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Acyclovir long term side effects: Acyclovir Side Effects: Common, Severe, Long Term

Acyclovir Side Effects: Common, Severe, Long Term

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Medically reviewed by Carmen Fookes, BPharm. Last updated on Apr 19, 2022.

Acyclovir is an antiviral drug that slows the growth and spread of the herpes virus in the body. It may be used to treat herpes infections such as:

  • Chickenpox
  • Cold sores
  • Genital herpes
  • Shingles.

Acyclovir can be given orally (by mouth) or as an injection.

What are the more common side effects of acyclovir?

Acyclovir is usually well-tolerated, and most side effects are mild. Examples of commonly reported side effects with oral acyclovir include:

  • Diarrhea
  • Headache
  • Itching
  • Mild skin pain
  • Mouth pain (if using an acyclovir buccal tablet)
  • Nausea
  • Rash
  • Vomiting

Examples of commonly reported side effects with injectable acyclovir include:

  • Nausea
  • Redness or inflammation around the injection site
  • Vomiting.

What are some mild side effects of acyclovir?

Acyclovir may cause mild side effects. Examples of mild side effects reported with acyclovir include:

  • Diarrhea
  • Difficulty sleeping
  • Dizziness
  • Fatigue (lacking in energy) or feeling tired
  • Fever
  • Flushing or skin redness or unusually warm skin
  • Headache
  • Itching
  • Loss of appetite
  • Menstrual abnormalities
  • Mild skin pain
  • Mouth or gum pain (if using an acyclovir buccal tablet)
  • Mouth ulcers (Canker sores) or other sores in the mouth
  • Muscle or leg pain
  • Nausea
  • Rash
  • Sleepiness
  • Sore throat
  • Stomach pain
  • Sweating
  • Taste disturbances
  • Thirst
  • Urticaria (hives)
  • Vomiting

What are some serious side effects of acyclovir?

Serious side effects may occur rarely with acyclovir. Examples of these serious side effects that have been reported with acyclovir include:

  • Blood in the urine (hematuria)
  • Chest pain or palpitations
  • Decreases in red or white blood cells or changes to the way the blood clots
  • Hair loss (alopecia)
  • Increases in laboratory test results for blood urea nitrogen or creatinine
  • Kidney problems, such as decreases in how often you urinate or pain during urination, pain in the kidneys, problems with the functioning of your kidneys (renal impairment), crystals in your urine (crystalluria), or your kidneys stop working (acute renal failure)
  • Liver enzyme changes, increases in bilirubin, or liver inflammation
  • Low blood pressure
  • Lymph node swelling
  • Mental health changes such as agitation or aggression, confusion, depression, hallucinations, psychotic symptoms
  • Problems with the nervous system (ataxia)
  • Seizures or convulsions
  • Serious skin reactions such as Stevens-Johnson syndrome or toxic epidermal necrolysis
  • Serious allergic reactions, such as angioedema or anaphylaxis
  • Severe reactions following an acyclovir injection such as tissue death (tissue necrosis)
  • Shortness of breath
  • Speech disturbances
  • Swelling in the lower legs, ankles, or feet (peripheral edema)
  • Tremors
  • Unconsciousness (coma) or brain damage (extremely rare)
  • Vision changes or eye inflammation (Pars planitis)

FAQs about acyclovir’s side effects

Here is a selection of our most commonly asked questions about acyclovir’s side effects.

Does acyclovir cause any long-term side effects?

In most cases, acyclovir’s side effects are only temporary, and go away once you stop taking the drug, or after you have been taking it for a couple of days.

Very rarely, some side effects may persist long term or require other medications to resolve. If you have any questions, talk with your doctor.

Can you drink alcohol while taking acyclovir?

Although there is no direct interaction between alcohol and acyclovir, alcohol will not interfere with the way acyclovir works and acyclovir will still be effective.

However, it is best to avoid alcohol if you have any type of infection, including herpes which acyclovir treats, because alcohol can suppress your immune system and also increase the risk of side effects, such as nausea, vomiting, dizziness, or a headache, when taken with acyclovir.

Can acyclovir cause an allergic reaction?

Like most medications, acyclovir can cause an allergic reaction in some people. Symptoms may include:

  • Difficulty breathing
  • Fast heartbeat
  • Rash
  • Skin flushing or redness
  • Swelling under the skin or around the face, eyes, or throat.

Call your doctor right away or seek emergency help by calling 911 if the reaction is severe. If your symptoms are mild, then an oral antihistamine, such as diphenhydramine can help resolve your symptoms.

More about acyclovir

  • Drug Information
  • During Pregnancy or
    Breastfeeding
  • Dosage Information
  • Patient Tips
  • Drug Images
  • Drug Interactions
  • Compare Alternatives
  • Pricing & Coupons
  • User Reviews
  • Drug class: purine nucleosides

Side Effects, Dosage, Uses, and More

Highlights for acyclovir

  1. Acyclovir oral tablet is only available as a generic drug. It doesn’t have a brand-name version.
  2. Acyclovir is also available as a capsule, suspension, and buccal tablet that you take by mouth. It also comes in a cream and ointment you apply to your skin. In addition, acyclovir is available as an intravenous (IV) drug, which is only given by a healthcare professional.
  3. Acyclovir is used to treat viral infections. These include herpes zoster (shingles), genital herpes, and varicella (chickenpox).
  • Kidney failure: This drug may cause your kidneys to stop working. Tell your doctor if you have any kidney problems before taking this medication.
  • Low red blood cells and platelets: This drug may cause thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). These conditions cause dangerously low levels of red blood cells and platelets in your body. This may be fatal (cause death). Symptoms can include fatigue and low energy.
  • Sexual contact: You shouldn’t have sexual contact with your partner when you have signs of a genital herpes outbreak. This drug does not cure herpes infections. It may help lower the chance of spreading herpes to your partner. However, even with safe sex practices, it’s still possible to spread genital herpes. Talk to your doctor for information about safe sex practices.

Acyclovir oral tablet is a prescription drug that’s only available in a generic form. Generic drugs usually cost less than the brand-name version. In some cases, they may not be available in all strengths or forms as the brand-name drug.

Acyclovir also comes as an oral capsule, oral suspension, buccal tablet, topical cream, and topical ointment. In addition, acyclovir is available as an intravenous drug, which is only given by a healthcare professional.

This drug may be used as part of a combination therapy. This means you may need to take it with other medications.

Why it’s used

Acyclovir is used to treat viral infections. These include herpes zoster (shingles), genital herpes, and varicella (chickenpox).

This drug doesn’t cure herpes infections. The herpes virus can stay in your body for a long time and cause symptoms again later.

How it works

Acyclovir belongs to a class of drugs called antivirals. A class of drugs is a group of medications that work in a similar way. These drugs are often used to treat similar conditions.

Acyclovir works by lowering the ability of the herpes virus to multiply in your body. This treats the symptoms of your infection. However, this drug doesn’t cure herpes infections. Herpes infections include cold sores, chickenpox, shingles, or genital herpes. Even with this drug, the herpes virus may still live in your body. Your symptoms may occur again later even after the symptoms of your current infection go away.

Acyclovir oral tablet doesn’t cause drowsiness but it can cause other side effects.

More common side effects

Some of the more common side effects of acyclovir oral tablet include:

  • nausea
  • vomiting
  • diarrhea
  • headache
  • weakness

Serious side effects

Call your doctor right away if you have serious side effects. Call 911 if your symptoms feel life-threatening or if you think you’re having a medical emergency. Serious side effects and their symptoms can include the following:

  • Unusual changes in your mood or behavior. Symptoms can include:
    • aggressive behavior
    • unsteady or shaky movements
    • confusion
    • trouble speaking
    • hallucinations (seeing or hearing something that isn’t there)
    • seizures
    • coma (being unconscious for a long time)
  • Decrease in your red blood cells and platelets. Symptoms can include:
    • fatigue
  • Liver problems
  • Muscle pain
  • Skin reactions. Symptoms can include:
    • hair loss
    • rash
    • breaking or loosening of skin
    • hives
    • Stevens-Johnson syndrome. This is a rare, allergic skin reaction.
  • Changes in your vision
  • Kidney failure. Symptoms can include:
    • kidney or flank pain (pain in your side and back)
    • blood in your urine
  • Allergic reaction. Symptoms can include:
    • trouble breathing
    • swelling of your throat or tongue
    • rash
    • hives

Disclaimer: Our goal is to provide you with the most relevant and current information. However, because drugs affect each person differently, we cannot guarantee that this list includes all possible dosages. This information is not a substitute for medical advice. Always speak with your doctor or pharmacist about dosages that are right for you.

An interaction is when a substance changes the way a drug works. This can be harmful or prevent the drug from working well. To help prevent interactions, your doctor should manage all of your medications carefully. Be sure to tell your doctor about all medications, vitamins, or herbs you’re taking.

To find out how this drug might interact with something else you’re taking, talk to your doctor or pharmacist.

Disclaimer: Our goal is to provide you with the most relevant and current information. However, because drugs interact differently in each person, we cannot guarantee that this information includes all possible interactions. This information is not a substitute for medical advice. Always speak with your healthcare provider about possible interactions with all prescription drugs, vitamins, herbs and supplements, and over-the-counter drugs that you are taking.

This drug comes with several warnings.

Allergy warning

Acyclovir can cause a severe allergic reaction. Symptoms can include:

  • trouble breathing
  • swelling of your throat or tongue
  • rash
  • hives

Call 911 or go to the nearest emergency room if you develop these symptoms. Don’t take this drug again if you’ve ever had an allergic reaction to it. Taking it again could be fatal (cause death).

Warnings for certain groups

For people with kidney problems: If you have kidney problems or a history of kidney disease, you may not be able to clear this drug from your body well. This may increase the levels of this drug in your body and cause more side effects.

This medication may also decrease your kidney function. This means your kidney disease may get worse. Your doctor will adjust your dose depending on how well your kidneys are working.

For pregnant women: Acyclovir is a category B pregnancy drug. That means two things:

  1. Studies of the drug in pregnant animals have not shown a risk to the fetus.
  2. There aren’t enough studies done in pregnant women to show if the drug poses a risk to the fetus.

Talk to your doctor if you’re pregnant or planning to become pregnant. This drug should be used only if the potential benefit justifies the potential risk to the fetus.

Call your doctor right away if you become pregnant while taking this drug.

For women who are breastfeeding: Acyclovir may pass into breast milk and may cause side effects in a child who is breastfed. Talk to your doctor if you breastfeed your baby. You may need to decide whether to stop breastfeeding or stop taking this medication.

For seniors: The kidneys of older adults may not work as well as they used to. This can cause your body to process drugs more slowly. As a result, more of a drug stays in your body for a longer time. This raises your risk of side effects.

For children: This drug hasn’t been studied in children younger than 2 years.

This dosage information is for acyclovir oral tablet. All possible dosages and drug forms may not be included here. Your dosage, drug form, and how often you take the drug will depend on:

  • your age
  • the condition being treated
  • how severe your condition is
  • other medical conditions you have
  • how you react to the first dose

Forms and strengths

Generic: Acyclovir

  • Form: oral tablet
  • Strengths: 400 mg, 800 mg

Dosage for shingles, genital herpes, or chickenpox

Adult dosage (ages 18–64 years)

  • Shingles typical dosage: 800 mg every 4 hours, five times per day for 7–10 days.
  • Genital herpes:
    • Typical initial dosage: 200 mg every 4 hours, five times per day, for 10 days.
    • Typical dosage for prevention of recurrent herpes: 400 mg twice per day, every day for up to 12 months. Other dosing plans may include doses ranging from 200 mg three times daily to 200 mg five times daily. Your doctor will decide how long you should take this drug to avoid a flare-up of the infection.
    • Typical dosage for reinfection (flare-up of the infection): 200 mg every 4 hours, five times per day, for 5 days. You should take this drug as soon as the first signs of a flare-up appear.
  • Chickenpox typical dosage: Take 800 mg four times per day for 5 days. Start this drug as soon as your first symptom of chickenpox appears. It isn’t known if this drug is effective if you start it more than 24 hours after the first sign of chickenpox.

Child dosage (ages 2–17 years)

  • Chickenpox typical dosage:
    • Children who weigh 40 kg (88 lbs) or less: 20 mg/kg of body weight, given four times per day for 5 days
    • Children who weigh more than 40 kg: 800 mg four times per day for 5 days

Start this drug as soon as the first symptom of chickenpox appears. It isn’t known if this drug is effective if your child starts it more than 24 hours after the first sign of chickenpox.

Child dosage (ages 0–1 years)

It hasn’t been confirmed that acyclovir is safe and effective for children younger than 2 years.

Senior dosage (ages 65 years and older)

The kidneys of older adults may not work as well as they used to. This can cause your body to process drugs more slowly. As a result, more of a drug stays in your body for a longer time. This increases your risk of side effects.

Your doctor may start you on a lowered dose or a different medication schedule. This can help keep levels of this drug from building up too much in your body.

Disclaimer: Our goal is to provide you with the most relevant and current information. However, because drugs affect each person differently, we cannot guarantee that this list includes all possible dosages. This information is not a substitute for medical advice. Always to speak with your doctor or pharmacist about dosages that are right for you.

Acyclovir oral tablet is used for short-term treatment of genital herpes, shingles, and chicken pox. It’s used for long-term treatment of recurring genital herpes. This drug comes with serious risks if you don’t take it as prescribed.

If you stop taking the drug suddenly or don’t take it at all: The symptoms of your infection may not get better or may get worse.

If you miss doses or don’t take the drug on schedule: Your medication may not work as well or may stop working completely. If you’re taking this drug to prevent flare-ups of your infection, a certain amount needs to be in your body at all times. You shouldn’t stop taking this drug without talking to your doctor first.

What to do if you miss a dose: Take your dose as soon as you remember. But if you remember just a few hours before your next scheduled dose, take only one dose. Never try to catch up by taking two doses at once. This could result in dangerous side effects.

If you take too much: You could have dangerous levels of the drug in your body and experience more severe side effects. If you think you’ve taken too much of this drug, call your doctor or local poison control center. If your symptoms are severe, call 911 or go to the nearest emergency room right away.

How to tell if the drug is working: The symptoms of your infection will get better.

Keep these considerations in mind if your doctor prescribes acyclovir oral tablet for you.

General

  • Take this drug at the time(s) recommended by your doctor.
  • You can take acyclovir with or without food. Taking it with food may help reduce upset stomach.
  • Do not cut or crush this medication.
  • Not every pharmacy stocks this drug. When filling your prescription, be sure to call ahead to make sure your pharmacy carries it.

Storage

  • Store this drug at room temperature. Keep it between 59°F and 77°F (15°C and 25°C).
  • Keep it away from light.
  • Don’t store this medication in moist or damp areas, such as bathrooms.

Refills

A prescription for this medication is refillable. You should not need a new prescription for this medication to be refilled. Your doctor will write the number of refills authorized on your prescription.

Travel

When traveling with your medication:

  • Always carry your medication with you. When flying, never put it into a checked bag. Keep it in your carry-on bag.
  • Don’t worry about airport X-ray machines. They can’t hurt your medication.
  • You may need to show airport staff the pharmacy label for your medication. Always carry the original prescription-labeled box with you.
  • Don’t put this medication in your car’s glove compartment or leave it in the car. Be sure to avoid doing this when the weather is very hot or very cold.

Clinical monitoring

You and your doctor should monitor certain health issues. This can help make sure you stay safe while you take this drug. These issues include:

  • Kidney function. Your doctor may do blood tests to check how well your kidneys are working. If your kidneys aren’t working well, your doctor may lower your dose of this drug.
  • Mental health and behavioral problems. You and your doctor should watch for any unusual changes in your behavior and mood. This drug can cause new mental health and behavior problems. It can also worsen problems you already have.

Your diet

You should drink plenty of water to stay hydrated. This drug can harm your kidneys if you don’t stay well hydrated.

Sun sensitivity

Acyclovir can make your skin more sensitive to the sun. This increases your risk of sunburn. Avoid the sun if you can. If you can’t, be sure to wear protective clothing and apply sunscreen.

Insurance

Many insurance companies require a prior authorization for this drug. This means your doctor will need to get approval from your insurance company before your insurance company will pay for the prescription.

There are other drugs available to treat your condition. Some may be better suited for you than others. Talk to your doctor about other drug options that may work for you.

Disclaimer: Healthline has made every effort to make certain that all information is factually correct, comprehensive, and up-to-date. However, this article should not be used as a substitute for the knowledge and expertise of a licensed healthcare professional. You should always consult your doctor or other healthcare professional before taking any medication. The drug information contained herein is subject to change and is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. The absence of warnings or other information for a given drug does not indicate that the drug or drug combination is safe, effective, or appropriate for all patients or all specific uses.

Article resources

The use of acyclovir in the treatment of children with cancer

Antiviral drug

Trademarks:

Zovirax®, Sitavig®

Other names:

Aciclovir; ACV; Acycloguanosine

Often used for:

Viral infections

Acyclovir is an antiviral drug. Its action is aimed at suppressing infections caused by certain viruses in immunocompromised patients. This drug may be used to fight herpes simplex (HSV), chickenpox, herpes zoster (shingles), or cytomegalovirus (CMV) viruses. When applied topically, acyclovir is also used to treat cold sores on the lips and genital warts (genital warts).

Aciclovir may cause tissue damage in case of contact during intravenous administration. Irritation and damage to the skin can be observed at the injection site of the needle. Be sure to tell your doctor or nurse if you experience a burning sensation during administration.

During the course of aciclovir, the patient will need regular blood and urine tests to check quantitative indicators and to monitor the functioning of the liver and kidneys. Patients who are prescribed intravenous acyclovir should be monitored for symptoms of neurotoxicity. Tremor, confusion, agitation, or changes in consciousness may occur, especially in patients who are prescribed a high dose of the drug or who have been diagnosed with renal insufficiency.

Oral tablet or capsule form

Oral liquid form

Administered intravenously (through a drip) in liquid form

Skin application

  • Nausea and vomiting
  • Increased fatigue or general weakness
  • Headache
  • Diarrhea
  • Skin irritation at injection site or skin application site
  • Rash, itching, urticaria
  • Dizziness
  • Drowsiness
  • Kidney disorders
  • Liver disorders

The listed side effects are not observed in all patients who are prescribed acyclovir. The most common side effects are highlighted in bold, but others are not excluded. Report all possible side effects to your doctor or pharmacist.

Be sure to discuss these and other recommendations with your doctor or pharmacist.

  • It is important to drink plenty of fluids when taking this drug. It is necessary to drink the amount of liquid recommended by the doctor.
  • Pregnant or breastfeeding patients should notify their physician.
  • The course of taking the drug must be completed completely in accordance with the recommendations of the attending physician or pharmacist.
Taking acyclovir at home:
  • This drug may make you dizzy or drowsy. Do not drive or engage in hazardous activities until a drug reaction has been identified.
  • When taken orally, aciclovir can be taken with or without food.
  • Tablets or capsules should be swallowed whole. It is not allowed to cut, grind or chew the drug.
  • Liquid formulation must be shaken before use.
  • Aciclovir can be administered with an enteral feeding tube. Follow the instructions of your doctor or pharmacist.
  • Cream or ointment: Wash hands thoroughly before and after applying the drug to the skin. Avoid contact with eyes. Do not rub the affected area. Wear a glove when applying the ointment to prevent the spread of infection.
  • Buccal (buccal) tablets: A buccal tablet is placed in the mouth between the cheek and gum, where it dissolves over time. When taking aciclovir buccal tablets, place the round side of the tablet against the gum above the canine tooth on the same side as the labial herpes. Hold the tablet gently for at least 30 seconds until you are sure that it does not fall out. Do not swallow, chew or dissolve the tablet. Let the tablet dissolve; this may take at least 6 hours. Drink and eat with care to avoid spilling the pill.
  • Take your dose as soon as possible if you miss it. Do not do this only if there is little time left until the next appointment. In no case do not double the dose at the next dose!
  • Acyclovir should be stored at room temperature.
  • Do not use an expired drug.
  • Follow instructions for safe storage and disposal of the drug.

Find out more about aciclovir

Learn more about aciclovir (topical)

90,000 long-term approaches to therapy "lifelong infection"

The first description of herpes is found in the writings of Hippocrates, but so far herpes infection is a serious medical and social problem [1-3]. This is due to its prevalence in the population, lifelong presence in the body, a tendency to a recurrent course, and the possibility of severe complications. A few years ago, experts from the World Health Organization (WHO) presented a general epidemiological picture, indicating that almost 100% of the world’s population is infected with herpes simplex virus (HSV) types 1 and 2. According to the same sources, approximately 10–20% of those infected have clinical manifestations of herpes infection [4–7]. All data point to a progressive increase in infection and incidence of herpes infection worldwide. By the end of the 20th century, the number of registered cases of only genital herpes (HH) increased by 13–40% compared to the 80s in the United States, by 7–16% in Europe, and by 30–40% in Africa [7, 8] . Particular attention is drawn to the lack of a complete picture of the prevalence of this dangerous disease in the world [9, 10].

The WHO Regional Office for Europe lists herpesvirus infections as one of the diseases that shape the future of infectious disease. The scale of the disease, combined with the damage it causes (psychological and physiological), determine the important medical and social significance of these infections [11]. In the Russian Federation, anogenital herpes has been officially registered only since 1994. The long-term absence of national statistics and monitoring the effectiveness of the diagnostic methods used do not allow an objective assessment of the epidemiological and medical and social significance of the problem in our country. This is confirmed by the data of the global clinical and epidemiological study of the international herpes forum IHMF (International Herpes Management Forum), which does not contain information on the Russian Federation [12]. Moreover, the lack of consensus among experts on diagnostics, patient management tactics, and standardized diagnostic test systems characterizes this disease as a “problem” infection [13–15].

HSV is a typical member of the herpes virus family. Having entered the body, the virus reaches the regional ganglion, where it persists. The latent state of the virus is determined by the biological balance between the micro- and macroorganism [4, 16, 17]. Various provoking factors (psycho-emotional component, hypothermia, intoxication, insolation, overheating, etc.) contribute to the recurrence of the disease. The frequency of relapses can vary widely in each individual, and the range of clinical manifestations of the disease is determined by both the biological properties of the pathogen and the reactivity of the organism [2, 13, 14, 16, 18].

Despite numerous studies in the field of virology, the problems of herpesvirus infections do not lose their relevance. Over the past 3-5 years, most studies have been aimed at finding new methods and approaches to the treatment of herpesvirus infections. It is the development of effective means of treating herpes infection that is of particular interest to both doctors and representatives of pharmacological firms. Available antiviral drugs for the treatment and control of genital HSV (aciclovir, Valaciclovir , famciclovir) have the same quantitative mechanism of action, i.e. selective phosphorylation in HSV-infected cells and competitive substrate inhibition of deoxyribonucleic acid (DNA) polymerase, leading to the end of reading the DNA chain of the virus. However, they differ in their specificity and affinity for their target virus enzymes [13, 16, 19, 20].

Aciclovir is the first selective nucleoside analog with an acceptable safety profile for widespread use. This drug, which causes minimal side reactions, was used in patients for the relief of HH up to 10 years [5, 13, 18]. The latest drugs have expanded the choice of treatment methods for doctors [17]. Despite the successes achieved, the problem of herpes simplex therapy remains relevant, which is associated with a variety of clinical manifestations, the development of drug resistance of the virus, the presence of molecular mimicry in herpes viruses, the need to take into account the provoking factor, and many other reasons [16].

Valaciclovir (Aciclovir L-valyl ester) has been developed to improve the bioavailability of aciclovir. Taking Valaciclovir orally provides 3-5 times greater bioavailability of acyclovir in a wide dose range [2, 13, 14, 16, 20, 21]. An extensive program of clinical studies to evaluate the positive effect of Valaciclovir in HH has shown that it is no less effective than acyclovir. Valaciclovir is taken twice a day (acyclovir 5 times a day) as an occasional treatment and once a day to suppress the reproduction of the virus (acyclovir 2-4 times a day). During treatment Valaciclovir prevents recurrence of infection caused by HSV in 70-80% of cases [20, 21]. Suppressive therapy for HH has a positive psychosocial effect, and also reduces the risk of its transmission.

The aim of the study was to conduct a comparative clinical and immunological analysis of the efficacy and safety of immunosuppressive therapy with acyclovir and Valaciclovir in patients with recurrent HH.

Material and methods

To achieve this goal, a comparative open randomized study was conducted at the Department of Dermatovenereology, South Ural State Medical University, which included 48 women of reproductive age. The average age of the participants was 28.3±0.2 years. Scrapings of the cervical canal epithelium, taken with disposable cytobrushes, served as the material for isolation and subsequent amplification of HSV DNA. The design of the study was in accordance with the provisions of the Declaration of Helsinki of the World Medical Association (WMA) of the last revision (Edinburgh, Scotland, 2000), taking into account the explanatory note p. 29, approved by the General Assembly of the VMA (Seoul, 2008), and was approved by the ethics committee of the State Budgetary Educational Institution of Higher Professional Education of the South Ural State Medical University of the Ministry of Health of Russia. All patients underwent a comprehensive examination, which included a doctor’s examination, microscopic examination of the cervical canal, a cytological examination of smears of prints, and a study of local immunity indicators. All women underwent a microbiological examination in accordance with the methodological recommendations of the Ministry of Health of the Russian Federation “Standardization of medical care for patients with gonococcal infection” (Order No. 176 of February 28, 2005) and the Regulations of the Ministry of Health of Russia “On measures to prevent the spread of sexually transmitted diseases” (Order No. 291 dated 30.07.01). Microscopy was subjected to native, as well as Gram-stained and methylene blue smears of scrapings of the vagina and cervical canal. The material for the study of local immunity of the reproductive tract was cervical mucus, which was taken using a special graduated pipette. The mucus was placed in 1.0 ml of saline or medium 199 and thoroughly suspended. The total number and proportion of viable leukocytes were determined using trypan blue. All women underwent a study of the phagocytic activity of cervical mucus neutrophils. The ability of neutrophils to phagocytosis was determined on the model of absorption of latex particles. To do this, 0.2 ml of a suspension of these cells was mixed with 0.02 ml of latex suspension with a diameter of 1.7 μm (10 particles per 1 ml) obtained from VNIISK (St. Petersburg). The study of intracellular oxygen-dependent metabolism was carried out using the NBT-test. In parallel, the ability of neutrophils to respond with an increase in metabolic activity to stimulation with latex particles was determined. The functional reserve of neutrophils was also calculated, which is the ratio between the reaction intensity coefficients of the NBT-induced and NBT-spontaneous tests. The number of lysosomes in the cytoplasm of phagocytes was studied by in vivo staining with acridine orange, which was carried out in a suspension of neutrophils. For this, 0.2 ml of a suspension of neutrophils in physiological saline was mixed with 0.02 ml of acridine orange solution at a concentration of 2 μg/ml. After a 30-minute incubation at 37°C, a drop of the suspension was placed on a glass slide, covered with a coverslip, and studied under immersion in a blue-violet light flux of a fluorescent microscope. The results were expressed as the percentage of neutrophils containing lysosomes. The concentration of IgM, IgG in the peripheral blood was determined using the appropriate test systems for enzyme immunoassay (OOO Vector-Best, Novosibirsk).

Inclusion criteria for further study were the presence of clinical manifestations of herpes infection, the frequency of relapses 4-6 times a year, the detection of HSV DNA, reproductive age, the consent of patients to participate in the study. The exclusion criteria were the presence of severe somatic pathology, hormonal disorders, pregnancy, lactation, other sexually transmitted infections (STIs), human immunodeficiency virus, and non-consent of patients to participate in the study. In accordance with the International Classification of Diseases of the 10th revision and the clinical guidelines of the RODVK for the management of patients with STIs and urogenital infections, the diagnosis was “A.60.0 Herpetic infection of the genital organs and genitourinary tract, recurrent course, moderate severity.” The frequency of relapses was 4-6 times a year, the inter-relapse period was at least 2-3 months. Several groups were formed. The 1st of them included 30 women who did not have clinical manifestations of herpes infection. Patients of the 2nd group (26) received therapy Valaciclovir 500 mg once a day for 6 months, group 3 (22) – acyclovir 400 mg 2 times a day also for 6 months. The groups were stratified among themselves at the initial stage (before the appointment of treatment) according to all signs characterizing the disease: complaints, clinical manifestations, laboratory parameters.

Results and discussion

Patients with herpetic infection of the urogenital tract were worried about itching, burning in the genital area of ​​varying intensity, 26 (54.1%) women from the 2nd and 3rd groups had pain during urination. In 16.6% of cases (in 8 women), patients of the 2nd and 3rd groups complained of mucous secretions and discomfort in the vulva. In 100% of cases, women were anxious, noted a decrease in the quality of life due to fear of a relapse, fear of infecting their sexual partner. In the 2nd and 3rd groups, 5 (10.4%) women noted that during a relapse they avoid even additional household contacts with relatives. All patients sought medical help during the next relapse.

From the anamnesis it was possible to establish that the average duration of the disease was 3.8±0.4 years. Clinically, all women suffering from genital herpes infection at the time of examination revealed erosive lesions of the genitals. In 17 (35.4%) patients, erosions were in the region of the labia minora, in 19 (39. 5%) – on the posterior commissure, in 16 (33.3%) there was a lesion of the cervix.

In 8.3% (4) of women, lesions were found on the posterior commissure and cervix. Erosions on the external genitalia, as a rule, had scalloped edges, 0.3-1.0 cm in size, were moderately painful, the skin was hyperemic, slightly swollen. Damage to the cervix, in addition to erosive elements, was accompanied by a significant amount of mucous secretions. Involvement in the pathological process of the urethra was manifested by significant soreness, swelling and hyperemia of the urethral sponges. A laboratory study revealed an increase in the number of leukocytes in the cervical canal – 47.6 ± 2.9in the field of view, layers of epithelial cells, the number of leukocytes in the urethra was 18.3±1.2. Assessment of the local immunological status showed a significant increase in the total number of leukocytes, viable cells, a decrease in spontaneous and induced HBT-test, and a functional reserve of neutrophils. A decrease in the apoptotic ability of cervical secretion neutrophils was established. The level of CD95 and CD11b was reduced compared to healthy women by 2.6 and 1.13 times, respectively. IgM was not detected in any of the patients. The mean IgG level in healthy women was 3.9g / l, in patients with recurrent herpes infection – 9.9 g / l.

Control studies were conducted 6 and 12 months after the start of treatment. During the 6-month intake of acyclovir, a recurrence of herpes infection was noted in 2 (9.09%) patients, while the intensity of clinical manifestations was less pronounced than before treatment. Against the background of taking Valacyclovir , no relapses were noted. From the 7th to the 12th month of observation, the recurrence rate in 5 (22.7%) patients treated with acyclovir averaged 2.0±1.5. Group Valaciclovir during the same observation period, one episode of HH recurrence was noted in 2 (7.69%) women. The duration of relapse was 3.0±1.5 days. Assessing the adherence of patients to therapy, we found that 7 (31. 8%) patients who received acyclovir violated the prescribed regimen of taking the drug. Explaining the reasons, 3 patients noted the appearance of heaviness in the right hypochondrium, dysphagia, 4 women missed the appointment due to forgetfulness.

In group Valaciclovir only 2 (7.69%) patients did not fully follow the prescriptions due to forgetfulness. Evaluation of the etiological efficacy of the therapy performed showed the absence of HSV DNA after 6 months in the acyclovir group in 9.09% and in the Valaciclovir group in 7.69%. The frequency of detection of HSV after 1 year was 13.6 and 7.69%, respectively. The data obtained were significant (p<0.05). A comparative analysis of the dynamics of immunological parameters after therapy showed a decrease in the total number of leukocytes in the cervical secretion, the absolute and relative number of viable cells, an increase in the functional activity of neutrophils, and an increase in their apoptotic activity in both groups. The phagocytic activity of cervical secretion neutrophils in patients with herpes infection was significantly lower than in healthy women, which indicates dysfunctions in the antiviral protection of the macroorganism (p<0.02). Dynamic observation during the year showed that immediately after therapy there was a clear trend towards normalization of cellular factors of local immunity, 6 months after the end of therapy in women treated with acyclovir, there was a tendency to increase the total number of leukocytes, reduce the activity and intensity of phagocytosis. Group Valaciclovir these indicators were more stable. Data on the dynamics of changes in immunological parameters during treatment are presented in table . During the study of the level of IgG, no significant changes were found between the studied groups.

We consider the achievement of psychological comfort for our patients to be one of the significant results of the therapy. Thus, 42 (87.5%) women noted that their quality of life has noticeably improved, and suppressive therapy provides a psychological advantage over treatment for relapses.