ANTIVIRAL THERAPY

DR.RISHIKESAN K.VSPECIALIST PHYSICIAN

VENNIYIL MEDICAL CENTRESHARJAH

UNDERSTANDING THE VIRUSES:THEY ARE DIFFERENT FROM OTHER

MICROBESVIRUSES ARE OBLIGATE INTRACELLULAR PARASITES. A VIRUS CANNOT REPLICATE ON ITS OWN. IT MUST ATTACH TO AND ENTER A HOST CELL ,THEN USES HOST CELL’S ENERGY, METABOLIC ENZYMES, AND RIBOSOMES TO SYNTHESISE PROTEIN , DNA AND RNA.

THEY CANNOT MAKE ANYTHING OF THEIR OWN. THEY USE THE HOST CELL’S MATERIALS TO BUILD THEMSELVES.

ANTIVIRAL DRUGS: HOW THEY ACTKey characteristics of antiviral drugs1.Able to enter the cells infected with virus2.Interfere with viral nucleic acid synthesis and/or regulation3.Some drugs interfere with ability of virus to bind to cells4.Some drugs stimulate the body’s immune systemBest responses to antiviral drugs are in patients with competent immune systemsA healthy immune system works synergistically with the drug to eliminate or suppress viral activity

HOWEVER ANTIVIRAL THERAPY IS CHALLENGING:

1. Rapid replication of viruses makes it difficult to develop effective antiviral.

2. Viruses can rapidly mutate and drug becomes ineffective.3. Difficulty for drug to find virus without injuring normal

cells.(Nonselective inhibitors of virus replication may interfere with host cell function and result in toxicity.)

4. Antiviral drugs share the common property of being virustatic; they are active only against replicating viruses and do not affect latent virus.

5. Clinical efficacy depends on achieving inhibitory conc. at the site of infection within the infected cells

WE HAVE GOT A SMALL ARSENAL OF ANTIVIRAL DRUGS

DESPITE 50 YEARS OF INTENSE RESEARCH OUR ARSENAL OF ANTIVIRAL DRUGS REMAIN DANGEROUSLY SMALLONLY ABOUT 30 ANTIVIRAL DRUGS AVAILABLE IN THE U.S MARKET.MOSTLY AGAINST HIV AND HERPES INFECTIONS

RESPIRATORY INFECTIONSTHE MOST COMMON VIRAL INFECTIONS ARE PROBABLY URIs.SEVERE SYMPTOMS IN INFANTS, THE ELDERLY AND PATIENTS WITH A LUNG OR HEART DISEASE.RESPIRATORY VIRUSES TYPICALLY SPREAD BY CONTACT WITH INFECTED RESPIRATORY DROPLETS.RHINOVIRUS INFECTIONS ARE UNIVERSAL ESPECIALLY DURING COLD MONTHS.NO SPECIFIC THERAPYNO SPECIFIC PREVENTION

THE RESPIRATORY VIRUSES INCLUDE:

ANTIRESPIRATORY ANTIVIRAL AGENTS

AMANTADINERIMANTADINEZANAMIVIROSELTAMIVIRRIBAVIRINPERAMIVIR

ZANAMAVIR AND OSELTAMIVIR• Indications•Treament of influenza A and B within 24-48 hrs of symptom onset•Prophylaxis •Neither drug interferes with antibody response to influenza vaccination

Resistance•Reports appearing• Incidence may be increasing

VIRAL PNEUMONIA FROM INFLUENZA

A 35 YEAR OLD MALE IN GOOD HEALTH DEVELOPED FEVER COUGH AND SOB. ADMITTED TO THE ICU WITH DIFFUSE INFILTRATES AND HYPOXAEMIA. HIS RAPID INFLUENZA TEST IS POSITIVE.WHICH OF THE FOLLOWING HAS BEEN DEMONSTRATED TO HAVE GOOD EFFICACY FOR TREATING THIS VIRAL PNEUMONIA ? A.OSELTAMIVIR ,B.ZANAMIVIR,C.PARAMAVIR ,D.NONE OF THE ABOVE

A.OSELTAMIVIR ,B.ZANAMIVIR,C.PARAMAVIR ,D.NONE OF THE ABOVE

INFLUENZA PNEUMONIA

RSV AND HUMAN METAPNEUMOVIRUS

THESE VIRUSES ARE KNOWN TO PRODUCE LOWER RESPIRATORY ILLNESS IN INFANTS AND MILD UPPER RESPIRATORY ILLNESS IN ADULTSRIBAVIRIN IS USED IN

IMMUNOCOMPROMISED PATIENTS.

Palivizumab IM MONTHLY FOR CERTAIN INFANTS AT

HIGH RISK OF RSV INFECTION

RSV AND HUMAN METAPNEUMOVIRUSRSV bronchiolitis RibavirinPharmacology• Aerosol and oral

administration• Hepatically metabolized

and renally excretedMajor toxicity AnemiaIndications• Aerosol treatment of RSV

in children• Effectiveness debated

RESPIRATORY SYNCITIAL VIRUS AEROSOL RIBAVIRINUNCERTAIN EFFICACY IN CHILDREN OR ADULTSADMINISTRATION BY AEROSOL2GM. OVER 2 HOURS EVERY 8 HOURSADV EFFECTS:

TERATOGENIC FOR PATIENT AND STAFF HAEMOLYTIC ANAEMIABRONCHOSPASM ALTERNATIVE PALIVIZUMAB

GASTROINTESTINAL INFECTIONSTRANSMITTED FROM PERSON TO PERSON BY ORAL FAECAL ROUTE.ROTAVIRUS : CHILDREN , NOROVIRUS: OLDER CHILDREN AND ADULTS , ASTROVIRUS : USUALLY INFANTS AND YOUNG CHILDREN , ADENOVIRUS : INFANTS , CORONA VIRUS – LIKE AGENTS :INFANTSMAIN SYMPTOMS : VOMITING AND DIARRHOEANO SPECIFIC TREATMENT , BUT SUPPORTIVE CARE PARTICULARLY REHYDRATION IS IMPORTANT

AN EFFECTIVE ROTA VIRUS VACCINE IS PART OF THE RECOMMENDED INFANT VACCINATION SCHEDULE

THIS PATIENT PRESENTED WITH CUTANEOUS LESIONS ON THE HANDS, FEET, AND BUTTOCKS. THE 2- TO 10-MM ERYTHEMATOUS MACULES DEVELOPED A CENTRAL, GRAY, OVAL VESICLE. THE LESIONS ARE ELLIPTICAL WITH THE LONG AXIS PARALLEL TO THE SKIN LINES. WHAT IS THE CAUSE OF THESE SKIN LESIONS?HMFD is most commonly caused by coxsackievirus A16 and typically affects children and infants. HMFD is highly contagious during the first week of infection Care is typically supportive with antipyretics and anesthetics for symptomatic relief on a case-by-case basis.

CMV INFECTIONSCMV infection in immunocompetent pt. is often asymptomatic or manifested as IMN like syndrome (fever, lymphadenopathy, and atypical lymphocytosis).In immunocompetent people, infection is usually self-limiting; therefore, treatment is usually not indicated.In immunocompromised people (AIDS and transplant recipients), disease manifests with fever, bone marrow suppression, pneumonia, hepatitis, colitis, nephritis, and retinitis.TREATMENT : IV GANCICLOVIR or oral valganciclovir.

TREATMENT OF CMV RETINITS

Intranuclear inclusions (arrows) found in cytomegalovirus retinitis. Referred to as owl's eye because of the dark intranuclear inclusion surrounded by a clear halo.

Intra-ocular administration of GANCICLOVIR, and less commonly fomivirsen, is also used in CMV retinitis.IV foscarnet and cidofovir are less preferred agents.

HAV INFECTIONS• Treatment for HAV infection is primarily supportive, including appropriate rest when necessary. • Avoidance of excessive paracetamol and alcohol, and having a balanced diet are important. •There are no specific antiviral therapies available.• Once acute infection occurs, management is largely outpatient-based. • Rarely, hospitalisation may become necessary for volume depletion, coagulopathy, or encephalopathy.•  In <1% of patients a fulminant course of illness occurs, characterised by worsening jaundice and encephalopathy. Prompt referral for TRANSPLANTATION is warranted in such cases

HBV INFECTIONSMost people are asymptomatic, although some will present with complications such as cirrhosis, hepatocellular carcinoma, or liver failure.Serological markers are essential in making the diagnosis and evaluating disease activity, including differentiating between people with acute and chronic infection and chronic asymptomatic carriers.Therapy for acute infection is almost always supportive care alone. However, some patients with acute infection may develop liver failure, and these patients may require referral to liver transplant centre.Therapy for chronic infection includes nucleoside/nucleotide analogues, interferon- alfa , and pegylated interferon-alfa .

HEPATITIS BINDICATIONS FOR ANTIVIRALSPATIENTS WITH ELEVATED AMINOTRANSFERASE LEVELSCLINICAL OR BIOPSY EVIDENCE OF PROGRESSIVE DISEASE OR BOTHGOAL IS TO ELIMINATE HBV – DNA, TO PREVENT CIRRHOSIS AND LIVER FAILURE , TO PREVENT HEPATOCELLULAR CARCINOMA NEEDS INDEFINITE TREATMENT EXPENSIVERELAPSES ARE COMMON ON STOPPING TREATMENT PREMATURELY.TREATMENT MAY BE STOPPED ONCE IF HBeAg CONVERTS TO anti HBe OR HBsAg BECOMES NEGATIVE

Hepatitis B is a disease caused by the hepatitis B virus (HBV), discovered in 1965 . Millions of people worldwide are infected . Without adequate diagnosis and treatment, these individuals may go on to develop liver failure, hepatocellular carcinoma, or die

NIH RECOMMENDATIONS• The NIH indicates that immediate therapy is not routinely indicated for patients who have the following :• Chronic hepatitis B with high levels of serum HBV DNA but normal serum ALT levels or little activity on liver biopsy (immune-tolerant phase)• Low levels of or no detectable serum HBV DNA and normal serum ALT levels (inactive chronically infected/low replicative phase)• Positive serum HBV DNA but not HBsAg+ (latent HBV infection), unless the patient is undergoing immunosuppression

104 - 105COPIES/ML Therapy is currently recommended for patients with evidence of chronic active hepatitis B disease (ie, abnormal aminotransferase levels, positive HBV DNA findings, positive or negative HBeAg. HBeAg- positive patients with chronic HBV disease Treatment is advised when the HBV DNA level is at or above 20,000 IU/mL (105copies/mL) and when serum alanine aminotransferase (ALT) is elevated for 3-6 months. HBeAg-negative patients with chronic hepatitis B disease Treatment can be administered when the HBV DNA is at or above 2000 IU/mL (104 copies/mL) and the serum ALT is elevated (ALT levels >20 U/L for females; 30 U/L for males) for 3-6 months.

GLOBAL APPROVALCurrently, Pegylated interferon alfa (PEG-IFN-a), Entecavir (ETV), and Tenofovir disoproxil fumarate (TDF) are the first-line agents in the treatment of hepatitis B disease. These are the main treatment drugs approved globally for this disease.

Lamivudine (3TC), telbivudine, and adefovir are of historical interest.

These agents are currently considered second- or third-line

therapy, or “nonpreferred” treatment.

INTERFERONSProteins with antiviral, anti proliferative, and immunomodulatory effects.GOOD PROGNOSTIC MARKERS:High levels of aminotransferases, A low viral load, and infection with the wild type virus . POOR RESPONDERS:Asian patients, patients with the pre core mutant virus .

Pegylated IFN-a 2a#Enhanced half-life . #Slow absorption following subcutaneous (SC) injection, #Slow renal clearance, and #Less immunogenicity . OTHER INDICATIONS:Chronic hepatitis C, andHDV infection.

INTERFERONDOSAGE : 5 MIU sc ONCE/DAY OR 10 MIU sc 3 TMES / WEEK X 16-24 WEEKS.PEG IFN : DOSAGE: 180mcg BY INJECTION ONCE/WEEK FOR 48WEEKS.AD.EFFECTS ARE SIMILAR BUT LESS SEVEREIN ABOUT 40% OF PTS. THIS REGIMEN ELIMINATES HBV- DNA ; CAUSES SEROCONVERSION TO anti- HBe

PEG IFN CAN BE USED INSTEAD OF IFN IN

CASE OF INTOLERABLE ADVERSE EFFECTS

PREGNANCY AND HBV

Mothers with chronic hepatitis B infection are often treated in the third trimester if the serum HBV DNA level is greater than 106 -108 copies/mL, especially if she is positive for the HBeAg. For newborns born to mothers with chronic hepatitis B infection, administer combined immune- prophylaxis with HBIG and hepatitis B vaccine within 12 hours of birth.

Breastfeeding is not contraindicated in women chronically infected with hepatitis B if the infant

receives HBIG and vaccine active prophylaxis

HCV : APPROACH CONSIDERATIONSPatients with acute HCV infection appear to have an excellent chance of responding to 6 months of standard therapy with IFN. Because spontaneous resolution is common, no definitive timing of therapy initiation can be recommended; however, waiting 2-4 months after the onset of illness seems reasonable. Following acute exposure, about 55% to 85% of patients develop chronic hepatitis C.Most infections are asymptomatic; however, hepatic inflammation is often present and can lead to progressive hepatic fibrosis

THE GOAL OF TREATMENT

Treatment of chronic HCV infection has 2 goals. The first is to achieve sustained eradication of HCV (ie, SVR), which is defined as the persistent absence of HCV RNA in serum 6 months or more after completing antiviral treatment. The second goal is to prevent progression to cirrhosis, hepatocellular carcinoma (HCC), and decompensated liver disease requiring liver transplantation.

TREATING HEPATITIS C INFECTIONS

• RIBAVIRIN: MAINSTAY FOR HEPATITIS C TREATMENT• HIGHLY TERATOGENIC• ADV.EFFECTS : HAEM.ANAEMIA, JAUNDICE etc.• PEG – Interferon alpha 2A• ADV EFFECTS : FLU LIKE SYNDROME, MYALGIAS,LEUKOPAENIA, ANAEMIA

BOTH DRUGS SHOULD BE INITIATED IMMEDIATELY UPON DIAGNOSIS AND TITRES SHOULD BE RECHECKED AT 6 MONTHS, IF POSITIVE DIAGNOSIS IS CHRONIC HCV

RECOMMENDATIONAntiviral therapy should be determined on a case-by-case basis. However, treatment is widely recommended for patients with elevated serum alanine aminotransferase (ALT) levels who meet the following criteria :Age greater than 18 yearsPositive HCV antibody and serum HCV RNA test resultsCompensated liver disease (eg, no hepatic encephalopathy or ascites)Acceptable hematologic and biochemical indices (hemoglobin at least 13 g/d L for men and 12 g/d L for women; neutrophil count >1500/mm 3, serum creatinine < 1.5 mg/d L)Willingness to be treated and to adhere to treatment requirementsNo contraindications for treatment

SHIFTING PARADIGMThe treatment of hepatitis C has evolved over the years. Initial studies used IFN monotherapy. Subsequently, combination of ribavirin and IFN or of IFN to which PEG molecules have been added (ie, PEG-IFN) were used. Therapy has shifted away from the use of pegylated interferon towards oral antiviral therapies.Protease inhibitors have emerged as a third feature of combination therapy. 

VIEKIRA PAKThe FDA approved the combination of Ombitasvir/ Paritaprevir/ Ritonavir and Dasabuvir for the treatment of GT1 chronic HCV in adults, including patients with compensated cirrhosis. This can be used with or without ribavirin.The recommended dosing regimen is the Ombitasvir/ Paritaprevir / Ritonavir fixed-dose combination 2 tablets once daily plus Dasabuvir 1 tablet twice daily

VARIOUS PROTEASE INHIBITORS HAVE BEEN

USED IN CHRONIC

INFECTIONS

AN ALL ORAL REGIMEN

The FDA approved an all oral regimen of Simeprevir plus Sofosbuvir for treatment-naïve or treatment-experienced patients. The treatment duration is 12 weeks for patients without cirrhosis and 24 weeks for those with cirrhosis.

ACUTE HIV SYNDROMEOCCURS SOON AFTER INFECTION ; CORRESPONDS WITH A RAPID INCREASE IN VIRAL LOAD AND A MILD DROP IN CD4 COUNT.CAN BE ASYMPTOMATIC OR SUBCLINICAL.SYMPTOMS : OFTEN CONFUSED WITH FLU. FEVER, MALAISE , GEN.LYMPHADENOPATHY AND MACULOPAPULAR RASH.DSIS : HIV TESTING (ELISA AND WESTERN BLOT)TREATMENT : IF HIV +,TREAT ACCORDINGLY

HAART EFAVIRENZ IS PREFERRED IN NON PREGNANT WOMEN.MAY USE 2 NRTIs and 2PIs.GOAL : THE VIRAL LOAD SHOULD BE CUT IN HALF IN THE FIRST MONTH. IDEALLY IT SHOULD DROP TO UNDETECTABLE EVENTUALLY. CD COUNT SHOULD ALSO RISE. MONITOR FOR HIV METABOLIC SYNDROME

ALWAYS 3 OR 4 DRUGS:SHOULD ALWAYS INCLUDE 2 NRTIs3rd CAN BE EITHER A PI or AN NNRTI

ANTIRETROVIRAL THERAPYART has dramatically reduced the mortality associated with HIV, which can now be considered a chronic treatable disease. ART does not, however, cure HIV so treatment is life longEffective ART reduces the risk of onward transmission of HIV to sexual partners and mother to child transmissionAntiretroviral therapy can only be initiated once a diagnosis of HIV is made.Delayed diagnosis of HIV and delayed initiation of ART can be associated with increased mortality

TREATING THE PATIENT WITH HIVFIRST A BASELINE WORK UP WHICH INCLUDES:• HIV VIRAL GENOTYPING• CD4 COUNT• VIRAL LOAD• TEST FOR TB,CMV,OTHER STDs,

TOXOPLASMA Abs• CBC , CMP, TFTs, LFTs, LIPIDS• OPHTHALMOLOGIC EXAMRECHECK EVERY 3-6 MONTHSTREATMENT: ANTIRETROVIRALSSTART THERAPY WHEN CD4 <350/MICROLITRE OR VIRAL LOAD >55000

ANTIRETROVIRAL THERAPY GENERALLY BE STARTED AT CD4 COUNT <350 AND >200/mm3. 3 or 4 DRUGS REGIMENS INCLUDING : 2 NRTIs AND EITHER 1 NNRTI or 1 OR 2 PROTEASE INHIBITORS ARE VERY EFFECTIVE.

BEFORE STARTING,CLINICIAN SHOULD GET VIRAL SENSITIVITY TO DETERMINE THE MOST EFFECTIVE DRUG.

RECOMMENDATIONS FROM IAS-USA

ALL PATIENTS WITH CLINICAL AIDS OR IMMUNOLOGICAL AIDS (CD4 COUNT <200 CELLS/mm3)PATIENTS WITH SYMPTOMATIC HIV DISEASE REGARDLESS OF CD4 COUNTPATIENTS WITH CD4 COUNT LESS THAN OR EQUAL TO 500 CELLS/mm3 with asymptomatic disease

PATIENTS WITH CD4 COUNT LESS THAN OR EQUAL TO 500 CELLS/mm3 with asymptomatic diseaseHIV ASSOCIATED NEPHROPATHY, HBV CO INFECTION AND PREGNANCY

HAART

HIV AND PREGNANCYAll pregnant women be tested for HIV infection as early as possible in their pregnancy .A negative test does not preclude diagnosis.AZT IS RECOMMENDED TO ALL PREGNANT HIV WOMEN ASAP.To prevent perinatal HIV transmission, combination antiretroviral (cART) therapy is initiated as soon as possible preferably at 14 weeks gestation ; cART should be continued in women already on therapy.

LSCS at 38 wks’ gestation for women with HIV RNA levels >1000 copies/mL, or unknown.BABY should be on AZT for at least 6 weeks, monitored until 18 months.NO BREAST FEEDING NEVER,NEVER, NEVER,NEVER

NO BREAST FEEDING

ANTIRETROVIRAL PROPHYLAXISART RECOMMENDED FOR TREATMENT OR POST EXP. PROPHYLAXIS.COMBINATION THERAPY (HAART) IS ALWAYS RECOMMENDED FOR 4 WEEKS.THREE DRUGS ARE USUALLY GIVENZDV + LMV+ INV PREVENTS RECEPIENT INFECTION AFTER ACCIDENTAL INFUSION OF HIV+ve INFECTED BLOOD.AZT (ZIDOVUDINE) ITSELF REDUCES RISK BY 80%

HERPES VIRUSES: ANTI-HERPESVIRUS AGENTS

ACYCLOVIRValacyclovirFamciclovirGanciclovirValganciclovirFoscarnetCidofovirFormivirsenTrifluridineIdoxuridine

Development represents a watershed in the field of antiviral chemotherapy

Acyclic guanosine analogActive vs. HSV, VZV and modestly CMV

Mechanism of action• Preferentially taken up by virally infected cells

• Monophosphorylated by virally encoded thymidine kinases• Di- and triphosphorylation completed by cellular kinases

• ACV-TP is the active moietyCompetitive inhibitor of viral DNA

polymeraseCellular DNA polymerases much less

susceptible to inhibitionLeads to viral DNA chain termination

WHAT IS THE DRUG OF CHOICE FOR HERPES SIMPLEX ENCEPHALITIS IN AN IMMUNOLOGICALLY NORMAL 20 YEAR OLD INDIVIDUAL PREVIOUSLY IN GOOD HEALTH

1.ACYCLOVIR ALONE 2.ACICLOVIR PLUS CORTICOSTEROIDS3.GANCICLOVIR4.FOSCARNET5.CIDOFOVIR

ACYCLOVIR ALONE

HERPES SIMPLEX ENCEPHALITIS

VIRAL ENCEPHALITISAll cases of suspected CAVE (community-acquired viral encephalitis) are started empirically on aciclovir until the cause is determined. As most cases of sporadic viral encephalitis are secondary to HSV, this is good clinical practice . In an immunocompromised patient, CMV encephalitis is a consideration. If suspected, Ganciclovir and Foscarnet are given with Aciclovir until HSV PCR is available. If HSV encephalitis is excluded, then aciclovir can be discontinued. In some cases, MRI findings and clinical features strongly suggest a diagnosis of CMV encephalitis, so aciclovir may not be necessary.

CHICKEN POXThe disease usually resolves spontaneously over 5-10 days, and Rx. is generally supportive. Adults and immunocompromised persons have a more complicated course than that occurring in children, and ,the condition necessitates a more aggressive approach. IV acyclovir is recommended for immunosuppressed

Avoid Aspirin in children (associated with Reyes syndrome) Ibuprofen   (associated with severe secondary infections).

TREATMENT IN THE IMMUNOCOMPROMISED OR IMMUNOSUPPRESSED

IV Acyclovir therapy is recommended because of the life-threatening complications of primary varicella infection . Severe disseminated disease, with the development of varicella pneumonia, encephalitis, hepatitis, and hemorrhagic complications, is much more common in this population than in other populations. Vidarabine, and IFN-alpha are effective in the treatment of primary varicella infection of immunocompromised hosts. Foscarnet is a potentially efficacious drug in patients with acyclovir-resistant VZV strains. 

TREATMENT IN HEALTHY CHILDREN

The nucleoside analogue acyclovir (20 mg/kg PO qid for 5 d), though shown to decrease the symptoms and duration of primary varicella infection when administered within 24 hours of onset of symptoms, is not commonly prescribed for otherwise healthy children.

Given the high risk of varicella-related complications, children should be treated if any of the following conditions are a medical concern:• Defects in cell-mediated

immunity• Chronic atopic dermatitis• Chronic asthma• Iatrogenic immunosuppression• Long-term systemic steroid use• Splenic dysfunction• Nephrotic syndrome

IMMUNOCOMPETENT ADULTOral acyclovir should be considered for healthy persons at increased risk of severe varicella infections, most notably patients older than 12 years. Oral acyclovir therapy in this population (800 mg 5 times/d for 7 d), begun within 24 hours of onset of symptoms, has been shown to decrease the duration of lesions and pyrexia, while reducing other symptoms and disease duration.

Valacyclovir:Has higher oral bioavailability.Used in the treatment of herpes zoster.No better efficacy in primary varicella infection of healthy, immunocompetent individuals.Famciclovir is a prodrug of penciclovir.Better efficacy in the treatment of HZ , but it has not been extensively studied for use in primary varicella infection of healthy populations.

SHINGLESKeeping in mind the limitations of treatment effectiveness, antiviral medicines may be considered for patients with:• Age > 50 years• Ophthalmic involvement• Immunocompromised status• Atypical presentation of rash, e.g. shingles affecting the neck, limbs or perineum• Moderate or severe pain• Moderate or severe rash

HERPES ZOSTEROral Aciclovir : first-line antiviral treatment Aciclovir 800 mg, 5Xdaily, for 7days.Valaciclovir is an alternative antiviral.Valaciclovir have greater overall effectiveness than Aciclovir as it produces higher levels of antivirals. May be a better alternative to aciclovir in patients at increased risk of complications.A meta-analysis of aciclovir Vs aciclovir with corticosteroids failed to show a benefit of corticosteroids in improving QOL or reducing PHN.

GENITAL HERPES ?Your patient is a 24 year old student who wants to talk to you about genital herpes. She had her first symptomatic infection 3 years ago and tends to get a recurrence every 6-8 weeks. She has a new partner and is worried about passing the virus on to him.

They have not yet had sexual intercourse. She has read about suppressive therapy and would like to discuss its benefits. What would be the most accurate advice to give her?

GENITAL HERPESTaking suppressive therapy will reduce but not eliminate the risk both of symptomatic recurrence and of passing HSV on to her partner.Long-term daily suppressive treatment with oral antivirals is safe and effectively reduces both symptomatic recurrences and the risk of transmission to a sexual partner.

But it doesn’t eliminate the risk of either

GENITAL HERPES AND GESTATIONShe gets regular outbreaks of genital herpes and has had these for several years, although she has not had one so far during this pregnancy. She is reluctant to take medication and asks you how likely it is that she will transmit the HSV infection to her baby if she does not take suppressive therapy and has a vaginal delivery.What should you tell her?

You see a worried patient who is 22wks. pregnant.

GENITAL HERPESThis woman is at risk of a recurrent episodes of genital herpes . The risk of neonatal infection is low, just 3% even if herpes lesions are present at the time of labour. The RCOG/BASHH guidance states that daily suppressive aciclovir can be considered from 36 weeks of gestation .For those women who do opt for suppressive antiviral therapy in late pregnancy, a dose of 400 mg three times daily is recommended.The risk of neonatal transmission is over 40% in women who have a first episode of clinically apparent genital herpes in the last 6 wks. of pregnancy, Caesarean section is recommended for any woman who develops a first episode HSV infection in the third trimester. 

BELL PALSY: ORGANISM- SPECIFIC THERAPY

Some evidence suggests combination of antivirals with corticosteroids is more effective .HSV-1 or HSV-2 : Prednisone 1 mg/kg or 60 mg/day x 6d, followed by a taper, for a total of 10d plus Acyclovir  400 mg PO 5 times daily for10d. or  valacyclovir 500 mg PO BID for 5d.VZV: Prednisone 1 mg/kg or 60 mg/day for 6 d, followed by a taper, for a total of 10 d plus Acyclovir 800 mg PO 5 times daily for 10 days or Valacyclovir 1000 mg PO TID for 5d

EBV HSV TYPE1

Herpes simplex virus type 1. Primary herpes can affect the lips, and the ruptured vesicles may appear as bleeding of the lips. 

Mono, like many viral illnesses, just needs to run its course and it usually resolves without treatment.Antiviral drugs are not effective for treating mono.

CONCLUSIONTHE ADVANCES MADE IN SPECIFIC TREATMENT OF VIRAL DISEASE HAVE BEEN ? DISAPPOINTINGLY SLOW IN THE PAST THREE DECADES. WE HAVE GOT ONLY A SMALL NUMBER OF ANTIVIRALS WHICH ARE USEFUL IN A RESTRICTED NUMBER OF CLINICAL SITUATIONS. MOST ANTIVIRAL DRUGS NON SELECTIVELY INHIBIT VIRUS REPLICATION WITH SIMULTANEOUSLY INJURING THE HOST CELL, AND ARE ACCOMPANIED BY SERIOUS SIDE EFFECTS. POSSIBLE BENEFICIAL EFFECTS OF ANTIVIRAL DRUGS MUST BE BALANCED AGAINST POTENTIAL IMMUNOSUPPRESSIVE AND OTHER UNDESIRABLE SIDE EFFECTS.

VACCINESANTIVIRALS

Field of antiviral therapy has matured dramatically in past 30+ yearsGreatest progress made for Herpes viruses, HIV, Respiratory viruses and Hepatitis virusesResistance to any antiviral drug must be anticipated : Viruses replicate so efficientlyViruses have modest to high mutation frequenciesPreventive vaccination remains the key to global control of viral infections

TAKE HOME MESSAGE

FOR PATIENT HEARING