The fourth generation AlereTM HIV Combo rapid test improves detection of acute infection in MTN-003 (VOICE) samples

Edward Livant; Amy Heaps; Cliff Kelly; Rashika Maharaj; Natasha Samsunder; Lindiwe Nhlangulela; Patrick Karugaba; Ravindre Panchia; Jeanne Marrazzo; Zvavahera Mike Chirenje; Urvi M Parikh; VOICE Study Team

doi:10.1016/j.jcv.2017.06.006

The fourth generation Alere^TM HIV Combo rapid test improves detection of acute infection in MTN-003 (VOICE) samples

J Clin Virol. 2017 Sep:94:15-21. doi: 10.1016/j.jcv.2017.06.006. Epub 2017 Jun 29.

Authors

Affiliations

¹ Magee-Womens Research Institute, Pittsburgh, PA, United States.
² University of Pittsburgh, Pittsburgh, PA, United States.
³ SCHARP, Seattle, WA, United States.
⁴ South Africa Medical Research Council HIV Prevention Research Unit, Durban, South Africa.
⁵ CAPRISA, Durban, South Africa.
⁶ Aurum Institute, Klerksdorp, South Africa.
⁷ MU-JHU Research Collaboration, Kampala, Uganda.
⁸ Perinatal HIV Prevention Unit, University of the Witwatersrand, Johannesburg, South Africa.
⁹ University of Washington, Seattle, WA, United States.
¹⁰ UZ-UCSF, Harare, Zimbabwe.
¹¹ University of Pittsburgh, Pittsburgh, PA, United States. Electronic address: ump3@pitt.edu.

Abstract

Background: Early and accurate detection of HIV is crucial when using pre-exposure prophylaxis (PrEP) for HIV prevention to avoid PrEP initiation in acutely infected individuals and to minimize the risk of drug resistance in individuals with breakthrough infection.

Objective: To determine if fourth-generation antigen/antibody (Ag/Ab) rapid diagnostic tests (RDT) would have detected HIV infection earlier than the third-generation RDT used in MTN-003 (VOICE).

Study design: 5029 VOICE participants were evaluated with third-generation Alere Determine™ HIV-1/2, OraQuick ADVANCE^® Rapid HIV-1/2, Uni-Gold™ Recombigen^® HIV-1/2 and Bio-Rad GS HIV-1/2+O EIA; and fourth-generation Alere Determine™ HIV-1/2 Ag/Ab Combo, Conformité Européene (CE)-Marked Alere™ HIV Combo and Bio-Rad HIV Combo Ag/Ab EIA. Multispot^®, GS HIV-1 Western Blot (WB) and Geenius™ (Bio-Rad) were also evaluated.

Results: Of 57 antibody-negative pre-seroconversion plasma samples with HIV RNA >20 copies/mL identified, 16 (28%) were reactive by CE-Marked Alere™ HIV Combo (1 Ab; 9 Ag; 6 Ag/Ab reactive) and 4 (7%) by Alere Determine™ HIV-1/2 Ag/Ab Combo (2 Ab; 2 Ag; 0 Ag/Ab reactive) (p=0.0005). Multispot^® confirmed only 1 of 16 acute infections while WB and Geenius™ confirmed none. GS HIV Combo Ag/Ab EIA identified 27 of 57 (47%) pre-seroconversion RNA-positive samples.

Conclusion: In VOICE, 28% of infections missed by current third-generation RDT would have been identified with the use of CE-Marked Alere™ HIV Combo. Geenius™, Multispot^® and WB were all insensitive (<10%) in confirming infections detected by fourth-generation assays. An improved diagnostic algorithm that includes a fourth-generation RDT with HIV RNA testing will be essential for efficiently identifying seroconverters on PrEP.

Keywords: 4th generation rapid test; Acute infection; HIV confirmatory test; HIV diagnostics; HIV-1; Pre-exposure prophylaxis.

Publication types

Clinical Trial, Phase II
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

HIV Antibodies / blood*
HIV Infections / diagnosis*
HIV Infections / immunology
HIV Infections / virology
HIV-1 / immunology*
HIV-1 / isolation & purification
Humans
Immunoassay
Pre-Exposure Prophylaxis
Reproducibility of Results
Sensitivity and Specificity
Serologic Tests* / methods
Serologic Tests* / standards
Virology

Substances

HIV Antibodies

Abstract

Publication types

MeSH terms

Substances

Grants and funding