What is HIV?
retrovirusthat can cause acquired immunodeficiency syndrome (AIDS) - acts by binding to and then depleting cells that express CD4 receptors (so a lot of your WBCs) - leads to destruction of the immune system
What are the two types of HIV?
HIV-1 is a subtype found all over the world with subtype B being the most common in the US / HIV-2 is a type found only in West Africa
How low must the CD4 count get to diagnose AIDS?
< 200 cells/mm3 or <14% - also need an AIDS defining illness (infection, malignancy, dementia or wasting syndrome)
How is HIV transmitted?
occurs via infected body fluids (blood, semen, breast milk) - other fluids contain traces amounts but are not implicated in transmission (tears/saliva) - transmission occurs via unprotected sexual activity, sharing of needles, mother to newborn or breast feeding, occupational exposure, household contact or transfusion of blood products
What are the steps in HIV infection?
Binding/Fusion, Reverse Transcription, Integration, Transcription, Translation, Assembly/Budding,
Which specific HIV glycoprotein binds to the CD4 receptor?
After gp120 binds to CD4, which glycoprotein is exposed and what does it bind to?
gp41 that binds to co-receptor CCR5 or CXCR4 (one or the other or both)
What is the enzyme that helps HIV turn its viral RNA into viral DNA?
HIV Reverse Transcriptase
How does the HIV integrate its DNA into the host cell?
migrates to the nucleus and uses the Integrase enzyme to incorporate the viral DNA
Which phase of HIV pathology is not targeted and why?
Transcription - b/c the viral DNA uses host cell transcription enzymes and would harm the host if you stop them
What enzyme is used to cleave viral proteins that have been translated via the new viral mRNA?
When is HIV in the Acute or Primary Infection phase?
defined as the time between infection and development of detectable antibody response
What are the common signs/symptoms of Acute/Primary HIV Infection?
mono-like illness that begins 1-4 weeks post-exposure and lasts ~14 days with Fever, Lethargy and Myalgia being the most common
What are clinical presentations of Chronic HIV Infection?
Lymphadenopathy, Weight Loss, Lethargy, Frequent Fever/Night Sweats, Persistent Rash or Fungal Infections, and Short Term Memory Loss
What are the clinical presentations of AIDS?
Coughing/SOB, Seizures, Confusion/Forgetfulness, Severe Diarrhea, Fever, Vision Loss, N/V, Cachexia or Coma
How is one diagnosed with HIV?
based on the presence of antibodies to HIV - done via Rapid Tests like OraQuick, Reveal G2, Uni-Gold Recombigen or Multi-Spot OR Enzyme-Linked Immunosorbent Assay (ELISA) OR Western Blot Assay
What is seroconversion and how long does it take to occur?
development of detectable antibodies to a specific antigen - takes 2 weeks to 6 months post acute infection
Of the diagnosis tests for HIV, which is the most common?
ELISA (tho it can have false positives from other diseases lik Lyme, Syphilis, Lupus or Hepatitis
What is Viral Load?
the amount of HIV copies per mL of blood (aka viral body or HIV-RNA) - used to assess disease progression and efficacy of antiretroviral therapy
How often should Viral Load be measured?
If on antiretroviral therapy, VL should be measured at baseline, 2-8 weeks after initiation of therapy and then every 3-4 months therafter
What is the goal VL for antiretroviral therapy?
< 50 copies/mL = undetectable
Aside from VL, what other levels should be monitored in HIV patients?
CD4 levels every 3-4 months
What is a normal range for CD4?
What is considered a significant change in CD4 count?
> 30% is considered significant
What are the 5 Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)?
What is the NNRTI MOA?
Inhibits reverse transcriptase in HIV-1 virus - binding to the hydrophobic pocket on RT. Affects the flexibility of RT and prevents further ability to synthesize DNA
What drug interactions as a class do NNRTIs do?
As a class, what toxicities do NNRTIs exhibit?
Rash and Hepatic Toxicity
What is the class resistance seen in NNRTIs?
How should Efavirenz be administered?
NNRTI administered at bedtime on an empty stomach
What are some hallmark AE with Efavirenz?
Common: Dreams, fatigue and impaired concentration
Rare but Serious: Confusion, Hallucination, Paresthesias, Somnolence, Psychosis and Depression
What pregnancy category is Efavirenz?
Preg Cat D
What test can Efavirenz cause a false positive in?
What is the monitoring for Efavirenz?
LFTs: Baseline / 4 weeks after initiation and 3-4 months thereafter
CNS SE and Rash
Which NNRTI is the most commonly seen overseas?
What are the AE associated with Nevirapine?
Common: HA, N/V/D
Rare: Hepatitis/Liver Failure, Stevens-Johnson Syndrome and Anemia
When should one not use Nevirapine?
in males with CD4>400 or females CD4>250
What is unique about Nevirapine's metabolism?
Induces its own metabolism via CYP3A4
What is the monitoring for Nevirapine?
LFTs: Baseline/ 2, 4, and 6 weeks after initiation / Monthly for 18 weeks and then 3-4 months thereafter
Rash and CBC
Which NNRTI isn't used much b/c of its Q8H dosing?
Which of the NNRTIs are considered 1st gen and as such, susceptible to resistance?
Efavirenz, Nevirapine, Delavirdine
Which of the NNRTIs are considered 2nd gen and don't see the K103N mutation resistance?
Etravirine and Rilpivirine
What is unique about the administration of Etravirine?
Tablet form can be dissolved in water
What are some common AE with Etravirine?
Common: Peripheral Neuropathy / Rare: Hepatitis or SJS
What is the monitoring with Etravirine?
LFTs: Baseline, 1 month after initiation and 3-4 months thereafter
What three protease inhibitors are approved for use with Etravirine?
Darunavir, Lopinavir, Saquinavir (all others cause interactions)
What is specific about Rilpivirine and its administration?
Needs to be taken with a meal containing fat
What class of drugs besides CYP3A4 drugs is contraindicated with Rilpivirine?