HIV treatment

Question 1

what are the primary goals of ART?

Answer 1

• maximal and durable viral suppression
• restoration and preservation of immune function (CD4 count)
• improved quality of life
• reduced HIV-related opportunistic infections (OIs)
• reduced morbidity and mortality

Question 2

what is the recommended treatment for most people with HIV?

Answer 2

INSTI (integrase strand transfer inhibitor) + 2 NRTIs (nucleoside/nucleotide reverse transcriptase inhibitors)

Question 3

what are some examples of treatments recommended for most people with HIV?

Answer 3

• *BIC/FTC/TAF -> bictegravir/emtricitabine/tenofovir alafenamide
• *DTG/ABC/3TC -> dolutegravir/abacavir/lamivudine
• DTG + XTC + (TAF or TDF) -> dolutegravir + lamivudine + (tenofovir alafenamine or tenofovir disoproxil fumarate)
• RAL + XTC + (TAF or TDF) -> raltegravir + lamivudine + (tenofovir alafenamine or tenofovir disoproxil fumarate)

Question 4

what is an example of a INSTI + 1 NRTI treatment?

Answer 4

DTG/3TC -> dolutegravir/lamivudine

Question 5

what are some side effects of integrase inhibitors?

Answer 5

• GI distress
• CNS disturbances
• Rash (less with BIC)
• False elevation in creatinine
• weight gain! (~10 pounds)

Question 6

what are some DDIs with integrase inhibitors?

Answer 6

• CATIONS (acid reducers), Metformin
• others related to the other drugs used in the combination (like tenofovir and salicylates or nephrotoxic drugs)

Question 7

what are the integrase inhibitors for first-line ART?

Answer 7

• Bictegravir (BIC)
• Dolutegravir (DTG)
• Raltegravir (RAL)

Question 8

what are some advantages and disadvantages of Bictegravir (BIC)?

Answer 8

advantages
- STR (single tablet regimen) once daily with FTC/TAF
- few drug/food interaction
- high barrier to resistance

disadvantages
- least amount of data
- only available STR
- limited safety data in pregnancy

Question 9

what are some advantages and disadvantages of Dolutegravir (DTG)?

Answer 9

advantages
- STR once daily with 3TC or 3TC/ABC
- also available as a single agent
- few drug/food interactions
- high barrier to resistance
- a preferred option for pregnant women in every trimester

disadvantages
- ABC coformulation requires HLA-B*5701 testing
- increases metformin levels
- limited safety data at conception

Question 10

what are some advantages and disadvantages of Raltegravir (RAL)?

Answer 10

advantages
- longest experience
- few drug/food interactions
- a preferred option for pregnant women

disadvantage
- multiple pills (no STR)
- lower barrier to resistance than BIC or DTG
- limited safety data at conception

Question 11

what are some INSTI STRs available for initial ART?

Answer 11

• BIC/FTC/TAF (INSTI + dual NRTI)
• DTG/3TC (INSTI + single NRTI)
• DTG/3TC/ABC (INSTI + dual NRTI)
• EVG/COBI/FTC/(TAF OR TDF) (Boosted INSTI + dual R+NRTI)

Question 12

clinical caveats of DTG/3TC

Answer 12

do NOT use if HIV-1 RNA > 500,000 c/mL, HBV coinfection, or without resistance testing results

Question 13

which STR treatment requires HLA-B*5701 test to be NEGATIVE?

Answer 13

DTG/3TC/ABC

Question 14

what are some NNRTI STRs available for initial ART?

Answer 14

• DOR/3TC/TDF
• EFV/3TC/TDF
• EFV/FTC/TDF
• RPV/FTC/(TAF or TDF)

Question 15

what are some boosted PI STRs available for initial ART?

Answer 15

DRC/COBI/FTC/TAF

Question 16

what is important about RPV/FTC/(TAF or TDF)?

Answer 16

ONLY use if HIV-1 RNA < 100,000 c/mL AND CD4+ cell count > 200 cells/mm^2

Question 17

which integrase inhibitors should NOT be given with antacids?

Answer 17

DTG/RPV -> causes decrease in RPV
-> MOSTLY due to RPV

Question 18

what are the preferred regimen for ART in pregnancy and in non-pregnant women who are trying to conceive?

Answer 18

preferred regimens: ual NRTI backbone plus INSTI or boosted PI

alternative regimens: dual NRTI backbone plus NNRTI

Question 19

NRTI backbone for treatment in pregnant women/non-preg trying to conceive

Answer 19

preferred:
- 3TC/ABC
- FTC/TDF
- 3TC/TDF

alternative:
- FTC/TAF
- 3TC/ZDV

Question 20

what is significant about TAF?

Answer 20

spares kidneys

Question 21

preferred INSTI treatment in preg/non-preg trying to conceive?

Answer 21

• DTG
• RAL BID
  NO BIC due to caution in preg

Question 22

alternative NNRTI for preg/trying to conceive?

Answer 22

• EFV
• RPV

Question 23

preferred boosted PIs in preg/trying to conceive?

Answer 23

• ATV/RTV
• DRV/RTV BID

Question 24

when do we go to boosted PIs in therapy?

Answer 24

if know of resistance!

Question 25

rapid ART initiation

Answer 25

• treat with RART immediately as soon as diagnosed
• treat with RART regardless of CD4+ count, especially in older patients

Question 26

why rapid ART/same day ART initiation?

Answer 26

• reduce loss to follow-up (i.e. patient forget to come back) and decrease tie to viral suppression

Question 27

what are some adverse effects of NNRTIs? (class effect)

Answer 27

• liver toxicity
• rash usually 6 weeks
• hyperglycemia
• hyperlipidemia

Question 28

what is the clinical significance of Efavirenz (EFV)?

Answer 28

dosed at night due to side effects

Question 29

what is the clinical significance of Rilpivirine (RPV)?

Answer 29

can cause neuropsychiatric effects

Question 30

what is the clinical significance of Doravarine (DOR)?

Answer 30

only NNRTI that does not share NNRTI class effect adverse effects OR DDIs
- despite not as many side effects, not as much efficacy

Question 31

DDIs of NNRTIs

Answer 31

• Efavirenz, Nevirapine, and Etravirine are CYP3A4 INHIBITORS
• Rilpivirine is a substrate of CYP3A4

Question 32

TDF vs TAF

Answer 32

TDF
- longer experience
- preferred in pregnancy
- available as generic NRTI combinations with 3TC and FTC

TAF
- less impact on markers of renal tubular dysfunction (NO RENAL TOXICITY)