HIV serologic reactivity varies with time of ART initiation in persons on long-term ART

HIV serologic responses measured by clinical screening assays may be blunted when antiretroviral treatment (ART) suppresses HIV replication from the initial infection stages, with further decay following long-term treatment. Sensitivity may vary according to the timing of ART initiation after HIV acquisition, antigens (Ags) utilized to detect anti-HIV antibodies (Abs), and HIV subtype. We obtained samples from long-term ART-suppressed persons with HIV (PWH) who started ART at acute/early or during chronic infection, from blood donors with undetectable HIV RNA and nonreactive serology, and from blood donors with positive RNA and reactive serology (presumably untreated infections) spanning multiple HIV subtypes to compare patterns of serologic reactivity using two Ag/Ab screening assays (Alinity and VITROS). We found that earlier ART initiation was associated with progressively lower signal-to-cutoff ratios (S/CO) in both assays. Serologic reactivity in clinical samples from participants initiating ART at Fiebig 2 was somewhat lower for CRF01_AE (67%) than other HIV subtypes (91%) on the Alinity platform. In the late-ART initiation group, reactivity was high for both assays despite long-term treatment, with higher S/CO values in samples from blood donors with presumably untreated infection. We observed no strong evidence of S/CO waning >96 weeks after ART initiation in the early-ART initiation group. Our findings suggest potential limitations for HIV infection ascertainment in clinical samples from long-term treated PWH who started ART at early infection stages using currently approved serologic tests.IMPORTANCEThis manuscript increases our understanding of how the timing of initiation of HIV treatment affects our ability to detect the infection using commercial blood tests that measure HIV antigens or antibodies. Being able to detect HIV is important for clinical diagnostics and blood screening, and HIV is not as easily detected in persons who begin therapy shortly after infection using serological tests. In contrast to prior work, we show that current clinical HIV tests have stable reactivity over time in persons on long-term HIV treatment.