Top

AIDS Research and Therapy

Published in:

Open Access 01-12-2014 | Short report

Prophylactic and therapeutic effect of AZT/3TC in RT-SHIV infected Chinese-origin rhesus macaques

Authors: Wei Wang, Nan Yao, Zhe Cong, Hong Jiang, Chuan Qin, Qiang Wei

Published in: AIDS Research and Therapy | Issue 1/2014

Abstract

Background

The precise efficacy of nucleoside analogue reverse-transcriptase inhibitors (NRTIs) in preventing and inhibiting virus replication remains unknown in RT-SHIV infected Chinese-origin rhesus macaques (Ch RM).

Findings

Ch RM were inoculated intravenously with 200 TCID₅₀ RT-SHIV and treated by gavage with NRTIs (20 mg AZT and 10 mg 3TC twice per day) for four consecutive weeks beginning at one hour, on day 217 or 297 post inoculation, respectively. Treatment with AZT/3TC inhibited transiently RT-SHIV replication during chronic infection, but did not significantly affect peripheral blood CD4⁺ T cells in macaques. Treatment with AZT/3TC at 1 hour post infection prevented RT-SHIV infection in two out of four animals during the 120-day observation period.

Conclusions

Therefore, the Ch RM model with RT-SHIV infection can be used to evaluate the efficacy of new NRTIs.

Available only for authorised users

Jiang Y, Tian B, Saifuddin M, Agy MB, Emau P, Cairns JS, Tsai CC: RT-SHIV, an infectious CCR5-tropic chimeric virus suitable for evaluating HIV reverse transcriptase inhibitors in macaque models. AIDS Res Ther. 2009, 6: 23- 10.1186/1742-6405-6-23PubMedCentralCrossRefPubMed

Walker BD, Ahmed R, Plotkin S: Moving ahead an HIV vaccine: use both arms to beat HIV. Nat Med. 2011, 17: 1194-1195. 10.1038/nm.2529CrossRefPubMed

Hatziioannou T, Evans DT: Animal models for HIV/AIDS research. Nat Rev Microbiol. 2012, 10: 852-867. 10.1038/nrmicro2911PubMedCentralCrossRefPubMed

Balzarini J, Weeger M, Camarasa MJ, De Clercq E, Uberla K: Sensitivity/resistance profile of a simian immunodeficiency virus containing the reverse transcriptase gene of human immunodeficiency virus type 1 (HIV-1) toward the HIV-1-specific non-nucleoside reverse transcriptase inhibitors. Biochem Biophys Res Commun. 1995, 211: 850-856. 10.1006/bbrc.1995.1890CrossRefPubMed

Soderberg K, Denekamp L, Nikiforow S, Sautter K, Desrosiers RC, Alexander L: A nucleotide substitution in the tRNA(Lys) primer binding site dramatically increases replication of recombinant simian immunodeficiency virus containing a human immunodeficiency virus type 1 reverse transcriptase. J Virol. 2002, 76: 5803-5806. 10.1128/JVI.76.11.5803-5806.2002PubMedCentralCrossRefPubMed

Ambrose Z, Boltz V, Palmer S, Coffin JM, Hughes SH, Kewalramani VN: In vitro characterization of a simian immunodeficiency virus-human immunodeficiency virus (HIV) chimera expressing HIV type 1 reverse transcriptase to study antiviral resistance in pigtail macaques. J Virol. 2004, 78: 13553-13561. 10.1128/JVI.78.24.13553-13561.2004PubMedCentralCrossRefPubMed

Portsmouth SD, Scott CJ: The renaissance of fixed dose combinations: combivir. Ther Clin Risk Manag. 2007, 3: 579-583.PubMedCentralPubMed

Panlilio AL, Cardo DM, Grohskopf LA, Heneine W, Ross CS: Updated U.S. Public Health Service guidelines for the management of occupational exposures to HIV and recommendations for postexposure prophylaxis. MMWR Recomm Rep. 2005, 54: 1-17.PubMed

Shao W, Kearney M, Maldarelli F, Mellors JW, Stephens RM, Lifson JD, KewalRamani VN, Ambrose Z, Coffin JM, Palmer SE: RT-SHIV subpopulation dynamics in infected macaques during anti-HIV therapy. Retrovirology. 2009, 6: 101- 10.1186/1742-4690-6-101PubMedCentralCrossRefPubMed

10.

Cole AM, Patton DL, Rohan LC, Cole AL, Cosgrove-Sweeney Y, Rogers NA, Ratner D, Sassi AB, Lackman-Smith C, Tarwater P, Ramratnam B, Ruchala P, Lehrer RI, Waring AJ, Gupta P: The formulated microbicide RC-101 was safe and antivirally active following intravaginal application in pigtailed macaques. PLoS One. 2010, 5: e15111- 10.1371/journal.pone.0015111PubMedCentralCrossRefPubMed

11.

Pal R, Nuttall J, Galmin L, Weiss D, Chung HK, Romano J: Characterization of vaginal transmission of a simian human immunodeficiency virus (SHIV) encoding the reverse transcriptase gene from HIV-1 in Chinese rhesus macaques. Virology. 2009, 386: 102-108. 10.1016/j.virol.2009.01.002CrossRefPubMed

12.

Joag SV, Stephens EB, Adams RJ, Foresman L, Narayan O: Pathogenesis of SIVmac infection in Chinese and Indian rhesus macaques: effects of splenectomy on virus burden. Virology. 1994, 200: 436-446. 10.1006/viro.1994.1207CrossRefPubMed

13.

Marthas ML, Lu D, Penedo MC, Hendrickx AG, Miller CJ: Titration of an SIVmac251 stock by vaginal inoculation of Indian and Chinese origin rhesus macaques: transmission efficiency, viral loads, and antibody responses. AIDS Res Hum Retroviruses. 2001, 17: 1455-1466. 10.1089/088922201753197123PubMedCentralCrossRefPubMed

14.

Uberla K, Stahl-Hennig C, Bottiger D, Matz-Rensing K, Kaup FJ, Li J, Haseltine WA, Fleckenstein B, Hunsmann G, Oberg B: Animal model for the therapy of acquired immunodeficiency syndrome with reverse transcriptase inhibitors. Proc Natl Acad Sci U S A. 1995, 92: 8210-8214. 10.1073/pnas.92.18.8210PubMedCentralCrossRefPubMed

15.

North TW, Van Rompay KK, Higgins J, Matthews TB, Wadford DA, Pedersen NC, Schinazi RF: Suppression of virus load by highly active antiretroviral therapy in rhesus macaques infected with a recombinant simian immunodeficiency virus containing reverse transcriptase from human immunodeficiency virus type 1. J Virol. 2005, 79: 7349-7354. 10.1128/JVI.79.12.7349-7354.2005PubMedCentralCrossRefPubMed

16.

Le Grand R, Vaslin B, Larghero J, Neidez O, Thiebot H, Sellier P, Clayette P, Dereuddre-Bosquet N, Dormont D: Post-exposure prophylaxis with highly active antiretroviral therapy could not protect macaques from infection with SIV/HIV chimera. AIDS. 2000, 14: 1864-1866. 10.1097/00002030-200008180-00029CrossRefPubMed

17.

Yoshimura K, Ido E, Akiyama H, Kimura T, Aoki M, Suzuki H, Mitsuya H, Hayami M, Matsushita S: The impact of highly active antiretroviral therapy by the oral route on the CD8 subset in monkeys infected chronically with SHIV 89.6P. J Virol Methods. 2003, 112: 121-128. 10.1016/S0166-0934(03)00201-5CrossRefPubMed

18.

Xue J, Cong Z, Xiong J, Wang W, Jiang H, Chen T, Wu F, Liu K, Su A, Ju B, Chen Z, Couto MA, Wei Q, Qin C: Repressive effect of primary virus replication on superinfection correlated with gut-derived central memory CD4(+) T cells in SHIV-infected Chinese rhesus macaques. PLoS One. 2013, 8: e72295- 10.1371/journal.pone.0072295PubMedCentralCrossRefPubMed

19.

Ambrose Z, Palmer S, Boltz VF, Kearney M, Larsen K, Polacino P, Flanary L, Oswald K, Piatak M, Smedley J, Shao W, Bischofberger N, Maldarelli F, Kimata JT, Mellors JW, Hu SL, Coffin JM, Lifson JD, KewalRamani VN: Suppression of viremia and evolution of human immunodeficiency virus type 1 drug resistance in a macaque model for antiretroviral therapy. J Virol. 2007, 81: 12145-12155. 10.1128/JVI.01301-07PubMedCentralCrossRefPubMed

20.

Burdo TH, Marcondes MC, Lanigan CM, Penedo MC, Fox HS: Susceptibility of Chinese rhesus monkeys to SIV infection. AIDS. 2005, 19: 1704-1706. 10.1097/01.aids.0000186823.76230.33CrossRefPubMed

21.

Landovitz RJ, Currier JS: Clinical practice. Postexposure prophylaxis for HIV infection. N Engl J Med. 2009, 361: 1768-1775. 10.1056/NEJMcp0904189CrossRefPubMed

Title: Prophylactic and therapeutic effect of AZT/3TC in RT-SHIV infected Chinese-origin rhesus macaques
Authors: Wei Wang
Nan Yao
Zhe Cong
Hong Jiang
Chuan Qin
Qiang Wei
Publication date: 01-12-2014
Publisher: BioMed Central
Published in: AIDS Research and Therapy / Issue 1/2014
Electronic ISSN: 1742-6405
DOI: https://doi.org/10.1186/1742-6405-11-12

ACC 2024 Congress Coverage

Heart Failure Video

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Prophylactic and therapeutic effect of AZT/3TC in RT-SHIV infected Chinese-origin rhesus macaques

Abstract

Background

Findings

Conclusions

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Findings

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2014

The development of simple anthropometric measures to diagnose antiretroviral therapy-associated lipodystrophy in resource limited settings

The D-amino acid peptide D3 reduces amyloid fibril boosted HIV-1 infectivity

Brain biopsy in AIDS patients: diagnostic yield and treatment applications

Cobicistat-boosted darunavir in HIV-1-infected adults: week 48 results of a Phase IIIb, open-label single-arm trial

Highlights from the 2014 International Symposium on HIV & Emerging Infectious Diseases (ISHEID): from cART management to the end of the HIV pandemic

Influence of providers and nurses on completion of non-targeted HIV screening in an urgent care setting

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page