HIV Antibody Level as a Marker of HIV Persistence and Low-Level Viral Replication

Keating, Sheila M.; Pilcher, Christopher D.; Jain, Vivek; Lebedeva, Mila; Hampton, Dylan; Abdel‐Mohsen, Mohamed; Deng, Xutao; Murphy, Gary; Welte, Alex; Facente, Shelley N.; Hecht, Frederick M.; Deeks, Steven G.; Pillai, Satish K.; Busch, Michael P.

doi:10.1093/infdis/jix225

Cited by 42 publications

(34 citation statements)

References 47 publications

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“…Frequent false-negative serological results were reported in HIV-1-infected infants who were breast-fed by mothers on ART or in postexposure prophylaxis (PEP) programs to prevent mother-to-child transmission (45)(46)(47). A significant reduction in HIV Ab levels, including a lack of HIV-1 WB assay reactivity and an increase in the rate of false-negative serological results following ART initiation, was previously reported in other studies (9,48,49). Individuals from the RV254/SEARCH010 cohort described in this study who initiated treatment at FI remained HIV-1 infected, despite the full suppression of HIV-1 plasma viremia with no detectable serological markers for over a 2-year period, as HIV RNA rebound occurred when ART was discontinued (50).…”

Section: Discussionmentioning

confidence: 75%

Decreased Seroreactivity in Individuals Initiating Antiretroviral Therapy during Acute HIV Infection

et al. 2019

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Antiretroviral therapy (ART) during acute HIV infection (AHI) interrupts viral dynamics and may delay the emergence of serological markers targeted by current HIV screening and confirmatory assays, thus creating challenges for correctly classifying HIV infection status. The performance of three HIV antigen/antibody combination (HIV Ag/Ab Combo) assays (the Bio-Rad GS, Abbott Architect, and Bio-Rad BioPlex 2200 assays) was evaluated with samples collected from RV254/South East Asia Research Collaboration in HIV 010 (RV254/SEARCH010) study (Bangkok, Thailand) participants at weeks 12 and 24 following the initiation of ART at Fiebig stage I (FI) (n = 23), FII (n = 39), or FIII/IV (n = 22). Supplemental, confirmatory testing was performed by the Geenius HIV 1/2 and HIV-1 Western blot assays (Bio-Rad). Samples from 30 untreated, HIV-1-infected individuals demonstrated robust HIV Ag/Ab Combo assay reactivity with well-developed HIV-1 Western blotting profiles by 24 weeks after infection. In contrast, 52.2% of samples from individuals initiating ART at FI, 7.7% of samples from individuals initiating ART at FII, and 4.5% of samples from individuals initiating ART at FIII/IV were nonreactive by the HIV Ag/Ab Combo assays, with 36.4 to 39.1% of samples having low signal-to-cutoff (S/CO) results by the Architect and BioPlex assays (S/CO < 10). Seroreversion from a reactive to a nonreactive status was observed in 10 individuals initiating ART at FII and 3 individuals initiating ART at FIII/IV. The Geenius and HIV-1 Western blot assay results were negative or indeterminate for 73.9% and 69.6% of individuals, respectively, treated at FI; 50.0% and 26.3% of individuals, respectively, treated at FII; and 54.5% and 40.9% of individuals, respectively, treated at FIII/IV. Virologic suppression of HIV-1 by ART during AHI impedes seroconversion to biomarkers of infection, limiting the utility of HIV Ag/Ab Combo and supplemental, confirmatory assays for infection status determination.

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Section: Discussionmentioning

confidence: 75%

Decreased Seroreactivity in Individuals Initiating Antiretroviral Therapy during Acute HIV Infection

et al. 2019

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“…In untreated HIV-1-infected adults, anti-HIV-1 Ab levels are stable over time and correlate with viral loads [25]. Anti-HIV-1 Ab levels decline but do not totally clear with the suppression of HIV-1 replication on ART; higher levels of HIV-1-specific antibodies on suppressive therapy are associated with later initiations of ART after infection and with higher cell-associated DNA and RNA levels.…”

Section: Discussionmentioning

confidence: 99%

Quantitative HIV-1 antibodies correlate with plasma HIV-1 RNA and cell-associated DNA levels in children on ART

McManus

Henderson

Gautam

et al. 2018

Clinical Infectious Diseases

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Background. This study measured serial plasma human immunodeficiency virus (HIV)-1-specific antibody (Ab) levels in children who initiated antiretroviral therapy (ART) prior to 2 years of age, and evaluated their relationship to peripheral blood HIV-1 RNA and DNA levels. Methods. We studied 46 HIV-1-infected children, stratified by age at ART initiation (<3 mo, early therapy [ET]; >3 mo-2 years, late therapy [LT]) and by virologic response (R) or non-response (NR), before and up to 4 years following ART. We studied 20 HIV-1-uninfected children born to HIV-1-infected mothers (seroreverters [SR]) as controls. Plasma immunoglobulin G (IgG) Ab levels directed against HIV-1 envelope (gp160, gp41), gag (capsid, p24; matrix, p17), reverse transcriptase (p66/51), and integrase (p31) were serially measured using quantitative enzyme-linked immunosorbent assays. HIV-1 Ab rates of decline were estimated over the first 15 months of the study. Results. The HIV-1 Ab rates of decline in the ET-R group were similar to those in the SR group for all Ab specificities, except for p17 (P = .01). Ab decline rates in the LT-R group and the NR group were significantly slower than in the SR group for all tested Ab specificities. After 1 year of age, Ab levels to p31 and p17 were significantly associated with HIV-1 RNA levels (P < .001); Ab levels to gp160 (P < .001) and gp41 (P < .001) were significantly associated with cell-associated HIV-1 DNA levels. Conclusions. Quantitative HIV-1-specific Ab levels may be useful for screening children on ART for viral suppression or for residual, cell-associated HIV-1 DNA levels. Clinical Trials Registration. NCT00000872. Keywords. pediatric early antiretroviral therapy; HIV-1 persistence; HIV-1 quantitative antibodies. Combination antiretroviral therapy (ART) markedly reduces human immunodeficiency virus (HIV)-1-related morbidity and mortality in children [1]. Early ART initiation in children prior to 3-6 months of age can be particularly effective for long-term control of HIV-1 replication, preserving immune functions [2, 3], reducing HIV-1-related illnesses and mortality [4], and limiting residual HIV-1 reservoirs [5, 6]. International treatment guidelines [7-9] now recommend ART initiation in HIV-1-infected children as soon as possible after birth. Methods for quantifying plasma HIV-1 RNA and peripheral blood mononuclear cell (PBMC)-associated HIV-1 DNA

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“…Levels of anti‐HIV‐1 antibodies can reflect the degree of HIV persistence and low‐level viral replication, yet little is known about the IgG and plasma glycomic determinants of persistent HIV and reservoir size after ART in vivo. Here, for the first time, we report novel plasma and IgG glycomic alterations that are associated with suppressed HIV infection as well as with CD4 T‐cell lymphocyte levels of HIV DNA and RNA during suppressive antiretroviral therapy.…”

Section: Discussionmentioning

confidence: 99%

Frontline Science: Plasma and immunoglobulin G galactosylation associate with HIV persistence during antiretroviral therapy

Vadrevu

Trbojević‐Akmačić

Kossenkov

et al. 2018

Journal of Leukocyte Biology

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Global antibody glycosylation is dynamic and plays critical roles in shaping different immunological outcomes and direct antibody functionality during HIV infection. However, the relevance of global antibody or plasma glycosylation patterns to HIV persistence after antiretroviral therapy (ART) has not been characterized. First, we compared glycomes of total plasma and isolated immunoglobulin G (IgG) from HIV+ ART-suppressed, HIV+ viremic, and HIV-negative individuals. Second, in ART-suppressed individuals, we examined the associations between glycomes and (1) levels of cell-associated HIV DNA and RNA in PBMCs and isolated CD4+ T cells, (2) CD4 count and CD4%, and (3) expression of CD4+ T-cell activation markers. HIV infection is associated with persistent alterations in the IgG glycome including decreased levels of disialylated glycans, which is associated with a lower anti-inflammatory activity, and increased levels of fucosylated glycans, which is associated with lower antibody-dependent cell-mediated cytotoxicity (ADCC). We also show that levels of certain mono- and digalactosylated nonfucosylated glycomic traits (A2G1, A2G2, and A2BG2), which have been reported to be associated with higher ADCC and higher anti-inflammatory activities, exhibit significant negative correlations with levels of cell-associated total HIV DNA and HIV RNA in ART-suppressed individuals. Finally, levels of certain circulating anti-inflammatory glycans are associated with higher levels of CD4 T cells and lower levels of T-cell activation. Our findings represent the first proof-of-concept evidence that glycomic alterations, known to be associated with differential states of inflammation and ADCC activities, are also associated with levels of HIV persistence in the setting of ART suppression.

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HIV Antibody Level as a Marker of HIV Persistence and Low-Level Viral Replication

Cited by 42 publications

References 47 publications

Decreased Seroreactivity in Individuals Initiating Antiretroviral Therapy during Acute HIV Infection

Decreased Seroreactivity in Individuals Initiating Antiretroviral Therapy during Acute HIV Infection

Quantitative HIV-1 antibodies correlate with plasma HIV-1 RNA and cell-associated DNA levels in children on ART

Frontline Science: Plasma and immunoglobulin G galactosylation associate with HIV persistence during antiretroviral therapy

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