The Antiretroviral Pipeline
(see the chapter on Immune-Based Therapies and Preventive Technologies Pipeline). However, the ideals of universal access to treatment, and widespread use of treatment at high CD4 cell counts, is in stark contrast to the current reality in which the median CD4 count for patients in developed countries upon diagnosis remains <250 copies/mm3 and is significantly lower in most resource-poor settings.13 Finally, any discussion of ARVs in the context of earlier treatment involves the question of when to start therapy. This raises the importance of accurate data on both the benefits and the risks of treatment in order to define a CD4 threshold for when to start, acknowledging that absolute CD4 counts are imperfect surrogate markers. This is currently the focus of the National Institute of Allergy and Infectious Diseasesâ&#x20AC;&#x201C;funded START study that will randomize 4,000 patients with a CD4 count >500 copies/mm3 to either immediate HIV treatment or to defer initiation until the CD4 count reaches 350 cells/mm3. Notably, large randomized studies also provide the opportunity to study the pathology of HIV disease and its interaction with treatment, other illnesses, and age-related morbidity. With ARV treatment options unlikely to change radically in the next few years, this is a stable and opportune time for such research.14 We need new drugs. The antiretroviral pipeline in 2010 that is detailed below, focusing predominantly on compounds in phase II or phase III development or with in vivo data on virologic activity, looks surprisingly strong. Many of these compounds will be active against MDR HIV. However, the development of some compounds with potential activity has been suspended due, at least in part, to financial reluctance from investors. The global demand for alternatives to lifelong treatment, compounded by economics that are beginning to cap treatment programs both in the United States and internationally, is discussed more fully in the introduction to this report and has reinvigorated the urgency for strategies focused on a cure (see the chapter on Immune-Based Therapies and Preventive Technologies Pipeline).
Activity since 2008 There are no guarantees in drug development, even for compounds that complete phase III studies. Predicting pipeline development is a similar process. It is therefore perhaps most significant that none of the ARVs that were listed as pipeline compounds in TAGâ&#x20AC;&#x2122;s 2008 Pipeline Report have been approved as new treatment. The only new ARV to be approved by the U.S. Food and Drug Administration (FDA) since 2008 for sale in the United States has been a Meltrex formulation of the protease inhibitor ritonavir in Janu-
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