Hoffman V F, Skiest D J
Department of Pharmacy, Parkland Health and Hospital System, 5201 Harry Hines, Boulevard, Dallas, TX 75235, USA.
Expert Opin Investig Drugs. 2000 Feb;9(2):207-20. doi: 10.1517/13543784.9.2.207.
The incidence of cytomegalovirus (CMV) retinitis in AIDS has declined significantly due to the use of highly active antiretroviral therapy (HAART). However, patients with HIV, especially those failing HAART, may still suffer with CMV retinitis, which can lead to significant loss of vision and blindness. Ganciclovir has traditionally been considered the recommended treatment for CMV retinitis; however, due to side effects and the possibility of developing viral resistance, other agents may be preferred in certain situations. Foscarnet, which has similar efficacy to ganciclovir but a different side effect profile, is more difficult to administer and is less well-tolerated. Intravenous cidofovir, which may be more effective than either iv. ganciclovir or foscarnet, can also be used as a first line agent; however, it is associated with toxicity (renal and ocular) and thus needs careful use. Local therapy for CMV retinitis has been a significant advance. The intraocular ganciclovir implant has the highest efficacy of the approved agents and is well-tolerated. Fomivirsen, an oligonucleotide injected intravitreally, is a newly approved agent which offers alternative treatment. Intravitreal ganciclovir or foscarnet, although not approved, have been used successfully in some patients especially those with recurrent or refractory disease. The development of new anti-CMV agents has been stalled by the decreased incidence of the disease. Valganciclovir, a prodrug of ganciclovir, offers excellent oral bioavailability and is the closest to approval of all the new anti-CMV drugs. High ganciclovir blood levels are achieved without the complications associated with the requirement for long-term iv. access. The monoclonal antibody (mAb) MSL-109, did not offer a significant advantage when added to traditional anti-CMV therapy. Development plans of other agents such as cyclic HPMPC and lobucavir have been put on hold by their respective manufacturers. Adefovir is a nucleotide analogue that possesses anti-CMV activity, but is currently only being pursued for the treatment of hepatitis B virus. Other compounds possessing significant anti-CMV activity, including BAY 38-4766 and GW1263W94 are still in the early stages of development.
由于使用高效抗逆转录病毒疗法（HAART），艾滋病患者中巨细胞病毒（CMV）视网膜炎的发病率已显著下降。然而，HIV患者，尤其是那些HAART治疗失败的患者，仍可能患有CMV视网膜炎，这可能导致严重的视力丧失和失明。传统上，更昔洛韦一直被认为是CMV视网膜炎的推荐治疗药物；然而，由于副作用以及产生病毒耐药性的可能性，在某些情况下可能更倾向于使用其他药物。膦甲酸钠与更昔洛韦疗效相似，但副作用不同，给药更困难，耐受性也较差。静脉注射西多福韦可能比静脉注射更昔洛韦或膦甲酸钠更有效，也可作为一线药物使用；然而，它与毒性（肾脏和眼部）有关，因此需要谨慎使用。CMV视网膜炎的局部治疗是一项重大进展。眼内植入更昔洛韦在已获批药物中疗效最高，耐受性良好。福米韦生是一种经玻璃体内注射的寡核苷酸，是一种新获批的药物，提供了替代治疗方法。玻璃体内注射更昔洛韦或膦甲酸钠虽未获批，但已在一些患者中成功使用，尤其是那些复发性或难治性疾病患者。由于该疾病发病率的下降，新的抗CMV药物的研发已陷入停滞。缬更昔洛韦是更昔洛韦的前体药物，具有出色的口服生物利用度，是所有新的抗CMV药物中最接近获批的。无需长期静脉通路即可达到高更昔洛韦血药浓度，且无相关并发症。单克隆抗体（mAb）MSL-109在添加到传统抗CMV治疗中时并未显示出显著优势。其他药物如环状HPMPC和洛布卡韦的研发计划已被各自的制造商搁置。阿德福韦是一种具有抗CMV活性的核苷酸类似物，但目前仅用于治疗乙型肝炎病毒。其他具有显著抗CMV活性的化合物，包括BAY 38-4766和GW1263W94仍处于研发早期阶段。
