Michael G Berg1, Ana Olivo2, Barbara J Harris2, Mary A Rodgers2, Linda James3, Samuel Mampunza4, Jonathan Niles5, Franklin Baer6, Julie Yamaguchi2, Lazare Kaptue7, Oliver Laeyendecker8, Thomas C Quinn8, Carole McArthur9, Gavin A Cloherty2. 1. Infectious Diseases Research, Abbott Diagnostics, Abbott Park, IL, United States. Electronic address: michael.berg@abbott.com. 2. Infectious Diseases Research, Abbott Diagnostics, Abbott Park, IL, United States. 3. Université Protestante au Congo, Croisement de l'avenue de Libération et du Boulevard Triomphal, Kinshasa, Democratic Republic of Congo; IMA World Health, 1730 M St NW Suite 1100, Washington DC, United States. 4. Université Protestante au Congo, Croisement de l'avenue de Libération et du Boulevard Triomphal, Kinshasa, Democratic Republic of Congo. 5. IMA World Health, 1730 M St NW Suite 1100, Washington DC, United States. 6. SANRU NGO, 76 Ave. de la Justice, Kinshasa-Gombe, Democratic Republic of Congo. 7. Université des Montagnes, Bangangté, Cameroon. 8. Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH, Baltimore MD, United States; Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD, United States. 9. Pathology Department, Truman Medical Center, Kansas City, MO, United States; Department of Oral and Craniofacial Sciences, University of Missouri-Kansas City School of Dentistry, Kansas City, MO, United States; University of Missouri-Kansas City School of Medicine, Kansas City, MO, United States.
Abstract
BACKGROUND: In-depth analysis of the HIV pandemic at its epicenter in the Congo basin has been hampered by 40 years of political unrest and lack of functional public health infrastructure. In recent surveillance studies (2017-18), we found that the prevalence of HIV in Kinshasa, Democratic Republic of Congo (11%) far exceeded previous estimates. METHODS: 10,457 participants were screened in Kinshasa with rapid tests from 2017-2019. Individuals confirmed as reactive by the Abbott ARCHITECT HIV Ag/Ab Combo assay (n=1968) were measured by the Abbott RealTime HIV-1 viral load assay. Follow up characterization of samples was performed with alternate manufacturer viral load assays, qPCR for additional blood borne viruses, unbiased next generation sequencing, and HIV Western blotting. FINDINGS: Our data suggested the existence of a significant cohort (n=429) of HIV antibody positive/viral load negative individuals. We systematically eliminated collection site bias, sample integrity, and viral genetic diversity as alternative explanations for undetectable viral loads. Mass spectroscopy unexpectedly detected the presence of 3TC antiviral medication in approximately 60% of those tested (209/354), and negative Western blot results indicated false positive serology in 12% (49/404). From the remaining Western blot positives (n=53) and indeterminates (n=31) with reactive Combo and rapid test results, we estimate 2.7-4.3% of infections in DRC to be potential elite controllers. We also analyzed samples from the DRC collected in 1987 and 2001-03, when antiretroviral drugs were not available, and found similarly elevated trends. INTERPRETATION: Viral suppression to undetectable viral loads without therapy occurs infrequently in HIV-1 infected patients around the world. Mining of global data suggests a unique ability to control HIV infection arose early in central Africa and occurs in <1% of founder populations. Identification of this group of elite controllers presents a unique opportunity to study potentially novel genetic mechanisms of viral suppression. FUNDING: Abbott Laboratories funded surveillance in DRC and subsequent research efforts. Additional funding was received from a MIZZOU Award from the University of Missouri. Research was supported in part by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH.
BACKGROUND: In-depth analysis of the HIV pandemic at its epicenter in the Congo basin has been hampered by 40 years of political unrest and lack of functional public health infrastructure. In recent surveillance studies (2017-18), we found that the prevalence of HIV in Kinshasa, Democratic Republic of Congo (11%) far exceeded previous estimates. METHODS: 10,457 participants were screened in Kinshasa with rapid tests from 2017-2019. Individuals confirmed as reactive by the Abbott ARCHITECT HIV Ag/Ab Combo assay (n=1968) were measured by the Abbott RealTime HIV-1 viral load assay. Follow up characterization of samples was performed with alternate manufacturer viral load assays, qPCR for additional blood borne viruses, unbiased next generation sequencing, and HIV Western blotting. FINDINGS: Our data suggested the existence of a significant cohort (n=429) of HIV antibody positive/viral load negative individuals. We systematically eliminated collection site bias, sample integrity, and viral genetic diversity as alternative explanations for undetectable viral loads. Mass spectroscopy unexpectedly detected the presence of 3TC antiviral medication in approximately 60% of those tested (209/354), and negative Western blot results indicated false positive serology in 12% (49/404). From the remaining Western blot positives (n=53) and indeterminates (n=31) with reactive Combo and rapid test results, we estimate 2.7-4.3% of infections in DRC to be potential elite controllers. We also analyzed samples from the DRC collected in 1987 and 2001-03, when antiretroviral drugs were not available, and found similarly elevated trends. INTERPRETATION: Viral suppression to undetectable viral loads without therapy occurs infrequently in HIV-1 infectedpatients around the world. Mining of global data suggests a unique ability to control HIV infection arose early in central Africa and occurs in <1% of founder populations. Identification of this group of elite controllers presents a unique opportunity to study potentially novel genetic mechanisms of viral suppression. FUNDING: Abbott Laboratories funded surveillance in DRC and subsequent research efforts. Additional funding was received from a MIZZOU Award from the University of Missouri. Research was supported in part by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH.
Authors: Francisco Averhoff; Michael Berg; Mary Rodgers; Saladin Osmanov; Xinxin Luo; Mark Anderson; Todd Meyer; Alan Landay; Amiran Gamkrelidze; Esper G Kallas; Karl Ciuoderis; Juan Pablo Hernandez; Jean Hugues Henry; Jorge Osorio; John Lindo; Johnson Deshommes; Joshua Anzinger; Justen Manasa; Maia Alkashvili; Mboup Souleyman; Pontiano Kaleebu; Rodrigo Correa-Oliveira; Sunil Solomon; Tulio de Olivera; Yupin Suputtamongkol; Gavin Cloherty Journal: Int J Infect Dis Date: 2022-02-05 Impact factor: 12.074