BACKGROUND Antiretroviral therapy (ART) can down-regulate antibody responses to HIV infection. We evaluated the impact of early vs. delayed ART on the performance of HIV diagnostic and incidence assays. METHODS Samples were obtained from 207 participants in the HPTN 052 trial who were stably suppressed on ART for ≥4 years (Malawi sites; pre-ART CD4 cell count 350–550 cells/mm3 [early ART arm, N=180] or <250 cells/mm3 or an AIDS-defining illness [delayed ART arm, N=27]). Samples were tested with two HIV rapid tests and two HIV incidence assays; selected samples were also tested with two 4th-generation immunoassays and a Western blot (WB) assay. A pre-ART sample was analyzed if the follow-up sample had a false negative or weakly-reactive rapid test result, or had an incidence assay result indicative of recent infection (false-recent result). RESULTS Ten (4.8%) samples had a non-reactive or weakly-reactive rapid test result (7/180 early ART arm, 3/27 delayed ART arm, p=0.13); one sample had non-reactive 4th-generation assay results and three had indeterminate WBs. Forty (18.9%) samples had a false-recent incidence assay result; 16 (7.8%) had false-recent results with both incidence assays. Baseline samples had stronger rapid test and WB bands, higher 4th-generation assay signal-to-cutoff values, and fewer HIV incidence assay results indicative of recent infection. CONCLUSIONS False-negative/weakly-reactive HIV rapid tests and false-recent HIV incidence assay results were observed in virally-suppressed individuals, regardless of pre-ART CD4 cell count. Down-regulation of the antibody response to HIV infection in the setting of ART may impact population-level surveys of HIV prevalence and incidence.

Detection of acute HIV infection was similar for the BioPlex assay and two other Ag/Ab assays. All three tests were less sensitive than a qualitative RNA assay and only detected HIV Ag when the viral load was high. The BioPlex assay detected acute infection in about half of the cases, and identified most of those infections as Ag positive/Ab negative.