Pharm E1- HIV & STIs

What are the 3 main phases of HIV infection?

acute (retroviral syndrome or mono like illness), chronic, terminal (AIDs)

When monitoring HIV patients, you want CD4 count _____ and viral load _____

high ; low

What would indicate a maximal and durable suppression of HIV replication (tx is working)?

undetectable viral load

What does CD4 count indicate?

extent of immune damage

What do plasma HIV RNA levels (viral load) indicate?

magnitude of replication

When should treatment for HIV be started?

ASAP - regardless of CD4 count (reduces transmission, fewer AIDs events)

What are the main drugs classes used to treat HIV?

Nucleotide reverse transcriptase inhibitors

Non nucleoside reverse transcriptase inhibitors

Protease inhibitors

Integrase Inhibitors

Entry/fusion inhibitions

Coreceptor inhibitors

What class of drugs?

• used in treatment of HIV

• based off purine and pyrimidine nucleotides/nucleosides

• targets reverse transcriptase

  • acts as chain terminator to prevent viral RNA from being copied & incorporated into our DNA

NRTIs

Which NRTIs do not have as many side effects?

abacavir, tenofovir, emtricitabine, lamivudine (newer agents)

Which NRTIs are the side effects more pronounced with?

stavudine, didanosine, zidovudine

What are SE associated with NRTIs?

peripheral neuropathy, pancreatitis, lipoatrophy, myopathy, anemia, lactic acidosis w/ fatty liver

*monitor liver function

Before starting treatment, which drug requires testing for a HLA-B5701 mutation that causes a hypersensitivity reaction to the drug?

Abacavir

Which drugs belong to the nucleoside (nucleotide) reverse transcriptase inhibitors (NRTIs) class?

Stavudine

Zidovudine

Emtricitabine

Lamivudine

Abacavir

Didanosine

Tenofovir

Which class of drugs?

• treats HIV

• binds to reverse transcriptase forcing conformational change preventing DNA production

  • (can’t read viral RNA anymore)

NNRTIs

What drugs belong to the non nucleoside reverse transcriptase inhibitor (NNRTI) class?

Delavirdine

Efavirenz

Nevirapine

Etravirine

Rilpivirine

What SEs are associated with NNRTIs?

rash, transaminitis

*monitor liver function

With which class of drugs used to treat HIV would a single viral mutation confer resistance to the entire class (lose whole category of drugs)?

NNRTIs (except etravirine)

Which class of drugs?

• used to treat HIV

• inhibits protease enzyme preventing virus from making mature proteins

• most metabolized in liver, often given w/ boosters (CYP3A4 inhibitors)

Protease inhibitors (PIs)

What drugs belong to the protease inhibitor class?

Atazanavir

Darunavir

Fosamprenavir

Indinavir

Lopinavir

Nelfinavir

Ritonavir

Saquinavir

Tipranavir

What SEs are associated with protease inhibitors (PIs)?

GI distress, elevated lipids, glucose intolerance, altered fat distribution (buffalo hump / lipodystrophy)

Why are strong CYP3A4 inhibitors such as ritonavir or cobicistat given along with protease inhibitors?

utilize the drug interaction to increase drug levels for less frequent dosing (better for compliance)

What drugs belong to the fusion inhibitor class?

Enfuvirtide (Fuzeon)

What class of drugs?

• inhibits HIV1 envelope fusion (no activity for HIV2)

• not PO, given SC injection

  • injection site rxns common - pain, erythema, nodules

fusion inhibitors

What drugs are CCR5 antagonists?

Maraviroc (Selzentry)

What class of drugs?

• treats HIV1-2

• blocks human receptor to prevent virus from getting in

  • works on human cell NOT virus

• can only use against correct strain → must test BEFORE starting tx

CCR5 antagonist

What side effects are associated with CCR5 antagonists (Maraviroc)?

rash and hepatotoxicity

What drugs are Integrase Inhibitors (InSTI)?

Raltegravir

Dolutegravir

Elvitagravir (coformulated w/ cobicistat)

Bictegravir (coformulated w/ emtricitabine + tenofovir [Biktarvy])

What class of drugs?

• treats HIV

• often with booster to reduce frequency of dosing

• effective and better tolerated - most pts start on these

• bind to integrate & prevent viral DNA incorporation into chromosomal DNA

Integrase inhibitors

What are side effects associated with integrate inhibitors?

rash, N, HA

Efavirenz, Etravirine, and Nevirapine ______ CYP3A4

induce (lower drug levels)

Most protease inhibitors ______ CYP3A4

inhibit (increase drug levels)

What should be the initial treatment regimen for a new diagnosis of HIV?

(**test question, know drugs in each class)

minimum of 3 antiretroviral agents- 2 must be NRTIs

Ex: InSTI + 2 NDRTIs, PI + 2 NRTIs, NNRTI + 2 NRTIs

What is the current preferred initial regimen for HIV?

integrase inhibitors + 2 NRTI

(Dolutegravir + tenofovir + emtricitabin or lamivudine or biktarvy)

What should be used whenever possible in HIV treatment to increase compliance?

combo formulas (ex- Atripla, genvoya, Complera, biktarvy)

What would elevated viral loads indicate after being on treatment?

virus is resistant to drug regimen or patient is not compliant with meds

Which resistance testing for HIV treatment provides the most information but is more expensive and has a slower turnaround?

phenotype testing

Which resistance testing for HIV treatment is easier and faster but not as informative?

genotype testing

Which HIV medication should be avoided in pregnancy due to risk of neural tube defects (spina bifida)?

efavirenz

Which drug is recommended intrapartum to prevent HIV transmission to fetus?

Zidovudine

What should fetuses receive if their mother is HIV+?

zidovudine 4-6 wks

Should HIV+ mothers breastfeed?

no

What is the post exposure prophylaxis after high risk HIV exposure?

Tenofovir, emtricitabine, raltegravir x 4 wks

start ASAP

What is the HIV pre-exposure prophylaxis for serodiscordant couples, NSN, or IV drug abusers?

(*must be seronegative before starting)

daily tenofovir/emtricitabine (Truvada)

What integrase inhibitor is started orally then converted to long-acting IM and given every 2 months (good for noncompliant patients and patients who can’t tolerate oral medications)?

Cabotegravir (Vocabria)

When should CD4 counts and HIV RNA loads be measured?

before treatment initiation and every 3 months

What are reasons for changing HIV treatment regimen?

intolerable SEs, tx failure (viral RNA > 200), resistance to drugs

As CD4 count drops ______

risk of opportunistic infx increases (life threatening)

What is immune reconstitution syndrome (IRIS)?

ART therapy initiation → major increase in inflammatory cascade (immune system starts working) → OI symptoms start showing (worsening fever & OI manifestations)

What is the MC life threatening OI in AIDs patients?

PCP

What is the treatment for PCP?

bactrim x 21 days

When is PCP prophylaxis indicated?

CD4 < 200 or hx of oropharyngeal candidiasis or hx PCP PNA

What is the prophylaxis for PCP?

bactrim 3x weekly (MWF)

What is the treatment for candidiasis (thrush) in AIDs patients?

Fluconazole (Diflucan) IV/PO 7-21 days OR

Nystatin oral liquid QID (*not recommended for esophageal infx)

What is the recommended treatment for gonorrhea?

Ceftriaxone 500 mg IM (single dose to ensure compliance)

What should also be treated in a gonorrhea patient due to high rate of co infx?

chlamydia

What is the treatment for chlamydia?

Doxy 100 mg PO BID x 7 days (preferred) OR

azithro 1g PO single dose

What is used for gonorrhea eye infection in infants?

topical erythromycin

What is an alternative treatment option for gonorrhea in patients with cephalosporin allergy?

no good alternative option; possible high dose azithromycin + gentamicin

What are alternative treatment options for chlamydia?

tetracyclines or FQs (avoid in pregnancy)

What is the treatment for chlamydial ophthalmia infection in children?

oral erythromycin

What is the treatment for syphilis?

Benzathine PCN G (Bicillin) single dose

alt: doxy or tetra x 2-4 wks

What is the treatment for advanced cases of syphilis (neurosyphilis)?

aqueous PCN G (IV)

Why is HSV a major public health risk?

many are asx & viral shedding occurs in absence of lessons

What are the goals of treatment for HSV?

relieve sx, shorten clinical course, prevent complications & recurrence, dec transmission

How can pain and discomfort associated with HSV infections be treated?

warm saline baths, analgesics, antipyretics, antipruritics, & good hygiene to prevent bacterial superinfection

What is the recommended treatment for the first episode of an HSV infection?

acyclovir, valacyclovir, or famciclovir x 7-10 days (start ASAP)

*topical tx not recommended

What is the treatment for immunocompromised patients with HSV?

IV acyclovir

What side effects is the IV form of acyclovir more associated with?

renal, bone marrow, & CNS toxicity

What is the episodic therapy regimen for HSV infections?

initiate 6-12 hrs after onset of prodrome sx (no later than 24 hrs after lesions appear)

What is the recommended treatment for patients with HSV who have prolonged recurrences & severe sx?

episodic therapy

Which HSV treatment regimen reduces frequency of recurrences by 80% and has less asymptomatic viral shedding?

chronic suppressive therapy

What is the treatment for trichomoniasis?

single 2g dose of either Metronidazole or Tinidazole

(*tx partners also)

What drug is an anti protozoal used to treat Trichomoniasis by damaging the DNA?

Tinidazole

What infection is usually acute & self limiting and confers immunity?

Hepatitis A

What is the post exposure prophylaxis for hepatitis A?

immunoglobulin (saved for extremes of age or immunocompromised)

What is the best form of prevention for Hep A?

vaccine (kids at 12 mos) & practice good hygiene

What infection is 50-100x more infectious than HIV?

Hepatitis B

What does a chronic hep B infection increase the risk for?

cirrhosis and hepatocellular carcinoma

What indicates a chronic HBV infection & cure is no longer possible (MC in perinatal infections)?

persistent antigen levels > 6 months

Which virus has a low vaccine response and requires 3 doses for optimal protection?

Hep B

What are the goals of treatment for hepatitis B?

maintain viral suppression, seroconversion to anti-HBeAg and lose HBeAg, & prevent progression to hepatic complications

When should a patient relieve treatment for hepatitis B?

(* possible test Q

HBeAg positive & HBV DNA >20,000 AND

ALT >2x ULN

What drug?

• first approved therapy for HBV

• acts as a host cytokine

• stimulates host immune system to mount defense (antiviral, antiproliferative, & immunomodulatory effects)

• required 3x weekly injections

Interferon-alfa (Intron A)

What are adverse effects of Interferon alfa?

black box- fatal neuropsychiatric, autoimmune, ischemic, & infectious disorders

also anaphylactic risk, flu sx, depression, SI, aggression, blood dyscrasias

What drug?

• activity against HV but not recommended first line

• can be given indefinitely but concerns of relapse & resistance

Lamivudine (Epivir)

What drug?

• activity against Lamivudine resistant HBV

• nephrotoxic- monitor serum creatinine

Adefovir (Hepsera)

What drug?

• considered first line for HBV due to safety & low resistance

• used in lamivudine resistant strains

Entecavir (Baraclude)

What drug is more effective than Lamivudine against HBV but has a high rate of resistance?

Telbivudine

What drug?

• also first line for HBV

• low resistance rates

Tenofovir (Viread)

What are the goals of treatment for hepatitis C?

eradicate infection (undetectable viral load 12 wks after end of tx) & prevent progression to end stage liver disease

What patients should receive treatment for Hep C?

all patients

What is the current standard regimen for HCV treatment?

all oral meds x 12-14 wks (depending on viral genotype)

What drug?

• treats HCV

• binds to NS5A to prevent viral RNA replication & vision assembly

  • disrupts protein structure/function- can’t produce new RNA

• no adjustment in renal/hepatic insufficiency

• SE: HA, fatigue, N, D

• expensive

Daclatasvir (Daklinza)

What drug?

• treats HCV

• work synergistically to inhibit NS5A to block viral replication

• no organ dose adjustment needed

• SE: HA and fatigue

• expensive

Ledipasvir/Sofosbuvir (Harvoni)

What drug?

• treats HCV

• inhibits NS3/4A protease

• SE: rash/photosensitivity, pruritus, N

• espensive

• can’t be used alone (give w/ sofosbuvir or interferon/ribavirin)

Simeprevir (Olysio)

What drug?

• treats HCV

• give in combo with Paritaprevir, Ritonavir, Technivie, or Dasabuvir

Ombitasvir

What drug?

• injectable to treat HCV

• MOA not fully understood

• used for complicated cases

• has bad SE

Ribavirin (Rebetol)

What drug is pregnancy category X, requiring women to use 2 forms of birth control for 6 months AFTER treatment ends?

Ribavirin (rebetol)

What are SEs of Ribavirin (Rebetol)?

SI, depression, insomnia, dyspnea, hemolytic anemia, pregnancy category X

What class of drugs are mainly used to treat HCV?

direct acting antivirals (DAAs)