Role of Mitochondria in HIV Infection and Associated Metabolic Disorders: Focus on Nonalcoholic Fatty Liver Disease and Lipodystrophy Syndrome

Table 1

Current employed anti-HIV drug families and reported mitochondrial toxicity (modified from Apostolova et al., 2011) [17].

Drug family (antiretroviral)	Mechanism of action	Mitochondrial dysfunction
Nucleoside/nucleotide reverse transcriptase inhibitor (Abacavir, Didanosine, Emtricitabine, Lamivudine, Stavudine, Tenofovir, and Zidovudine)	Interferes with the HIV reverse transcriptase protein, needed by the virus to make new copies of itself	Inhibition of Pol-γ
		Depletion of mtDNA
		Reduction of mtDNA-encoded proteins
		Respiratory chain dysfunction
		Direct inhibition of ETC complexes (I, IV)
		Reduction of ATP levels
		ROS production
		Decrease in 𝐴𝜓𝑚
		Impairment of ADP/ATP translocase
		Impairment of fatty acid oxidation
Nonnucleoside reverse transcriptase inhibitor (Efavirenz, Etravirine, and Nevirapine)	Stops HIV replication within cells by inhibiting the reverse transcriptase protein	Respiratory chain dysfunction
		Reduction of ATP levels
		ROS production
		Decrease in 𝐴𝜓𝑚
		Apoptosis
Protease inhibitor (Atazanavir, Darunavir, Fosamprenavir, Lopinavir, Ritonavir, and Saquinavir)	Inhibits the HIV protease activity, a protein required for HIV replication	Inhibition of MPP (mitochondrial protease processing)
		Fragmentation of mitochondrial network
		Increase in mitochondrial Ca^2+ accumulation
		Apoptosis
		ROS production
Fusion inhibitor (Enfuvirtide)	Prevents HIV from binding to or from entering human immune cells	Unknown
CCR5 inhibitor (Maraviroc)	Prevents HIV from binding to or from entering human immune cells	Unknown
Integrase inhibitor (Raltegravir)	Interferes with the integrase enzyme, which is needed to insert HIV genetic material into human cells	Unknown