Balzarini Jan, Schols Dominique
Department of Microbiology and Immunology, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.
Curr HIV Res. 2012 Jan 1;10(1):53-60. doi: 10.2174/157016212799304652.
Tenofovir, a highly prescribed drug for the treatment of HIV/AIDS infections, has recently also shown its effectiveness as a potential topical microbicide drug in the prevention of HIV transmission. Here, we discuss the combination of tenofovir with various other antiretrovirals (ARV) highlighting the large class of carbohydrate-binding agents (CBAs) targeting the glycans on the viral envelope gp120 for their anti-HIV activity and their favorable combinatory potential. The tenofovir/CBA and several other ARV combinations consistently showed synergistic antiviral activities. Also combinations of other classes of ARV such as receptor (i.e. CD4, CXCR4 and CCR5) inhibitors, various monoclonal antibodies (mAbs) directed against the HIV envelope gp120 and HIV gp41 inhibitors were demonstrated to have synergistic anti-HIV effects. Moreover, certain antimetabolite drugs that show limited, if any, anti-HIV activity when administered as a single drug, can potentiate the antiviral activity of anti-HIV nucleoside analogues (NRTIs) by creating a beneficial metabolic and/or competitive advantage for the combined NRTIs. Thus, well-defined combinations of ARV may synergize and/or enhance the antiviral potency of the individual drugs and should be envisioned in the design of future microbicide studies. Recently, drugs such as tenofovir and acyclovir were demonstrated to be endowed with a dual (concomitant) antiviral (i.e. anti-HIV/HSV) activity in different in vitro, ex vivo and animal models. They also deserve special attention for their potential to prevent HIV transmission and to concomitantly suppress co-pathogens of HIV such as herpes viruses.
替诺福韦是一种治疗艾滋病毒/艾滋病感染的高处方药物，最近还显示出其作为一种潜在的局部杀菌剂在预防艾滋病毒传播方面的有效性。在此，我们讨论替诺福韦与各种其他抗逆转录病毒药物（ARV）的联合使用，重点介绍一大类针对病毒包膜糖蛋白gp120上聚糖的碳水化合物结合剂（CBA）的抗艾滋病毒活性及其良好的联合潜力。替诺福韦/CBA以及其他几种ARV组合始终显示出协同抗病毒活性。其他类别的ARV组合，如受体（即CD4、CXCR4和CCR5）抑制剂、针对艾滋病毒包膜糖蛋白gp120的各种单克隆抗体（mAb）和艾滋病毒gp41抑制剂，也被证明具有协同抗艾滋病毒作用。此外，某些抗代谢药物单独使用时抗艾滋病毒活性有限（如果有的话），但通过为联合使用的核苷类逆转录酶抑制剂（NRTIs）创造有益的代谢和/或竞争优势，可以增强其抗病毒活性。因此，明确的ARV组合可能会协同和/或增强单个药物的抗病毒效力，在未来杀菌剂研究的设计中应予以考虑。最近，在不同的体外、离体和动物模型中，替诺福韦和阿昔洛韦等药物被证明具有双重（伴随）抗病毒（即抗艾滋病毒/单纯疱疹病毒）活性。它们在预防艾滋病毒传播以及同时抑制艾滋病毒的共病原体（如疱疹病毒）方面的潜力也值得特别关注。
