HIV Flashcards
List the mode of transmission for HIV
Mother to child transmission through pregnancy
Transfusion with contaminated blood and blood products
Sharing infected syringes and needles
Unprotected sexual intercourse with infected person
What are some of the indications for testing?
IV drug user
Person who have unprotected sex with multiple partners
Men who have sex with men
Commercial sex workers
Person treated for STDs
Recipient of multiple blood transfusions
Persons sexually assaulted
Pregnant women: mandatory for all who are pregnant in SG
What are the two diagnostics criteria used to diagnose HIV?
Serum antibody detection through EIA and western blot
HIV RNA detection through PCR
What are the goals of antiretroviral therapy?
Reduce HIV associated mortality and morbidity
Prolong duration and QOL
Restore and preserve immunological function
Maximally and durably suppress HIV viral load
Prevent HIV transmission
What are the surrogate markers used for antiretroviral therapy?
CD4 and viral load
What are the indications to use CD4 as a surrogate marker?
Lab indicator of immune function in HIV infected patients
Helps predict subsequent disease progression and survival
Discuss how CD4 is used as a surrogate marker
Determines urgency for initating anti-retroviral therapy
Assess response to anti-retroviral by detecting baseline, every 3-6 months upon initiation, every 12 months after adequate response
Assess need for initiating / discontinuing prophylaxis for opportunistic infections
What is defined as an adequate response to antiretroviral therapy?
When increase in CD4 count is in rage of 50-150 cells / mm3 during first month of therapy
How is viral load used as a surrogate marker?
Indicates the response to antiretroviral therapy
Act in predicting clinical progression
How often should viral load monitoring be done?
Before initiation of therapy
Within 2-4 weeks after treatment initiation/ modification
Every 4-8 weeks until viral load is suppressed
Upon suppression, every 3-6 months
What are the indications to initiating ART therapy?
All HIV infected individuals regardless of CD4 cell count
List the benefits of early initiation of ART.
Help in maintaining a higher CD4 cell count
Prevent potential irreversible damage to immune system
Decrease risk of HIV associated complications (occurs when CD4 cells < 350)
Decrease risk of non-opportunistic infections
Decrease risk of HIV transmission to others
What are the risks of initiating an early ART therapy?
Potential side effect and toxicities
Development of drug resistance due to incomplete viral suppression and cause a potential loss in future treatment
Decrease time to prepare for adherence
Cost and treatment fatigue
List out the factors to consider before initiating ART
Patient’s understanding of HIV
Cost and availability
Adherence issue and convenience
VIrulogic efficacy
Potential adverse effects
Childbearing potential
Genotypic drug resistance testing
Name the types of antiretroviral targets
CCR5/CXCR4 inhibitors
Fusion inhibitors
Nucleoside and non-nucleoside reverse transcription inhibitors
Integrase inhibitors
Protease inhibitors
What are the possible ART combinations for use?
2NRTI and 1INSTI:
- Tenofovir + Emtricitabine + Bictegravir (TEB)
- Tenofovir + Emtricitabine + Dolutegravir (TED)
- Abacavir + Lamivudine + Dolutegravir (ALD)
1NRTI + 1INSTI:
- Emtricitabine + Dolutegravir (ED)
What are the contraindications to using 1NRTI + 1INSTI regimens?
Individuals with HIV RNA > 500, 000 copies / mL (i.e. high viral load)
HBV coinfection
ART started before genotypic resistance or HBV testing results are available
What are some of the NRTI?
Tenofovir, Emtricitabine, Abacavir, Lamivudine, Zidovudine
What are the advantages and disadvantages of using NRTI?
Advantages: dual backbone for combination ART and is renally eliminated (decreasing risk of DDI)
Disadvantages: Adverse effects are related to mitochondrial toxicity (lipoatrophy, hepatic steatosis and lactic acidosis) and dose adjustment is needed for renally impaired patients
What are the adverse effects of Tenofovir?
Nausea, vomiting and diarrhea
Renal impairment
Lower bone mineral density
What are the two agents of NRTIs with minimal toxicity?
Emtricitabine
Lamivudine
Which NRTI agent requires genotypic testing before initation? What are its other associated adverse effects?
Abacavir
- Genotyping testing needed for those with HLA-B5701
Other ADR: Myocardial infarction, N/V/D
What is the main adverse effect of concern in NRTIs such as Zidovudine?
Bone marrow suppression
List the drugs which are INSTI inhibitors
Bictegravir
Dolutegravir
Raltegravir
Elvitegravir
What are the advantages and disadvantages of using INSTI inhibitors?
Advantages
- High genetic barrier to resistance
- Well tolerated
- Good virulogic effectiveness
Disadvantages
- Adverse drug reactions such as weight gain, N/V/D and headache
- Avoid in neuropsychiatric patients
- DDI with polyvalent cation and act as CYP3A4 substrates
What are the adverse reactions of INSTI?
Bictegravir and dolutegravir
- Increased serum creatinine
Raltegravir: pyrexia and creatinine kinase elevation
List the drugs that are NNRTIs
Efavirenz
Rilpivirine
What are the advantages and disadvantages of using NNRTIs?
Advantages: Long half lives, decreased metabolic toxicity than PI
Disadvantages: Decreased genetic barrier to resistance, cross resistance among approved NNRTI, ADR such as skin rash, SJS and QTc prolongation and DDI due to CYP450 substrates
What are the adverse drug reactions and DDI of NNRTIs Efavirenz?
Rash, hyperlipidemia, neuropsychiatric disorders, increase LDL and TG and hepatotoxicity
DDI: CYP3A4 substrate and CYP2B6 and 2C9 inducer
What are the adverse drug reactions and DDI of NNRTIs Rilpivirine?
Depression and headache
DDI: CYP3A4 substrate and oral absorption decreases with increased gastric pH
What are the drugs of protease inhibitors?
Ritonavir
Lopinavir
Atazanavir
Darunavir
Fosamprenavir
What are the advantages and disadvantages associated with protease inhibitors?
Advantages: Increase genetic barrier to resistance, decrease PI drug resistance
Disadvantages: ADR and DDI
What are the adverse drug reactions and DDI of PIs like Ritonavir?
ADR: Paresthesia and taste pervasion
DDI: Potent CYP2D6 and 3A4 inhibitor
What are the adverse drug reactions and DDI of PIs like Darunavir?
ADR: Skin rash and SJS
What are the adverse drug reactions and DDI of PIs like Atazanavir?
ADR: Hyperbilirubinemia, prolong QT interval, Skin rash
DDI: PPIs
What are the drugs that are fusion inhibitors and what is its adverse effects?
Enfuvirtide
ADR: Injection site reaction, increased bacterial pneumonia and rare hypersensitivity reactions
What are the drugs in CCR5 antagonist?
Maraviroc
What are the indications of using CCR5 antagonist?
Strain of HIV uses CCR5 receptor to enter CD4 cells
Should be checked using a co-receptor triopism assay
What are the DDI and ADR of CCR5 antagonist?
Abdominal pain, cough, dizziness, mucoskeletal symptoms, URTI, hepatotoxicity and orthostatic hypertension
DDI: CYP3A4 substrates
