You're using an outdated browser. Please upgrade to a modern browser for the best experience.
Submitted Successfully!
Thank you for your contribution! You can also upload a video entry or images related to this topic. For video creation, please contact our Academic Video Service.
Version Summary Created by Modification Content Size Created at Operation
1
Thabani Sibiya
 -- 2262 2022-08-31 15:19:26 |
2 Reference format revised.
Lindsay Dong
 Meta information modification 2262 2022-09-01 03:29:25 |

Video Upload Options

We provide professional Academic Video Service to translate complex research into visually appealing presentations. Would you like to try it?
No, upload directly Yes

Confirm

Are you sure to Delete?
Yes No
Cite
If you have any further questions, please contact Encyclopedia Editorial Office.
Sibiya, T.;  Ghazi, T.;  Chuturgoon, A. Combine Spirulina platensis and Highly Active Antiretroviral Therapy. Encyclopedia. Available online: https://encyclopedia.pub/entry/26739 (accessed on 09 July 2025).
Sibiya T,  Ghazi T,  Chuturgoon A. Combine Spirulina platensis and Highly Active Antiretroviral Therapy. Encyclopedia. Available at: https://encyclopedia.pub/entry/26739. Accessed July 09, 2025.
Sibiya, Thabani, Terisha Ghazi, Anil Chuturgoon. "Combine Spirulina platensis and Highly Active Antiretroviral Therapy" Encyclopedia, https://encyclopedia.pub/entry/26739 (accessed July 09, 2025).
Sibiya, T.,  Ghazi, T., & Chuturgoon, A. (2022, August 31). Combine Spirulina platensis and Highly Active Antiretroviral Therapy. In Encyclopedia. https://encyclopedia.pub/entry/26739
Sibiya, Thabani, et al. "Combine Spirulina platensis and Highly Active Antiretroviral Therapy." Encyclopedia. Web. 31 August, 2022.
Combine Spirulina platensis and Highly Active Antiretroviral Therapy
Edit
This entry is adapted from the peer-reviewed paper 10.3390/nu14153076

The human immunodeficiency virus (HIV) is one of the most prevalent diseases globally. The highly active antiretroviral therapy (HAART) involves combining various types of antiretroviral drugs that are dependent on the infected person’s viral load. HAART helps regulate the viral load and prevents its associated symptoms from progressing into acquired immune deficiency syndrome (AIDS). Despite its success in prolonging HIV-infected patients’ lifespans, the use of HAART promotes metabolic syndrome (MetS) through an inflammatory pathway, excess production of reactive oxygen species (ROS), and mitochondrial dysfunction. Interestingly, Spirulina platensis (SP), a blue-green microalgae commonly used as a traditional food by Mexican and African people, has been demonstrated to mitigate MetS by regulating oxidative and inflammatory pathways. SP is also a potent antioxidant that has been shown to exhibit immunological, anticancer, anti-inflammatory, anti-aging, antidiabetic, antibacterial, and antiviral properties. 

HAART/ARVs Spirulina platensis oxidative stress HIV MetS

1. Introduction

The human immunodeficiency virus (HIV) has continued to be a global public concern due to its widespread infection rate and alarming mortality rate [1]. The Joint United Nations Programme on HIV/AIDS (UNAIDS), in its most recent report in November 2021, estimated that 37.7 million people globally are living with HIV. It was also reported that about 1.5 million new HIV infections and 680,000 AIDS-related deaths have occurred in the year 2020 [1][2][3][4]. In South Africa, approximately 8.2 million people were living with HIV in the year 2021 [4]. According to the South African mid-year population statistics 2021, there has been an unprecedented increase from 79,420 to 85,154 HIV-AIDS-related deaths in 2021 [4]. Recently, the easy availability of antiretrovirals (ARVs) has tremendously changed the pattern of death. ARVs have also helped prolong the lifespan of HIV-infected people in South Africa. Globally, about 27.5 million HIV-infected persons had access to ARVs in 2020, while approximately 5.6 million infected South Africans accessed ARVs in 2020 [1][4][5].
The highly active antiretroviral therapy (HAART) entails combining three or more antiretroviral drugs that are subject to the HIV-infected person’s viral load. HAART assists in regulating viral loads and preventing the progression to AIDS. Despite its success in prolonging HIV-infected patients’ lifespans, the use of HAART promotes metabolic syndrome (MetS) through an inflammatory pathway, excess production of reactive oxygen species (ROS), and mitochondrial dysfunction. Over three decades since its discovery, HAART has significantly improved the diagnosis and management of persons with HIV [6][7][8][9][10][11][12]. The persistence of MetS before and during HAART treatment further highlights the need for more studies on MetS inhibitory compounds, such as Spirulina platensis (SP) [13], Moringa oleifera [14][15], Curcumin [16], and Mangiferin [17]. However, there are other alternatives to combat MetS and these include exercise training [18], life style changes, and properly balanced healthy food choices [19][20].
SP is a blue-green microalgae commonly used as a traditional food by some Mexican and African people [21][22]. SP is mostly found in the alkaline water of volcanic lakes. In addition to its popular nutritional value, SP possesses various medicinal properties. It can induce both the humoral and cellular mechanisms of the immune system when consumed [22]. Interestingly, SP was linked with MetS-lowering properties, such as hypoglycemia [23], hypolipidemia [24], and hypotension [13]. Studies in rodents suggested that SP is particularly useful in preventing MetS [13]. SP contains oxidative stress inhibitors, phycocyanin and phycocyanobilin [25][26][27]. Previous studies have also demonstrated that SP inhibits oxidative stress [21][25][28][29] and promotes mitochondrial health [30][31][32][33], thereby inhibiting inflammation [25][34]. Furthermore, SP can prevent the development of atherosclerosis [28] and diabetes [25]. The Food and Agriculture Organization (FAO) of the United Nations recommends Spirulina as a daily dietary supplement [35]. Microalgaes including Spirulina are environmentally friendly and have a high rate of yield in large-scale production under controlled conditions [36]. Spirulina, in addition to its nutritional and medicinal security, has the potential to eliminate poverty. The considerable potential for sustainable financial development in a small-scale crop for nutritional enhancement was evident in China, where the production increase resulted in a dramatic increase in profit from USD 7.6 million to USD 16.6 million. Spirulina production is possible for small and marginal farmers as well as enthusiastic urban gardeners; this makes it easily accessible to the population [37]. Moreover, the health system can provide SP as medication to control adverse effects in people living with HIV on HAART with minimal costs.

2. The Roles of HIV and HAART in MetS

HIV has often been associated with MetS [38], which results in cardiovascular diseases. Recent reports have linked some HIV-related features to MetS. These characteristic features include escalated cases of cardiovascular diseases, type 2 diabetes mellitus, dyslipidemia, immunodeficiency, high viral load, and atherosclerosis [7]. Recently, studies have suggested that HAART, in addition to the above-mentioned HIV-related features, actively induces MetS in persons with HIV [7][39][40][41]. Earlier studies by Palios et al. (2011) on arterial stiffness, displayed by pulse wave velocity (PWV), and markers of MetS, reported that persons with HIV exhibited an increased degree of PWV when compared with the healthy controls. Subsequently, persons on HAART have been shown to exhibit a similar PWV as persons with hypertension [39][40]. The prevalence of MetS in HIV-infected people receiving antiretroviral (ARV) treatment was higher when compared to the general population. This prevalence was attributed to age, physical inactivity, and a low cluster of differentiation 4 (CD4) count [42][43][44]. The patient response to HAART varies; some antiviral drugs can successfully suppress the plasma viral load without increasing the CD4 count; this allows the risks of opportunistic infections and abnormalities. Failure to increase the CD4 count during HAART may be due to several factors, including drug resistance, low CD4+ T-cell count at the initiation of HAART, the advanced stage of the disease, and a low adherence to HAART [45].

3. Spirulina Species

Spirulina has three commonly investigated species due to their potential therapeutic nature and high nutritional content. These Spirulina species include Spirulina platensis (SP) (otherwise known as Arthrospira platensis), Spirulina maxima (Arthrospira maxima), and Spirulina fusiformis (Arthrospira fusiformis). These Spirulina species are also classified as oxygenic photosynthetic bacteria under Cyanobacteria and Prochlorales [46][47][48][49][50][51]. SP is found in alkaline water with abundant bicarbonate and saline [22][52]. Spirulina species are generally three-dimensional helix microstructures [53] protected by a cell wall composed of complex sugars and proteins [22]; however, helical transformation results after mature trichomes divide into hormogonia, binary fission, and undergo length elongation [54]. SP is considered an antioxidant and anti-inflammatory agent [55]. 

SP contains several vital antioxidant and anti-inflammatory compounds as mentioned above, such as chlorophyll, phycocyanin, and carotenoids (β-carotene). The antioxidant and anti-inflammatory properties of phycocyanin have been determined in numerous studies [28][56][57][58][59][60][61][62][63][64][65][66][67]. Phycocyanin is responsible for reducing oxidative stress and NADPH oxidase [28]. It scavenges free radicals, such as alkoxy, hydroxyl, and peroxyl radicals, and decreases nitrite production and inducible nitric oxide synthase (iNOS) expression. Phycocyanin also inhibits liver microsomal lipid peroxidation [28][56][57][58][59][60][61][62][63][64][65][66][67].
Phycocyanin has been proven to inhibit the formation of the pro-inflammatory cytokine TNF-α and cyclooxygenase-2 (COX-2) expression. Additionally, it decreases prostaglandin E(2) production [28][56][57][58][59]. Phycocyanin prevents the degradation of cytosolic IκB-α, which suppresses the activation of nuclear factor-κB (NF-κB) [28]. Furthermore, the inhibitory activity of phycocyanin is associated with the suppression of TNF-α formation in the macrophages [59]. In addition, phycocyanin exerts regulatory effects on mitogen-activated protein kinase (MAPK) activation pathways, such as the p38, c-Jun N-terminal kinase (JNK), and extracellular-signal-regulated kinase (ERK1/2) pathways [68][69][70]. The second compound of SP, carotenoids, β-carotene to be specific, is an antioxidant that has anti-carcinogenic, antioxidant, and anti-inflammatory activities [71][72][73]. As a membrane antioxidant, β-carotene protects against singlet oxygen-mediated lipid peroxidation [71]. Beta carotene inhibits the production of nitric oxide and prostaglandin E(2) and suppresses the expression of inducible nitric oxide synthase (iNOS), COX-2, TNF-α, and IL-1β. The suppression of inflammatory mediators by β-carotene results from its’ ability to inhibit NF-κB activation by preventing nuclear translocation of the NF-κB p65 subunit [72][74][75]. Studies have shown that β-carotene suppressed the transcription of inflammatory cytokines such as IL-1β, IL-6, and IL-12 in vitro [73]; this takes place in the macrophages. The third compound of spirulina, chlorophyll, can perform antioxidant and antimutagenic activities [76][77]. Spirulina’s mechanism of action is a concert of compounds, but it is not clear whether they all act simultaneously during demanding events.

4. Common Highly Active Antiretroviral Therapy (HAART) Combinations

HAART has several classes: nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) [78][79][80][81][82][83][84][85][86], protease inhibitors (PIs) [86][87][88][89], integrase strand transfer inhibitors (INSTIs) [90][91][92][93][94][95], fusion inhibitors (FIs) [96], and chemokine receptor antagonists (CCR5 antagonists) [97][98][99]. HAART is a specifically selected combination of NRTI and NNRTI, PI, or INSTI drugs responsible for the inhibition of viral replication by multiple virus targets [85][100][101][102][103][104][105][106][107][108]. However, HAART can cause adverse drug reactions. Furthermore, 2′,3′-dideoxy-3′-thiacytidine (3TC), 2′,3′-dideoxy-5-fluoro-3′-thiacytidine (FTC), TDF (Tenofovir Disoproxil Fumarate), ZDV (Zidovudine), and d4T (Stavudine) are associated with mitochondrial toxicity and oxidative stress [109][110][111][112]. Additionally, NNRTIs are linked to toxic hepatitis, and PIs are implicated in insulin resistance and hyperlipidemia [86]. Chronic side effects linked to HAART include ROS-induced insulin resistance [113][114], lipodystrophy, gastrointestinal disorders [115], and cardiovascular disease [11][116]. Primarily, HAART is used for the treatment and prevention of HIV-1. These primary functions of HAART are achieved by attacking different components of the virus lifecycle which ensures inhibition regardless of the virus being resistant to one of the drugs [85][100][101][102][103][104][105][106][107][108]. A combination of two NRTIs (mostly FTC and TDF) and one NNRTI (e.g., EFV; Efavirenz) is a more favorable choice due to the convenience to dose, effectiveness, and less toxic effects compared to other drug combinations [86][117][118]. A combination of three NRTIs is less effective than two NRTIs with an NNRTI [119]. The d4T/ddI combination is associated with high toxicity and hence it is not often recommended [120]. The most popular NRTIs are cytidine analogs (XTC), FTC, 3TC, and TDF, which form part of the first-line therapy [121][122][123][124][125]. FTC and 3TC are similar in chemical structures with different pharmacokinetic and pharmacodynamic properties, and they have required deoxynucleosides for HIV DNA synthesis. They undergo phosphorylation through intracellular kinases to become FTC 50 -triphosphate (FTC-TP) and 3TC-TP; triphosphate metabolites with FTC-TP are more efficiently incorporated during HIV DNA synthesis than 3TC-TP [117][126][127][128][129]. Moreover, 3TC-TP has a shorter intracellular half-life compared to FTC-TP [127]. The TDF and FTC combination has a synergistic effect, increasing intracellular metabolites, and they are recommended for pre-exposure prophylaxis (PrEP) [127][130][131][132][133]. 

5. Mechanism of HAART-Induced Oxidative Stress, Inflammation, and Mitochondrial Dysfunction

The exact mechanism of HAART-induced oxidative stress has not been completely explored; however, studies have demonstrated the link between HAART use and oxidative stress. HAART is linked with lipid metabolism dysfunction through the induction of peripheral lipodystrophy. Lipodystrophy results from the impaired cytoplasmic retinoic-acid binding protein type 1 (CRABP1)-mediated cis-9-retinoic acid stimulation of peroxisome proliferator-activated receptor type gamma (PPAR-γ), leading to impaired differentiation and increased apoptosis of peripheral adipocytes. HIV-1 protease-inhibitors further inhibit the cytochrome P450 3A-mediated synthesis of cis-9-retinoic acid, one of the key activators of PPAR-γ [134]. Insulin resistance occurs following impaired fat storage and lipid release [113][114][134], which impacts the oxidant profile. The depletion of ATP production and mitochondrial dysfunction [8][9], and the depletion of mitochondrial DNA [135][136][137], are some of the ways HAART induces oxidative stress. HIV increases oxidative stress, and HAART increases lipid oxidation, which amplifies the ROS imbalance leading to increased oxidative stress complications [10][138].

6. Combined and Synergistic Therapeutic Actions of HAART and SP

Studies have shown that the possible therapeutic effects of antioxidants may provide strategies in suppressing oxidative stress-induced comorbidities that emerge with the use of HAART therapy in HIV-infected individuals [12]. The combination of HIV and HAART has been associated with increased oxidative stress and lipid peroxidation. Furthermore, HIV or HAART induces ROS by inducing NADPH oxidase [139][140]. Interestingly, SP is a potent antioxidant [26][27] with anti-inflammatory activities [34], which makes it a potential supplement in the mitigation of oxidative stress induced by HAART adverse drug reactions. Moreover, SP can inhibit NADPH oxidase which is considered one of the main sources of ROS and free radicals in HIV-infected persons on HAART [34][139][140], resulting in reduced oxidative stress [28]. Moreover, β-carotene from SP protects against singlet oxygen-mediated lipid peroxidation [71]. Among HAART complications, TDF and lopinavir cause acute and chronic renal dysfunction [141][142][143][144][145]. Herein, phycocyanin from SP can normalize urinary and renal oxidative stress markers and inhibit NADPH-dependent superoxide production in renal mesangial cells [25], ameliorating renal dysfunction. Lately, SP has been an effective therapeutic approach to preventing diabetic nephropathy through the inhibition of oxidative stress [25]. These properties indicate SP as a potential agent to mitigate renal dysfunction caused by HAART. As mentioned above, NRTIs can inhibit mitochondrial DNA polymerase [146][147]. Studies in vitro showed that SP can enhance cell nucleus enzyme function, repair DNA synthesis [54], and enhance mitochondrial health [30][31][32][33][148]. Mitochondrial toxicity presented as peripheral neuropathy and lactic acidosis can be corrected by SP through providing trace minerals for the synthesis of antioxidant enzymes [149] and reducing chronic inflammatory conditions [150].
NNRTIs are associated with life-threatening skin reactions and toxic hepatitis [86], these conditions may be ameliorated by SP. Phycocyanin from SP can inhibit liver microsomal lipid peroxidation [28][56][57][58][59][60][61][62][63][64][65][66][67], and hence reducing toxic hepatitis. Moreso, SP incorporated into skin creams showed promising results as an anti-inflammatory and a wound-healing agent [151]; this can be beneficial in the mitigation of NNRTI-induced skin reactions. PI therapy induces insulin resistance and hyperlipidemia [7]. Additionally, HAART may be associated with a higher risk of myocardial infarction [86][152][153]. SP has a therapeutic effect against vascular diseases, cancer, diabetes, and neurodegenerative diseases [154]. In addition, the Spirulina family has also shown central neuroprotective effects in rodents [155] and may exert its neuroprotective activities through antioxidant and anti-inflammatory effects [156]. Therefore, SP is a recommended antioxidant to use as a supplement; the list of benefits is evident. It also has antiallergic effects [51], prevents cellular aging and infectious diseases, and promotes a strong immune system [54]. Herein, promotion of a strong immune system by SP can help increase CD4 cell counts, lower HIV viral loads, and slow down the progression to AIDS. Moreover, SP prevents FR-induced apoptotic cell death [157]; this may help decrease apoptosis of peripheral adipocytes induced by HAART. Chemically, SP is a recommended source of proteins, vitamins, and minerals [54], important nutrients for individuals on the HAART program. Finally, SP can assist HAART in the inhibition of HIV-1 replication because it has been shown to inhibit viral production in PBMCs.

References

  1. WHO. HIV/AIDS. Available online: https://www.who.int/news-room/fact-sheets/detail/hiv-aids (accessed on 30 November 2021).
  2. UNAIDS. Joint United Nations Programme on HIV/AIDS (UNAIDS). Global Report: UNAIDS Report on the Global AIDS Epidemic 2021; Global HIV & AIDS Statistics: Fact Sheet; Joint United Nations Programme on HIV/AIDS: Geneva, Switzerland, 2021.
  3. UNAIDS. Global HIV & AIDS Statistics—2020 Fact. Available online: https://www.unaids.org/en/resources/fact-sheet (accessed on 11 September 2021).
  4. Release, S. Mid-Year Population Estimates 2021. Statistics South Africa. 2021. Available online: http://www.statssa.gov.za/publications/P0302/P03022021.pdf (accessed on 18 November 2021).
  5. UNAIDS. HIV and AIDS Estimates. Available online: https://www.unaids.org/en/regionscountries/countries/southafrica (accessed on 11 September 2021).
  6. National Institute on Drug Abuse (NIDA). What Is HAART? Available online: https://www.drugabuse.gov/publications/research-reports/hivaids/what-haart (accessed on 30 November 2021).
  7. Mohan, J.; Ghazi, T.; Chuturgoon, A.A. A Critical Review of the Biochemical Mechanisms and Epigenetic Modifications in HIV- and Antiretroviral-Induced Metabolic Syndrome. Int. J. Mol. Sci. 2021, 22, 12020.
  8. Manda, K.R.; Banerjee, A.; Banks, W.A.; Ercal, N. Highly active antiretroviral therapy drug combination induces oxidative stress and mitochondrial dysfunction in immortalized human blood–brain barrier endothelial cells. Free Radic. Biol. Med. 2011, 50, 801–810.
  9. Blas-Garcia, A.; Apostolova, N.; Esplugues, J.V. Oxidative stress and mitochondrial impairment after treatment with anti-HIV drugs: Clinical implications. Curr. Pharm. Des. 2011, 17, 4076–4086.
  10. Ngondi, J.L.; Oben, J.; Forkah, D.M.; Etame, L.H.; Mbanya, D. The effect of different combination therapies on oxidative stress markers in HIV infected patients in Cameroon. AIDS Res. Ther. 2006, 3, 19.
  11. Masiá, M.; Padilla, S.; Bernal, E.; Almenar, M.V.; Molina, J.; Hernández, I.; Graells, M.L.; Gutiérrez, F. Influence of antiretroviral therapy on oxidative stress and cardiovascular risk: A prospective cross-sectional study in HIV-infected patients. Clin. Ther. 2007, 29, 1448–1455.
  12. Mondal, D.; Pradhan, L.; Ali, M.; Agrawal, K.C. HAART drugs induce oxidative stress in human endothelial cells and increase endothelial recruitment of mononuclear cells. Cardiovasc. Toxicol. 2004, 4, 287–302.
  13. Finamore, A.; Palmery, M.; Bensehaila, S.; Peluso, I. Antioxidant, immunomodulating, and microbial-modulating activities of the sustainable and ecofriendly spirulina. Oxidative Med. Cell. Longev. 2017, 2017, 1–4.
  14. Nyakudya, T.T.; Tshabalala, T.; Dangarembizi, R.; Erlwanger, K.H.; Ndhlala, A.R. The potential therapeutic value of medicinal plants in the management of metabolic disorders. Molecules 2020, 25, 2669.
  15. Kim, D.S.; Choi, M.H.; Shin, H.J. Extracts of Moringa oleifera leaves from different cultivation regions show both antioxidant and antiobesity activities. J. Food Biochem. 2020, 44, e13282.
  16. Pérez-Torres, I.; Ruiz-Ramírez, A.; Baños, G.; El-Hafidi, M. Hibiscus sabdariffa Linnaeus (Malvaceae), curcumin and resveratrol as alternative medicinal agents against metabolic syndrome. Cardiovasc. Hematol. Agents Med. Chem. 2013, 11, 25–37.
  17. Mujawdiya, P.K.; Kapur, S. Mangiferin: A potential natural molecule for management of metabolic syndrome. Int. J. Pharm. Pharm. Sci. 2015, 7, 9–13.
  18. Kränkel, N.; Bahls, M.; van Craenenbroeck, E.M.; Adams, V.; Serratosa, L.; Solberg, E.E.; Hansen, D.; Dörr, M.; Kemps, H. Exercise training to reduce cardiovascular risk in patients with metabolic syndrome and type 2 diabetes mellitus: How does it work? Eur. J. Prev. Cardiol. 2019, 26, 701–708.
  19. Opie, L.H. Metabolic syndrome. Circulation 2007, 115, e32–e35.
  20. Marrone, G.; Guerriero, C.; Palazzetti, D.; Lido, P.; Marolla, A.; Di Daniele, F.; Noce, A. Vegan diet health benefits in metabolic syndrome. Nutrients 2021, 13, 817.
  21. Bashandy, S.A.; El Awdan, S.A.; Ebaid, H.; Alhazza, I.M. Antioxidant potential of Spirulina platensis mitigates oxidative stress and reprotoxicity induced by sodium arsenite in male rats. Oxidative Med. Cell. Longev. 2016, 2016, 1–6.
  22. Estrada, J.P.; Bescós, P.B.; del Fresno, A.V. Antioxidant activity of different fractions of Spirulina platensis protean extract. Il Farm. 2001, 56, 497–500.
  23. Iyer Uma, M.; Sophia, A.; Uliyar, V.M. Glycemic and lipemic responses of selected spirulina-supplemented rice-based recipes in normal subjects. Age Years 1999, 22, 1–8.
  24. Serban, M.C.; Sahebkar, A.; Dragan, S.; Stoichescu-Hogea, G.; Ursoniu, S.; Andrica, F.; Banach, M. A systematic review and meta-analysis of the impact of Spirulina supplementation on plasma lipid concentrations. Clin. Nutr. 2016, 35, 842–851.
  25. Zheng, J.; Inoguchi, T.; Sasaki, S.; Maeda, Y.; McCarty, M.F.; Fujii, M.; Ikeda, N.; Kobayashi, K.; Sonoda, N.; Takayanagi, R. Phycocyanin and phycocyanobilin from Spirulina platensis protect against diabetic nephropathy by inhibiting oxidative stress. Am. J. Physiol. -Regul. Integr. Comp. Physiol. 2013, 304, R110–R120.
  26. Hu, Z.; Liu, Z. Determination and purification of beta-carotene in Spirulina maximum. Chin. J. Chromatogr. 2001, 19, 85–87.
  27. Miranda, M.S.; Cintra, R.G.; Barros, S.; Mancini-Filho, J. Antioxidant activity of the microalga Spirulina maxima. Braz. J. Med. Biol. Res. 1998, 31, 1075–1079.
  28. Riss, J.; Décordé, K.; Sutra, T.; Delage, M.; Baccou, J.C.; Jouy, N.; Brune, J.P.; Oréal, H.; Cristol, J.P.; Rouanet, J.M. Phycobiliprotein C-phycocyanin from Spirulina platensis is powerfully responsible for reducing oxidative stress and NADPH oxidase expression induced by an atherogenic diet in hamsters. J. Agric. Food Chem. 2007, 55, 7962–7967.
  29. Abdelkhalek, N.K.; Ghazy, E.W.; Abdel-Daim, M.M. Pharmacodynamic interaction of Spirulina platensis and deltamethrin in freshwater fish Nile tilapia, Oreochromis niloticus: Impact on lipid peroxidation and oxidative stress. Environ. Sci. Pollut. Res. 2015, 22, 3023–3031.
  30. Nawrocka, D.; Kornicka, K.; Śmieszek, A.; Marycz, K. Spirulina platensis improves mitochondrial function impaired by elevated oxidative stress in adipose-derived mesenchymal stromal cells (ASCs) and intestinal epithelial cells (IECs), and enhances insulin sensitivity in equine metabolic syndrome (EMS) horses. Mar. Drugs 2017, 15, 237.
  31. Jadaun, P.; Yadav, D.; Bisen, P.S. Spirulina platensis prevents high glucose-induced oxidative stress mitochondrial damage mediated apoptosis in cardiomyoblasts. Cytotechnology 2018, 70, 523–536.
  32. Sun, J.Y.; Hou, Y.J.; Fu, X.Y.; Fu, X.T.; Ma, J.K.; Yang, M.F.; Sun, B.L.; Fan, C.D.; Oh, J. Selenium-containing protein from selenium-enriched spirulina platensis attenuates cisplatin-induced apoptosis in MC3T3-E1 Mouse preosteoblast by inhibiting mitochondrial dysfunction and ROS-Mediated oxidative damage. Front. Physiol. 2019, 9, 1907.
  33. Oriquat, G.A.; Ali, M.A.; Mahmoud, S.A.; Eid, R.M.; Hassan, R.; Kamel, M.A. Improving hepatic mitochondrial biogenesis as a postulated mechanism for the antidiabetic effect of Spirulina platensis in comparison with metformin. Appl. Physiol. Nutr. Metab. 2019, 44, 357–364.
  34. Izadi, M.; Fazilati, M. Extraction and purification of phycocyanin from spirulina platensis and evaluating its antioxidant and anti-inflammatory activity. Asian J. Green Chem. 2018, 2, 364–379.
  35. Pelizer, L.H.; Danesi, E.D.G.; de O Rangel, C.; Sassano, C.E.; Carvalho, J.C.M.; Sato, S.; Moraes, I.O. Influence of inoculum age and concentration in Spirulina platensis cultivation. J. Food Eng. 2003, 56, 371–375.
  36. Pina-Pérez, M.C.; Brück, W.M.; Brück, T.; Beyrer, M. Microalgae as healthy ingredients for functional foods. In The Role of Alternative and Innovative Food Ingredients and Products in Consumer Wellness; Elsevier: Amsterdam, The Netherlands, 2019; pp. 103–137.
  37. Uddin, A.J.; Mahbuba, S.; Rahul, S.; Ifaz, M.; Ahmad, H. Super food Spirulina (Spirulina platensis): Prospect and scopes in Bangladesh. Int. J. Bus. Soc. Sci. Res. 2018, 6, 51–55.
  38. Li Vecchi, V.; Maggi, P.; Rizzo, M.; Montalto, G. The metabolic syndrome and HIV infection. Curr. Pharm. Des. 2014, 20, 4975–5003.
  39. Aounallah, M.; Dagenais-Lussier, X.; El-Far, M.; Mehraj, V.; Jenabian, M.A.; Routy, J.P.; van Grevenynghe, J. Current topics in HIV pathogenesis, part 2: Inflammation drives a Warburg-like effect on the metabolism of HIV-infected subjects. Cytokine Growth Factor Rev. 2016, 28, 1–10.
  40. Palios, J.; Kadoglou, N.P.; Lampropoulos, S. The pathophysiology of HIV-/HAART-related metabolic syndrome leading to cardiovascular disorders: The emerging role of adipokines. Exp. Diabetes Res. 2011, 2012, 1–4.
  41. Barbaro, G.; Iacobellis, G. Metabolic syndrome associated with HIV and highly active antiretroviral therapy. Curr. Diabetes Rep. 2009, 9, 37–42.
  42. Rogalska-Płońska, M.; Grzeszczuk, A.; Rogalski, P.; Łucejko, M.; Flisiak, R. Metabolic syndrome in HIV infected adults in Poland. Kardiol. Pol. Pol. Heart J. 2018, 76, 548–553.
  43. Nguyen, K.A.; Peer, N.; Mills, E.J.; Kengne, A.P. A meta-analysis of the metabolic syndrome prevalence in the global HIV-infected population. PLoS ONE 2016, 11, e0150970.
  44. Ataro, Z.; Ashenafi, W. Metabolic syndrome and associated factors among adult HIV positive people on antiretroviral therapy in Jugal hospital, Harar, Eastern Ethiopia. East Afr. J. Health Biomed. Sci. 2020, 4, 13–24.
  45. Aiuti, F.; Mezzaroma, I. Failure to reconstitute CD4+ T-cells despite suppression of HIV replication under HAART. AIDS Rev. 2006, 8, 88–97.
  46. Turner, S. Molecular systematics of oxygenic photosynthetic bacteria. Orig. Algae Plast. 1997, 11, 13–52.
  47. Whitton, B.A. Diversity, ecology, and taxonomy of the cyanobacteria. In Photosynthetic Prokaryotes; Springer: Berlin/Heidelberg, Germany, 1992; pp. 1–51.
  48. Vonshak, A. Spirulina Platensis Arthrospira: Physiology, Cell-Biology and Biotechnology; CRC Press: Boca Raton, FL, USA, 1997.
  49. Gershwin, M.E.; Belay, A. Spirulina in Human Nutrition and Health; CRC Press: Boca Raton, FL, USA, 2007.
  50. Khan, Z.; Bhadouria, P.; Bisen, P. Nutritional and therapeutic potential of Spirulina. Curr. Pharm. Biotechnol. 2005, 6, 373–379.
  51. Karkos, P.D.; Leong, S.C.; Karkos, C.D.; Sivaji, N.; Assimakopoulos, D.A. Spirulina in clinical practice: Evidence-based human applications. Evid.-Based Complementary Altern. Med. 2011, 2011, 1–3.
  52. Ciferri, O. Spirulina, the edible microorganism. Microbiol. Rev. 1983, 47, 551.
  53. Kamata, K.; Piao, Z.; Suzuki, S.; Fujimori, T.; Tajiri, W.; Nagai, K.; Iyoda, T.; Yamada, A.; Hayakawa, T.; Ishiwara, M.; et al. Spirulina-templated metal microcoils with controlled helical structures for THz electromagnetic responses. Sci. Rep. 2014, 4, 1–7.
  54. Ali, S.K.; Saleh, A.M. Spirulina-an overview. Int. J. Pharm. Pharm. Sci. 2012, 4, 9–15.
  55. Henrikson, R. Earth Food Spirulina; Ronore Enterprises, Inc.: Laguna Beach, CA, USA, 1989; p. 187.
  56. Romay, C.; Delgado, R.; Remirez, D.; Gonzalez, R.; Rojas, A. Effects of phycocyanin extract on tumor necrosis factor-α and nitrite levels in serum of mice treated with endotoxin. Arzneimittelforschung 2001, 51, 733–736.
  57. Remirez, D.; Fernández, V.; Tapia, G.; González, R.; Videla, L.A. Influence of C-phycocyanin on hepatocellular parameters related to liver oxidative stress and Kupffer cell functioning. Inflamm. Res. 2002, 51, 351–356.
  58. Patel, A.; Mishra, S.; Ghosh, P. Antioxidant potential of C-phycocyanin isolated from cyanobacterial species Lyngbya, Phormidium and Spirulina spp. Indian J. Biochem. Biophys. 2006, 43, 25–31.
  59. Cherng, S.C.; Cheng, S.N.; Tarn, A.; Chou, T.C. Anti-inflammatory activity of c-phycocyanin in lipopolysaccharide-stimulated RAW 264.7 macrophages. Life Sci. 2007, 81, 1431–1435.
  60. Romay, C.H.; Armesto, J.; Remirez, D.; González, R.; Ledon, N.; Garcia, I. Antioxidant and anti-inflammatory properties of C-phycocyanin from blue-green algae. Inflamm. Res. 1998, 47, 36–41.
  61. Romay, C.; Ledon, N.; Gonzalez, R. Further studies on anti-inflammatory activity of phycocyanin in some animal models of inflammation. Inflamm. Res. 1998, 47, 334–338.
  62. Gonzalez, R.; Rodriguez, S.; Romay, C.; González, A.; Armesto, J.; Remirez, D.; Merino, N. Anti-inflammatory activity of phycocyanin extract in acetic acid-induced colitis in rats. Pharmacol. Res. 1999, 39, 55–59.
  63. Remirez, D.; Ledon, N.; González, R. Role of histamine in the inhibitory effects of phycocyanin in experimental models of allergic inflammatory response. Mediat. Inflamm. 2002, 11, 81–85.
  64. Romay, C.H.; Gonzalez, R.; Ledon, N.; Remirez, D.; Rimbau, V. C-phycocyanin: A biliprotein with antioxidant, anti-inflammatory and neuroprotective effects. Curr. Protein Pept. Sci. 2003, 4, 207–216.
  65. Khan, M.; Varadharaj, S.; Shobha, J.C.; Naidu, M.U.; Parinandi, N.L.; Kutala, V.K.; Kuppusamy, P. C-phycocyanin ameliorates doxorubicin-induced oxidative stress and apoptosis in adult rat cardiomyocytes. J. Cardiovasc. Pharmacol. 2006, 47, 9–20.
  66. Shih, C.M.; Cheng, S.N.; Wong, C.S.; Kuo, Y.L.; Chou, T.C. Antiinflammatory and antihyperalgesic activity of C-phycocyanin. Anesth. Analg. 2009, 108, 1303–1310.
  67. Manconia, M.; Pendás, J.; Ledón, N.; Moreira, T.; Sinico, C.; Saso, L.; Fadda, A.M. Phycocyanin liposomes for topical anti-inflammatory activity: In-vitro in-vivo studies. J. Pharm. Pharmacol. 2009, 61, 423–430.
  68. Khan, M.; Varadharaj, S.; Ganesan, L.P.; Shobha, J.C.; Naidu, M.U.; Parinandi, N.L.; Tridandapani, S.; Kutala, V.K.; Kuppusamy, P. C-phycocyanin protects against ischemia-reperfusion injury of heart through involvement of p38 MAPK and ERK signaling. Am. J. Physiol. -Heart Circ. Physiol. 2006, 290, H2136–H2145.
  69. Li, X.L.; Xu, G.; Chen, T.; Wong, Y.S.; Zhao, H.L.; Fan, R.R.; Gu, X.M.; Tong, P.C.; Chan, J.C. Phycocyanin protects INS-1E pancreatic beta cells against human islet amyloid polypeptide-induced apoptosis through attenuating oxidative stress and modulating JNK and p38 mitogen-activated protein kinase pathways. Int. J. Biochem. Cell Biol. 2009, 41, 1526–1535.
  70. Sadek, K.M.; Lebda, M.A.; Nasr, S.M.; Shoukry, M. Spirulina platensis prevents hyperglycemia in rats by modulating gluconeogenesis and apoptosis via modification of oxidative stress and MAPK-pathways. Biomed. Pharmacother. 2017, 92, 1085–1094.
  71. Schafer, F.Q.; Wang, H.P.; Kelley, E.E.; Cueno, K.L.; Buettner, S.M.A.G. Comparing β-carotene, vitamin E and nitric oxide as membrane antioxidants. Biol. Chem. 2002, 383, 671–681.
  72. Bai, S.K.; Lee, S.J.; Na, H.J.; Ha, K.S.; Han, J.A.; Lee, H.; Kwon, Y.G.; Chung, C.K.; Kim, Y.M. β-Carotene inhibits inflammatory gene expression in lipopolysaccharide-stimulated macrophages by suppressing redox-based NF-κB activation. Exp. Mol. Med. 2005, 37, 323–334.
  73. Katsuura, S.; Imamura, T.; Bando, N.; Yamanishi, R. β-Carotene and β-cryptoxanthin but not lutein evoke redox and immune changes in RAW264 murine macrophages. Mol. Nutr. Food Res. 2009, 53, 1396–1405.
  74. Strasky, Z.; Zemankova, L.; Nemeckova, I.; Rathouska, J.; Wong, R.J.; Muchova, L.; Subhanova, I.; Vanikova, J.; Vanova, K.; Vitek, L.; et al. Spirulina platensis and phycocyanobilin activate atheroprotective heme oxygenase-1: A possible implication for atherogenesis. Food Funct. 2013, 4, 1586–1594.
  75. Jensen, G.S.; Drapeau, C.; Lenninger, M.; Benson, K.F. Clinical safety of a high dose of Phycocyanin-enriched aqueous extract from Arthrospira (Spirulina) platensis: Results from a randomized, double-blind, placebo-controlled study with a focus on anticoagulant activity and platelet activation. J. Med. Food 2016, 19, 645–653.
  76. Ferruzzi, M.G.; Blakeslee, J. Digestion, absorption, and cancer preventative activity of dietary chlorophyll derivatives. Nutr. Res. 2007, 27, 1–12.
  77. Hosikian, A.; Lim, S.; Halim, R.; Danquah, M.K. Chlorophyll extraction from microalgae: A review on the process engineering aspects. Int. J. Chem. Eng. 2010, 2010, 1–10.
  78. Lucas, G.M.; Ross, M.J.; Stock, P.G.; Shlipak, M.G.; Wyatt, C.M.; Gupta, S.K.; Atta, M.G.; Wools-Kaloustian, K.K.; Pham, P.A.; Bruggeman, L.A.; et al. Clinical practice guideline for the management of chronic kidney disease in patients infected with HIV: 2014 update by the HIV Medicine Association of the Infectious Diseases Society of America. Clin. Infect. Dis. 2014, 59, e96–e138.
  79. Eggleton, J.S.; Nagalli, S. Highly Active Antiretroviral Therapy (HAART); StatPearls Publishing: Treasure Island, FL, USA, 2020.
  80. Chang, J.L.; Tsai, A.C.; Musinguzi, N.; Haberer, J.E.; Boum, Y.; Muzoora, C.; Bwana, M.; Martin, J.N.; Hunt, P.W.; Bangsberg, D.R.; et al. Depression and suicidal ideation among HIV-infected adults receiving efavirenz versus nevirapine in Uganda: A prospective cohort study. Ann. Intern. Med. 2018, 169, 146–155.
  81. Lyseng-Williamson, K.A.; Reynolds, N.A.; Plosker, G.L. Tenofovir disoproxil fumarate. Drugs 2005, 65, 413–432.
  82. Chen, Y.F.; Stampley, J.E.; Irving, B.A.; Dugas, T.R. Chronic nucleoside reverse transcriptase inhibitors disrupt mitochondrial homeostasis and promote premature endothelial senescence. Toxicol. Sci. 2019, 172, 445–456.
  83. Martin, A.M.; Nolan, D.; Gaudieri, S.; Almeida, C.A.; Nolan, R.; James, I.; Carvalho, F.; Phillips, E.; Christiansen, F.T.; Purcell, A.W.; et al. Predisposition to abacavir hypersensitivity conferred by HLA-B * 5701 and a haplotypic Hsp70-Hom variant. Proc. Natl. Acad. Sci. USA 2004, 101, 4180–4185.
  84. Kakuda, T. Pharmacology of nucleoside and nucleotide reverse transcriptase inhibitor-induced mitochondrial toxicity. Clin. Ther. 2000, 22, 685–708.
  85. Günthard, H.F.; Saag, M.S.; Benson, C.A.; Del Rio, C.; Eron, J.J.; Gallant, J.E.; Hoy, J.F.; Mugavero, M.J.; Sax, P.E.; Thompson, M.A.; et al. Antiretroviral drugs for treatment and prevention of HIV infection in adults: 2018 recommendations of the International Antiviral Society–USA Panel. JAMA 2018, 320, 379–396.
  86. Yeni, P. Update on HAART in HIV. J. Hepatol. 2006, 44, S100–S103.
  87. Eastone, J.A.; Decker, C.F. New-onset diabetes mellitus associated with use of protease inhibitor. Ann. Intern. Med. 1997, 127, 948.
  88. Soliman, E.Z.; Lundgren, J.; Roediger, M.P.; Duprez, D.A.; Temesgen, Z.; Bickel, M.; Shlay, J.C.; Somboonwit, C.; Reiss, P.; Stein, J.; et al. Boosted protease inhibitors and the electrocardiographic measures of QT and PR durations. AIDS 2011, 25, 367–377.
  89. Landovitz, R.J.; Ribaudo, H.J.; Ofotokun, I.; Na, L.H.; Godfrey, C.; Kuritzkes, D.R.; Sagar, M.; Brown, T.T.; Cohn, S.E.; McComsey, G.A.; et al. Efficacy and tolerability of 3 nonnucleoside reverse transcriptase inhibitor–sparing antiretroviral regimens for treatment-naive volunteers infected with HIV-1: A randomized, controlled equivalence trial. Ann. Intern. Med. 2014, 161, 461–471.
  90. Gutiérrez, F.; Fulladosa, X.; Barril, G.; Domingo, P. Renal tubular transporter-mediated interactions of HIV drugs: Implications for patient management. AIDS Rev. 2014, 16, 199–212.
  91. Hoffmann, C.; Welz, T.; Sabranski, M.; Kolb, M.; Wolf, E.; Stellbrink, H.J.; Wyen, C. Higher rates of neuropsychiatric adverse events leading to dolutegravir discontinuation in women and older patients. HIV Med. 2017, 18, 56–63.
  92. Fettiplace, A.; Stainsby, C.; Winston, A.; Givens, N.; Puccini, S.; Vannappagari, V.; Hsu, R.; Fusco, J.; Quercia, R.; Aboud, M.; et al. Psychiatric Symptoms in Patients Receiving Dolutegravir. JAIDS J. Acquir. Immune Defic. Syndr. 2017, 74, 423–431.
  93. Zash, R.; Makhema, J.; Shapiro, R.L. Neural-Tube Defects with Dolutegravir Treatment from the Time of Conception. N. Engl. J. Med. 2018, 379, 979–981.
  94. Schafer, J.J.; E Squires, K. Integrase Inhibitors: A Novel Class of Antiretroviral Agents. Ann. Pharmacother. 2010, 44, 145–156.
  95. Hazuda, D.J.; Felock, P.; Witmer, M.; Wolfe, A.; Stillmock, K.; Grobler, J.A.; Espeseth, A.; Gabryelski, L.; Schleif, W.; Blau, C.; et al. Inhibitors of Strand Transfer That Prevent Integration and Inhibit HIV-1 Replication in Cells. Science 2000, 287, 646–650.
  96. Hardy, H.; Skolnik, P.R. Enfuvirtide, a New Fusion Inhibitor for Therapy of Human Immunodeficiency Virus Infection. Pharmacother. J. Hum. Pharmacol. Drug Ther. 2004, 24, 198–211.
  97. Dorr, P.; Westby, M.; Dobbs, S.; Griffin, P.; Irvine, B.; Macartney, M.; Mori, J.; Rickett, G.; Smith-Burchnell, C.; Napier, C.; et al. Maraviroc (UK-427,857), a Potent, Orally Bioavailable, and Selective Small-Molecule Inhibitor of Chemokine Receptor CCR5 with Broad-Spectrum Anti-Human Immunodeficiency Virus Type 1 Activity. Antimicrob. Agents Chemother. 2005, 49, 4721–4732.
  98. Miao, M.; De Clercq, E.; Li, G. Clinical significance of chemokine receptor antagonists. Expert Opin. Drug Metab. Toxicol. 2020, 16, 11–30.
  99. De Luca, A.; Pezzotti, P.; Boucher, C.; Döring, M.; Incardona, F.; Kaiser, R.; Lengauer, T.; Pfeifer, N.; Schülter, E.; Vandamme, A.-M.; et al. Clinical use, efficacy, and durability of maraviroc for antiretroviral therapy in routine care: A European survey. PLoS ONE 2019, 14, e0225381.
  100. Shafer, R.; Vuitton, D. Highly active antiretroviral therapy (HAART) for the treatment of infection with human immunodeficiency virus type 1. Biomed. Pharmacother. 1999, 53, 73–86.
  101. Kitahata, M.M.; Koepsell, T.D.; Deyo, R.A.; Maxwell, C.L.; Dodge, W.T.; Wagner, E.H. Physicians’ experience with the acquired immunodeficiency syndrome as a factor in patients’ survival. N. Engl. J. Med. 1996, 334, 701–707.
  102. Cunningham, W.E.; Tisnado, D.M.; Lui, H.H.; Nakazono, T.T.; Carlisle, D.M. The effect of hospital experience on mortality among patients hospitalized with acquired immunodeficiency syndrome in California. Am. J. Med. 1999, 107, 137–143.
  103. Rackal, J.M.; Tynan, A.-M.; Handford, C.D.; Rzeznikiewiz, D.; Agha, A.; Glazier, R. Provider training and experience for people living with HIV/AIDS. Cochrane Database Syst. Rev. 2011, 6, CD003938.
  104. Ford, N.; Migone, C.; Calmy, A.; Kerschberger, B.; Kanters, S.; Nsanzimana, S.; Mills, E.J.; Meintjes, G.; Vitoria, M.; Doherty, M.; et al. Benefits and risks of rapid initiation of antiretroviral therapy. AIDS 2018, 32, 17–23.
  105. Group, I.S.S. Initiation of antiretroviral therapy in early asymptomatic HIV infection. N. Engl. J. Med. 2015, 373, 795–807.
  106. Thompson, M.A.; Aberg, J.A.; Hoy, J.F.; Telenti, A.; Benson, C.; Cahn, P.; Eron, J.J.; Günthard, H.F.; Hammer, S.M.; Reiss, P.; et al. Antiretroviral treatment of adult HIV infection: 2012 recommendations of the International Antiviral Society–USA panel. Jama 2012, 308, 387–402.
  107. Sax, P.E.; Tierney, C.; Collier, A.C.; Fischl, M.A.; Mollan, K.; Peeples, L.; Godfrey, C.; Jahed, N.C.; Myers, L.; Katzenstein, D.; et al. Abacavir–lamivudine versus tenofovir–emtricitabine for initial HIV-1 therapy. N. Engl. J. Med. 2009, 361, 2230–2240.
  108. Post, F.A.; Moyle, G.J.; Stellbrink, H.J.; Domingo, P.; Podzamczer, D.; Fisher, M.; Norden, A.G.; Cavassini, M.; Rieger, A.; Khuong-Josses, M.A.; et al. Randomized comparison of renal effects, efficacy, and safety with once-daily abacavir/lamivudine versus tenofovir/emtricitabine, administered with efavirenz, in antiretroviral-naive, HIV-1–infected adults: 48-week results from the ASSERT study. JAIDS J. Acquir. Immune Defic. Syndr. 2010, 55, 49–57.
  109. Glover, M.; Hebert, V.Y.; Nichols, K.; Xue, S.Y.; Thibeaux, T.M.; Zavecz, J.A.; Dugas, T.R. Overexpression of mitochondrial antioxidant manganese superoxide dismutase (MnSOD) provides protection against AZT- or 3TC-induced endothelial dysfunction. Antivir. Res. 2014, 111, 136–142.
  110. Brown, L.; Jin, J.; Ferrell, D.; Sadic, E.; Obregon, D.; Smith, A.J.; Tan, J.; Giunta, B. Efavirenz Promotes β-Secretase Expression and Increased Aβ1-40,42 via Oxidative Stress and Reduced Microglial Phagocytosis: Implications for HIV Associated Neurocognitive Disorders (HAND). PLoS ONE 2014, 9, e95500.
  111. Canale, D.; De Bragança, A.C.; Gonçalves, J.G.; Shimizu, M.H.M.; Sanches, T.R.; Andrade, L.; Volpini, R.A.; Seguro, A.C. Vitamin D Deficiency Aggravates Nephrotoxicity, Hypertension and Dyslipidemia Caused by Tenofovir: Role of Oxidative Stress and Renin-Angiotensin System. PLoS ONE 2014, 9, e103055.
  112. Venhoff, N.; Setzer, B.; Melkaoui, K.; A Walker, U. Mitochondrial Toxicity of Tenofovir, Emtricitabine and Abacavir Alone and in Combination with Additional Nucleoside Reverse Transcriptase Inhibitors. Antivir. Ther. 2007, 12, 1075–1086.
  113. Bonomini, F.; Rodella, L.F.; Rezzani, R. Metabolic Syndrome, Aging and Involvement of Oxidative Stress. Aging Dis. 2015, 6, 109–120.
  114. Dos Santos, W.; Paes, P.; dos Santos, A.; Machado, D.; Navarro, A.; Frenandes, A. Impact of progressive resistance training in Brazilian HIV patients with lipodystrophy. J. AIDS Clin. Res. 2013, 4, 2.
  115. Sharma, B. Anti-HIV-1 drug toxicity and management strategies. Neurobehav. HIV Med. 2011, 3, 27–40.
  116. Csányi, G. Oxidative Stress in Cardiovascular Disease; Multidisciplinary Digital Publishing Institute: Basel, Switzerland, 2014.
  117. McColl, D.J.; Margot, N.; Chen, S.-S.; Harris, J.; Borroto-Esoda, K.; Miller, M.D. Reduced Emergence of the M184V/I Resistance Mutation When Antiretroviral-Naïve Subjects Use Emtricitabine Versus Lamivudine in Regimens Composed of Two NRTIs Plus the NNRTI Efavirenz. HIV Clin. Trials 2011, 12, 61–70.
  118. Hong, S.Y.; Jonas, A.; DeKlerk, M.; Shiningavamwe, A.; Desta, T.; Badi, A.; Morris, L.; Hunt, G.M.; Ledwaba, J.; Sheehan, H.B.; et al. Population-Based Surveillance of HIV Drug Resistance Emerging on Treatment and Associated Factors at Sentinel Antiretroviral Therapy Sites in Namibia. JAIDS J. Acquir. Immune Defic. Syndr. 2015, 68, 463–471.
  119. Gulick, R.M.; Ribaudo, H.J.; Shikuma, C.M.; Lustgarten, S.; Squires, K.E.; Meyer, W.A., III; Acosta, E.P.; Schackman, B.R.; Pilcher, C.D.; Murphy, R.L.; et al. Triple-nucleoside regimens versus efavirenz-containing regimens for the initial treatment of HIV-1 infection. N. Engl. J. Med. 2004, 350, 1850–1861.
  120. Robbins, G.K.; De Gruttola, V.; Shafer, R.W.; Smeaton, L.M.; Snyder, S.W.; Pettinelli, C.; Dubé, M.P.; Fischl, M.A.; Pollard, R.B.; Delapenha, R.; et al. Comparison of sequential three-drug regimens as initial therapy for HIV-1 infection. N. Engl. J. Med. 2003, 349, 2293–2303.
  121. Rakhmanina, N.Y.; la Porte, C.J. Therapeutic drug monitoring of antiretroviral drugs in the management of human immunodeficiency virus infection. Ther. Drug Monit. Newer Drugs Biomark. 2012, 373, 374–389.
  122. EACS. European AIDS Clinical Society Guidelines. Amsterdam, The Netherlands, Version 6. 2011. Available online: https://www.eacsociety.org/media/2011_eacsguidelines-v6.0-english_oct.pdf (accessed on 6 December 2021).
  123. Gilks, C.F.; Crowley, S.; Ekpini, R.; Gove, S.; Perriens, J.; Souteyrand, Y.; Sutherland, D.; Vitoria, M.; Guerma, T.; De Cock, K. The WHO public-health approach to antiretroviral treatment against HIV in resource-limited settings. Lancet 2006, 368, 505–510.
  124. Kahana, S.Y.; Rohan, J.; Allison, S.; Frazier, T.W.; Drotar, D. A Meta-Analysis of Adherence to Antiretroviral Therapy and Virologic Responses in HIV-Infected Children, Adolescents, and Young Adults. AIDS Behav. 2012, 17, 41–60.
  125. Sliwa, K.; Hilfiker-Kleiner, D.; Petrie, M.C.; Mebazaa, A.; Pieske, B.; Buchmann, E.; Regitz-Zagrosek, V.; Schaufelberger, M.; Tavazzi, L.; van Veldhuisen, D.J.; et al. Current state of knowledge on aetiology, diagnosis, management, and therapy of peripartum cardiomyopathy: A position statement from the Heart Failure Association of the European Society of Cardiology Working Group on peripartum cardiomyopathy. Eur. J. Hear. Fail. 2010, 12, 767–778.
  126. Schinazi, R.F.; Lloyd, R.M.; Nguyen, M.H.; Cannon, D.L.; McMillan, A.; Ilksoy, N.; Chu, C.K.; Liotta, D.C.; Bazmi, H.Z.; Mellors, J.W. Characterization of human immunodeficiency viruses resistant to oxathiolane-cytosine nucleosides. Antimicrob. Agents Chemother. 1993, 37, 875–881.
  127. Maserati, R.; De Silvestri, A.; Uglietti, A.; Colao, G.; Di Biagio, A.; Bruzzone, B.; Di Pietro, M.; Re, M.C.; Tinelli, C.; Zazzi, M. Emerging mutations at virological failure of HAART combinations containing tenofovir and lamivudine or emtricitabine. AIDS 2010, 24, 1013–1018.
  128. Schinazi, R.F.; McMillan, A.; Cannon, D.; Mathis, R.; Lloyd, R.M.; Peck, A.; Sommadossi, J.P.; Clair, M.S.; Wilson, J.; A Furman, P. Selective inhibition of human immunodeficiency viruses by racemates and enantiomers of cis-5-fluoro-1-cytosine. Antimicrob. Agents Chemother. 1992, 36, 2423–2431.
  129. Margot, N.A.; Enejosa, J.; Cheng, A.K.; Miller, M.D.; McColl, D.J. Development of HIV-1 drug resistance through 144 weeks in antiretroviral-naive subjects on emtricitabine, tenofovir disoproxil fumarate, and efavirenz compared with lamivudine/zidovudine and efavirenz in study GS-01-934. JAIDS J. Acquir. Immune Defic. Syndr. 2009, 52, 209–221.
  130. Mugwanya, K.K.; John-Stewart, G.; Baeten, J. Safety of oral tenofovir disoproxil fumarate-based HIV pre-exposure prophylaxis use in lactating HIV-uninfected women. Expert Opin. Drug Saf. 2017, 16, 867–871.
  131. Spinner, C.D.; Boesecke, C.; Zink, A.; Jessen, H.; Stellbrink, H.J.; Rockstroh, J.K.; Esser, S. HIV pre-exposure prophylaxis (PrEP): A review of current knowledge of oral systemic HIV PrEP in humans. Infection 2016, 44, 151–158.
  132. Fonner, V.A.; Dalglish, S.L.; Kennedy, C.E.; Baggaley, R.; O’Reilly, K.R.; Koechlin, F.M.; Rodolph, M.; Hodges-Mameletzis, I.; Grant, R. Effectiveness and safety of oral HIV preexposure prophylaxis for all populations. AIDS 2016, 30, 1973–1983.
  133. Borroto-Esoda, K.; E Vela, J.; Myrick, F.; Ray, A.S.; Miller, M.D. In Vitro Evaluation of the Anti-HIV Activity and Metabolic Interactions of Tenofovir and Emtricitabine. Antivir. Ther. 2005, 11, 377–384.
  134. Carr, A.; Samaras, K.; Chisholm, D.J.; A Cooper, D. Pathogenesis of HIV-1-protease inhibitor-associated peripheral lipodystrophy, hyperlipidaemia, and insulin resistance. Lancet 1998, 351, 1881–1883.
  135. Del Valle, L.G.; Hernández, R.G.; Ávila, J.P. Oxidative stress associated to disease progression and toxicity during antiretroviral therapy in human immunodeficiency virus infection. J. Virol. Microbiol. 2013, 13, 15.
  136. Awodele, O.; O Olayemi, S.; A Nwite, J.; A Adeyemo, T. Investigation of the levels of oxidative stress parameters in HIV and HIV-TB co-infected patients. J. Infect. Dev. Ctries. 2011, 6, 79–85.
  137. Pinti, M.; Nasi, M.; Gibellini, L.; Roat, E.; De Biasi, S.; Bertoncelli, L.; Cossarizza, A. The Role of Mitochondria in HIV Infection and Its Treatment. J. Exp. Clin. Med. 2010, 2, 145–155.
  138. Mandas, A.; Iorio, E.L.; Congiu, M.G.; Balestrieri, C.; Mereu, A.; Cau, D.; Dessì, S.; Curreli, N. Oxidative Imbalance in HIV-1 Infected Patients Treated with Antiretroviral Therapy. J. Biomed. Biotechnol. 2009, 2009, 1–7.
  139. Yeligar, S.M.; Guidot, D.M.; Brown, L.A.S.; Cribbs, S.K. HIV Infection Induces NADPH Oxidase Expression in Alveolar Macrophages of Otherwise Healthy Subjects. In C55 HIV-Associated Lung Diseases and Infections; American Thoracic Society: New York, NY, USA, 2015; p. A4720.
  140. Wang, X.; Liao, D.; Lin, P.H.; Yao, Q.; Chen, C. Highly active antiretroviral therapy drugs inhibit in vitro cholesterol efflux from human macrophage-derived foam cells. Lab. Investig. 2009, 89, 1355–1363.
  141. Fernandez-Fernandez, B.; Montoya-Ferrer, A.; Sanz, A.B.; Sanchez-Niño, M.D.; Izquierdo, M.C.; Poveda, J.; Sainz-Prestel, V.; Ortiz-Martin, N.; Parra-Rodriguez, A.; Selgas, R.; et al. Tenofovir Nephrotoxicity: 2011 Update. AIDS Res. Treat. 2011, 2011, 1–11.
  142. Shafi, T.; Choi, M.; Racusen, L.; Spacek, L.; Berry, C.; Atta, M.; Fine, D. Ritonavir-induced acute kidney injury: Kidney biopsy findings and review of literature. Clin. Nephrol. 2011, 75, 60–64.
  143. Boffito, M. From concept to care: Pharmacokinetic boosting of protease inhibitors. PRN Noteb. 2004, 9, 15–18.
  144. Patel, A.K.; Ranjan, R.R.; Patel, A.R.; Patel, J.K.; Patel, K.K. Tenofovir-associated renal dysfunction in clinical practice: An observational cohort from western India. Indian J. Sex. Transm. Dis. AIDS 2010, 31, 30–34.
  145. Cao, Y.; Han, Y.; Xie, J.; Cui, Q.; Zhang, L.; Li, Y.; Li, Y.; Song, X.; Zhu, T.; Li, T. Impact of a tenofovir disoproxil fumarate plus ritonavir-boosted protease inhibitor-based regimen on renal function in HIV-infected individuals: A prospective, multicenter study. BMC Infect. Dis. 2013, 13, 301–308.
  146. Grigsby, I.F.; Pham, L.; Mansky, L.M.; Gopalakrishnan, R.; Mansky, K.C. Tenofovir-associated bone density loss. Ther. Clin. Risk Manag. 2010, 6, 41.
  147. Moss, D.M.; Neary, M.; Owen, A. The role of drug transporters in the kidney: Lessons from tenofovir. Front. Pharmacol. 2014, 5, 248.
  148. Kamble, S.P.; Gaikar, R.B.; Padalia, R.B.; Shinde, K.D. Extraction and purification of C-phycocyanin from dry Spirulina powder and evaluating its antioxidant, anticoagulation and prevention of DNA damage activity. J. Appl. Pharm. Sci. 2013, 3, 149.
  149. Nasirian, F.; Dadkhah, M.; Moradi-Kor, N.; Obeidavi, Z. Effects of Spirulina platensis microalgae on antioxidant and anti-inflammatory factors in diabetic rats. Diabetes Metab. Syndr. Obes. Targets Ther. 2018, 11, 375.
  150. Jensen, G.S.; Attridge, V.L.; Beaman, J.L.; Guthrie, J.; Ehmann, A.; Benson, K.F. Antioxidant and anti-inflammatory properties of an aqueous cyanophyta extract derived from arthrospira platensis: Contribution to bioactivities by the non-phycocyanin aqueous fraction. J. Med. Food 2015, 18, 535–541.
  151. Gunes, S.; Tamburaci, S.; Dalay, M.C.; Deliloglu Gurhan, I. In vitro evaluation of Spirulina platensis extract incorporated skin cream with its wound healing and antioxidant activities. Pharm. Biol. 2017, 55, 1824–1832.
  152. So-Armah, K.; Freiberg, M.S. HIV and Cardiovascular Disease: Update on Clinical Events, Special Populations, and Novel Biomarkers. Curr. HIV/AIDS Rep. 2018, 15, 233–244.
  153. Brouwer, E.S.; Napravnik, S.; Eron, J.J.; Stalzer, B.; Floris-Moore, M.; Simpson, R.J.; Stürmer, T. Effects of Combination Antiretroviral Therapies on the Risk of Myocardial Infarction Among HIV Patients. Epidemiology 2014, 25, 406–417.
  154. McCarty, M.F. ‘‘Iatrogenic Gilbert syndrome’’–A strategy for reducing vascular and cancer risk by increasing plasma unconjugated bilirubin. Med. Hypotheses 2007, 69, 974–994.
  155. Chamorro, G.; Pérez-Albiter, M.; Serrano-García, N.; Mares-Sámano, J.J.; Rojas, P. Spirulina maxima pretreatment partially protects against 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine neurotoxicity. Nutr. Neurosci. 2006, 9, 207–212.
  156. Lima, F.A.V.; Joventino, I.P.; Joventino, F.P.; de Almeida, A.C.; Neves, K.R.T.; do Carmo, M.R.; Leal, L.K.A.M.; de Andrade, G.M.; de Barros Viana, G.S. Neuroprotective activities of Spirulina platensis in the 6-OHDA model of Parkinson’s disease are related to its anti-inflammatory effects. Neurochem. Res. 2017, 42, 3390–3400.
  157. Chu, W.L.; Lim, Y.W.; Radhakrishnan, A.K.; Lim, P.E. Protective effect of aqueous extract from Spirulina platensis against cell death induced by free radicals. BMC Complementary Altern. Med. 2010, 10, 1–8.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.
Upload a video for this entry
Information
Subjects: Nutrition & Dietetics
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
Thabani Sibiya
,
Terisha Ghazi
,
Anil Chuturgoon
View Times: 711
Revisions: 2 times (View History)
Update Date: 01 Sep 2022
Table of Contents
    1000/1000
    Hot Most Recent
    Academic Video Service
    Feedback