Pathophysiology Screening & Diagnosis

• HIV = single-stranded RNA retrovirus that uses CD4 T-helper cells to replicate • HIV screening at least once for all patients
• When HIV replicates, the viral load increases and CD4 count decreases 13-64 years old
• AIDs is diagnosed when CD4 count < 200 or develops OI, wasting syndrome, • Annual screening for high-risk patients:
IRIS, or Kaposi’s sarcoma o Sharing needles
• Infection is spread via direct contact with blood, genital, or rectal secretions o High-risk sexual behaviors
or by ingestion of breast milk (can spread from mother-to-child) o History of STIs
o History of hepatitis or TB

Stages of Infection HIV Replication Sites and Antiretroviral Sites of Action

Acute HIV infection = non-specific, flu-like symptoms
CCR5 antagonist (maraviroc)
1. Binding & Attachment
OraQuick home test can detect HIV antibodies >3 months after Attachment inhibitor (fostemsavir)
exposure (if positive, must use lab test to confirm)
2. Fusion Fusion inhibitor (enfuvirtide)

Antibodies detected in most people ~4-12 weeks post-infection 3. Reverse Transcription NRTIs & NNRTIs
4. Integration INSTIs (-gravir)
>2 weeks post-infection, HIV RNA and p24 antigens can be
5. Replication
detected by antigen/antibody screening test
• If positive ® confirm with antibody diZerentiation 6. Assembly
immunoassay 7. Budding & Maturation Protease Inhibitors (-navir)

Antiretroviral Therapy
• Nothing warrants a delay in treatment! ART regimen should have backbone = 2 NRTIs + (PI or NNRTI or INSTI)
• Perform hepatitis B/C screening, pregnancy test, • Newly diagnosed HIV ® INSTI-based regimen (-gravir)
and HLA-B*5701 testing (for abacavir) • Most preferred regimens = 2 NRTIs + 1 INSTI
• Goal viral load = <200 o Alternative = 2 NRTIs + PI + booster

***dispense all 30-day HIV meds in original bottle ***pregnancy ® 2 NRTIs + INSTI (dolutegravir) or boosted PI (darunavir)
Completely Treatment-Naïve:
History of Using Cabotegravir for PrEP:
• Bictegravir/emtricitabine/TAF (Biktarvy)
• Wait for INSTI genotype resistance test first!
• Dolutegravir (Tivicay) + (Truvada or Descovy)
o Darunavir/cobicistat/TAF/emtricitabine (Symtuza)
• Dolutegravir/lamivudine (Dovato)
o Darunavir/cobicistat (Prezcobix) + (Descovy or Truvada)
o Cannot use if viral load > 500,000 or known
o Darunavir + ritonavir + (Descovy or Truvada)
Hep B virus co-infection

NRTI
Competitively inhibit the reverse transcriptase enzyme, preventing conversion of HIV RNA to DNA
in stage 3 of the HIV life cycle
Common side eZects: nausea, diarrhea, fatigue, ­ LFTs

Resistance develops early for NRTIs! ABC:

• HLA-B screening for severe HSR
All NRTIs (except ABC): ¯ dose in renal • Cardiac complications
impairment
TDF:
BBW: severe Hep B exacerbation; • ¯ bone mineral density
lactic acidosis and hepatomegaly • Avoid in CrCl < 60

TAF/TDF: once daily dosing TAF:

• Lipid abnormalities
• Avoid in CrCl < 30
 INSTIs (-gravir)
Block the integrase enzyme, preventing HIV DNA from inserting into the host cell DNA in stage 4
of the HIV life cycle
INSTIs have higher barrier to resistance Elvitegravir is only INSTI that needs
compared to NRTIs and NNRTIs boosted
• Do not start if CrCl < 70
Cabotegravir is only for PrEP, not treatment!
• Discontinue if CrCl < 50
Separate from polyvalent cations
DTG preferred in pregnancy
Side EZects:
• Nausea RTG, DTG:
• Diarrhea • Myopathy, rhabdomyolysis
• Weight gain • Hypersensitivity reactions
• Headache

NNRTIs (-vir- in the middle)

Non-competitively inhibit the reverse transcriptase enzyme, preventing conversion of HIV RNA to DNA
in stage 3 of the HIV life cycle
Resistance develops easily! Efavirenz
• Take on empty stomach
CYP3A4 inducers and substrates • CNS eZects
Risk of hepatotoxicity and severe rash • Increases lipids
(SJS/TEN) Rilpirivine
• Requires acidic environment (no PPIs!, can
separate antacids)
• Take with food > 390 calories

Protease Inhibitors (-navir)

Inhibit the HIV protease enzyme, preventing long viral protein chains from being broken down to produce
mature virus in stage 7 of HIV life cycle
Highest barrier to resistance Side EZects:
• Hyperglycemia
Needs to be taken with a booster! • Dyslipidemia
No renal dose adjustments • Weight gain
• Hepatic dysfunction
Take with food to lessen GI upset • Hypersensitivity reactions
• Diarrhea
Most PIs are CYP3A4 inhibitors and substrates: • Nausea
• Colchicine
• Dronedarone Darunavir: caution with sulfa allergy
• Lovastatin, simvastatin
• CYP3A4 inducers Atazanavir
• Anticoagulants, antiplatelets • Requires acidic gut
• Steroids • Causes jaundice
• Hormonal contraceptives

Boosters
Inhibit ART metabolism, which increases concentration of ART and therapeutic eZect
Not interchangeable! Ritonavir
• Technically a PI, but is only used for boosting
Take with food • Used in pregnancy
Strong CYP3A4 and CYP2D6 inhibitors: • Oral solution contains alcohol
• Tamsulosin
Cobicistat
• Colchicine
• Increases SCr with no eZect on GFR
• Lovastatin, simvastatin
• Azole antifungals
• Amiodarone
• PDE-5 inhibitors
• TKIs
• CYP3A4 inducers
 PrEP (Pre-Exposure)

***Must have negative HIV test before starting PrEP

Truvada (FTC/TDF) Descovy (FTC/TAF) Cabotegravir
Only oral PrEP approved for women (AFAB) Do not use if CrCl < 30 IM injection every 2 months

Do not use if CrCl < 60 Can cause lipid abnormalities Okay in renal impairment

Higher risk of bone mineral loss, renal toxicities Can cause injection site reactions

PEP (Post-Exposure)

Occupational Exposure Non-Occupational Exposure

Used for healthcare personnel Used after non-protected sex or injection drug use

Truvada + raltegravir for 28 days Truvada + raltegravir for 28 days