Background: Antiretroviral therapy (ART) can downregulate 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 2 HIV rapid tests and 2 HIV incidence assays; selected samples were also tested with two fourth-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 nonreactive or weakly-reactive rapid test result (7/180 early ART arm, 3/27 delayed ART arm, P = 0.13); one sample had nonreactive fourth-generation assay results and 3 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 fourth-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. Downregulation of the antibody response to HIV infection in the setting of ART may impact population-level surveys of HIV prevalence and incidence.
Departments of *Pathology; and
†Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD;
‡Laboratory of Immunoregulation, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Baltimore, MD;
§Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA;
‖Science Facilitation Department, FHI 360, Washington, DC;
¶Science Facilitation Department, FHI 360, Durham, NC;
#UNC Project Laboratory, Tidziwe Centre, Kamuzu Central Hospital, Lilongwe, Malawi;
**College of Medicine-Johns Hopkins Project, Blantyre, Malawi;
††Division of Infectious Diseases, University of North Carolina at Chapel Hill, Chapel Hill, NC;
‡‡UNC Project-Malawi, Institute for Global Health and Infectious Diseases, Lilongwe, Malawi;
§§Vaccine and Infectious Disease Division and Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA; and
‖‖Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC.
Correspondence to: Susan H. Eshleman, MD, PhD, Department of Pathology, The Johns Hopkins Medical Institutions, Ross Building, Room 646, 720 Rutland Avenue, Baltimore, MD 21205 (e-mail: seshlem@jhmi.edu).
Supported by the grants from the Division of AIDS of the U.S. National Institute of Allergy and Infectious Diseases (NIAID); and by the Office of AIDS Research of the U.S. National Institutes of Health (NIH) [UM1-AI068613 (Eshleman); UM1-AI068617 (Donnell); and UM1-AI068619 (Cohen/El-Sadr)]. Additional support was provided by R01-AI095068 (Eshleman). Study drugs used in HPTN 052 were donated by Abbott Laboratories, Boehringer-Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb, Gilead Sciences, Inc., GlaxoSmithKline/ViiV Healthcare, and Merck & Co., Inc. Additional support provided by the Division of Intramural Research, NIAID.
The authors have no conflicts of interest to disclose. M.C.H. has received honoraria for advisory board membership from ViiV Healthcare. M.S.C. receives honoraria for advisory board membership from Janssen Global Services, Roche Molecular Systems, and Merck Research. S.H.E. has collaborated with Abbott Diagnostics on evaluation of HIV-related assays; Abbott Diagnostics has provided reagents for other research studies.
J.M.F.: Reviewed and analyzed data; wrote the manuscript. E.P.-M.: HPTN 052 QA/QC Coordinator; coordinated and reviewed data for HIV diagnostic testing. B. D., T.W.: Assisted with sample management; performed HIV diagnostic testing. K.S.: Performed HIV incidence testing. O.L.: Coordinated and reviewed data for HIV incidence testing. E.A.W.: HPTN 052 Data Analyst. M.M., T.G.: HPTN 052 Study Coordinator. G.T., D.S.: Site Laboratory Lead. J.K., M.C.H.: HPTN 052 site Principal Investigator. Y.Q.C.: HPTN 052 Statistician. M.S.C.: HPTN 052 Protocol Chair. S.H.E.: HPTN 052 Virologist; designed the study, reviewed, and analyzed data; wrote the manuscript.
The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
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Received December 07, 2016
Accepted April 06, 2017
