Rational development of radiopharmaceuticals for HIV-1

Abstract

The global battle against HIV-1 would benefit from a sensitive and specific radiopharmaceutical to localize HIV-infected cells. Ideally, this probe would be able to identify latently infected host cells containing replication competent HIV sequences. Clinical and research applications would include assessment of reservoirs, informing clinical management by facilitating assessment of burden of infection in different compartments, monitoring disease progression and monitoring response to therapy. A "rational" development approach could facilitate efficient identification of an appropriate targeted radiopharmaceutical. Rational development starts with understanding characteristics of the disease that can be effectively targeted and then engineering radiopharmaceuticals to hone in on an appropriate target, which in the case of HIV-1 (HIV) might be an HIV-specific product on or in the host cell, a differentially expressed gene product, an integrated DNA sequence specific enzymatic activity, part of the inflammatory response, or a combination of these. This is different from the current approach that starts with a radiopharmaceutical for a target associated with a disease, mostly from autopsy studies, without a strong rationale for the potential to impact patient care. At present, no targeted therapies are available for HIV latency, although a number of approaches are under study. Here we discuss requirements for a radiopharmaceutical useful in strategies targeting persistently infected cells. The radiopharmaceutical for HIV should be developed based on HIV biology, studied in an animal model and then in humans, and ultimately used in clinical and research settings.

Keywords: Human Immunodeficiency Virus; Infectious disease imaging; Radiopharmaceutical.

Figure 1

Landmarks of the HIV-1 genome. Open reading frames are shown as rectangles. The gene start, indicated by the small number in the upper left corner of each rectangle, normally records the position of the a in the ATG start codon for that gene, while the number in the lower right records the last position of the stop codon. Los Alamos National Laboratory HIV Sequence database, 2013 [56]

Figure 2

Structure of an HIV Virion. NIAID, 2004[57]

Figure 3

Life cycle of HIV-1. NIAID, 2012 [59]

Figure 4

The effect of HIV infection and its treatment on inflammation and immunosenescence. Deeks, 2011 [80]