Viral and Retroviral Infections

Viral and Retroviral Infections

• Antivirals, reverse transcriptase inhibitors, protease inhibitors, and antiretrovirals are topics to be covered.

What is a virus?

• Viruses are small infectious agents that can reproduce only inside a host organism's living cells.
• Viruses introduce their genetic information into a host cell's nucleus and hijack its operations.
• The host cell will produce and release replicated virus particles, known as virions, and infection spreads.
• The infected host cell will eventually die.

Antivirals

• Rather than killing viruses, antivirals impede their ability to execute reproductive functions.
• Antivirals slow or halt viral replication inside host cells, making them virustatic, not virucidal.
• To slow or stop growth, antivirals block a virus from entering the host cell and act on target enzymes or proteins within to prevent virus replication.
• These drugs can help the immune system fight infection.
• Antivirals treat herpes, influenza, cytomegalovirus (CMV), RSV, hepatitis, and COVID-19.

Antivirals for Herpes

• Herpes Simplex Virus 1 (HSV-1): causes cold sores of the mouth.
• Herpes Simplex Virus 2 (HSV-2): causes genital sores.
• Herpes comes and goes in outbreaks, and is more likely to spread virus right before or during an outbreak, but can spread at anytime.
• Antiviral medications can have a role reducing outbreaks, lowering the chances of spread.
• Medications for herpes include acyclovir (Zovirax), famciclovir (Famvir), and valacyclovir (Valtrex).
• Acyclovir is hepatotoxic, should not be given with a milk allergy.
• Famiciclovir is also hepatotoxic.
• The common medications for herpes are DNA polymerase inhibitors.
• DNA polymerase inhibitors prevent viruses from producing more genetic material.
• These meds can help with chickenpox and shingles (VZV).

Antivirals for Influenza

• Enzyme called neuraminidase helps flu viruses burrow into cells of the respiratory tract.
• A flu virus' outer coat must be opened to fuse with the host cell's membranes.
• Medications for the flu include oseltamivir (Tamiflu) and zanamivir (Relenza), neuraminidase inhibitors, which should never be given with milk allergy or asthma.
• Neuraminidase inhibitors work best against Flu B, and are safe for children.
• Additional medications include amantadine (Symmeterel) and rimantadine (Flumadine).
• These are uncoating inhibitors, and work best against Flu A.
• Influenza medications should be given soon after exposure or within 48 hours of the start of symptoms.

Antivirals for Cytomegalovirus (CMV)

• Cytomegalovirus is from the herpes family.
• It causes few problems in immunocompetent people, such as those with AIDS or newborns.
• In immunocompromised people, CMV can cause encephalitis with brain damage and retinitis with blindness.
• Medications include cidofovir (Vistide) and foscarnet (Foscavir).
• Foscarnet and cidofovir are polymerase inhibitors, administered intravenously, are extremely toxic, and need to be handled with gloves and masks.

Antivirals for Respiratory Syncytial Virus (RSV)

• RSV affects the lungs and bronchial tubes.
• It is commonly responsible for chest colds, croup, and PNA in children.
• It is usually mild and resolves in 5-7 days.
• Premature infants, newborns, and small children with chronic illnesses can have serious infections that can lead to death.
• Ribavirin (Virazole) belongs to its own drug class as an Anti-RSV drug, and is administered as an aerosol.
• It is very toxic, needs to be handled with gloves, mask, and gown.
• Ribavirin has two black box warnings: it can cause birth defects in pregnant women, and it suppresses bone marrow, causing anemia.

Antivirals for Hepatitis

• Hepatitis B exhibits recurrence of symptoms from time to time.
• Hepatitis C may lie dormant for years then cause profound liver damage with cirrhosis.
• Hepatitis types B and C have a long incubation period of 2-26 weeks after infection.
• Therapeutic medications include polymerase inhibitors.
  • Some examples are, adefovir (Hepsera), entecavir (Baraclude), lamivudine (Epivir), and telbivudine (Tyzeka).
• Other meds include interferon (Peginterferon) and nucleoside reverse transcriptase inhibitors.
  • Given SBQ at 3x per week for 1 year and is a synthetic version of interferon.
• Lamivudine primarily treats HIV at higher dose, but HBV at lower dose, and it is technically an antiretroviral.
• Protease Inhibitors are also used and are technically antiretroviral meds
  • Simeprevir (Olysio) can cause sun sensitivity and has an enzyme that breaks down proteins necessary for virus replication
• There are also combination drugs
  • Harvoni (Ledipasvir and Sofosbusvir), Mavyret (Glecaprevir and Pibrentasvir), and Epclusa (Sofosbusvir and Velpatasvir), are very effective but cost prohibitive.

COVID-19

• COVID-19 is caused by coronavirus sars-cov-2 and is spread by droplets.
• Most people will have mild to moderate respiratory symptoms for 1-2 weeks and infectivity has around a 1% mortality rate
• Risk factors include cancer, COPD, diabetes, and cardiovascular disease.
• Remdesivir IV can be administered for up to 5 days.

Antivirals side effects and drug interactions

• Common side effects of antivirals include nausea, vomiting, diarrhea, and headache, and have many drug interactions.

Key concepts for antivirals and retrovirals

• Herpes
  • “cyclo” herpes follows a cycle of outbreaks
• Cytomegalovirus
  • Sounds like “sight” and “focus” for retinitis and brain damage
• Hepatitis
  • Symptoms show up L.A.T.E.
• RSV
  • Causes resp distress
• Flu A for Amantadine
• Entry Inhibitors
  • “Roc” being used for breaking and entering.
• NRTI's
  • "Tide" Become one with the Wave
• Integrase Inhibitors
  • tegr
• Protease Inhibitors
• "Navir" tease a pro

Practice Questions (Answers)

• Polymerase inhibitors treat herpes, CMV, and hepatitis.
• Famiciclovir treats herpes.
• Zanamivir is most effective against Flu B.
• Neuraminidase inhibitors work by blocking the enzyme of an influenza virus from burrowing into a host cell.

Antiretrovirals

• Antiretrovirals slow or prevent the duplication of retroviruses, are viristatic and not virucidal.
• A regular virus hijacks a cell to reproduce, but retrovirus inserts its own DNA into the host cells DNA.
• Retroviruses have special enzymes such as, reverse transcriptase, integrase, and protease, which allow them to use the cells own DNA factory to replicate itself.
• Antiretrovirals treat HIV/AIDS.

HIV/AIDS

• HIV/AIDS a virus that targets helper T cells also known as CD4+ cells.
• The destruction of helper T cells makes a person susceptible to opportunistic infections (like CMV).
• Normal CD4+ count is between 500-1500, and AIDS occurs when CD4+ levels are less than 200.
• Risk factors include homosexual/bisexual men (MSM), African American/Hispanic, transgender women that have sex with men, IV drug use, and 25-34 year age group.

HIV Life Cycle

• The HIV life cycle is a 7 step process: attachment, fusion, reverse transcription, integration, replication, assembly, and budding.
• There are drugs aimed at interfering with different steps.
• Drugs that bind to the HIV envelope protein and prevent the virus from attaching to the CD4 receptor work in step 1 and are classified as entry inhibitors
• Drugs that prevent the HIV protein from engaging with co-receptors work in step 1 and are classified as post-attachment inhibitors
• Drugs that prevent the HIV virus from fusing or bonding with the CD4 receptors work in step 2 and are classified as fusion inhibitors
• Drugs that prevent HIV from synthesizing its RNA to DNA work in step 3 and are classified as NRTI’s (nucleoside reverse transcriptase inhibitors)
• Drugs also bind directly to HIV's enzyme and prevent HIV from converting its RNA to DNA which also works in step 3 and are classified as NNRTI’s (non-nucleoside reverse transcriptase inhibitors)
• This drugs blocks HIV's enzyme from integrating DNA so it cannot be replicated. This works in step 4 and are classified as Integrase inhibitors
• Drugs block one of HIV's enzymes preventing chain proteins from being cut into mature and are classified as Protease inhibitors and effects step 7

HIV life cycle, drug interventions

• Step 1, Attachment: Entry inhibitors and Postattachment inhibitors
• Step 2, Fusion: Fusion inhibitors
• Step 3, Reverse Transcription: NRTI's and NNRTI's
• Step 4, Integration: Integrase inhibitors
• Step 5, Replication: No drugs
• Step 6, Assembly: No drugs
• Step 7, Budding: Protease Inhibitors

Key concepts for Antiretrovirals

• Entry Inhibitors
  • Break in "Roc"
• Fusion Inhibitors
  • "Tide" Become One with the Wave
• Integrase Inhibitors -Tegr
  • Inhibiting all "Navir".

Nursing Considerations for Antiretrovirals

• ART (antiretroviral therapy) is a combination of several HIV drugs.
• No single drug is effective against HIV on its own, must be on them for life.
• Those who are HIV positive women should not breastfeed, HIV can be transmitted in breastmilk.
• Avoid alcohol, it can cause further damage liver
• Common side effects include: Mouth ulcers, nausea, diarrhea, rashes, Headaches, vivid dreams/nightmares
• Check liver enzymes, amylase, lipase. hepatotoxicity and pancreatitis
• Complete blood count is important to monitor during therapy, infection, anemia, drug toxicity
• Many drug interactions
• Skipping doses can lead to resistance and medication must be taken as scheduled
• If change position slowly- This can cause hypotension
• Report symptoms: Jaundice, nausea/vomiting, and severe abd. pain-hepatotoxicity peripheral neuropathy

Practice Questions for antiretrovirals (answers):

• Step 5 (replication) and 6 (assembly) are the two phases of the HIV life cycle are there NO meds for.
• Reverse transcriptase, integrase, and protease are the three enzymes that the HIV virus has.
• Ribavirin is the the only indicated drug to treat RSV infection
• Tamiflu needs to be given within 48 hours of symptom onset
• CMV (cytomegalovirus) is the opportunistic infection that can cause encephalitis and retinitis.
• Protease, an HIV enzyme, acts like chemical scissors to cut HIV protein chains into smaller sizes.