Long-Acting HIV Therapy for Injection Drug Users

描述(申请人提供)：联合抗逆转录病毒疗法为许多艾滋病毒感染者提供了接近正常的预期寿命，前提是他们能够获得护理，并能够保持终身严格遵守每日或更频繁的治疗方案。抗逆转录病毒疗法病毒学失败的最重要因素是患者对完整和适当剂量的依从性差。感染艾滋病毒的注射吸毒者在保持最佳遵从性方面面临着有据可查的挑战。因此，这一群体--约占美国艾滋病毒流行的四分之一--尚未充分受益于现有的抗逆转录病毒疗法。改善抗逆转录病毒药物依从性的各种干预措施，从咨询到直接观察疗法和其他结构性干预措施，都只取得了不大的成功。我们提出了一种新的治疗策略，包括系统地给予长效抗逆转录病毒治疗，以确保在药物依从性较差的艾滋病毒感染人群中有效的药物输送和病毒抑制。我们提出了一项随机、双盲、安慰剂对照研究，将CCR5单抗PRO 140与标准护理口服抗逆转录病毒方案相结合，每周一次皮下治疗。PRO 140是唯一适合这种用途的药物，因为它是唯一一种不需要缓慢静脉输液就能证明长效病毒抑制的艾滋病毒药物。这项试点研究的成功将确定一项新的战略，以改善对感染艾滋病毒的注射吸毒者和其他弱势人群的护理，这些人群没有得到当前一代抗逆转录病毒药物的充分服务。积极的结果可能会促进这一领域的发展，并刺激在这一人群中开发和测试其他长效艾滋病毒药物。

DESCRIPTION (provided by applicant): Combination antiretroviral therapy has provided many HIV-infected individuals with a near-normal life expectancy, provided they have access to care and can maintain strict lifetime adherence to the daily or more frequent treatment regimens. The most important factor in the virologic failure of an antiretroviral regimen is poor adherence of the patient to complete and proper dosing. HIV-infected IDUs face well-documented challenges to maintaining optimal adherence. Accordingly, this group, which represents approximately one- quarter of the U.S. HIV epidemic, has yet to derive the full benefits of the available antiretroviral therapies. Various interventions to improve antiretroviral drug adherence, ranging from counseling to directly-observed therapy and other structural interventions, have had only modest success. We propose a novel treatment strategy involving systemic administration of long-acting antiretroviral therapy as a means to ensure effective drug delivery and viral suppression in HIV-infected populations prone to poor drug-adherence. We propose a randomized, double-blind, placebo-controlled study of weekly subcutaneous treatment with the CCR5 monoclonal antibody PRO 140 in combination with a standard-of-care oral antiretroviral regimen. PRO 140 is uniquely suited for this use as it is the only HIV drug to demonstrate long-acting viral suppression without the need for slow IV infusion. Success in this pilot study would identify a new strategy for improving the care of HIV-infected IDUs and other vulnerable populations that are underserved by the current generation of antiretroviral medications. Positive results could catalyze this field and spur development and testing of other long-acting HIV drugs in this population.