Is HIV drug resistance a limiting factor in the development of anti-HIV NNRTI and NRTI-based vaginal microbicide strategies?

被引:30
作者
Martinez, Jorge
Coplan, Paul
Wainberg, Mark A.
机构
[1] McGill Univ, AIDS Ctr, Lady Davis Inst Med Res, Jewish Gen Hosp, Montreal, PQ H3T 1E1, Canada
[2] IPM, Silver Spring, MD USA
关键词
HIV drug resistance; microbicides; NNRTIs; NRTIs;
D O I
10.1016/j.antiviral.2006.05.013
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Antiviral drugs that act at specific sites within the HIV life cycle have important rationale for development as anti-HIV microbicides. However, to be effective, such drugs must act by directly interfering with viral enzymatic function and eliminate the ability of HIV to mediate infection. Compounds that are developed as microbicides must have high potency, and should ideally not be well absorbed from the vaginal cavity in order to minimize any potential problems of drug resistance. Such compounds should also be active over long periods of time and should be able to be combined with other active agents, in order to promote the concept of synergy, such as that which has been demonstrated in HIV therapeutic studies. (c) 2006 Elsevier B.V. All rights reserved.
引用
收藏
页码:343 / 350
页数:8
相关论文
共 57 条
[31]   Effects of drug resistance on viral load in patients failing antiretroviral therapy [J].
Machouf, N ;
Thomas, R ;
Nguyen, VK ;
Trottier, B ;
Boulassel, MR ;
Wainberg, MA ;
Routy, JP .
JOURNAL OF MEDICAL VIROLOGY, 2006, 78 (05) :608-613
[32]  
MARTINSON N, 2004, 11 C RETR OPP INF SA, V91
[33]   The L74V mutation in human immunodeficiency virus type 1 reverse transcriptase counteracts enhanced excision of zidovudine monophosphate associated with thymidine analog resistance mutations [J].
Miranda, LR ;
Götte, M ;
Liang, F ;
Kuritzkes, DR .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2005, 49 (07) :2648-2656
[34]  
MORRIS L, 2004, 15 INT AIDS C BANGK, P238
[35]  
MOYLE G, 2005, ENTRY J VIRAL ENTRY, P2
[36]   Intravaginal practices, bacterial vaginosis, and women's susceptibility to HIV infection: epidemiological evidence and biological mechanisms [J].
Myer, L ;
Kuhn, L ;
Stein, ZA ;
Wright, TC ;
Denny, L .
LANCET INFECTIOUS DISEASES, 2005, 5 (12) :786-794
[37]   Intravaginal practices, HIV and other sexually transmitted diseases among South African women [J].
Myer, L ;
Denny, L ;
De Souza, M ;
Barone, MA ;
Wright, TC ;
Kuhn, L .
SEXUALLY TRANSMITTED DISEASES, 2004, 31 (03) :174-179
[38]   Genotypic analysis of the protease and reverse transcriptase of HIV type 1 subtype C isolates from antiretroviral drug-naive adults in Malawi [J].
Petch, LA ;
Hoffman, IF ;
Jere, CS ;
Kazembe, PN ;
Martinson, FE ;
Chilongozi, D ;
Fiscus, SA ;
Cohen, MS .
AIDS RESEARCH AND HUMAN RETROVIRUSES, 2005, 21 (09) :799-805
[39]  
Petrella Marco, 2002, AIDS Reviews, V4, P224
[40]   Viral load and heterosexual transmission of human immunodeficiency virus type 1 [J].
Quinn, TC ;
Wawer, MJ ;
Sewankambo, N ;
Serwadda, D ;
Li, CJ ;
Wabwire-Mangen, F ;
Meehan, MO ;
Lutalo, T ;
Gray, RH .
NEW ENGLAND JOURNAL OF MEDICINE, 2000, 342 (13) :921-929