Medroxyprogesterone acetate increases HIV-1 infection of unstimulated peripheral blood mononuclear cells in vitro

Research output: Contribution to journalArticle

Abstract

Objective: Several observational studies suggest that medroxyprogesterone acetate (MPA) injectable contraceptives may increase a woman's risk of sexual HIV-1 acquisition. In-vitro studies are conflicting, mainly due to differences in the type of progestin studied or activation status of the primary cells. We sought to determine whether MPA increases infection of unstimulated peripheral blood mononuclear cells (PBMCs). Methods: Freshly isolated PBMCs from normal blood donors were treated with physiologic MPA concentrations ranging from 0.003 to 5 ng/ml and infected with GFP-tagged R5-tropic or X4-tropic HIV-1 pseudoviruses by spinoculation. The infection was limited to a single cycle. Cells were stained with CD3, CD8 and CD14. Infection was quantified as the percentage of GFP cells by flow cytometry. Results: Absolute infection was greater among unstimulated MPA-treated CD3+CD8- T cells vs. untreated cells across MPA concentrations of 0.003-3 ng/ml using R5 (P+CD8- T cells in MPA-treated whole PBMC cultures but not after monocytes were depleted (P0.5). Conclusion: The CD3+CD8- T-cell population of MPA-treated unstimulated PBMCs were more susceptible to HIV-1 infection than untreated cells. The increased infection was partly due to monocytes and was lost when PBMC were exogenously stimulated. These data provide confirmation of a biological association between MPA exposure and increased susceptibility to HIV-1 infection, particularly among women who inject drugs.

Original languageEnglish (US)
Pages (from-to)1137-1146
Number of pages10
JournalAIDS
Volume29
Issue number10
DOIs
StatePublished - Jun 19 2015

Fingerprint

Medroxyprogesterone Acetate
HIV Infections
HIV-1
Blood Cells
Infection
T-Lymphocytes
Monocytes
In Vitro Techniques
Progestins
Contraceptive Agents
Blood Donors
Observational Studies
Flow Cytometry
Cell Culture Techniques
Injections

Keywords

  • Contraception
  • Depo provera
  • HIV
  • HIV acquisition
  • Infectivity
  • Injectables
  • Medroxyprogesterone acetate

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

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title = "Medroxyprogesterone acetate increases HIV-1 infection of unstimulated peripheral blood mononuclear cells in vitro",
abstract = "Objective: Several observational studies suggest that medroxyprogesterone acetate (MPA) injectable contraceptives may increase a woman's risk of sexual HIV-1 acquisition. In-vitro studies are conflicting, mainly due to differences in the type of progestin studied or activation status of the primary cells. We sought to determine whether MPA increases infection of unstimulated peripheral blood mononuclear cells (PBMCs). Methods: Freshly isolated PBMCs from normal blood donors were treated with physiologic MPA concentrations ranging from 0.003 to 5 ng/ml and infected with GFP-tagged R5-tropic or X4-tropic HIV-1 pseudoviruses by spinoculation. The infection was limited to a single cycle. Cells were stained with CD3, CD8 and CD14. Infection was quantified as the percentage of GFP cells by flow cytometry. Results: Absolute infection was greater among unstimulated MPA-treated CD3+CD8- T cells vs. untreated cells across MPA concentrations of 0.003-3 ng/ml using R5 (P+CD8- T cells in MPA-treated whole PBMC cultures but not after monocytes were depleted (P0.5). Conclusion: The CD3+CD8- T-cell population of MPA-treated unstimulated PBMCs were more susceptible to HIV-1 infection than untreated cells. The increased infection was partly due to monocytes and was lost when PBMC were exogenously stimulated. These data provide confirmation of a biological association between MPA exposure and increased susceptibility to HIV-1 infection, particularly among women who inject drugs.",
keywords = "Contraception, Depo provera, HIV, HIV acquisition, Infectivity, Injectables, Medroxyprogesterone acetate",
author = "Sampah, {Maame Efua S} and Gregory Laird and Blankson, {Joel N} and Siliciano, {Robert F} and {Coleman Fennell}, {Jenell S.}",
year = "2015",
month = "6",
day = "19",
doi = "10.1097/QAD.0000000000000681",
language = "English (US)",
volume = "29",
pages = "1137--1146",
journal = "AIDS",
issn = "0269-9370",
publisher = "Lippincott Williams and Wilkins",
number = "10",

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TY - JOUR

T1 - Medroxyprogesterone acetate increases HIV-1 infection of unstimulated peripheral blood mononuclear cells in vitro

AU - Sampah, Maame Efua S

AU - Laird, Gregory

AU - Blankson, Joel N

AU - Siliciano, Robert F

AU - Coleman Fennell, Jenell S.

PY - 2015/6/19

Y1 - 2015/6/19

N2 - Objective: Several observational studies suggest that medroxyprogesterone acetate (MPA) injectable contraceptives may increase a woman's risk of sexual HIV-1 acquisition. In-vitro studies are conflicting, mainly due to differences in the type of progestin studied or activation status of the primary cells. We sought to determine whether MPA increases infection of unstimulated peripheral blood mononuclear cells (PBMCs). Methods: Freshly isolated PBMCs from normal blood donors were treated with physiologic MPA concentrations ranging from 0.003 to 5 ng/ml and infected with GFP-tagged R5-tropic or X4-tropic HIV-1 pseudoviruses by spinoculation. The infection was limited to a single cycle. Cells were stained with CD3, CD8 and CD14. Infection was quantified as the percentage of GFP cells by flow cytometry. Results: Absolute infection was greater among unstimulated MPA-treated CD3+CD8- T cells vs. untreated cells across MPA concentrations of 0.003-3 ng/ml using R5 (P+CD8- T cells in MPA-treated whole PBMC cultures but not after monocytes were depleted (P0.5). Conclusion: The CD3+CD8- T-cell population of MPA-treated unstimulated PBMCs were more susceptible to HIV-1 infection than untreated cells. The increased infection was partly due to monocytes and was lost when PBMC were exogenously stimulated. These data provide confirmation of a biological association between MPA exposure and increased susceptibility to HIV-1 infection, particularly among women who inject drugs.

AB - Objective: Several observational studies suggest that medroxyprogesterone acetate (MPA) injectable contraceptives may increase a woman's risk of sexual HIV-1 acquisition. In-vitro studies are conflicting, mainly due to differences in the type of progestin studied or activation status of the primary cells. We sought to determine whether MPA increases infection of unstimulated peripheral blood mononuclear cells (PBMCs). Methods: Freshly isolated PBMCs from normal blood donors were treated with physiologic MPA concentrations ranging from 0.003 to 5 ng/ml and infected with GFP-tagged R5-tropic or X4-tropic HIV-1 pseudoviruses by spinoculation. The infection was limited to a single cycle. Cells were stained with CD3, CD8 and CD14. Infection was quantified as the percentage of GFP cells by flow cytometry. Results: Absolute infection was greater among unstimulated MPA-treated CD3+CD8- T cells vs. untreated cells across MPA concentrations of 0.003-3 ng/ml using R5 (P+CD8- T cells in MPA-treated whole PBMC cultures but not after monocytes were depleted (P0.5). Conclusion: The CD3+CD8- T-cell population of MPA-treated unstimulated PBMCs were more susceptible to HIV-1 infection than untreated cells. The increased infection was partly due to monocytes and was lost when PBMC were exogenously stimulated. These data provide confirmation of a biological association between MPA exposure and increased susceptibility to HIV-1 infection, particularly among women who inject drugs.

KW - Contraception

KW - Depo provera

KW - HIV

KW - HIV acquisition

KW - Infectivity

KW - Injectables

KW - Medroxyprogesterone acetate

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U2 - 10.1097/QAD.0000000000000681

DO - 10.1097/QAD.0000000000000681

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C2 - 26035316

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VL - 29

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JO - AIDS

JF - AIDS

SN - 0269-9370

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