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Brief Report: HIV Antibodies Decline During Antiretroviral Therapy but Remain Correlated With HIV DNA and HIV-Specific T-Cell Responses.

ABSTRACT: BACKGROUND:In people with HIV on antiretroviral therapy (ART), the relationship between HIV-specific immune responses and measures of HIV persistence is uncertain. METHODS:We evaluated 101 individuals on suppressive ART in the AIDS Clinical Trials Group A5321 cohort. Cell-associated (CA) HIV DNA and RNA levels and HIV antibody concentrations and avidity to Env/p24 were measured longitudinally at years 1, 4, and 6-15 after ART initiation. Plasma HIV RNA by single copy assay and T-cell responses (IFN-? ELISPOT) against multiple HIV antigens were measured at the last time point. RESULTS:HIV antibody levels declined significantly with increasing time on ART (19%/year between year 1 and 4). HIV antibody levels correlated with T-cell responses to HIV Pol (r = 0.28, P = 0.014) and to Nef/Tat/Rev (r = 0.34; P = 0.002). HIV antibody and T-cell responses were positively associated with HIV DNA levels; for example, at the last time point (median 7 years on ART), r = 0.35 for antibody levels and HIV DNA (P < 0.001); r = 0.23 for Nef/Tat/Rev-specific T-cell responses and HIV DNA (P = 0.03). Neither antibody nor T-cell responses correlated with cell-associated HIV RNA or plasma RNA by single copy assay. CONCLUSIONS:In individuals on long-term ART, HIV-specific antibody and T-cell responses correlate with each other and with HIV DNA levels. The positive correlation between HIV immune responses and HIV DNA implies that the immune system is sensing, but not clearing, infected cells, perhaps because of immune dysfunction. Measuring immune responses to HIV antigens may provide insight into the impact of reservoir-reducing strategies.

SUBMITTER: Keating SM

PROVIDER: S-EPMC6625873 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Brief Report: HIV Antibodies Decline During Antiretroviral Therapy but Remain Correlated With HIV DNA and HIV-Specific T-Cell Responses.

Keating Sheila M SM Jones Richard Brad RB Lalama Christina M CM Bosch Ronald J RJ McMahon Deborah D Hampton Dylan D Cyktor Joshua J Eron Joseph J JJ Mellors John W JW Busch Michael P MP Gandhi Rajesh T RT

Journal of acquired immune deficiency syndromes (1999) 20190801 5

<h4>Background</h4>In people with HIV on antiretroviral therapy (ART), the relationship between HIV-specific immune responses and measures of HIV persistence is uncertain.<h4>Methods</h4>We evaluated 101 individuals on suppressive ART in the AIDS Clinical Trials Group A5321 cohort. Cell-associated (CA) HIV DNA and RNA levels and HIV antibody concentrations and avidity to Env/p24 were measured longitudinally at years 1, 4, and 6-15 after ART initiation. Plasma HIV RNA by single copy assay and T-c ...[more]

PMID: 31045647

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Project description:BackgroundA major challenge to HIV eradication strategies is the lack of an accurate measurement of the total burden of replication-competent HIV (the "reservoir"). We assessed the association of anti-HIV antibody responses and the estimated size of the reservoir during antiretroviral therapy (ART).MethodsWe evaluated anti-HIV antibody profiles using luciferase immunoprecipitation systems (LIPS) assay in relation to several blood-based HIV reservoir measures: total and 2-LTR DNA (rtPCR or droplet digital PCR); integrated DNA (Alu PCR); unspliced RNA (rtPCR), multiply-spliced RNA (TILDA), residual plasma HIV RNA (single copy PCR), and replication-competent virus (outgrowth assay). We also assessed total HIV DNA and RNA in gut-associated lymphoid tissue (rtPCR). Spearman correlations and linear regressions were performed using log-transformed blood- or tissue-based reservoir measurements as predictors and log-transformed antibody levels as outcome variables.ResultsAmong 51 chronically HIV-infected ART-suppressed participants (median age = 57, nadir CD4+ count = 196 cells/mm3, ART duration = 9 years), the most statistically significant associations were between antibody responses to integrase and HIV RNA in gut-associated lymphoid tissue (1.17 fold-increase per two-fold RNA increase, P = 0.004) and between antibody responses to matrix and integrated HIV DNA in resting CD4+ T cells (0.35 fold-decrease per two-fold DNA increase, P = 0.003). However, these associations were not statistically significant after a stringent Bonferroni-adjustment of P<0.00045. Multivariate models including age and duration of ART did not markedly alter results.ConclusionsOur findings suggest that anti-HIV antibody responses may reflect the size of the HIV reservoir during chronic treated HIV disease, possibly via antigen recognition in reservoir sites. Larger, prospective studies are needed to validate the utility of antibody levels as a measure of the total body burden of HIV during treatment.

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Brief Report: HIV Antibodies Decline During Antiretroviral Therapy but Remain Correlated With HIV DNA and HIV-Specific T-Cell Responses.

Publications

Brief Report: HIV Antibodies Decline During Antiretroviral Therapy but Remain Correlated With HIV DNA and HIV-Specific T-Cell Responses.

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