HIV ADR

Question 1

Lamivudine

Answer 1

 Lamivudine – minimal toxicity, nausea/vomiting/diarrhea (N/V/D)

NRTI

Question 2

Emtricitabine

Answer 2

 Emtricitabine – minimal toxicities, hyperpigmentation, nausea, diarrhoea

NRTI

Question 3

Tenofovir

Answer 3

 Tenofovir: – N/V/D, can cause renal impairment, decrease in bone mineral density
- Tenofovir Alafenamide (TAF) less than Tenofovir Disoproxil Fumarate (TDF)

NRTI

Question 4

Abacavir

Answer 4

 Abacavir – N/V/D,

Hypersensitivity reaction in patients with HLAB*5701.
Symptoms incl: rash,fever, rash, malaise or fatigue, loss of appetite, sore throat, cough, shortness of breath. Can be fatal. Discontinue if it occurs,DO NOT RECHALLENGE.

Testing for absence of HLA-B*5701 is required before initiating abacavir. (Concern for association with myocardial infarction – not to be used in high cardiovascular risk patients.)

NRTI

Question 5

Zidovudine

Answer 5

 Zidovudine –N/V/D, myopathy, bone marrow suppression causing anemia or neutropenia. (MONITOR FULL BLOOD COUNT)

NRTI

Question 6

Raltegravir

Answer 6

 Raltegravir- pyrexia, creatine kinase elevation (rhabdomyolysis), severe skin reactions and systemic hypersensitivity reactions (rare)

INSTI

Question 7

Dolutegravir

Answer 7

 Dolutegravir- Increase in serum creatinine and bilirubin*

• Inhibits Cr secretion and decrease billirubin CL. NO impact on glomerular filtration.
  therefore Cr [] increase but does not mean pt renal (f) is impaired.

INSTI

Question 8

Elvitegravir

Answer 8

 Elvitegravir (co-formulated with cobicistat)- cobicistat causes increase in serum creatinine and bilirubin*

• Inhibits Cr secretion and decrease billirubin CL. NO impact on glomerular filtration.
  therefore Cr [] increase but does not mean pt renal (f) is impaired.

INSTI

Question 9

Ritonavir

Answer 9

 Ritonavir- is a potent CYP3A4, 2D6 inhibitor; frequently combined with other PI to “boost” their levels (eg Lopinavir/ritonavir). Additional SE: paresthesia (numbness of extremities), taste perversion

PI

Question 10

Darunavir

Answer 10

 Darunavir- good GI tolerability, less lipids effects. Skin rash (10%), SJS (it is a sulphonamide)

PI

Question 11

Atazanavir

Answer 11

 Atazanavir- good GI tolerability, less lipids effects. Absorption depends on low pH (contraindicated concurrent use with PPIs). Additional SE: hyperbilirubinemia, prolong QT interval, skin rash

PI

Question 12

Lopinavir

Answer 12

 Lopinavir- GI intolerance (N/V). PR and QT interval prolongation have been reported. Use with caution in patients at risk of cardiac conduction abnormalities or in patients receiving other drugs with similar effect. Possible nephrotoxicity.

PI

Question 13

Efavirenz

Answer 13

 Efavirenz – rash, hyperlipidemia, neuropsychiatric SE (dizziness, insomnia, abnormal dreams, hallucination), increase in LDL-C and triglycerides

NNRTI

Question 14

Etravirine

Answer 14

 Etravirine – rash, hypersensitivity reaction, nausea

NNRTI

Question 15

Nevirapine

Answer 15

 Nevirapine – more rash (SJS,TEN) and hepatotoxicity (necrosis).

NNRTI

Question 16

Enfuvirtide

Answer 16

 Enfuvirtide (LAST LINE)
 ADR-

• Injection site reaction (erythema/induration, nodules/cyst, pruritis, ecchymosis in 98%),
• rare hypersensitivity reaction reported (fever, rash, chills, decr BP).
• Increased bacterial pneumonia

FUSION inhibitor

Question 17

Maraviroc

Answer 17

• ADR- Abdominal pain, cough, dizziness, musculoskeletal symptoms, pyrexia, rash, upper respiratory tract infections, hepatotoxicity, orthostatic hypotension.

Maraviroc = CCR5 antagonist (fusion inhibitor )

Question 18

Nucleoside Reverse Transcriptase Inhibitors (NRTIs)

adv and disadv

Answer 18

Class advantages
 Established dual backbone of combination ART
 Renal elimination, little concerns for drug interactions.

Class disadvantages
 Adverse effect related to mitochondrial toxicity (rare but serious)
- Lactic acidosis and hepatic steatosis (fatty infiltrate)
- Lipoatrophy (lost of fat)
- Zidovudine>Tenofovir=Abacavir=Lamivudine
Requires dose adjustment in renal impaired patients (except abacavir = metabolise by alcohol dehydrogenase)

Question 19

Integrase Strand Transfer Inhibitor (INSTI)

Adv and disadv

Answer 19

Advantages
 Virologic response non-inferior to efavirenz
 Generally well tolerated
 No significant CYP 3A4 drug interactions (except for elvitegravir)
elevitegravir co-formulated with cobicistat which is a cyp inhibitor

Disadvantages
 Bioavailability lowered by concurrent administration of polyvalent cations
 ADR - GI (Diarrhoea/Nausea), headache, fatigue; Insomnia, depression, and suicidality have been infrequently reported with INSTI use, primarily in patients with preexisting psychiatric conditions

Question 20

Protease Inhibitors (PIs) ADV AND DIS

Answer 20

PI Class Advantage:
 Higher genetic barrier to resistance
 PI resistance less common

PI Class Disadvantages:
 Metabolic complications (dyslipidemia, insulin resistance)
 Gastrointestinal side effects (nausea, vomiting, diarrhoea)
 Liver toxicity (especially with chronic hepatitis B or C)  CYP3A4 inhibitors and substrates: potential for drug interactions
 Morphologic Complications: Fat maldistribution (Lipohypertrophy)
 Increased risk of osteopenia/osteoporosis

Question 21

Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs) ADV AND DIS

Answer 21

Class Advantages
 Long half-lives
 Less metabolic toxicity (hyperlipidemia, insulin resistance) than with some PIs

Class Disadvantages
 Low genetic barrier to resistance
 Cross resistance among approved NNRTIs
 Skin rash (nevirapine > efavirenz, etravirine)
 Potential for CYP450 drug interactions (some are inducers and some are inhibitors)
 Lactic acidosis, hepatic steatosis

Question 22

 Mixed CYP inducer/inhibitor

NNRTI

Answer 22

 Mixed CYP inducer/inhibitor
Efavirenz, nevirapine – CYP 3A4 substrate and inducers
Etravirine - CYP3A4, 2C9, 2C19 substrate; 3A4 inducer; 2C9 and 2C19 inhibitor

Efavirenz cause up LDL so need give statin –> check statin interaction with CYP