Publication:

Occurrence of false positivity in a fourth generation (Ag/Ab) HIV screening assay: horns of a dilemma

Background Universal screening for HIV with Ag/Ab combo assays has reduced the window period significantly due to its high sensitivity. However, occurrence of false positives is common and in a country like India, it may lead to social distress and loss of livelihood. We wanted to ascertain the occurrence of false positives in our laboratory.

Methods There were 21817 samples analysed retrospectively from Jan 2015 to Jul 2017 (31 months). Architect HIV Ag/Ab Combo (Abbott Laboratories, Abbott Park, IL) was used as the first test. Repeatedly reactive samples with a signal to cutoff (S/CO) ratio greater than or equal to 1.00 was considered reactive. Strategy III (3 test algorithm) of NACO guidelines was followed uniformly.

Results In this study, 147 samples tested reactive (0.67%) and 40 samples tested false positive (repeatedly reactive; 0.18%). 6 samples were indeterminate (0.027%). Overall, the sensitivity of the Architect HIV Ag/Ab Combo was 100%, the specificity varied between 99.74% and 99.91%. The PPV from June 2016 to July 2017 was 68.63% (32 false positives). The S/CO values of 72.8% (117/147) reactive samples ranged between 201- 800, whereas 72% (29/40) of false positive samples, the S/CO values ranged between 1.0-2.0. The specificity of the test improved to 99.98% when S/CO value was adjusted at 2 and 100% when adjusted at 5. Similarly, the PPV too improved to 93.04% and 98.66% at S/CO values of 2 and 5 respectively.

Conclusions Further studies are needed to ascertain the optimal or ‘grey-zone’ S/CO values for India to minimise the false positive results and avoid further supplemental tests routinely.