HIV-1 specific antibody titers and neutralization among chronically infected patients on long-term suppressive antiretroviral therapy (ART): a cross-sectional study
The majority of potent and broadly neutralizing antibodies against HIV-1 have been isolated from untreated patients with acute or chronic infection. To assess the extent of HIV-1 specific antibody response and neutralization after many years of virologic suppression from potent combination ART, we e...
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| Veröffentlicht in: | PloS one 2014-01, Vol.9 (1), p.e85371-e85371 |
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| description | The majority of potent and broadly neutralizing antibodies against HIV-1 have been isolated from untreated patients with acute or chronic infection. To assess the extent of HIV-1 specific antibody response and neutralization after many years of virologic suppression from potent combination ART, we examined antibody binding titers and neutralization of 51 patients with chronic HIV-1 infection on suppressive ART for at least three years. In this cross-sectional analysis, we found high antibody titers against gp120, gp41, and the membrane proximal external region (MPER) in 59%, 43%, and 27% of patients, respectively. We observed significantly higher endpoint binding titers for gp120 and gp41 for patients with >10 compared to ≤ 10 years of detectable HIV RNA. Additionally, we observed higher median gp120 and gp41 antibody titers in patients with HIV RNA 10 years of detectable HIV RNA (8/20 [40.0%] versus 3/31 [9.7%] for ≤ 10 years, p = 0.02) and a trend toward greater neutralization in patients with ≤ 5 years of HIV RNA 5 years, p = 0.08). All patients with neutralizing activity mediated successful phagocytosis of VLPs by THP-1 cells after antibody opsonization. Our findings of highly specific antibodies to several structural epitopes of HIV-1 with antibody effector functions and neutralizing activity after long-term suppressive ART, suggest continuous antigenic stimulation and evolution of HIV-specific antibody response occurs before and after suppression with ART. These patients, particularly those with slower HIV progression and more time with detectable viremia prior to initiation of suppressive ART, are a promising population to identify and further study functional antibodies against HIV-1. |
| doi_str_mv | 10.1371/journal.pone.0085371 |
| format | Article |
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To assess the extent of HIV-1 specific antibody response and neutralization after many years of virologic suppression from potent combination ART, we examined antibody binding titers and neutralization of 51 patients with chronic HIV-1 infection on suppressive ART for at least three years. In this cross-sectional analysis, we found high antibody titers against gp120, gp41, and the membrane proximal external region (MPER) in 59%, 43%, and 27% of patients, respectively. We observed significantly higher endpoint binding titers for gp120 and gp41 for patients with >10 compared to ≤ 10 years of detectable HIV RNA. Additionally, we observed higher median gp120 and gp41 antibody titers in patients with HIV RNA <50 copies/mL for ≤ 5 years. 22% of patients neutralized a HIV-1 primary isolate (HIV-1(JR-FL)) and 8% neutralized a HIV-2/HIV-1 MPER chimera. Significantly greater HIV-1(JR-FL) neutralization was found among patients with >10 years of detectable HIV RNA (8/20 [40.0%] versus 3/31 [9.7%] for ≤ 10 years, p = 0.02) and a trend toward greater neutralization in patients with ≤ 5 years of HIV RNA <50 copies/mL (7/20 [35.0%] versus 4/31 [12.9%] for >5 years, p = 0.08). All patients with neutralizing activity mediated successful phagocytosis of VLPs by THP-1 cells after antibody opsonization. Our findings of highly specific antibodies to several structural epitopes of HIV-1 with antibody effector functions and neutralizing activity after long-term suppressive ART, suggest continuous antigenic stimulation and evolution of HIV-specific antibody response occurs before and after suppression with ART. These patients, particularly those with slower HIV progression and more time with detectable viremia prior to initiation of suppressive ART, are a promising population to identify and further study functional antibodies against HIV-1.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0085371</identifier><identifier>PMID: 24454852</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Acquired immune deficiency syndrome ; AIDS ; Analysis ; Anti-HIV Agents - therapeutic use ; Antibodies ; Antibodies, Neutralizing - blood ; Antibody response ; Antigenic determinants ; Antigens ; Antiretroviral agents ; Antiretroviral drugs ; Antiretroviral therapy ; B cells ; Binding ; Binding sites ; Biological products industry ; Biology ; Care and treatment ; Chronic infection ; Cross-Sectional Studies ; Development and progression ; Drug therapy ; Enzyme-Linked Immunosorbent Assay ; Epitopes ; Female ; Gastroenterology ; Glycoprotein gp120 ; Glycoprotein gp41 ; Glycoproteins ; Health aspects ; Highly active antiretroviral therapy ; HIV ; HIV Antibodies - blood ; HIV Infections - drug therapy ; HIV Infections - immunology ; HIV patients ; HIV-1 - genetics ; HIV-1 - immunology ; Human health and pathology ; Human immunodeficiency virus ; Humans ; Immunoglobulins ; Infection ; Infections ; Infectious diseases ; Life Sciences ; Male ; Medical diagnosis ; Medical research ; Medicine ; Middle Aged ; Neutralization ; Neutralizing ; Opsonization ; Patients ; Phagocytosis ; Ribonucleic acid ; RNA ; RNA, Viral - blood ; Vaccines ; Viral Load ; Viremia ; Virus diseases ; Viruses</subject><ispartof>PloS one, 2014-01, Vol.9 (1), p.e85371-e85371</ispartof><rights>COPYRIGHT 2014 Public Library of Science</rights><rights>2014 Gach et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Attribution</rights><rights>2014 Gach et al 2014 Gach et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c588t-c0c349f62e8b931022ea9bc342689a4061db91c481d2a065c2ac6427493534563</citedby><cites>FETCH-LOGICAL-c588t-c0c349f62e8b931022ea9bc342689a4061db91c481d2a065c2ac6427493534563</cites><orcidid>0000-0002-5093-4800</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3893210/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3893210/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79569,79570</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24454852$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.sorbonne-universite.fr/hal-01358316$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Gach, Johannes S</creatorcontrib><creatorcontrib>Achenbach, Chad J</creatorcontrib><creatorcontrib>Chromikova, Veronika</creatorcontrib><creatorcontrib>Berzins, Baiba</creatorcontrib><creatorcontrib>Lambert, Nina</creatorcontrib><creatorcontrib>Landucci, Gary</creatorcontrib><creatorcontrib>Forthal, Donald N</creatorcontrib><creatorcontrib>Katlama, Christine</creatorcontrib><creatorcontrib>Jung, Barbara H</creatorcontrib><creatorcontrib>Murphy, Robert L</creatorcontrib><title>HIV-1 specific antibody titers and neutralization among chronically infected patients on long-term suppressive antiretroviral therapy (ART): a cross-sectional study</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>The majority of potent and broadly neutralizing antibodies against HIV-1 have been isolated from untreated patients with acute or chronic infection. To assess the extent of HIV-1 specific antibody response and neutralization after many years of virologic suppression from potent combination ART, we examined antibody binding titers and neutralization of 51 patients with chronic HIV-1 infection on suppressive ART for at least three years. In this cross-sectional analysis, we found high antibody titers against gp120, gp41, and the membrane proximal external region (MPER) in 59%, 43%, and 27% of patients, respectively. We observed significantly higher endpoint binding titers for gp120 and gp41 for patients with >10 compared to ≤ 10 years of detectable HIV RNA. Additionally, we observed higher median gp120 and gp41 antibody titers in patients with HIV RNA <50 copies/mL for ≤ 5 years. 22% of patients neutralized a HIV-1 primary isolate (HIV-1(JR-FL)) and 8% neutralized a HIV-2/HIV-1 MPER chimera. Significantly greater HIV-1(JR-FL) neutralization was found among patients with >10 years of detectable HIV RNA (8/20 [40.0%] versus 3/31 [9.7%] for ≤ 10 years, p = 0.02) and a trend toward greater neutralization in patients with ≤ 5 years of HIV RNA <50 copies/mL (7/20 [35.0%] versus 4/31 [12.9%] for >5 years, p = 0.08). All patients with neutralizing activity mediated successful phagocytosis of VLPs by THP-1 cells after antibody opsonization. Our findings of highly specific antibodies to several structural epitopes of HIV-1 with antibody effector functions and neutralizing activity after long-term suppressive ART, suggest continuous antigenic stimulation and evolution of HIV-specific antibody response occurs before and after suppression with ART. These patients, particularly those with slower HIV progression and more time with detectable viremia prior to initiation of suppressive ART, are a promising population to identify and further study functional antibodies against HIV-1.</description><subject>Acquired immune deficiency syndrome</subject><subject>AIDS</subject><subject>Analysis</subject><subject>Anti-HIV Agents - therapeutic use</subject><subject>Antibodies</subject><subject>Antibodies, Neutralizing - blood</subject><subject>Antibody response</subject><subject>Antigenic determinants</subject><subject>Antigens</subject><subject>Antiretroviral agents</subject><subject>Antiretroviral drugs</subject><subject>Antiretroviral therapy</subject><subject>B cells</subject><subject>Binding</subject><subject>Binding sites</subject><subject>Biological products industry</subject><subject>Biology</subject><subject>Care and treatment</subject><subject>Chronic infection</subject><subject>Cross-Sectional Studies</subject><subject>Development and progression</subject><subject>Drug therapy</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Epitopes</subject><subject>Female</subject><subject>Gastroenterology</subject><subject>Glycoprotein gp120</subject><subject>Glycoprotein gp41</subject><subject>Glycoproteins</subject><subject>Health aspects</subject><subject>Highly active antiretroviral therapy</subject><subject>HIV</subject><subject>HIV Antibodies - blood</subject><subject>HIV Infections - drug therapy</subject><subject>HIV Infections - immunology</subject><subject>HIV patients</subject><subject>HIV-1 - genetics</subject><subject>HIV-1 - immunology</subject><subject>Human health and pathology</subject><subject>Human immunodeficiency virus</subject><subject>Humans</subject><subject>Immunoglobulins</subject><subject>Infection</subject><subject>Infections</subject><subject>Infectious diseases</subject><subject>Life Sciences</subject><subject>Male</subject><subject>Medical diagnosis</subject><subject>Medical research</subject><subject>Medicine</subject><subject>Middle Aged</subject><subject>Neutralization</subject><subject>Neutralizing</subject><subject>Opsonization</subject><subject>Patients</subject><subject>Phagocytosis</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>RNA, Viral - blood</subject><subject>Vaccines</subject><subject>Viral Load</subject><subject>Viremia</subject><subject>Virus 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Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>Hyper Article en Ligne (HAL) (Open Access)</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gach, Johannes S</au><au>Achenbach, Chad J</au><au>Chromikova, Veronika</au><au>Berzins, Baiba</au><au>Lambert, Nina</au><au>Landucci, Gary</au><au>Forthal, Donald N</au><au>Katlama, Christine</au><au>Jung, Barbara H</au><au>Murphy, Robert L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>HIV-1 specific antibody titers and neutralization among chronically infected patients on long-term suppressive antiretroviral therapy (ART): a cross-sectional study</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2014-01-15</date><risdate>2014</risdate><volume>9</volume><issue>1</issue><spage>e85371</spage><epage>e85371</epage><pages>e85371-e85371</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>The majority of potent and broadly neutralizing antibodies against HIV-1 have been isolated from untreated patients with acute or chronic infection. To assess the extent of HIV-1 specific antibody response and neutralization after many years of virologic suppression from potent combination ART, we examined antibody binding titers and neutralization of 51 patients with chronic HIV-1 infection on suppressive ART for at least three years. In this cross-sectional analysis, we found high antibody titers against gp120, gp41, and the membrane proximal external region (MPER) in 59%, 43%, and 27% of patients, respectively. We observed significantly higher endpoint binding titers for gp120 and gp41 for patients with >10 compared to ≤ 10 years of detectable HIV RNA. Additionally, we observed higher median gp120 and gp41 antibody titers in patients with HIV RNA <50 copies/mL for ≤ 5 years. 22% of patients neutralized a HIV-1 primary isolate (HIV-1(JR-FL)) and 8% neutralized a HIV-2/HIV-1 MPER chimera. Significantly greater HIV-1(JR-FL) neutralization was found among patients with >10 years of detectable HIV RNA (8/20 [40.0%] versus 3/31 [9.7%] for ≤ 10 years, p = 0.02) and a trend toward greater neutralization in patients with ≤ 5 years of HIV RNA <50 copies/mL (7/20 [35.0%] versus 4/31 [12.9%] for >5 years, p = 0.08). All patients with neutralizing activity mediated successful phagocytosis of VLPs by THP-1 cells after antibody opsonization. Our findings of highly specific antibodies to several structural epitopes of HIV-1 with antibody effector functions and neutralizing activity after long-term suppressive ART, suggest continuous antigenic stimulation and evolution of HIV-specific antibody response occurs before and after suppression with ART. These patients, particularly those with slower HIV progression and more time with detectable viremia prior to initiation of suppressive ART, are a promising population to identify and further study functional antibodies against HIV-1.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24454852</pmid><doi>10.1371/journal.pone.0085371</doi><orcidid>https://orcid.org/0000-0002-5093-4800</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2014-01, Vol.9 (1), p.e85371-e85371 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1477787561 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Acquired immune deficiency syndrome AIDS Analysis Anti-HIV Agents - therapeutic use Antibodies Antibodies, Neutralizing - blood Antibody response Antigenic determinants Antigens Antiretroviral agents Antiretroviral drugs Antiretroviral therapy B cells Binding Binding sites Biological products industry Biology Care and treatment Chronic infection Cross-Sectional Studies Development and progression Drug therapy Enzyme-Linked Immunosorbent Assay Epitopes Female Gastroenterology Glycoprotein gp120 Glycoprotein gp41 Glycoproteins Health aspects Highly active antiretroviral therapy HIV HIV Antibodies - blood HIV Infections - drug therapy HIV Infections - immunology HIV patients HIV-1 - genetics HIV-1 - immunology Human health and pathology Human immunodeficiency virus Humans Immunoglobulins Infection Infections Infectious diseases Life Sciences Male Medical diagnosis Medical research Medicine Middle Aged Neutralization Neutralizing Opsonization Patients Phagocytosis Ribonucleic acid RNA RNA, Viral - blood Vaccines Viral Load Viremia Virus diseases Viruses |
| title | HIV-1 specific antibody titers and neutralization among chronically infected patients on long-term suppressive antiretroviral therapy (ART): a cross-sectional study |
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