The sensitivity of transmitted/founder HIV-1 to anti-HIV drugs

DING Ji-wei1 ZHAO Jian-yuan1,2,3 MI Ze-yun1 WEI Tao3 CEN Shan1

(1.Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China 100050)
(2.College of Arts and Science of Beijing Union University, Beijing, China 100050)
(3.College of Arts and Science of Beijing Union University, Beijing, China 100192)

【Abstract】The majority of mucosal HIV-1 infection is initially established by a few HIV-1 viral variants, followed by the development of overt systemic infection, and these viral variants are known as transmitted/founder viruses (T/F viruses). Investigation of the sensitivity of T/F virus to different anti-HIV-1 drugs will provide the best strategies of pre-exposure prophylaxis (Pr EP) for high-risk groups of HIV-infected patients. Herein we constructed for the first time, a luciferase reporter system for HIV-1 T/F viruses, and then compared the drug sensitivity between T/F viruses and chronic infection virus. The result showed that the 50% inhibitory concentration (IC50) of nucleoside reverse transcriptase inhibitors (NRTIs), integrase inhibitors (INIs) and protease inhibitors (PIs) were not significantly different between the T/F viruses and chronic infection viruses of the same subtype (P > 0.05), while non-nucleoside reverse transcriptase inhibitors (NNRTIs) showed a moderate resistance to T/F viruses, with a significant increase in IC50 (P < 0.05). The conclusion suggests that when patients are in high-risk or in the acute infection of HIV-1, NNRTIs should be avoided in the first-line antiretroviral therapy regimens.

【Keywords】 HIV-1; pre-exposure prophylaxis; founder virus; reporter gene; anti-HIV drug;


【Funds】 National Natural Science Foundation of China—Fund Project of Canada Institute of Health Research (CHR) Research Fund Project (81361128017).

Download this article


    [1]Barré-Sinoussi F, Chermann JC, Rey F, et al. Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome(AIDS)[J]. Science, 1983, 220: 868-871.

    [2]Lu XF, Chen ZW. The development of anti-HIV-1 drugs[J]. Acta Pharm Sin(药学学报), 2010, 45: 165-176. (in Chinese)

    [3]Shaw GM, Hunter E. HIV transmission[J]. Cold Spring Harb Perspect Med, 2012, 2: a006965.

    [4]Ramana LN, Anand AR, Sethuraman S, et al. Targeting strategies for delivery of anti-HIV drugs[J]. J Control Release, 2014, 192: 271-283.

    [5]Han Y, Wind-Rotolo M, Yang HC, et al. Experimental approaches to the study of HIV-1 latency[J]. Nat Rev Microbiol, 2007, 5: 95-106.

    [6]Serrao E, Odde S, Ramkumar K, et al. Raltegravir, elvitegravir, and metoogravir: the birth of“me-too”HIV-1 integrase inhibitors[J]. Retrovirology, 2009, 6: 25.

    [7]Neff CP, Ndolo T, Tandon A, et al. Oral pre-exposure prophylaxis by anti-retrovirals raltegravir and maraviroc protects against HIV-1 vaginal transmission in a humanized mouse model[J]. PLo S One, 2010, 5: e15257.

    [8]Massud I, Aung W, Martin A, et al. Lack of prophylactic efficacy of oral maraviroc in macaques despite high drug concentrations in rectal tissues[J]. J Virol, 2013, 87: 8952-8961.

    [9]Veselinovic M, Yang KH, Le Cureux J, et al. HIV pre-exposure prophylaxis: mucosal tissue drug distribution of RT inhibitor tenofovir and entry inhibitor maraviroc in a humanized mouse model[J]. Virology, 2014, 464-465: 253-263.

    [10]Keele BF. Identifying and characterizing recently transmitted viruses[J]. Curr Opin HIV AIDS, 2010, 5: 327-334.

    [11]Salazar-Gonzalez JF, Bailes E, Pham KT, et al. Deciphering human immunodeficiency virus type 1 transmission and early envelope diversification by single-genome amplification and sequencing[J]. J Virol, 2008, 82: 3952-3970.

    [12]Sagar M, Laeyendecker O, Lee S, et al. Selection of HIV variants with signature genotypic characteristics during heterosexual transmission[J]J Infect Dis, 2009, 199: 580-589.

    [13]Salazar-Gonzalez JF, Salazar MG, Keele BF, et al. Genetic identity, biological phenotype, and evolutionary pathways of transmitted/founder viruses in acute and early HIV-1 infection[J]. J Exp Med, 2009, 206: 1273-1289.

This Article



Vol 51, No. 03, Pages 367-372

March 2016


Article Outline


  • Materials and methods
  • Results
  • Discussion
  • References