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SOM 302 > WEEK 1 : ARV TREATMENT FOR HIV > Flashcards

WEEK 1 : ARV TREATMENT FOR HIV Flashcards

1
Q

State the 7 classes of ARV.

A
  1. nucleoside reverse transcriptase inhibitors (NRTIs)
  2. non-nucleoside reverse transcriptase inhibitors (NNRTIs)
  3. protease inhibitors (PIs)
  4. integrase strand transfer inhibitors (INSTIs).
  5. fusion inhibitors (FIs)
  6. CCR5 antagonists
  7. post-attachment inhibitors - CCR5/CXCR4 co-receptor
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2
Q

zidovudine (Retrovir)
lamivudine (Epivir)
abacavir sulfate (Ziagen)
didanosine (Videx)
stavudine (Zerit)
emtricitabine (Emtriva)
tenofovir disoproxil fumarate TDF (Viread)
Tenofovir alafenamide TAF

What class of anti-virus are the above-mentioned drugs?

A

Nucleoside Reverse Transcriptase Inhibitors (NTRIs)

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3
Q

Delavirdine (Rescriptor)
Efavirenz (Sustiva)
Etravirine (Intelence)
Nevirapine (Viramune, Viramune XR)
Rilpivirine (Edurant)
Doravirine (Pifeltro)

What class of anti-virus are the above-mentioned drugs?

A

Non-Reverse Transcriptase Inhibitors (NNRTIs)

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4
Q

atazanavir (Reyataz)
darunavir (Prezista)
fosamprenavir (Lexiva)
indinavir (Crixivan)
lopinavir/ritonavir (Kaletra)
nelfinavir (Viracept)
ritonavir (Norvir)
saquinavir (Invirase)

What class of anti-virus are the above-mentioned drugs?

A

Protease Inhibitors (PIs)

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5
Q

raltegravir (isentress)
dolutegravir (tivicay)
elvitegravir (available in combination with other drugs; no longer available alone)
bictegravir (available in combination with other drugs; not available alone)

What class of anti-virus are the above-mentioned drugs?

A

Integrase Strand Transfer Inhibitors (INSTIs)

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6
Q

Name the class of anti-virus and the MOA of the following drugs.
Enfuvirtide
Maraviroc
Chemokines

A

Enfuvirtide- gp41 inhibitor: Fusion Inhibitors,
Maraviroc- CCR5 antagonist
Chemokines- CCR5/CXCR4: Post Attachment Inhibitors

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7
Q

State the 6 NTRI’s in the Botswana National Program.

A

Zidovudine
Lamivudine
Abacavir sulfate (ABC)
Emtricitabine (FTC)
Tenofovir disoproxil fumarate TDF
Tenofovir alafenamide (TAF)

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8
Q

State the 2 NNTRI’s in the Botswana National Program.

A

Efavirenz (EFZ)
Nevirapine (NVP)

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9
Q

Principles of ART Regimens in Botswana HIV Guidelines

State the general structures of first- and second-line regimens for adult.

A

First line regimen- 2 N[t]RTIs + DTG
Second- and third-line regimens- Determined by resistance Assay.

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10
Q

Describe Adults (including pregnant women) and adolescents ART 1st line regimen.

A

1st line:
-TDF/3TC/DTG (weight ≥30kg and Cr.Cl ≥60cc/min)

-TAF/FTC/DTG (weight ≥25 kg and Cr.Cl ≥30cc/min)

*If Tenofovir nephrotoxicity w/o
CV risk: ABC/3TC/DTG
*If nephrotoxicity with CV risk or DTG Toxicity:
Discuss w specialist.

2nd line: Based on Resistance Testing Results &
Consultation with HIV Specialist

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11
Q

Describe ART Regimens for Newly Initiated Infants and Children.

A

< 1 month (Prophylaxis: AZT+3TC+NVP

> 1 month to < 25Kg of body weight: ABC/3TC + DTG

If ABC reaction: AZT/3TC + DTG

2nd Line: Based on genotypic assay results & consultation with HIV Specialist

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12
Q

State the Co-formulated ARVs.

“Combivir®” or “Lamzid®”
“Truvada®”
Paediatric Dispersible tablets
“Acriptega®” or “TLD”.
“TAF-ED”
“Triumeq®” (In Botswana currently available in the private sector).

A

Co-formulated ARVs, which improve medication adherence:

AZT/3TC “Combivir®” or “Lamzid®”

TDF/FTC “Truvada®”

ABC /3TC Paediatric Dispersible tablets

TDF/3TC/DTG “Acriptega®” or “TLD”.

TAF/FTC/DTG “TAF-ED”

ABC/3TC/DTG “Triumeq®” (In Botswana currently available in the private sector).

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13
Q

Describe PEP: Botswana Guidelines

1.PEP prophylactic ARV regimen for adults and adolescents:

  1. For Children:
    I) If weighing less than 25 kg:
    ii) From body weight of 25kg.
    iii) If ≥ 30 kg:
A

PEP prophylactic ARV regimen for adults and adolescents:
TDF/3TC/DTG or TAF/FTC/DTG, whichever is readily available.

For Children:
If weighing less than 25 kg: ABC/3TC + DTG

TAF/FTC/DTG(TAF-ED) can be used from body weight of 25kg.

If ≥ 30 kg: TDF/3TC/DTG

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14
Q

Name the drugs with the following Abbreviations and the class of anti-virus they belong to.
AZT
3TC
TDF
TAF
FTC
ABC
NVP
EFV
DTG

A

AZT: Zidovudine
3TC: Lamivudine
TDF: Tenofovir Disoproxil Fumarate
TAF: Tenofovir Alafenamide
FTC: Emtricitabine
ABC: Abacavir
All above are NRTI’s.

NVP: Nevirapine
EFV: Efavirenz
Are all NNRTI’s.

DTG: Dolutegravir
Integrase Inhibitor

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15
Q

Up to how many % if mothers not treated or fully suppressed (<400 copies/ml) may transmit HIV to the infant?

Early studies suggested that AZT-containing regimens conferred how many % risk reduction when used for 4 weeks?

A

Up to 40% if mothers not treated or fully suppressed (<400 copies/ml) may transmit HIV to the infant.

Early studies suggested that AZT-containing regimens conferred ~80% risk reduction when used for 4 weeks.

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16
Q

How many % does it of the following risk the transmission of HIV via vertical transmission?

Pregnancy
Delivery
Breastfeeding

A

Pregnancy ———- (5 - 10%)
Delivery ——- (10 -15%)
Breastfeeding —– (10 - 15%)

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17
Q

Pregnant Mothers: ARV Prophylaxis

I) Recommended regiment
II) Special considerations
Renal insufficiency –
if high cardiovascular risk

A

The recommended regimen is:

Tenofovir (TDF) + lamivudine (3TC/FTC) + dolutegravir (DTG)

Special considerations

Renal insufficiency –
Abacavir (ABC) +lamivudine (3TC) + dolutegravir (DTG)
ABC to be avoided if high cardiovascular risk.

18
Q

Infant: ARV Prophylaxis

Prophylaxis should be started within how long for all infants exposed.
How long is the Prophylaxis given for?
When is infant testing done?

What is given to low-risk babies?
What is given to high-risk babies?

A

Prophylaxis should be started within 72 hours for all infants exposed.
Prophylaxis for 1 month
Infant testing at week 4-6

  Low risk babies: Sd- nevirapine (NVP) Zidovudine (AZT)

High risk babies:
Zidovudine (AZT) + lamivudine (3TC) + nevirapine (NVP)
Abacavir (ABC)+lamivudine (3TC) + Lopinavir/ritonavir (LPV/r

19
Q

What is an adverse drug reaction?

A

Any noxious undesired or unintended response to a drug that occurs at normal dosages.

20
Q

What is an Adverse Event?

A

Adverse Event:

Any untoward medical occurrence that may present during treatment with a pharmaceutical product.

21
Q

Side effects and toxicities are adverse drug events.

State 4 characteristics of side effects.

A

Side effect:
*Unintended effect due to drug’s pharmacological properties.
*Usually self-limited and not life threatening
*Usually resolves over a short period of time and with symptomatic support.
*Usually occurs early after ARV initiation

22
Q

What is toxicity?

A

Toxicity:

Ability of a substance to cause poisonous effects

Results in severe biological harm or death

More severe, potentially life threatening

May occur at any time.

23
Q

State 3 effects of adverse events of antiretroviral drugs?

A

Adverse events of antiretroviral drugs:

Occur commonly

*May lead to a reduction in the quality of life

*Can result in non-adherence to therapy

*May be a potential barrier to successful therapy

24
Q

Tenofovir Disoproxil Fumarate (TDF)

TDF is generally a well-tolerated drug.

State the 2 main adverse effects associated with it.

A

TDF is generally a well-tolerated drug, the main adverse effects associated with it are renal and bone toxicity:

TDF-associated nephrotoxicity includes gradual declines in glomerular filtration rate (GFR), phosphate wasting, and can lead to Fanconi syndrome.

25
Q

What is fanconi syndrome?

What drug results in Fanconi syndrome?

A

Fanconi syndrome is a rare and complex disorder that affects the proximal renal tubules in the kidneys.
It results in certain substances normally absorbed into the bloodstream by the kidneys being released into the urine.

TDF

26
Q

Why is TAF better than TDF?

A

When compared with TDF, Tenofovir Alafenamide generates significantly lower serum tenofovir levels, which offers a relatively better renal and bone safety profile.

TAF is more likely than TDF to increase certain lipid parameters (total cholesterol and HDL) but not others (total cholesterol/HDL ratio, triglycerides).

27
Q

No longer recommended for first line use in the current antiretroviral era.

An array of adverse effects have been associated with this drug use, including:
*Fatigue, Headache, GI upset
*Headache,
*Lactic Acidosis: rare but potentially fatal
*Lipoatrophy,
*Bone marrow suppression → Anemia; *Neutropenia.
*Myopathy, Peripheral Neuropathy
*Skin discoloration (palms and soles)

Name the drug described above.

A

Zidovudine (AZT)

28
Q

3TC and FTC

Common side effects:
-None: these two ARVs are very well tolerated.

State the less common side effects of 3TC & FTC.

State the serious side effects of 3TC & FTC.

A

Less common:
-3TC and FTC: nausea, headaches, vomiting, diarrhea
-FTC:
rash
mild hyperpigmentation of palms or soles

Serious:
-Pancreatitis (very rare)

29
Q

State the side effects of Abacavir.

A

Well tolerated ARV drug.

Potentially life-threatening hypersensitivity reaction occurs in up to 5% of individuals taking ABC in the West.

Signs and symptoms typically develop within 6 weeks of starting ABC (the median onset of symptoms is at 11 days) and may include:
fever, myalgia, arthralgia, skin rash, body malaise, vomiting, diarrhea, sore throat and dyspnea.

The reaction occurs more frequently in Caucasians than African Americans, due to a higher HLA-B*5701 allele frequency in Caucasians.
ABC must be stopped whenever hypersensitivity reaction is suspected!

30
Q

Who should not use ABC?

A

Patients taking ABC have a higher rate of cardiovascular disease than those taking other NRTIs.

Avoid use of Abacavir in persons with cardiovascular disease (or significant risk factors for cardiovascular disease).

31
Q

State the 7 main side effects of DTG.

A
  1. Hypersensitivity reactions in < 1% of cases: skin rash with constitutional findings sometimes.
  2. nsomnia: In randomized trial settings, the incidence of insomnia in patients taking dolutegravir ranged from 3 to 15%. Clinical experience has shown that some patients develop insomnia while taking dolutegravir, but this rarely requires discontinuation of Dolutegravir.
  3. Hepatotoxicity: ↑ transaminases especially in patients with underlying viral hepatitis B or C.
  4. GIT disturbance: Nausea (1%), Diarrhea (<1%).
    Fatigue (<1%).
  5. Weight gain:
    Dolutegravir, leads to greater weight gain than other antiretrovirals.
    Weight gain more pronounced when Dolutegravir is combined with TAF than with TDF.
  6. ↑ plasma creatinine:
    Modest increase in serum creatinine and a decrease in estimated creatinine clearance due to inhibition of active tubular secretion of creatinine via blockade of the organic cation transporter 2 (OCT2).
  7. DTG associated elevations in serum creatinine are typically in the range of 0.1 to 0.2 mg/dl (mean change 0.15 mg/dl), occur within 4 weeks after starting Dolutegravir, and remain stable thereafter.
32
Q

Highly potent NNRTI, but no longer recommended as a component of preferred antiretroviral regimens.

What is the primarily reason why Efavirenzis no longer prescribed?

State 3 other adverse effects Efavirenz has been associated with.

A

Highly potent NNRTI, but no longer recommended as a component of preferred antiretroviral regimens, primarily due to neuropsychiatric adverse effects:

Sleep disturbance: nightmares/abnormal dreams, impaired concentration, hallucinations, irritability, confusion, suicidal ideation and depression, feeling of depersonalization, light-headedness, dizziness – usually resolve in a few days to weeks after initiation of treatment.

Further, Efavirenz has been associated with:

*Lipohypertrophy : Gynecomastia/breast enlargement, Lipomas,…..
*Hepatotoxicity
*Skin rash: 10 to 25% of patients receiving EFV

33
Q

Severe skin reaction and hepatotoxicity, which can occur together or separately with hypersensitivity reactions occurs more commonly in women and in persons with higher CD4 cell counts:
up to 20% of patients

mild to moderate maculopapular rash

occurs typically on the face, trunk, and/or extremities

may be associated with pruritis

occurs within the first few weeks to months of therapy

usually resolves within a few weeks

may progress to Stevens-Johnson Syndrome (SJS) in < 1.0% of cases

Name the drug described above.

A

NEVIRAPINE (NVP)

34
Q

Severe, rare, and potentially fatal hypersensitivity reaction: NVP > EFV

Occurs within the first 1-8 weeks of ARV therapy

Symptoms:
Fever
Conjunctivitis
Extensive, moist, peeling rash with bullae formation
Mucous membrane involvement (lip, vaginal, or rectal sores/ulcers/swelling)
Patient appears unwell compared to previous visit

Name the disorder described above.
What drug results in the disorder.

A

Severe, rare, and potentially fatal hypersensitivity reaction: NVP > EFV

Stevens-Johnson Syndrome
Nevirapine

35
Q

What is the full name for LPVr?

A

RITONAVIR-BOOSTED LOPINAVIR (LPVr)

36
Q

Why is RITONAVIR-BOOSTED LOPINAVIR (LPVr) less recommended?

State its 2 major side effects.

A

Less recommended currently because of its larger pill burden and greater toxicity.

Hyperlipidemia: Lopinavir-ritonavir frequently causes elevations in lipid levels, particularly total cholesterol and triglycerides more than either Atazanavir or Darunavir.

Diarrhea: Gastrointestinal side effects may occur with any protease inhibitor, but they are more prevalent with Lopinavir-ritonavir than with Atazanavir or Darunavir.

37
Q

State the 3 side effects of RITONAVIR-BOOSTED ATAZANAVIR (ATVr).

A

A preferred, first-line agent for many years, relatively lower potency and hyperbilirubinemia has limited its use compared with newer antiretroviral therapy options.

Hyperbilirubinemia: blockade of normal glucuronidation of bilirubin through inhibition of uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1). Does not cause or reflect liver damage but can lead to icterus and jaundice; reversible with discontinuation of Atazanavir.

Nephrolithiasis: Atazanavir-induced kidney stones develop in approximately 1% of persons taking ATV/r. The onset of nephrolithiasis occurs, on average, two years after starting ATV.

Cholelithiasis: Several reports suggest ritonavir boosted Atazanavir is associated with the development of cholelithiasis.

38
Q

State the adverse reactions of DARUNAVIR (DAR).

Why does it result in skin rash?

A

Remains a cornerstone of second line and salvage antiretroviral therapy.

May cause: Abdominal pain and diarrhea in approximately 5 to 14% of persons.
Incidence of rash is approximately 10%, with most cases of mild severity.

The mild rash typically begins during the first 4 weeks of treatment and resolves, even with continuation of darunavir.

Severe skin rash has been reported in less than 1% of persons taking darunavir, and it can be accompanied by fever and/or increases in hepatic aminotransferase levels.

Darunavir should be promptly discontinued if a severe skin rash develops.

Darunavir contains a sulfonamide; history of sulfa allergy is not considered a Darunavir contraindication, but Darunavir should be used with caution in this situation, especially if the prior sulfa reaction was severe → Educate patients on occurrence of skin rash.

39
Q

State the Metabolic Complications of ARVs.

A

*Insulin Resistance/Diabetes Mellitus (PI’s)

*Lipodystrophy Syndrome (body habitus changes)

*Lipid Abnormalities
increased cholesterol and triglyceride levels

40
Q

What is Lipodystrophy?

A

Lipodystrophy: Body Habitus Changes

41
Q

What is the medical term for fat accumulation?

State the symptoms of lipohypertrophy.

A

Fat accumulation: (lipohypertrophy)*

*Neck fat pad

*Breast enlargement in men and women

*Visceral/central obesity

*Lipomas

*EFV and PIs

42
Q

What is the medical term for fat loss?

State symptoms associated with fat loss.

A

Fat loss: (lipoatrophy)**

*Facial fat loss

*Subcutaneous fat loss in the extremities

*Fat loss in buttocks

**NRTIs, especially d4T and, to a lesser extent, AZT

SOM 302 (27 decks)

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