Novel Criteria for Diagnosing Acute and Early Human Immunodeficiency Virus Infection in a Multinational Study of Early Antiretroviral Therapy Initiation

Abstract

Background: Antiretroviral therapy (ART) initiation during acute and early human immunodeficiency virus infection (AEHI) limits HIV reservoir formation and may facilitate post-ART control but is logistically challenging. We evaluated the performance of AEHI diagnostic criteria from a prospective study of early ART initiation.

Methods: AIDS Clinical Trials Group A 5354 enrolled adults at 30 sites in the Americas, Africa, and Asia who met any 1 of 6 criteria based on combinations of results of HIV RNA, HIV antibody, Western blot or Geenius assay, and/or the signal-to-cutoff (S/CO) ratio of the ARCHITECT HIV Ag/Ab Combo or GS HIV Combo Ag/Ab EIA. HIV status and Fiebig stage were confirmed by centralized testing.

Results: From 2017 through 2019, 195 participants were enrolled with median age of 27 years (interquartile range, 23-39). Thirty (15.4%) were female. ART was started by 171 (87.7%) on the day of enrollment and 24 (12.3%) the next day. AEHI was confirmed in 188 (96.4%) participants after centralized testing, 4 (2.0%) participants were found to have chronic infection, and 3 (1.5%) found not to have HIV discontinued ART and were withdrawn. Retrospectively, a nonreactive or indeterminate HIV antibody on the Geenius assay combined with ARCHITECT S/CO ≥10 correctly identified 99 of 122 (81.2%) Fiebig II-IV AEHI cases with no false-positive results.

Conclusions: Novel AEHI criteria that incorporate ARCHITECT S/CO facilitated rapid and efficient ART initiation without waiting for an HIV RNA result. These criteria may facilitate AEHI diagnosis, staging, and immediate ART initiation in future research studies and clinical practice.

Clinical trials registration: NCT02859558.

Keywords: acute HIV infection; antigen/antibody assays; antiretroviral agents; same-day therapy; signal-to-cutoff ratio.

Figure 1.

Associations between timing of enrollment, initial HIV screening test, and actual Fiebig stage. Actual Fiebig stage at enrollment was plotted against the number of days elapsed since initial HIV testing for all participants (panel A) and separately for participants who enrolled with estimated Fiebig I/II (panel B), estimated Fiebig III/IV (Panel C), and estimated Fiebig V (panel D). The left and right edges of each box in the figure indicate the interquartile range. The line inside the box indicates the median. Points plotted on panel A using the log-scale were binned in order to accurately present the number of data points. Abbreviation: HIV, human immunodeficiency virus.

Figure 2.

ARCHITECT S/CO ratios of participants with negative/indeterminate Geenius HIV-1/2 antibody results by Fiebig stage. ARCHITECT and Geenius HIV-1/2 antibody assays were run using samples from the day of enrollment for all participants. The bottom and top edges of each box indicate the interquartile range. The line inside the box indicates the median. Filled circles represent actual data points. *Two Fiebig II participants had an indeterminate Geenius with cross-reacting immunoglobulin G antibody to gp140/p31 and a negative third-generation HIV-1/2 result. Points plotted were binned in order to accurately present the number of data points. Abbreviation: HIV, human immunodeficiency virus; S/CO, signal-to-cutoff.