Aikeqing Decreases Viral Loads in SHIV89.6-infected Chinese Rhesus Macaques

Overview

Journal Chin Med

Publisher Biomed Central

Specialty Biomedical Engineering

Date 2016 Jul 5

PMID 27375770

Authors

Gao-Hong Zhang

Jian-Bao Han

Lin Zhu

Rong-Hua Luo

Xi-He Zhang

Xin Chen

Ying-Jie Hu

Lin-Chun Fu

Yong-Tang Zheng

Affiliations

Soon will be listed here.

Abstract

Background: Aikeqing (AKQ) has been shown in clinical studies to improve quality of life of HIV/AIDS patients, but anti-HIV activity has not been determined. The SHIV-infected macaque is an important animal model for testing antiviral drugs. This study aimed to determine the anti-HIV activity of AKQ in chronically SHIV89.6-infected Chinese rhesus macaques.

Methods: Nine Chinese rhesus macaques were inoculated intravenously with SHIV89.6 virus. At 11 weeks post-infection, the animals were arbitrarily divided into three groups: high-dose (AKQ 1.65 g/kg; n = 3), low-dose (AKQ 0.55 g/kg; n = 3), and control (water 1 mL/kg; n = 3). Treatment was administered by the intragastric gavage route once-daily for 8 weeks. Blood (5 mL) was collected biweekly. Viral loads were analyzed by real-time quantitative RT-PCR assays, and T cell counts were monitored by FACS analyses throughout the treatment.

Results: AKQ induced a persistent decline (P = 0.02) in plasma viral loads during treatment in the high-dose group compared with their baseline levels, and cessation of the therapy caused viral load rebound to the pretreatment levels. No significant difference (P = 0.06) was found in the plasma viral loads during treatment in the low-dose group. The CD4(+) T cell counts and CD4/CD8 ratios remained at stable high levels during the treatment period.

Conclusion: AKQ reduced plasma viral loads in the SHIV89.6-infected Chinese rhesus macaque model.

References

Weber R, Christen L, Loy M, Schaller S, Christen S, JOYCE C . Randomized, placebo-controlled trial of Chinese herb therapy for HIV-1-infected individuals. J Acquir Immune Defic Syndr. 1999; 22(1):56-64. DOI: 10.1097/00042560-199909010-00007. View

Tang X, Chen H, Zhang X, Quan K, Sun M . Screening anti-HIV Chinese materia medica with HIV and equine infectious anemic virus reverse transcriptase. J Tradit Chin Med. 1994; 14(1):10-3. View

Liu X, Han Y, Peng K, Liu Y, Li J, Liu H . Effect of traditional Chinese medicinal herbs on Candida spp. from patients with HIV/AIDS. Adv Dent Res. 2011; 23(1):56-60. DOI: 10.1177/0022034511399286. View

Zou W, Liu Y, Wang J, Li H, Liao X . Traditional Chinese Herbal Medicines for Treating HIV Infections and AIDS. Evid Based Complement Alternat Med. 2013; 2012:950757. PMC: 3545408. DOI: 10.1155/2012/950757. View

Xia H, Zhang G, Ma J, Dai Z, Li S, Han J . Dendritic cell subsets dynamics and cytokine production in SIVmac239-infected Chinese rhesus macaques. Retrovirology. 2010; 7:102. PMC: 3003241. DOI: 10.1186/1742-4690-7-102. View

Heredia A, Natesan S, Le N, Medina-Moreno S, Zapata J, Reitz M . Indirubin 3'-monoxime, from a Chinese traditional herbal formula, suppresses viremia in humanized mice infected with multidrug-resistant HIV. AIDS Res Hum Retroviruses. 2014; 30(5):403-6. PMC: 4010160. DOI: 10.1089/aid.2013.0249. View

Castagna A, Galli L, Torti C, Monforte A, Mussini C, Antinori A . Predicting the magnitude of short-term CD4+ T-cell recovery in HIV-infected patients during first-line highly active antiretroviral therapy. Antivir Ther. 2010; 15(2):165-75. DOI: 10.3851/IMP1513. View

Helleberg M, Kronborg G, Larsen C, Pedersen G, Pedersen C, Obel N . CD4 decline is associated with increased risk of cardiovascular disease, cancer, and death in virally suppressed patients with HIV. Clin Infect Dis. 2013; 57(2):314-21. DOI: 10.1093/cid/cit232. View

Mothe B, Southwood S, Sidney J, English A, Wriston A, Hoof I . Peptide-binding motifs associated with MHC molecules common in Chinese rhesus macaques are analogous to those of human HLA supertypes and include HLA-B27-like alleles. Immunogenetics. 2013; 65(5):371-86. PMC: 3633659. DOI: 10.1007/s00251-013-0686-9. View

10.

Nelson A, Zhang X, Ganapathi U, Szekely Z, Flexner C, Owen A . Drug delivery strategies and systems for HIV/AIDS pre-exposure prophylaxis and treatment. J Control Release. 2015; 219:669-680. PMC: 4879940. DOI: 10.1016/j.jconrel.2015.08.042. View

11.

Tornqvist E, Annas A, Granath B, Jalkesten E, Cotgreave I, Oberg M . Strategic focus on 3R principles reveals major reductions in the use of animals in pharmaceutical toxicity testing. PLoS One. 2014; 9(7):e101638. PMC: 4108312. DOI: 10.1371/journal.pone.0101638. View

12.

Ono K, Nakane H, Fukushima M, Chermann J, Barre-Sinoussi F . Differential inhibitory effects of various flavonoids on the activities of reverse transcriptase and cellular DNA and RNA polymerases. Eur J Biochem. 1990; 190(3):469-76. DOI: 10.1111/j.1432-1033.1990.tb15597.x. View

13.

Zhou Y, Bao R, Haigwood N, Persidsky Y, Ho W . SIV infection of rhesus macaques of Chinese origin: a suitable model for HIV infection in humans. Retrovirology. 2013; 10:89. PMC: 3765527. DOI: 10.1186/1742-4690-10-89. View

14.

Deeks S . Immune dysfunction, inflammation, and accelerated aging in patients on antiretroviral therapy. Top HIV Med. 2009; 17(4):118-23. View

15.

Ling B, Veazey R, Luckay A, Penedo C, Xu K, Lifson J . SIV(mac) pathogenesis in rhesus macaques of Chinese and Indian origin compared with primary HIV infections in humans. AIDS. 2002; 16(11):1489-96. DOI: 10.1097/00002030-200207260-00005. View

16.

Burack J, Cohen M, Hahn J, Abrams D . Pilot randomized controlled trial of Chinese herbal treatment for HIV-associated symptoms. J Acquir Immune Defic Syndr Hum Retrovirol. 1996; 12(4):386-93. DOI: 10.1097/00042560-199608010-00009. View

17.

Serrano-Villar S, Gutierrez C, Vallejo A, Hernandez-Novoa B, Diaz L, Abad Fernandez M . The CD4/CD8 ratio in HIV-infected subjects is independently associated with T-cell activation despite long-term viral suppression. J Infect. 2012; 66(1):57-66. DOI: 10.1016/j.jinf.2012.09.013. View

18.

Ling B, Rogers L, Johnson A, Piatak M, Lifson J, Veazey R . Effect of combination antiretroviral therapy on Chinese rhesus macaques of simian immunodeficiency virus infection. AIDS Res Hum Retroviruses. 2013; 29(11):1465-74. PMC: 3809389. DOI: 10.1089/AID.2012.0378. View

19.

Takuva S, Maskew M, Brennan A, Long L, Sanne I, Fox M . Poor CD4 recovery and risk of subsequent progression to AIDS or death despite viral suppression in a South African cohort. J Int AIDS Soc. 2014; 17:18651. PMC: 3942566. DOI: 10.7448/IAS.17.1.18651. View

20.

Persidsky Y, Limoges J . HIV-1 infection: new treatment paradigms. Eur J Clin Invest. 2001; 31(3):190-2. DOI: 10.1046/j.1365-2362.2001.00805.x. View