Background: HIV diagnosis relies on detecting HIV-specific antibody, viral antigens, genome, or whole virions. Certain rare individuals with persistently indeterminate test results have to live with uncertainty as to their true HIV status, and their best clinical management remains unknown. This may become increasingly an issue with the widespread availability of PrEP, PEP and early ART initiation, potentially delaying or altering the development of HIV-specific antibodies. We describe a new national referral clinical service, established to explore novel diagnostic algorithms and offer counselling and management of individuals with persistently indeterminate HIV test results.
Description: Eligible individuals were referred to our clinic by their medical provider via the Virus Reference Department of Public Health England, with the following results: multiple “reactive” or indeterminate HIV antibody tests on different platforms with indeterminate Western Blot profiles, in the absence of confirmed HIV RNA, DNA or p24 antigen tests. Additional blood was drawn for repeat multiple HIV antibody EIAs including in-house typing assays, HIV Western blot, HIV RNA (including ultralow copy HIV RNA to 1 copy /ml) HIV DNA (total and sorted CD4+ T-cells) including multiple primer sets, p24 antigen; infection screen including EBV, CMV, VZV, HTLV, HBV, HCV, STS; auto-antibodies; immune activation markers; HLA-DR and CD25 expression on CD4 and CD8 cells and CD4, CD8 counts and CD4:8 ratio.
Lessons learned: The first six individuals attended the service between October 2017 and January 2018: five were diagnosed with HIV infection, with one awaiting further investigation. Western blots sometimes yielded greater clarity, no co-infections were found, and CD4 counts and T-cell activation markers were normal. Ultra-sensitive RNA viral load and DNA testing on freshly-processed samples were useful adjuvants to traditional tests (see table).
Conclusions/Next steps: This preliminary report of a novel HIV testing strategy has shown that with freshly processed samples, increased blood volumes and new technology, it has been possible to reach a definitive HIV diagnosis. As no data exist to inform the clinical management of cases identified as HIV+ in this setting, prolonged follow-up is required with support and counselling for people who have had to live with uncertainty for many years. Increased patient numbers will be presented.

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