Currently Approved HIV Antiretrovirals

Chessa R. Nyberg, Pharm.D. Melissa Badowski, PharmD, BCPS, AAHIVE Adapted from Rodrigo Burgos PharmD Characteristics of Protease Inhibitors (PIs) Advantages: higher generic barrier o resistance to NNRTIs and RAL Disadvantages: metabolic complications such as HL, insulin resistance, and hepatotoxicity GI effects, CYP 3A4 inhibitors and subtrates Recommended Dosing Adverse Effects Interactions Comments
Regular dose: once daily Co-administration with efavirenz: ATV effect may be reduced when coadministering with efavirenz Dose in pregnancy:
Hyperbilirubinemia GI adverse effects Nephrolithiasis Cholelithiasis Skin rash ATV/r requires acidic gastric pH for dissolution. Thus, concomitant use of drugs that raise gastric pH (e.g., antacids, H2 antagonists, and particularly PPIs), may impair absorption of ATV ATV/r enhance ATV concentration and improve virologic activity more than unboosted ATV, however has more GI side effects and HL. Food requirement

Drug
Atazanavir ATV Reyataz

Fosamprenavir f-APV Lexiva

ART-nave: once or twice daily PI-experienced:

Skin rash HL

For FPV/r 1400/200 mg: requires 200 mg of RTV

Co-administration with efavirenz: f-APV effect can be reduce when coadministering with EFV Indinavir /Crixivan Lopinavir / Ritonavir Kaletra No need to know dose Regular dose: once or twice daily Co-administration with EFV: should not use once daily dosing
Diarrhea Insulin resistance hyperlipidemia Boosted with 200mg rtv, associated with more GI adverse effects and hyperlipidemia

Dose in pregnancy: twice daily Ritonavir Norvir Tipranavir /Aptivus Darunavir Prezista Regular dose: twice daily No need to know dose ART-nave: 800mg-1000mg once daily PI-experienced:
GI adverse effects Hepatotoxicity Insulin resistance
Skin rash Food requirement

Usually used as boosted dose

Characteristics of Nucleoside Reverse Transcriptase Inhibitors (NRTIs)

Drug
Abacavir ABC Ziagen

Recommended Dosing
Regular dose: Twice daily

Adverse Effects
Lactic acidosis/severe hepatomegaly with steatosis Immune reconstitution syndrome Fat redistribution Myocardial infarction Hypersensitivity: Fever, rash, GI adverse effects
Pancreatitis

Interact ions

Comments
Studies have shown that carriage of the HLAB*5701 allele is associated with a significantly increased risk of a hypersensitivity reaction to abacavir. Genotype for HLA-B* if plan to initiate ABC

Didanosine DDI Videx

Based on body weight and CrCl: 60 Kg: 400kg once daily

Lactic acidosis/severe hepatomegaly with steatosis

Hepatotoxicity Non-cirrhosis portal hypertension Fat redistribution Renal function impairment

< 60 Kg: 250mg once daily

Emtricitabine FTC Emtriva

Once daily dosing

Lamivudine 3TC Epivir

Once (300mg) or twice (150mg) daily

Lactic acidosis/severe hepatomegaly with steatosis Fat redistribution Immune reconstitution syndrome Lactic acidosis/severe hepatomegaly with steatosis
Panreatitis Fat distribution Renal function impairment

Effective against HBV

Effective agains HBV

Stavudine D4T Zerit

Based on body weight: 60 Kg: 40mg q12 h < 60 Kg: 30mg q12h

Lactic acidosis/severe hepatomegaly with steatosis

Hepatotoxicity pancretitis Neurologic symptoms Fat redistribution Renal impairment Immune reconstitution syndrome

Tenofovir TDF Viread

300mg qdaily

Lactic acidosis/severe hepatomegaly with steatosis

Renal impairement Bone mineral density Fat redistribution Immune reconstitution syndrome

Effective against HBV

Zidovudine AZT Retrovir

600 mg daily in dividing doses (100mg, 300mg or 600mg tablets)

Renally reduction dose when CrCL<15 Significant anemia or neutropenia may require dose interruption

Characteristics of Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) Advantages: Long half life Disadvantages: Greater risk of resistance compared to PIs , skin rash, potential cross resistance, CYP450 drug drug interaction Drug
Efavirenz EFV Sustiva

Recommended Dosing
Regular dose: Once a day dosing

Adverse Effects
CNS adverse effects, such as abnormal dreams, dizziness, HA, and depression (usually resolve over a few weeks in some pt Not recommended in pregnant during the first 5-6 weeks dyslipidemia Higher incidence of rash than other NNRTIs Higher incidence of hepatotoxicity Fewer lipid effects than EFV

Interactions

Comments
In combination with tenofovir and emtricitabine for once daily dosing (ATRIPLA)

Nevirapine NVP Viramune

Regular dose: once daily with ER tablet formulation

ART-naive patients with high pre-treatment CD4 counts (>250 cells/mm3 for females, >400 cells/mm3 for males) are at higher risk of symptomatic hepatic events. NVP is not recommended in these patients unless the benefit clearly outweighs the risk.

NO food requirement

Etravirene ETV Intellence

Regular dose

Rilpivirine RPV Edurant

Regular dose: Once daily

Compared with EFV: fewer d/c for CNS adverse effects, fewer lipid effects, fewer rashes, smaller pill sizes

Co-formulated with TDF/FTC Not recommended in pt with HIV RNA > 100,000 due to higher rate of virologic failure Contraindicated with PPIs

RVP- associated depression Use with caution when co-administer with a drug having known risk of torsades de pointes

Characteristics of Fusion Inhibitors Drug Enfuvirtide T-20 Fuzeon Recommended Dosing Injection bid Adverse Effects
PNA Local injection site hypersensitivity

Interactions

Comments

CCR-5 Entry Inhibitors Drug Maraviroc MVC Selzentry Recommended Dosing Twice daily Adverse Effects
Fewer than EFV

Interactions
CYP3A4 substrage

Comments
Require viral tropism before initiating therapy

Integrase Inhibitors Drug Raltegravir RTG Isentress Recommended Dosing Twice daily Adverse Effects
Increase cpk, rhabdomyolysis, and myopathy

Interactions
Fewer drug-related adverse events and lipid changes than with EFV Fewer drug-drug interactions than with EVG/COBI/TDF/FTC-, PI-, NNRTI-, or MVC-based regimen No food effect
Potent CYP 3A4 inhibitor

Comments
Lower genetic barrier to resistance than PIs

Elvitegravir EVG

Once daily

Pharmacokinetic Booster Drug Recommended Dosing Adverse Effects Interactions Comments

Cobicistat COBI

Potent CYP 3A4 inhibitor

Only recommend in pt with baseline CRCL > 70, d/c if CrCL<50 Food reqirement

(TDF/FTC/EVG/COBI)

mg + COBI

Antiretroviral Combination Dosage Forms Drug

Combivir (Zidovudine/Lamivudine) (AZT/3TC) Epzicom Abacavir/Lamivudine (ABC/3TC) Trizivir Abacavir/Lamivudine/Zidovudine (ABC/3TC/AZT) Truvada Tenofovir/Emtricitabine (TDF/FTC) Atripla Tenofovir/Emtricitabine/Efavirenz (TDF/FTC/EFV) Complera Tenofovir/Emtricitabine/Rilpivirine (TDF/FTC/RPV) Stribild Tenofovir/Emtricitabine/Elvitegravir/Cobicistat

Recommended Dosing
1 tab po bid (AZT 300 mg + 3TC 150 mg) 1 tab po daily (ABC 600 mg + 3TC 300 mg) 1 tab po bid (ABC 300 mg + 3TC 150 mg + AZT 300 mg) 1 tab po daily (TDF 300 mg + FTC 200 mg) 1 tab po daily (TDF 300 mg + FTC 200 mg + EFV 600 mg) 1 tab po daily (TDF 300 mg + FTC 200 mg + RPV 25 mg) 1 tab po daily (TDF 300 mg + FTC 200 mg + EVG 150

To consider when choosing drug therapy: Pill burden Home situation Disclosure Expense Concomitant diseases Food access Compliance Side effects Prior HAART Route of HIV acquisition