*9.1.3. GS-7340*

[140]. Tetradecylthioacetic acid (TTA), an agent whose mechanism is still unknown, promotes a reduction in levels of plasma lipoproteins [141]. Additionally, Acipimox, a drug with sustained action and a structure similar to niacin, has been associated with decreased insulin resistance and significantly reduced levels of TG in HIV-1 adults [142]. In a double-blind study, the use of cholestin was able to reduce the levels of TC and LDL without modifying HDL and TG, and without showing adverse effects [143]. The use of L-carnitine (3 g/day) resulted in a significant reduction in serum TG in patients with HIV-associated dyslipidemia [144]. These and other drugs studied aimed to revert the HIV-associated dyslipidemia but require more

Since the introduction of zidovudine (1987) for the treatment of HIV-1 infection, followed by the emergence of the fusion inhibitors, such as enfuvirtide/T-20 (2003), and more recently the introduction of raltegravir (2007) and dolutegravir (2013) (Table 1), both InSTIs drugs, treatment for HIV-1 infection has been adapting to new challenges. Once the inability to eradicate viremia by the different HAART regimens was recognized, new drugs, strategies and therapeutic regimens were developed for greater efficiency associated with safety and reduced adverse effects. The common adverse effects observed by the use of the first class of drugs such as zidovudine, and the dyslipidemia caused by the use of PIs, are obstacles that are being minimized in newer drugs that are in the experimental phase. Currently, more than 30 drugs are approved and available in various forms (the different classes of antiretroviral

Festinavir (BMS986001) is a thymidine analogue drug, derived from stavudine but with less potential toxicity [145]. It has been used in cases where there is resistance of HIV-1 to abacavir and tenofovir and is an oral drug recommended for HIV-1 patients with MDR. The compound has a 50% effective concentration (EC50) in the inhibition of mtDNA-polymerase γ and is 100 times less toxic to the mtDNA-polymeraseγ in renal proximal tubular cells, muscle cells, and adipocytes and on the cellular levels of adenosine triphosphate and/or lactate production (ATP) than stavudine. The mitochondrial toxic effects of stavudine are the main cause of the adverse effects associated with lipodystrophy and peripheral neuropathy, which has led to the decline in its use and indicated that festinavir, has a minor impact on lipid metabolism

Apricitabine (AVX754, formerly SPD754) is a drug for oral administration and is in the experimental phase (Phase IIB clinical trial). It is structurally related to lamivudine and

control to be considered appropriate for the treatment of dyslipidemia.

**9. Current antiretroviral drugs and dyslipidemia**

144 Trends in Basic and Therapeutic Options in HIV Infection - Towards a Functional Cure

drugs), and many others are in experimental stages.

**9.1. NRTIs**

[145-147].

*9.1.2. Apricitabine*

*9.1.1. Festinavir*

GS-7340 is a prodrug of tenofovir called tenofovir disoproxil fumarate (TDF). Unlike tenofovir, GS-7340 is stable in plasma and then converted to tenofovir inside the cell by the cellular enzyme cathepsin, which is highly expressed in lymphoid tissue [151]. Within the cell, the drug is transformed into the active metabolite tenofovir diphosphate, an inhibi‐ tor of RT. Phase III studies are underway to better define the safety profile and efficacy, and initially, the drug does not show effects on lipid metabolism. However, formulations with 300 mg promoted adverse effects on the kidneys and bone marrow toxicity [151-153].

Other drugs of the NRTIs class are in the experimental phase, such as racivir (an enantiomer of emtricitabine), elvucitabine (Phase II clinical trial), and amdoxovir (AMDX or DAPD). For these drugs, current data about the adverse effects are insufficient to characterize the impact on lipid metabolism [154-156].

#### **9.2. NNRTIs**
