IC18 HIV Flashcards
mode of transmission for HIV
HIV is transmitted from one person to another through specific body fluids — blood, semen, genital fluids, and breast milk. These happens through:
- Unprotected sexual intercourse with an infected person
- Sharing infected syringes and needles (e.g.between intravenous drug users)
- Mother-to-child transmission during pregnancy, at birth or through breast-feeding
- Transfusion with contaminated blood and blood products
who should be tested for HIV?
- Intravenous drug users
- Person who have unprotected sex with multiple partners
- Man who have sex with man
- Commercial sex workers
- Persons treated for STDs
- Recipients of multiple blood transfusion
- Persons who have been sexually assaulted
- Pregnant women (compulsory)
Diagnosis of HIV infection
- serum antibody detection (HIV EIA test, western blot)
- HIV RNA detection/ quantification (viral load) using PCR
Presentation of HIV (different stages)
- Acute (primary) HIV infection
- flu like illness - asymptomatic stage
- no S/S, persist for many years - persistent generalised lymphadenopathy
- lymph node enlargement in the neck, underarms, groins for more than 3 mths - AIDS (CD4 <200/mm3)
- advanced stage many organs involved, systemic sx
- even with normal CD4 count, can still have AIDS if have any opportunistic infection
- Rare cancer: Lymphoma and Kaposi sarcoma
Goals of ART
- Reduce HIV-associated morbidity and mortality
- Prolong the duration and quality of survival
- Restore and preserve immunologic function
- Maximally and durably suppress plasma HIV viral load
- Prevent HIV transmission
Surrogate markers in HIV - CD4
- normal: 500-1200 cells/mm3
- strongest indicator of immune function and disease progression
- use to determine urgency for initiation
- use to assess response of ART
-> take at baseline
-> every 3-6mths after tx initiation
-> every 12 mths after adequate responses
=> adequate CD4 cells response = CD4 50-150 during first year of tx
- used to assess the need for initiating or discontinuing prophylaxis for opportunistic infections
at what CD4 cell count should prophylaxis abx for pnuemocystis pneumonia be started?
<200 cells/mm3
surrogate markers in HIV - viral load
amt of virus in the plasma
- most important indicator of response to ART
- measured
-> before initiation
-> within 2 to 4 weeks (no later than 8 weeks) after initiation/ modification
-> every 4-8 weeks until viral load suppressed
-> stable regimen 3-6mths (or every 12mths)
effective regimen generally achieve viral suppression by… (HIV)
8 to 24 weeks
when to start ART for HIV? for who?
advice to pt
when to defer tx
start ASAP for all HIV infected individuals regardless of CD4 cell count
- to prevent HIV transmission
- educate pt on the benefits and consideration for ART
- strategies to optimise adherence
- may be deferred due to clinical and/or psychosocial factors
ASAP if possible!!
Benefits of earlier ART initiation
- maintenance of higher CD4 count, prevent irreversible damage
- decrease risk for HIV associated complications
- decreased risk of non opportunistic conditions (CVD, renal, liver, non AIDS diseases)
- decrease risk of HIV transmission
Limitations of earlier initiation (ART)
- SE and toxicities
- drug resistance
- transmission of drug resistant virus
- less time to prepare, non-adherence
- treatment fatigue
- increased cost
list of common ART
- NRTI - nucleoside reverse transcriptase inhibitors
- INSTI - integrase strand transfer inhibitor
- NNRTI - non-nucleoside reverse transcriptase inhibitors
- PI - protease inhibitors
- Fusion inhibitors
- CCR5 antagonist
NRTI drugs
Tenofovir
Emtricitabine
Abacavir
Lamivudine
Zidovudine
advantage of NRTI
backbone of combination ART
renal elimination (less concern for DDI)
class disadvantage of NRTI
mitochondrial toxicity (rare but serious)
- lactic acidosis, hepatic steatosis
- lipoatrophy (loss of fat)
- zidovudine > rest
dose adjustment in renal impaired pt (except abacavir)
AE for NRTI (each drug)
Tenofovir: N/V/D, renal impairment, decrease bone mineral density (TAF<TDF)
Emtricitabine: minimal toxicities
Abacavir: N/V/D, hypersensitivity rx in pt with HLA B5701 (rash, fever, malaise, cough, SOB) can be fatal need gene testing, do not rechallenge
- also cause MI (avoid in high CV risk)
Lamivudine: minimal toxicity, N/V/D
Zidovudine: N/V/D, bone marrow suppression (anemia, neutropenia)
INSTI drugs
Bictegravir
Dolutegravir
Raltegravir
Elvintegravir
Advantages of INSTI
- bictegravir and dolutegravir has good virologic effectiveness
- high genetic barrier to resistance (B,D > R,E)
- generally tolerated
Disadvantages of INSTI
- ADR - weight gain, N/D, headache
- depression and suicide (usually in pt with preexisiting psychiatric conditions)
- DDI:
-> decrease bioavailability with polyvalent cations
-> BDE - CYP3A4 substrates
INSTI AE
- Bictegravir, Dolutegravir: increase in SCr
(inhibit tubular secretion of creatinine, no impact on glomerular function) - Raltegravir - pyrexia (fever), CK elevation (rhabdomyolysis)
NNRTI drugs
Efavirenz
Rilpivirine
advantage of NNRTI
- long half lives
- less metabolic toxicity (hyperlipidemia, insulin resistance) than PI
disadvantage of NNRTI
- low genetic barrier to resistance
- cross resistance among NNRTI
- skin rash, SJS (R<E)
- potential CYP450 DDI (inducers/ inhibitors)
- QTc prolongation
AE of NNRTI
Efavirenz
- skin rash, SJS
- neuropsychiatric SE (dizziness, depression, insomnia)
- CYP3A4 susbtrate, CYP2B6, 2C19 inducer
Rilpivirine
- depression, headache
- CYP3A4 susbtrate
- oral absorption reduced with increased gastric pH (CI: PPI)
PI drugs
Ritonavir
Lopinavir
Atazanavir
Darvunavir
Fosamprenavir
advantage of PI
- high genetic barrier to resistance
- PI resistance less common
disadvantage of PI
- metabolic complications (dyslipidemia, insulin resistance)
- GI SE (N/V/D)
- liver toxicity (esp those with chronic hepatitis B or C)
- CYP3A4 inhibitors and substrates: potential for DDI
- lipohypertrophy (fat maldistribution)
- increased risk of osteopenia/osteoporosis
PI AE
ritonavir (PK enhancer): potent CYP3A4, 2D6 inhibitors
- commonly combined with other PI to boost their levels (eg lopinavir + ritonavir)
(additonal SE)
- paresthesia (numbness of extremities)
- taste perversion
atazanavir: good GI tolerability
- less lipids effect
- absorption depends on low pH (CI: PPI)
(additonal SE)
- hyperbilirubinemia
- prolong QT interval
- skin rash
Darunavir: skin rash (10%), concern for SJS (it is a sulphonamide), dont take with sulfa allergy
Fusion Inhibitor, ADR
Enfuvirtide
ADR:
- injection site reaction (erythema, induration, bruises/ecchymosis)
- rare hypersensitivity reaction (fever, rash, chills, decrease BP)
- increased bacterial pneumonia
CCR5 Antagonist
- for who?
- DDI
- ADR
Maraviroc (Selzentry)
- only for pt whose strain of HIV uses CCR5 receptor to enter the CD4 cells (test using co-receptor tropism assay before initation)
- cannot use for CXCR4/ mixed
- CYP 3A4 substrate
- ADR: abdominal pain, cough, dizziness, musculoskeletal symptoms, pyrexia, rash, upper respiratory tract infections, hepatotoxicity, orthostatic hypotension
reason for failure for ART
non-adherence
- Establish readiness to start therapy
- Provide education on medication dosing
- Review potential side effects
- Anticipate and treat side effects
- Utilize educational aids including pictures, pillboxes, and calendars
- Engage family, friends
- Simplify regimens, dosing, and food requirements (taking ARV with or without food)
- Utilize team approach with nurses, pharmacists, and peer counselors
- Provide accessible, trusting health care team
Combination therapy for HIV
2 NRTI + 1 INSTI:
Tenofovir + emtricitabine + bictegravir
Tenofovir + emtricitabine + dolutegravir
Abacavir + lamivudine + dolutegravir
1 NRTI + 1 INSTI
Emtricitabine + dolutegravir
2 drugs combination tx NOT for individuals with
- HIV RNA >500,000 copies/mL
- HBV coinfection
- in whom ART is to be started before the results of HIV genotypic resistance testing or HBV testing are available
