Are there situations where a person tests recent on the assay but was infected over a year ago?
Similar to other incidence assays, the RTRI may misclassify some persons as recent (e.g., absence of long-term line on RTRI) who have had HIV for a longer duration of time. The proportion false recent (PFR) may be affected by various factors listed below. To control for these factors, the addition of viral load testing in a RITA can minimize false-recent cases but may not capture all false-recent cases.
- PLHIV on ART: All persons on ART should be excluded from RTRI testing. A proportion of persons on ART will misclassify as “recent” due to declining antibody avidity when viral load is suppressed for longer duration. If a person has a lapse in ART or develops drug resistance and experiences viral rebound, he/she could test as recent on the RITA.
- Elite Controllers: Some persons with long-term infection may test recent in the absence of ART even after years of infection due to naturally low viral load resulting in low-avidity antibodies. Though this is a rare occurrence (<1% of HIV-infected persons), the proportion of elite controllers is expected to be higher in older epidemics than younger epidemics.
- HIV-2 positive persons:As described earlier, the HIV diagnostic verification line does not distinguish between HIV-1 and 2 but includes both antigens. The long-term line includes only HIV-1-specific antigen, to which HIV-2 antibody would not bind. Therefore, all HIV-2 positive persons will be classified as HIV-1 recent infection irrespective of duration of their infections. If the RTRI is used in geographical areas where HIV-2 is prevalent or if HIV-2 infection is suspected, it is important to perform type-specific diagnosis before final recent infection classification can be made. Dually infected persons can be tested on RTRI with interpretation similar to HIV-1 infected persons.
- HIV-1 subtypes: Misclassification may vary by HIV-1 subtypes and may be higher in certain subtypes than others (e.g., clade D virus). Ongoing evaluations are being conducted to confirm the PFR among persons infected for >1 year across different subtype infections. However, the impact of subtype variation should have little or no impact for the intended use of the assay.