Impact of antiretroviral therapy on lipid metabolism of human immunodeficiency virus-infected patients: Old and new drugs

Table 1 Antiretroviral drugs class

Antiretroviral class	Generic name drug	Trade name/manufacturer/approval (yr)
Nucleos(t)ide reverse transcriptase inhibitors	Abacavir (ABC)	Ziagen® ViiV Healthcare (1998)
	Didanozine (ddl)	Videx® Bristol-Myers Squibb Co. (1991)
	Emtricitabine (FTC)	Emtriva® Gilead Sci. (2003)
	Lamivudine (3TC)	Epivir® GlaxoSmithKline (1995)
	Stavudine (d4T)	Zerit® Bristol-Myers Squibb Co. (1994)
	Tenofovir (TDF)	Viread® Gilead Sci. (2001)
	Zidovudine (AZT)	Retrovir® ViiV Healthcare (1987)
	Zalcitabine (ddC)	Hivid® Roche (1992)
Non-nucleoside reverse transcriptase inhibitors	Delavirdine (DLV)	Rescriptor® Pfizer (1997)
	Efavirenz (EFV)	Sustiva® Bristol-Myers Squibb Co. (1998)
		Stocrin® Merck Sharp, Dohme (1998)
	Nevirapine (NVP)	Viramune® Boehringer Ingelheim (1996)
	Etravirine (ETR)	Intelence® Janssen-Cilag (2008)
	Rilpivirine (RPV)	Edurant® Janssen-Cilag (2011)
Protease inhibitors	Amprenavir	Agenerase® GlaxoSmithKline (1999)
	Atazanavir	Reyataz® Bristol-Myers Squibb Co. (2003)
	Darunavir	Prezista® Janssen-Cilag (2006)
	Fosamprenavir	Lexiva® ViiV Healthcare (2003)
	Indinavir	Crixivan® Merck and Co. (1996)
	Lopinavir	Kaletra® Abbott (2000)
	Nelfinavir	Viracept® ViiV Healthcare (1997)
	Ritonavir	Norvir® AbbVie Inc. (1996)
	Saquinavir	Invirase® Roche (1995)
	Tipranavir	Aptivus® Boehringer Ingelheim (2005)
Fusion inhibitors	Enfuvirtide, T-20	Fuzeon® Hoffmann La Roche (2003)
Integrase strand transfer inhibitors	Dolutegravir (DTG)	Tivicay® GlaxoSmithKline (2013)
	Elvitegravir (EVG)	Stribild® Gilead Sci. (2012)
	Raltegravir (RAL)	Isentress® Merck and Co. (2007)
Entry inhibitors (CC chemokine receptor 5 antagonists)	Selzentry	Maraviroc® Pfizer (2007)

Table 2 Antiretroviral drugs: Impact on lipid and glucose metabolism

Antiretroviral class	Drug	Effects on lipids	Effects on glucose
NRTIs	Abacavir (ABC)	↑ Dyslipidemia	No effect
	Didanozine (ddl)	↑↑ Dyslipidemia	Insulin resistance
	Emtricitabine (FTC)	↑ Dyslipidemia	No effect
	Lamivudine (3TC)	↑ Dyslipidemia	No effect
	Stavudine (d4T)	↑↑ Dyslipidemia	Insulin resistance
	Tenofovir (TDF)	↑ Dyslipidemia	No effect
	Zidovudine (AZT)	↑↑ Dyslipidemia	Insulin resistance
NNRTIs	Efavirenz (EFV)	↑↑ HDL, ↑ Dyslipidemia	No effect
	Etravirine (ETR)	Neutral effects	No effect
	Nevirapine (NVP)	↑↑ HDL, ↑LDL
	Rilpivirine (RPV)	Neutral effect
PIs	Amprenavir/ritonavir	↑↑↑ Dyslipidemia	Insulin resistance
	Atazanavir/ritonavir	↑ Dyslipidemia	Insulin resistance
	Darunavir/ritonavir	↑ Dyslipidemia	Insulin resistance
	Fosamprenavir/ritonavir	↑↑↑ Dyslipidemia	Insulin resistance
	Indinavir	↑↑ Dyslipidemia	Insulin resistance
	Lopinavir/ritonavir	↑↑↑ Dyslipidemia	Insulin resistance
	Nelfinavir	↑↑ Dyslipidemia	Insulin resistance
	Saquinavir	↑ Dyslipidemia	Insulin resistance
	Tipranavir/ritonavir	↑↑↑ Dyslipidemia	Insulin resistance
Fusion inhibitors	Enfuvirtide, T-20	Neutral effect	No effect
InSTIs	Dolutegravir (DTG)	Neutral effect	No effect
	Elvitegravir (EVG)	Neutral effect	No effect
	Raltegravir (RAL)	Neutral effect	No effect
Entry inhibitors	Selzentry	Neutral effect	No effect

NRTIs: Nucleos(t)ide reverse transcriptase inhibitors; NNRTIs: Non-nucleoside reverse transcriptase inhibitors; PIs: Protease inhibitors; InSTIs: Integrase strand transfer inhibitors.

Table 3 Clinical diagnosis and treatment to human immunodeficiency virus-associated lipodystrophy syndrome

Clinical diagnosis	Treatment options
Lipoatrophy
Sunken eyes, sunken cheeks, prominent zygomatic arch, prominent veins, skinny or muscular appearance, loose skin folds loss of contour	Switching antiviral therapies: stavudine or zidovudineto abacavir or tenofovir, other switch, and/or reconstructive procedures
Lipohypertrophy
Increased abdominal girth with visceral fat accumulation, dorsocervical or supraclavicular fat pad	Diet, exercise, liposuction
Related findings
Hypertriglyceridemia, usually with depressed HDL, hypercholesterolemia, insulin resistance, glucose intolerance	Statins, fibrates, inhibits intestinal cholesterol absorption, fish oils, diet, exercise, drugs (metformin, acarbose, sulfonylureas, glinides or leptin)

Table 4 Statins to highly active antiretroviral therapy-associated dyslipidemia

Drug	Metabolism and interactions
Simvastatin	Considerable CYP3A4 metabolism. ↑ simvastatin levels with PIs and ↓↓ levels with efavirenz. Not recommended with atazanavir, atazanavir/ritonavir, fosamprenavir/ritonavir, saquinavir/ritonavir, tipranavir/ritonavir, lopinavir/ritonavir, indinavir/ritonavir, darunavir/ritonavir and nelfinavir. Doses of 80 mg/d with NNRTIs, raltegravir and selzentry
Lovastatin	Not recommended with atazanavir, atazanavir/ritonavir, fosamprenavir/ritonavir, saquinavir/ritonavir, tipranavir/ritonavir, lopinavir/ritonavir, indinavir/ritonavir, darunavir/ritonavir and nelfinavir. Doses of 80 mg/d with NNRTIs, raltegravir and selzentry
Atorvastatin	Somewhat CYP3A4 metabolism, ↑ levels with PIs darunavir, lopinavir, saquinavir/ritonavir, fosamprenavir. ↓levels with efavirenz. Doses of 20 mg/d with PIs, 80 mg/d with NNRTIs, raltegravir and selzentry
Pravastatin	Reduced interaction with CYP450 metabolism, primarily renal excretion but 50% ↓ with lopinavir/ritonavir, 45% ↓with nelfinavir, 80% ↑with darunavir/ritonavir, and 40% ↓ with efavirenz. Doses of 80 mg/d with PIs, NNRTIs, raltegravir and selzentry
Fluvastatin	Metabolized by CYP2C9, and occasional interactions with nelfinavir and efavirenz. Doses of 80 mg/d with PIs, NNRTIs, raltegravir and selzentry
Rosuvastatin	Not CYP3A4 metabolized but 5 ×↑ levels with lopinavir/ritonavir and darunavir/ritonavir (uncertain). Low starting doses (5-10 mg) recommended with PIs. Doses of 20 mg/d with PIs, 40 mg/d with NNRTIs, raltegravir and selzentry

NNRTIs: Non-nucleoside reverse transcriptase inhibitors.