Antivirals/HIV Flashcards
Why are there only a few antivirals?
- Often the virus has finished replicating by the time S&S develop
- Antivirals only work during cell replication
- Viruses live inside the body’s cells, so the drugs that kill a virus could also kill healthy cells
How do antivirals kill viruses?
Inhibit their ability to replicate
-Allows the body’s immune system to destroy the virus
Antiviral used to suppress replication of:
HSV 1 (oral)
HSV 2 (genital)
VZV (herpes zoster and varicella/chickenpox)
acyclovir
Used for BOTH initial and recurrent infection (may require MULTIPLE TREATMENTS)
Reduces viral shedding and decreases local symptoms
MOA of acyclovir
Works in 3 ways:
-Interferes with viral nucleic acid synthesis, its regulation or both (DNA and RNA)
-Prevents virus from binding to cells so VIRUS CAN NOT GET INTO CELLS thus preventing viral replication
-Stimulates the body’s immune system to kill the virus
Acyclovir Routes
Routes: Oral, tablet and liquid, topical cream and ointment, IV
Acyclovir
AE and considerations
AE: GI distress, renal impairment, seizures, ITP
Considerations:
-IV form: tissue necrosis if not IV is not patent
-Decreases symptom severity and frequency of outbreaks, NOT a cure
-May require multiple treatments
Antiviral drug for “the flu”
oseltamivir
oseltamivir
MOA and route
MOA: inhibit neuraminidase in influenza viruses
Mostly active against influence A, some action against influenza B
Route:ONLY PO
oseltamivir
Indications and AE
Indications:
-Used for prophylaxis and to treat active disease (48H of symptom onset)
-most often given to the elderly/immunocompromised after known exposure to influenza A or B
-CDC approved April 2009 for treatment of H1N1 (swine flu)
AE: nausea and vomiting, seizures, renal impairment
Antiviral to treat cytomegalovirus (CMV)
ganciclovir
ganciclovir
MOA and indications
MOA: inhibits viral DNA polymerase resulting in change termination
Indications: CMS
Patients typically include: immunocompromised, AIDS, immunosuppressed, transplant patients
Controls but doesn’t cure
ganciclovir
Route and considerations
Route: IV and PO
Considerations:
Black box warning: hematologic toxicity, fertility impairment, fetal toxicity, carcinogenesis
Teratogenic in pregnant patients
Do NOT give with imipenem/cilastatin→ seizure potential
Watch kidneys if given with other nephrotoxic drugs
HIV (Human Immunodeficiency Virus
A retrovirus that destroys CD4 and T cells
HIV 1- discovered first and is most prevalent
HIV 2-less pathogenic and confined to West Africa
AIDS (Acquired Immune Deficiency Syndrome)
Caused by HIV
Typically UNTREATED HIV infection turns to AIDs in 8-10 years
Severe immune system dysfunction is present when AIDS occurs
Epidemiology of HIV
South Africa has the highest prevalence of HIV
76% of adults and adolescents with HIV are men
-Black men have the highest rate of new infections
-Men who have sex with men accounts for most new and existing HIV infections
New cases among women are increasing
What is a retrovirus?
A type of virus that uses an enzyme, reverse transcriptase, to translate its genetic information into DNA
4 pathophysiology components of retrovirus
- Cannot replicate outside living host cells
- Contains only RNA; no DNA
- Destroys the body’s ability to fight infections
- Infects CD4 cells-the primary target of HIV infection
Which viral enzyme assists the viral DNA copy to be inserted into the genetic material of the infected cell?
HIV integrase
Which viral enzyme is responsible for the virus particles that are released to attack, replicate, and release more viruses?
HIV protease
HIV targets CD4 on:
T lymphocytes, monocytes, macrophages
What is the primary target of HIV protease?
Helper T lymphocytes
Seven stages of HIV life cycle
- Binding
- Fusion
- Reverse transcription
- Integration
- Replication
- Assembly
- Budding
Event: HIV invades CD4+ cells and becomes a part of cell DNA
Significance:
The individual is infected for life
Event: Virus proliferates in infected cells and sheds virus particles
Significance:
Virus present in blood and body fluids
Event: Body forms anti-HIV antibodies
Significance:
Antibodies are a marker of infection but it is not protective
Event: Progressive destruction of Helper T cells
Significance:
Compromised cell-mediated immunity
Event: Immune defense collapse
Significance:
Opportunistic infection, neoplasms
Why is HIV such a problem?
Decreases the number of CD4 and T Helper cells
HIV replicates prolifically
Completely overwhelms the body’s defenses
Stage 1
Early infection (Acute)
-Rapid replication
-Not detectable by traditional lab tests (no symptoms)
-Infectious
Seroconversion
-Antibodies are detectable
-Flu-like symptoms for several weeks
HIGHLY INFECTIOUS
Stage 2
Clinical Latency (Chronic)
-Virus levels have stabilized
-Body is fighting infection
-Lasts 3-12 years
-Asymptomatic or mild symptoms
Rapid virus production
-Persistent drop in CD4 and T cell count
-Antiviral fight becomes less effective
-Viral load increases
Stage 3
Symptomatic HIV Infection
AIDS
-CD4 cells fall below 200 cells/mm
-Without treatment, people typically survive 3 years
Initial Symptoms of HIV
Sore throat
Fever
Muscle Aches
Night sweats
Fatigue
Mouth ulcers
Chills
Swollen lymph nodes
Rash
Diagnosis of AIDS
- Must have an AIDs-defining condition
-Kaposi’s Sarcoma
-Wasting syndrome
-Cancers
-Pervasive candidiasis - CD4 count less than 200 cell/mm regardless if an AIDs-defining condition is present
What manifestation is linked to a higher risk of progression to AIDS
Oral manifestations
-Seen with falling CD4+ counts
Examples of oral manifestations
Oral hairy leukoplakia
periodontal disease
HIV-Associated Dementia
“AIDS dementia complex”
Symptoms:
-poor concentration
-forgetfulness
-changes in behavior
-difficulty word finding
-depression
-motor/speech/balance/visual problems
How is HIV transmitted?
-Sex without a condom
-Passed from mother to baby
-Sharing equipment
-Contaminated blood transfusion or organ transplant
Why doesn’t everyone who is exposed develop HIV?
-Duration and frequency of contact
-Volume, virulence, and concentration of virus
-Host immune status
-Genetic protective factors
Drug to treat individuals with HIV
Antiretroviral therapy (ART)
-NRTIs
-Given in PAIRS with other NRTIs most commonly
Most common ART
Dual nucleoside and a third agent from other class
NRTI MOA
Inhibits reverse transcriptase
-Thus blocking the HIV retrovirus to incorporate its RNA into the host cell’s DNA
NRTI Adverse Effects
peripheral neuropathy, pancreatitis,
lipoatriphy, hepatic steatosis
ART Principals
Start AS SOON AS POSSIBLE after diagnosis
GOAL: Decrease viral load to undetectable level
Treatment guided by CD4 count, viral load, and patient
preferences
True/False
A low CD4 and high viral load is healthy
False
Measured in drop of blood:
CD4 cells should be high
Viral load is better low
What is PrEP used for?
Pre-exposure prophylaxis
-Use of antiretroviral medications
-Detailed sexual and drug use history to determine risk
-Determine potential barriers
-Condom use
-Can reduce risk of HIV transmission by greater than 90%
What is PEP used for?
Post-exposure prophylaxis
-Recommendations based on exposure and barriers
-Treatments include ART for 28 days
-HIV testing initially and at 6-12 weeks after exposure
