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Toronto Notes 2019
HIV and AIDS
Infectious Diseases ID31
Table 23. Anti-Retroviral Drugs
Class
Nucleoside reverse transcriptase inhibitors (NRTIs)
Non-nucleoside reverse transcriptase inhibitors (NNRTIs)
Protease inhibitors (PIs)*
Integrase strand transfer inhibitors (INSTIs)
Fusion inhibitor
(only used if resistance)
CCR5 antagonist
CCR5 antagonist
Drugs
abacavir (ABC)
didanosine (ddI) emtricitabine (FTC) lamivudine (3TC)
stavudine (d4T)
tenofovir alafenamide (TAF) tenofovir disoproxil fumarate (TDF)
zidovudine (AZT)
Combination Tablets:
AZT/3TC (Combivir®) AZT/3TC/ABC (Trizivir®) ABC/3TC (Kivexa®) TDF/FTC (Truvada®)
delavirdine (DLV) efavirenz (EFZ) etravirine (ETR) nevirapine (NVP) rilpivirine (RPV)
amprenavir (APV) atazanavir (ATV) darunavir (DRV) fosamprenavir (FPV) indinavir (IDV) lopinavir/ritonavir (LPV/r) nelfinavir (NFV)
ritonavir (RTV) saquinavir (SQV) tipranavir (TPV)
bictegravir dolutegravir (DTG) elvitegravir (EVG) raltegravir (RAL)
enfuvirtide (T-20)
maraviroc maraviroc (MVC)
Mechanism
Incorporated into the growing viral DNA chain, thereby competitively inhibiting reverse transcriptase and terminating viral DNA growth
Non-competitively inhibit function of reverse transcriptase, thereby preventing viral RNA replication
Prevent maturation of infectious virions by inhibiting the cleavage of polyproteins
Inhibits integration of HIV DNA into the human genome thus preventing HIV replication
Inhibit viral fusion with T-cells by inhibiting gp41, preventing cell infection
Inhibit viral entry by blocking host CCR5 co-receptor
Inhibit viral entry by blocking host CCR5 co-receptor
Adverse Effects
Lactic acidosis (often secondary to mitochondrial toxicity)
Lipodystrophy
Rash nausea/vomiting/diarrhea Bone marrow suppression (AZT)
Peripheral neuropathy (ddI, d4T)
Drug-induced hypersensitivity (ABC)
Pancreatitis (ddI/d4T) Myopathy (AZT)
Rash, Stevens-Johnson syndrome
CNS: dizziness, insomnia, somnolence, abnormal dreams (efavirenz)
Lactic Acidosis
• Occurs secondary to mitochondrial toxicity
• Symptoms include abdominal pain, fatigue,
nausea/vomiting, muscle weakness
Lipodystrophy
Body fat redistribution (mainly with old ARVs) • Lipohypertrophy(e.g.dorsalfatpad,breast
enlargement, increased abdominal girth) thought to be caused primarily by protease inhibitors
Hepatotoxicity (nevirapine
– avoid in females with CD4
>250, men with CD4 >400)
CYP3A4 interactions such as d4T and AZT
Lipodystrophy, metabolic syndrome Nausea/vomiting/diarrhea Nephrolithiasis (indinavir) Rash (APV) Hyperbilirubinemia (atazanavir, indinavir)
CYP3A4 interactions Hyperlipidemia
Injection site reactions, rash, infection, diarrhea, nausea, fatigue
Fever, cough, dizziness Fever, cough, dizziness
• Metabolicabnormalities:lipids(increased LDL, increased TGs), glucose (insulin resistance, type 2 DM), increased risk of CVD
• Lipoatrophy(e.g.facialthinning,decreased adipose tissue in the extremities) is thought to be caused by thymidine analogue NRTIs
*Standard of care is to pharmacologically boost most PIs with ritonavir to increase concentrations
Single Tablet ART Regimens
• reducespillburdenandincreasesadherence • generallybettertolerated
Table 24. Single Tablet ART Regimens
Name
Genvoya® Complera® Odefsey® Stribild® Triumeq® Atripla®
Contents
tenofovir/emtricitabine/elvitegravir/cobicistat rilpivirine/emtricitabine/tenofovir rilpivirine/emtricitabine/tenofovir alafenamide elvitegravir/cobicistat/emtricitabine/tenofovir dolutegravir/abacavir/lamivudine efavirenz/tenofovir/emtricitabine
Common Side Effects
good side effect profile
good side effect profile
good side effect profile
good side effect profile
good side effect profile; use only in HLAB*5701 negative patients psychiatric events, vivid dreams
Recommended ARV Regimens for Treatment-Naïve HIV-infected Adults
• initialregimensfortreatment(allincludeanintegraseinhibitorandapairofNRTIs): 1. Bictegravir/TAF/FTC
2. Dolutegravir/ABC/3TC
3. Dolutegravir + TAF (or TDF)/FTC
4. Elvitegravir/cobicistat/TAF (or TDF)/FTC 5. Raltegravir + TAF (or TDF)/FTC
Note: Not all regimens available in all regions.