Research Project
9467284
Pan-HIV Incidence Assay Development Abstract HIV-1 continues to cause the largest number of yearly deaths from a single infectious agent in the world today. Despite considerable advances in treatment of HIV-1 infection and AIDS, which it causes, there is an urgent need for better methods of prevention and treatment of HIV-1 infection and AIDS. As part of this effort, the World Health Organization (WHO) and the Joint United Nations Program on HIV/AIDS (UNAIDS) conduct worldwide surveys of HIV infection incidence, prevalence and mortality. Incidence data are vitally needed by governments and non-governmental organizations to best direct efforts and limited resources aimed at prevention of HIV transmission and treatment of HIV infection. The limiting antigen avidity enzyme immunoassay (Lag assay) is currently widely used to test for HIV incidence but this assay only detects very recent infections and does not work well for all subtypes of HIV-1. Antigen Discovery Inc. (ADI), of Irvine California, has created a pan-HIV proteomic microarray (pan-HIV chip) that contains all proteins and many protein fragments and epitopes from nine HIV-1 subtypes and circulating recombinant forms as well as both major groups of HIV-2, which together comprise over 90% of HIV infections worldwide. We also added glycosylated and disulfide-bound forms of HIV glycoproteins and glycoprotein fragments resulting in a total of over 280 immunoreactive HIV proteins, proteins fragments and epitopes. Moreover, we assayed the reactivity of this HIV protein microarray with IgG, IgA and IgM in a panel of 125 sera and saliva samples, obtained from the Consortium for the Evaluation and Performance of HIV Incidence Assays (CEPHIA), that comprise the HIV Recency Biomarker Screening (HRBS) set. Our preliminary data show that certain HIV antigens, Vif, Vpu, p6, Tat, Rev, Env and Env fragments are much less strongly recognized by IgG in sera and saliva from recently infected individuals compared to those with longer-term infection. In contrast, Env, Env fragments, Tat, Rev, CA and PR are more strongly recognized by IgM in sera and saliva from recently infected individuals compared to those with longer-term infection. Based on these extensive preliminary data, we hypothesize that we can develop a highly sensitive and specific HIV recency of infection testing algorithm (RITA) that will be useful for individuals infected with all types and subtypes of HIV.
