluid from the vesicles or discharge of ulcers). With a negative PCR result, serological diagnosis can help – a study of whether there are specific antibodies to type I and type II viruses in the blood.

If no rash or other symptoms (pain, burning) have ever been reported, routine examination is not indicated. True, there are two exceptions: planning pregnancy (it is necessary to check both partners) or a high risk of genital herpes (more than 10 sexual partners in a lifetime, HIV infection or detection / treatment of other sexually transmitted infections beforehand).

But if there is even the slightest suspicion that you may have genital herpes, especially when some moderate rashes appear, even those that are not very similar to herpes in description, you should consult a doctor to clarify their cause.

How to treat genital herpes

What men and women do when rashes appear in intimate areas, what they don’t smear, what candles and where they just don’t insert. In fact, there is nothing more effective than a real antiviral therapy that has been proven to work. This is the basis of the treatment of herpes. The main thing is to understand what and who we are going to treat.

For antiviral treatment, widely known drugs are used: acyclovir, valaciclovir or famciclovir. Further in the article we will focus only on the forms of drugs for oral administration. There is also an ointment of acyclovir, it is even very popular, but in fact, bioavailability, the ability of the active component to penetrate into the site of the fight against the virus, local therapy (ointment) is low. Such therapy will not be effective and may lead to the formation of virus resistance to acyclovir.

In some cases, the treatment is given intravenously, but often these are severe cases that require hospitalization, so only tablets are discussed.

Different clinical situations require us to have a completely different approach to how to treat herpes on the genitals (labia, penis). Of great importance is whether this is a primary episode or a repeated one, and if it is repeated, then how often do relapses occur?

The initial episode can be quite intense and prolonged, with a large lesion and severe ulcerative defects, so treatment is necessary to reduce the duration of the process and accelerate healing.

Almost all people who have had a symptomatic initial episode of genital herpes experience recurrences later on. Of course, subsequent relapses may be less intense and not as long.

Each episode of exacerbation of genital herpes should be treated with standard courses of antiviral therapy, which in the future can reduce the number of episodes and the intensity of manifestations, and maybe remission will occur for some time.

Taking medications should be started as early as possible, preferably in the first 24 hours from the appearance of rashes or even in the prodromal phase – when discomfort appears: for example, burning / itching, where rashes should appear, but they are not there yet. Some people know their triggers for genital herpes flare-ups and start taking medication early (eg, before menstruation, climate change, stressful situations), but there are no official recommendations for proactive therapy.

According to WHO and European recommendations, as well as CDC recommendations, if a patient has more than six relapses of a herpes infection per year, this is already an indication for the so-called suppressive / suppressive therapy: taking the drug in one dose daily for a long period (usually at least a year or more reassessing the need for further intake every year). Suppressive therapy reduces relapse rate by 70-80%! And it’s safe – there are studies that confirm the safety of long-term use of drugs (for several years in a row).

But, again, if there are more than six relapses, but less than ten, these are the same dosages, and if there are more than ten relapses, they are completely different.

Genital herpes during pregnancy and

in HIV positive

In some cases, daily antiviral drugs are given to men during conception to prevent transmission of the virus to a partner. And in late pregnancy, antiviral drugs can be prescribed to the mother to prevent infection of the fetus.

In the treatment of genital herpes in people with positive and negative HIV status, there are also differences in the doses and duration of the drugs. And, in general, many factors can influence the choice of drug, dose, regimen and duration of administration: age, pregnancy (it all depends on the timing of pregnancy and whether it is a primary infection or a repeated one), the effectiveness of previous therapy and other factors, so here you can not do without a specialist who will help sort everything out. Let’s go back to the fact that if you are not sure that it is herpes, only a doctor can correctly assess the situation and choose tactics.

Is vaccination possible

Despite the fact that the effectiveness of long-term use of anti-herpetic drugs is quite high, not all patients can achieve significant improvements, so in Russia one can resort to the last attempt to control the herpes virus – this is vaccination. Why only in Russia? Because there are no registered vaccines against herpes infection types I, II in the world. In Russia, there is and has been used since 1985 a vaccine against herpes viruses of types I and II – it is called Vitagerpavak . The mechanism of action is to enhance the specific immune response of the organism itself against the background of the introduction of virus antigens. The vaccination course includes two series with an interval of six months, and each series consists of 5 doses, 1 dose per week. To our great regret, clinical studies on its testing were carried out only in our country, and the evidence base for its effectiveness is small. But clinical experience shows that it can improve the quality of life in most patients suffering from severe manifestations and / or frequent recurrences of infections caused by herpes simplex viruses.

It is impossible to cure herpes once and for all, but there are many ways to effectively fight it, reduce the number of relapses, the duration and severity of their course, and improve the quality of life of patients. And which of these methods is suitable for each specific person, the doctor will tell you. In our clinic, we prescribe only informative tests and effective treatment for herpes, and we treat each patient in a friendly and understanding manner.

Author:

Infectious disease specialist, parasitologist Konovalova Anastasia Aleksandrovna

Sources:

https://apps.who.int/iris/bitstream/handle/10665/250693/9789241549875-eng.pdf

https://www.cdc.gov/std/treatment-guidelines/herpes. htm

https://emedicine.medscape.com/article/783113-treatment

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Recommendations for the treatment of genital herpes uMEDp

Genital herpes is a sexually transmitted disease that causes recurrent genital lesions. The causative agents are herpes simplex viruses, predominantly type II, although the etiological role of type I virus has increased significantly over the past two decades.

Table. Doses of drugs for the treatment of genital herpes

Despite the severe clinical manifestations of the primary infection and potentially dangerous complications leading to hospitalization and death, genital herpes has received insufficient attention in the non-specialized medical literature. Meanwhile, the spread of the disease has become epidemic, which is associated with a large number of undiagnosed and untreated cases and a high frequency of asymptomatic and subclinical course (2). Symptomatic genital herpes affects 86 million people worldwide. The total number of people infected with the virus cannot be determined, but it is assumed that, for example, in the United States, every fourth to sixth inhabitant of the virus is a carrier (3-4).

The main means for the treatment of genital herpes are antiviral drugs from the group of nucleoside analogues. The most widely used drug continues to be acyclovir, which appeared on the world pharmaceutical market about 20 years ago. Being an analogue of nucleosides, the drug undergoes phosphorylation under the influence of viral thymidine kinase, and then, with the help of host cell enzymes, it turns into di- and triphosphate. The latter acts as a substrate for viral DNA polymerase, thus leading to disruption of DNA virus replication.

The effectiveness of acyclovir for the treatment of genital herpes has been shown in numerous clinical studies. When taken orally, the drug is well tolerated by patients and has an excellent benefit/risk ratio. Side effects develop in less than 10% of patients and are usually limited to nausea, vomiting and headache (5).

The main disadvantages of acyclovir include low bioavailability (15-20%) and a short half-life from tissues (0.7 h) and blood plasma (2.7 h) (5). To maintain therapeutic concentrations in the body, the drug must be taken up to 5 times a day, which negatively affects the accuracy of the treatment regimen by patients and may lead to a decrease in the effectiveness of therapy.

The pharmacokinetic shortcomings of acyclovir were largely overcome in the development of valaciclovir, a prodrug metabolized in the intestinal wall and liver to form acyclovir. Valaciclovir has a significantly higher oral bioavailability (54%) and provides higher and longer serum concentrations of acyclovir (6-8), which allows it to be taken twice a day. With repeated oral administration of valaciclovir in high doses (4-8 g/day), the concentrations of the active substance in the blood are comparable to the concentrations created by intravenous administration of acyclovir (5-10 mg/kg 3 times/day) (8, 9).

The kinetics of acyclovir released from valacyclovir is similar to that of acyclovir preparations in healthy volunteers, patients with kidney disease, HIV infection (10), elderly patients and senile volunteers, both receiving and not receiving concomitant diuretic therapy (11).

The safety profile of valacyclovir does not differ significantly from that of acyclovir. Better absorption results in fewer gastrointestinal adverse reactions (5). Thrombotic microangiopathy has been described in patients with AIDS and other immune disorders when using valaciclovir in high doses (8 g/day), but the causal relationship between the drug and this complication has not been conclusively confirmed (12). In patients receiving high doses of valaciclovir after kidney transplantation, thrombotic microangiopathy was not observed (13). In addition, for the treatment of genital herpes, the drug is used in much lower doses.

The third analogue of nucleosides, famciclovir, like valaciclovir, is a prodrug that is converted in the intestinal wall and in the liver into penciclovir. Penciclovir has a similar mechanism and spectrum of antiviral action to acyclovir, however, due to low bioavailability, it can only be used topically (5). With oral famciclovir, the bioavailability of penciclovir is 77% (14). Compared to acyclovir, penciclovir has a significantly longer half-life from tissues (10-20 hours) (15). Intracellular concentrations of penciclovir triphosphate exceed those of acyclovir triphosphate by about 30 times (16). However, herpes simplex virus DNA polymerase has a greater affinity for acyclovir triphosphate than for penciclovir triphosphate. Thus, the differences in mechanism of action between penciclovir and aciclovir are predominantly quantitative and tend to balance each other out (16).

Aciclovir and penciclovir do not differ in their activity against herpes simplex virus in cell culture, however, after acyclovir is discontinued, virus replication resumes much faster than after penciclovir is discontinued (13). Famciclovir is superior to valaciclovir in its ability to eliminate “competent latency”, i. e., the state in which the virus is able to reactivate and cause relapses of the disease (18, 19). In an observational study in patients treated with famciclovir (250 mg 3 times / day for 5 days), relapses within 1-6 months after the first episode developed less frequently than in patients treated with acyclovir (200 mg 5 times / day . within 5 days) (20).

Famciclovir has an excellent safety profile. A tolerability analysis based on the results of 13 clinical studies showed that the adverse reaction profile of famciclovir in patients with genital herpes (791 patients) did not differ from placebo (21). In studies on healthy male volunteers, no clinically significant pharmacokinetic interactions of famciclovir with allopurinol, digoxin, cimetidine, zidovudine, or theophylline have been identified (22). The bioavailability of penciclovir, which is formed during the metabolism of famciclovir, does not depend on food intake (23). Its pharmacokinetics do not differ between young and old people (24). When taken for 4–12 months in healthy male volunteers, the drug did not adversely affect sperm (25).

Aciclovir, valaciclovir and famciclovir show comparable clinical efficacy in reducing the duration and severity of genital herpes episodes and reducing virus shedding (26-28). However, they have no effect on dormant viruses.

Treatment first episode genital herpes

The first episode of primary genital herpes is considered the clinical manifestation of the disease in patients without antibodies to herpes simplex viruses type I or II. The first episode is characterized by the most severe course. As a rule, in addition to local lesions that persist for 2-3 weeks, systemic symptoms and regional adenopathy are observed. A small number of patients, more often immunocompromised, develop viral meningitis.

Symptomatic therapy of the first episode consists in the appointment of analgesics. Opioid drugs should be avoided as they cause constipation. Nucleoside analogues are used for etiotropic treatment.

Efficacy of oral acyclovir at a dose of 200 mg 5 times / day.
within 5-10 days is indicated in double-blind, placebo-controlled clinical trials (29, 30). In patients treated with acyclovir, the virus shedding period, crusting time, and healing time were significantly shortened. An increase in the oral daily dose of the drug to 4 g did not lead to an increase in the effectiveness of therapy (31). In addition, gastrointestinal side effects (8%) were significantly more common with the high dose than with the standard dose (0%).

In order to improve patient adherence to treatment, the US Centers for Disease Control and Prevention (CDC) recommends the use of acyclovir 400 mg 3 times a day, but this regimen is not approved by the FDA. Topical acyclovir cream is not effective (6). The addition of cream to oral therapy also did not improve clinical outcomes (32). In severe cases with neurological complications, acyclovir is recommended to be administered intravenously at 5-10 mg/kg 3 times a day (5).

Valaciclovir at a dose of 1 g 2 times / day. shows equal efficacy with acyclovir at a dose of 200 mg 5 times / day. in the first episode of genital herpes in immunocompetent patients (33). The tolerability of valacyclovir is similar to that of acyclovir (33). In different countries, valaciclovir is approved for the treatment of the first episode of genital herpes at a dose of 500 mg or 1 g 2 times a day. within 10 days (25).

Famciclovir has been studied in comparative clinical trials with acyclovir (200 mg 5 times a day) at doses of 125, 250 and 500 mg 3 times a day (27, 28). None of the studies showed significant differences between the comparison groups. For the treatment of genital herpes, famciclovir is recommended to prescribe 250 mg 3 times / day. within 5 days, with severe infection – 10 days (25).

Episodic treatment relapses genital virus

In clinical studies, with the use of acyclovir at a standard daily dose (200 mg 5 times / day) for the episodic treatment of relapses of genital herpes, a shortening of the period of virus shedding, crusting time and healing time was noted. The duration of symptoms and the time of occurrence of new relapses did not change under the influence of the drug (28, 34). The guidelines for the management of genital herpes, issued in 1998. The US Centers for Disease Control and Prevention (CDC) suggested the use of acyclovir in doses of 400 mg 3 times / day. or 800 mg 2 times / day. within 5 days. However, these treatment regimens have not been studied in adequate clinical trials.

When applied topically in the form of a 5% polyethylene glycol ointment, acyclovir resulted in a decrease in the period of virus shedding, but did not cause clinical improvement (6).

Valaciclovir at a dose of 500 or 1000 mg 2 times / day. for 5 days, administered on the first day after the onset of symptoms, significantly reduced the period of virus shedding and accelerated the healing of lesions compared with placebo (35). Tolerability of the drug did not differ from that of placebo. One study showed that fewer patients developed vesiculo-ulcerative lesions (by 10%) with valaciclovir than with placebo (25). The results of another study suggest, based on the natural period of virus shedding, that a 3-day course of treatment with valacyclovir is as effective as a 5-day course (36). In July 2001, the FDA approved a 3-day course of treatment for recurrences of genital herpes with valaciclovir (500 mg 2 times a day). Comparative studies with acyclovir showed equal clinical efficacy of both drugs (37). An important advantage of valaciclovir is a more convenient mode of application.

Famciclovir at doses of 125, 250, and 500 mg twice daily given within the first 6 hours of symptom onset resulted in a reduction in healing time, viral shedding time, and duration of edema of the lesions compared with placebo (38). When it was used, pain, burning, tingling, and soreness when touched were significantly reduced. The side effects of famciclovir did not differ from those of placebo. Famciclovir is recommended for the episodic treatment of recurrences of genital herpes at a dose of 125 mg 2 times a day. within 5 days. The advantages of famciclovir, as well as valaciclovir, are in a more convenient treatment regimen compared to acyclovir.

The effectiveness of episodic treatment of recurrences of genital herpes depends on the time of the start of taking the drugs. A Canadian study showed that when famciclovir was started within the first 6 hours after the onset of prodromal symptoms or the first genital lesions, there was a significant reduction in virus shedding and faster healing of the lesions. Moreover, taking the drug before the onset of virus shedding increased the likelihood of preventing virus shedding during a relapse (39). Relapse treatment should be started as soon as possible, so patients should always have a supply of the drug.

Ongoing suppressive therapy

Patients with frequent (more than 6-8 per year) and severe relapses, psychological trauma or disruption of a normal lifestyle caused by the disease are shown to continue suppressive therapy. For this purpose, acyclovir 400 mg 2 times / day is used for a long time (within 6-12 months); valaciclovir 500 mg 1 time / day. (with the number of relapses 10 or less per year) or 1000 mg 1 time / day. (with the number of relapses more than 10 per year) or famciclovir 250 mg 2 times / day. Daily aciclovir has been shown to reduce relapse rates by 80%, with 25-30% of patients not relapsing (40). Similar results were obtained in studies with valaciclovir and famciclovir. When using famciclovir at a daily dose of 500 mg, divided into 2 doses, for 16 weeks, relapses did not develop during the treatment period in 78% of patients (41), when using valaciclovir at the same dose – in 69% of patients (33). All three drugs have proven to be effective agents for long-term suppressive therapy of recurrent genital herpes. Apparently, the cost of the annual dose and the convenience of the regimen for the patient should be the decisive factors in choosing a particular drug.

Suppressive therapy is well tolerated. It has been shown to be safe with daily use for 5 years (42). However, before prescribing suppressive therapy, it is recommended to conduct hematological and biochemical studies and determine the state of kidney function. During the treatment period, patients should be under medical supervision, women are advised to avoid pregnancy.

Daily suppressive therapy leads to a significant reduction in asymptomatic viral shedding, but does not completely eliminate it. The patient should be warned when deciding on its appointment. As an alternative, the patient should be offered selective prophylaxis (for example, during periods of stress). To date, a reduction in the risk of infection transmission under the influence of suppressive therapy has not been proven.

Regardless of whether suppressive treatment is given or not, the recurrence rate decreases on average 7 years after the first episode, so lifelong treatment is usually not needed.

Treatment of genital herpes in pregnant women

Women suffering from genital herpes during pregnancy have an increased risk of spontaneous abortions and the birth of children with low weight. In rare cases, a congenital infection may develop in the fetus. The highest risk of infection is during the passage of the child through the birth canal. The risk of transmission has been estimated at 50% for primary maternal herpes during delivery and 0–3% for recurrent herpes (43). Most often, infection occurs from asymptomatic mothers (44).

In newborns, the disease occurs in three main forms: localized, with damage to the central nervous system, and disseminated. Mortality is 15% for infections involving the central nervous system and 57% for disseminated infection (45).

In order to reduce the risk of subclinical viral shedding and relapse episodes during labor, many clinicians recommend that pregnant women receive suppressive antiviral therapy. Nucleoside analogues are not officially approved for use during pregnancy, but many studies have shown the safety of acyclovir (46, 47). Valaciclovir and famciclovir, according to the FDA classification, belong to group B, i. e. to drugs for which no teratogenic effect has been detected in experiments on animals, and adequate clinical trials in humans have not been conducted. Studies are currently underway to determine the efficacy and safety of valaciclovir during pregnancy.

Data on the effectiveness of suppressive therapy in preventing infection in the fetus are extremely limited. In a randomized trial including 46 women with a first episode of genital herpes, it was not possible to determine the effectiveness of treatment with acyclovir started on
36 weeks of gestation, as none of the newborns developed an infection. However, in the group of patients receiving suppressive therapy, a significant decrease in the frequency of caesarean section was noted (48). In another placebo-controlled study that included 150 women with a history of genital herpes (49), it has been shown that acyclovir (200 mg 3 times / day), taken from the 38th week of pregnancy, is able to prevent recurrence of the disease. In patients treated with acyclovir, no relapse occurred in any case, while in the control group there were 33 relapses, 21 of them during childbirth.

Treatment of genital herpes , caused by aciclovir – resistant strains

Long-term treatment with nucleoside analogs is generally not associated with the risk of developing viral resistance. In immunocompetent patients receiving suppressive therapy, acyclovir-resistant strains of the herpes simplex virus were isolated, but no correlation was observed between in vitro resistance and the therapeutic efficacy of the drug (25). The most common mechanism for the development of resistance is a gene mutation that leads to impaired thymidine kinase production (50), so aciclovir-resistant strains usually show cross-resistance to penciclovir. Much less common are mutations that lead to dysfunction of thymidine kinase and DNA polymerase (50, 51). In these cases, selective resistance to one of the drugs is possible. Mathematical methods of analysis suggest that decades are needed to change the current model of virus resistance (52).

In immunocompromised patients with long-term use of antiviral drugs, resistance develops in about 5% of cases and can lead to treatment failure (53, 54). Clinically significant resistance has also been described in patients undergoing bone marrow transplantation (55).

Currently, foscarnet is considered as the drug of choice for the treatment of acyclovir-resistant infections caused by herpes simplex virus (56). It belongs to non-competitive inhibitors of viral DNA polymerase. The drug blocks the receptors for binding to viral DNA pyrophosphate and disrupts the elongation of its chain. Unlike acyclovir and penciclovir, it does not require thymidine kinase-mediated phosphorylation and is active against acyclovir-resistant thymidine kinase-deficient strains (56).

Foscarnet has a low oral bioavailability, so it is administered intravenously and topically. The effectiveness of intravenous foscarnet in genital herpes caused by acyclovir-resistant strains has been shown in several clinical studies. In an uncontrolled study, the drug was effective in 81% of patients with acyclovir-resistant genital herpes that developed on the background of HIV infection (57). In another study in patients with HIV infection, foscarnet was superior to vidarabine in terms of the healing time of herpes mucocutaneous lesions caused by acyclovir-resistant strains and the period of cessation of virus shedding (58). When applied topically, the drug did not show sufficient effectiveness (25).

Foscarnet is potentially toxic. Side effects include impaired kidney function, gastrointestinal disturbances, magnesium and calcium metabolism disorders, anemia, genital ulceration, and seizures (59). To prevent serious side effects, treatment should be carried out under close medical supervision, maintain an adequate level of hydration, and avoid the simultaneous administration of pentamidine.

The use of foscarnet limits the intravenous route of administration. It can develop resistance due to mutation of DNA polymerase (60). Clinical strains of herpes simplex virus have been described that are simultaneously resistant to acyclovir and foscarnet (61).

Cidofovir shows pronounced activity against herpes simplex virus in vitro and in vivo (62, 63). It is an acyclic analog of phosphonate and has a wide spectrum of antiviral activity. The drug undergoes phosphorylation under the influence of cellular enzymes into active diphosphate, bypassing the first stage of phosphorylation with the participation of virus enzymes, which is necessary for acyclovir and penciclovir (64). Cidofovir has a low oral bioavailability (less than 5%), which allows it to be used only topically. The advantage is a long half-life from the cell. Intracellular concentrations of cidofovir mono- and diphosphate are maintained for 24 and 65 hours, respectively (65).

The effectiveness of a single dose of the drug compared with placebo has been shown in immunocompetent patients with recurrent genital herpes (66). In this study, 12 hours after the onset of the first lesions, patients received cidofovir gel at a concentration of 1.3 or 5% or placebo. Local toxic reactions of the drug slowed down the healing of lesions in a number of patients. They were dose-dependent and were observed in three of 23 patients treated with 5% gel and in 1 of 21 patients treated with 3% gel. Further studies are needed to determine the maximum gel concentration well tolerated by patients.

In a clinical placebo-controlled study, cidofovir gel applied once a day for 5 days showed a pronounced virological and clinical effect in patients with acyclovir-resistant genital herpes on the background of HIV infection (67). Complete resolution of clinical symptoms was observed in 27% of patients treated with cidofovir 0.3%, in 33% of patients treated with cidofovir 1%, and in 0% of patients treated with placebo. The median reduction in the area of ​​damage was 58% in patients treated with cidofovir compared with 0% in the control group. Unfortunately, the small number of patients who participated in this study does not allow us to assess the statistical significance of the results obtained.

In a clinical study in bone marrow transplant recipients, cidofovir was effective in treating genital herpes caused by virus strains resistant to acyclovir and foscarnet (61).

There is experience with the use of tifluridine ophthalmic solution for the treatment of genital herpes caused by acyclovir-resistant strains (). Tifluridine is a pyrimidine nucleoside analog that, like cidophyr, acts independently of viral thymidine kinase. High toxicity does not allow the drug to be taken orally. Small clinical studies have shown a beneficial effect of tifluridine in acyclovir-resistant genital herpes in patients with HIV infection (68). In infections caused by acyclovir- or acyclovir/foscarnet-resistant herpes simplex viruses, tifluridine showed a synergistic effect with interferon-a (69). However, to determine the therapeutic value of tifluridine in genital herpes, further study is needed in large controlled studies.

Several studies examining the efficacy of topical interferon formulations for the treatment of genital herpes have yielded conflicting results. Local application of interferon α-2a 6 times / day. in the form of an aqueous solution proved to be ineffective for the treatment of herpes genital lesions (70). In a placebo-controlled study that included 387 patients, on the contrary, the effectiveness of interferon α-2a gel was shown when applied 4 times / day. within 4 days in case of recurrence of genital herpes (71). In patients of both sexes, the period of virus shedding decreased, in addition, in men, there was a significant decrease in pain, itching, and crusting time. In a study including 25 patients, a beneficial effect of interferon ß was shown (72).

In Germany and Canada, edoxudin, an analogue of deoxythymidine, has been approved for the treatment of genital herpes, showing pronounced antiherpes activity in vitro and in vivo (73, 74). The mechanism of action of the drug is similar to that of acyclovir. When applied topically, it is better absorbed than polyethylene glycol-based acyclovir ointment. In a multicentre, placebo-controlled study, edoxudin 3% cream applied for 5 days significantly reduced viral shedding in both sexes (75). In women, there was also a decrease in soreness and adenopathy in the groin.

A dosage form of acyclovir with controlled release of the active substance has been developed (76). Its advantage is the prolongation of the half-life of acyclovir. Clinical trials conducted in Europe show that long-acting acyclovir is equally effective as short-acting acyclovir. It has been suggested that the use of a drug with an extended half-life may lead to a decrease in the number of relapses during suppressive therapy, but it requires further study.

In experiments on guinea pigs and in a clinical study, the beneficial effect of resiquimod, an immune response modifier from the imidazoquinoline group, has been shown (77, 78). In patients with genital herpes, when topical treatment was started within a day after the onset of symptoms, there was an increase in the time before a relapse occurred. In 52 immunocompetent patients with a history of at least 6 relapses per year, the median time to the first relapse was 169days with resiquimod and 57 days with placebo (79). The drug is currently undergoing phase III clinical trials.

Despite advances in the treatment of genital herpes over the past few years, the epidemic of the disease continues to spread throughout the world. The main drugs for the treatment of infection are nucleoside analogues. The emergence of generic acyclovir preparations has significantly reduced the cost of treatment. New drugs from this group – the prodrugs valaciclovir and famciclovir – have better pharmacokinetic properties compared to acyclovir, which allows to increase the degree of patient compliance with the treatment regimen. In the treatment of the first episode of genital herpes, the drugs show comparable clinical efficacy.

Direct comparative studies between the three nucleoside analogues in the episodic treatment of relapses of genital herpes have not been conducted.