Safety of Excisional Inguinal Lymph Node Biopsies Performed for Research Purposes in HIV-1-Infected Women and Men

Meditz, Amie L.; Connick, Elizabeth; McCarter, Martin D.

doi:10.1089/sur.2013.218

Cited by 5 publications

(6 citation statements)

References 21 publications

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“…For LN biopsy–associated complications, the grade 1 AE rate in the RV254/SEARCH010 study was 7.7%, which was slightly lower than the rate for minor complications reported by an HIV-infected cohort study in the United States. 6 The grade 1 AEs in our study, which did not require medical intervention, were similar to the “minor complications” in the U.S. study. While that study reported 6 seromas, 1 lymphedema, 1 hematoma, and 1 reaction to adhesive tape in 95 procedures, our grade 1 AEs seemed milder in comparison: 5 cases of biopsy-site discomfort and 1 hematoma.…”

Section: Discussionsupporting

confidence: 80%

“…While that study reported 6 seromas, 1 lymphedema, 1 hematoma, and 1 reaction to adhesive tape in 95 procedures, our grade 1 AEs seemed milder in comparison: 5 cases of biopsy-site discomfort and 1 hematoma. 6 Biopsy-site discomfort was not reported in previous studies most likely because it was considered expected and relatively minor from the surgical perspective.…”

Section: Discussionmentioning

confidence: 97%

“…14 Our grade 2 LN-associated AE rate was 5.1%, comparable with the complication rate of 5%–10% reported in other HIV cohorts. 5 , 6 Rothenberger et al 7 reported a 2.4% (1/41 procedures) complication rate in HIV-infected participants but used a different methodology for defining AEs. Our complication rate is also similar to the reported rates of LN-related AEs in HIV-uninfected populations in Netherlands and Germany.…”

Section: Discussionmentioning

confidence: 99%

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Brief Report: Safety and Tolerability of Inguinal Lymph Node Biopsy in Individuals With Acute HIV Infection in Thailand

Chintanaphol

Sacdalan

Chottanapund

et al. 2018

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Introduction:Latent HIV reservoirs are rapidly established in lymphoid tissues during acute HIV infection (AHI). Sampling these tissues provides important information about HIV pathogenesis. This period is associated with viral replication and immune activation that may affect procedure-related adverse events (AEs). We examined the safety and tolerability of inguinal lymph node (LN) biopsy in research participants with AHI in Bangkok, Thailand.Methods:Between 2013 and 2016, 67 AHI participants in the RV254/SEARCH010 study underwent at least one optional inguinal LN biopsy during AHI at the baseline visit and/or after antiretroviral therapy (median 48 weeks after antiretroviral therapy). Biopsy-related AEs were graded according to NIH Division of AIDS guidelines. Poisson regression was used to calculate incidence rate ratios and 95% confidence intervals to evaluate associations of demographic and HIV characteristics, procedure timing, and repetition with AE incidence.Results:Of the 67 participants, 97% were male with a median age of 26. Among 78 LN biopsies (39 at baseline and 39 at follow-up), 10 (12.8%) AEs were reported: 6 (7.7%) grade 1 and 4 (5.1%) grade 2. The AEs were biopsy-site discomfort (n = 8, 10.2%) and hematoma (n = 2, 2.6%). No factors were significantly associated with AE incidence. All biopsy-related AEs were transient and self-limited.Conclusions:Inguinal LN biopsies were safe and well tolerated in mostly Thai men with AHI. As LN biopsies become an integral part of HIV research, this study provides information to participants, researchers, and institutional review boards that these samples can be safely obtained.

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Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

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Brief Report: Safety and Tolerability of Inguinal Lymph Node Biopsy in Individuals With Acute HIV Infection in Thailand

Chintanaphol

Sacdalan

Chottanapund

et al. 2018

JAIDS Journal of Acquired Immune Deficiency Syndromes

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“…Inguinal lymph nodes were obtained as previously described (16, 17) from individuals who had documented HIV-1 infection for at least 6 months, were not receiving antiretroviral therapy, and had CD4+ T-cells ≥ 300/mm 3 . None of these subjects had an opportunistic infection, malignancy or an acute illness at the time of lymph node excision.…”

Section: Methodsmentioning

confidence: 99%

Germinal Center T Follicular Helper Cells Are Highly Permissive to HIV-1 and Alter Their Phenotype during Virus Replication

Kohler

Pham

Folkvord

et al. 2016

The Journal of Immunology

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HIV-1 replication is concentrated within CD4+ T cells in B-cell follicles of secondary lymphoid tissues during asymptomatic disease. Limited data suggest that a subset of T follicular helper cells (TFH) within germinal centers (GC) is highly permissive to HIV-1. Whether GC TFH are the major HIV-1 virus-producing cells in vivo has not been established. Here, we investigated TFH permissivity to HIV-1 ex vivo by spinoculating and culturing tonsil cells with HIV-1 GFP reporter viruses. Using flow cytometry, higher percentages of GC TFH (CXCR5highPD-1high) and CXCR5+PD-1low cells were GFP+ than non-GC TFH (CXCR5+PD-1intermediate) or extrafollicular (CXCR5-) cells. When sorted prior to spinoculation, however, GC TFH were substantially more permissive than CXCR5+PD-1low or extrafollicular cells, suggesting that many GC TFH transition to a CXCR5+PD-1low phenotype during productive infection. In situ hybridization on inguinal lymph node sections from untreated HIV-1-infected individuals without AIDS revealed higher frequencies of HIV-1 RNA+ cells in GC than non-GC regions of follicle or extrafollicular regions. Superinfection of HIV-1-infected individuals’ lymph node cells with GFP reporter virus confirmed the permissivity of follicular cells ex vivo. Lymph node immunostaining revealed 96% of CXCR5+CD4+ cells were located in follicles. Within sorted lymph node cells from four HIV-infected individuals, CXCR5+ subsets harbored 11- to 66-fold more HIV-1 RNA than CXCR5-subsets, as determined by RT PCR. Thus, GC TFH are highly permissive to HIV-1, but downregulate PD-1 and to a lesser extent CXCR5 during HIV-1 replication. These data further implicate GC TFH as the major HIV-1-producing cells in chronic asymptomatic HIV-1 infection.

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“…Human LN. Inguinal LN were obtained as previously described (43,44). In this study, four HIVseronegative LN were used.…”

Section: Methodsmentioning

confidence: 99%

Follicular Regulatory T Cells Are Highly Permissive to R5-Tropic HIV-1

Miller

Brodie

Guo

et al. 2017

J Virol

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Follicular regulatory T (TFR) cells are a subset of CD4 T cells in secondary lymphoid follicles. TFR cells were previously included in the follicular helper T (TFH) cell subset, which consists of cells that are highly permissive to HIV-1. The permissivity of TFR cells to HIV-1 is unknown. We find that TFR cells are more permissive than TFH cells to R5-tropic HIV-1 TFR cells expressed more CCR5 and CD4 and supported higher frequencies of viral fusion. Differences in Ki67 expression correlated with HIV-1 replication. Inhibiting cellular proliferation reduced Ki67 expression and HIV-1 replication. Lymph node cells from untreated HIV-infected individuals revealed that TFR cells harbored the highest concentrations of HIV-1 RNA and highest levels of Ki67 expression. These data demonstrate that TFR cells are highly permissive to R5-tropic HIV-1 both and This is likely related to elevated CCR5 levels combined with a heightened proliferative state and suggests that TFR cells contribute to persistent R5-tropic HIV-1 replication In chronic, untreated HIV-1 infection, viral replication is concentrated in secondary lymphoid follicles. Within secondary lymphoid follicles, follicular helper T (TFH) cells have previously been shown to be highly permissive to HIV-1. Recently, another subset of T cells in secondary lymphoid follicles was described, follicular regulatory T (TFR) cells. These cells share some phenotypic characteristics with TFH cells, and studies that showed that TFH cells are highly permissive to HIV-1 included TFR cells in their definition of TFH cells. The permissivity of TFR cells to HIV-1 has not previously been described. Here, we show that TFR cells are highly permissive to HIV-1 both and The expression of Ki67, a marker of proliferative capacity, is predictive of expression of viral proteins, and downregulating Ki67 leads to concurrent decreases in expression of viral proteins. Our study provides new insight into HIV-1 replication and a potential new cell type to target for future treatment.

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Safety of Excisional Inguinal Lymph Node Biopsies Performed for Research Purposes in HIV-1-Infected Women and Men

Cited by 5 publications

References 21 publications

Brief Report: Safety and Tolerability of Inguinal Lymph Node Biopsy in Individuals With Acute HIV Infection in Thailand

Brief Report: Safety and Tolerability of Inguinal Lymph Node Biopsy in Individuals With Acute HIV Infection in Thailand

Germinal Center T Follicular Helper Cells Are Highly Permissive to HIV-1 and Alter Their Phenotype during Virus Replication

Follicular Regulatory T Cells Are Highly Permissive to R5-Tropic HIV-1

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