Physiologic doses of depot-medroxyprogesterone acetate do not increase acute plasma simian HIV viremia or mucosal virus shedding in pigtail macaques

Jessica Ann Radzio-Basu, Krisztina Hanley, James Mitchell, Shanon Ellis, Frank Deyounks, Leecresia T. Jenkins, Debra Hanson, Walid Heneine, J. Gerardo García-Lerma

Research output: Contribution to journalArticle

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Abstract

OBJECTIVE:: Epidemiologic studies remain inconclusive on whether the injectable contraceptive depot-medroxyprogesterone acetate (DMPA) increases mucosal HIV shedding and transmissibility. Nonhuman primate models may help to determine the effects of DMPA on acute HIV replication. DESIGN:: We defined a physiologic dose of DMPA in macaques and assessed the impact of DMPA on acute simian HIV (SHIV) replication. METHODS:: Pigtail macaques received 1-30 mg of DMPA intramuscularly followed by measurements of progesterone and medroxyprogesterone acetate (MPA). Vaginal epithelial thickness, number of cell layers and density of intraepithelial CD3 cells were measured. The effect of DMPA on SHIV viremia and genital virus shedding was investigated in six pigtail macaques infected during monthly treatment cycles with 3 mg DMPA. Six DMPA-untreated macaques were controls. RESULTS:: Plasma MPA concentrations directly correlated with changes in epithelial thickness (correlation =0.84; P<0.001) and density of intraepithelial CD3 cells (correlation=0.41; P=0.02). A 3mg DMPA dose recapitulated plasma MPA concentrations and changes in vaginal epithelial thickness seen in women. DMPA-treated and untreated macaques showed similar peak plasma viremia and RNA area under the curve values over 12 weeks (P=0.94), although treated macaques had higher odds of having virus being detected in plasma (odds ratio 6.6, P=0.02). Rectal and vaginal virus shedding was similar between treated and untreated macaques (P=0.72 and P=0.53, respectively). CONCLUSION:: In this pigtail macaque model of DMPA and vaginal SHIV infection, we found little or no effect of DMPA on plasma viremia and mucosal virus shedding during acute infection. These results do not support a role of DMPA in increasing mucosal HIV shedding.

Original languageEnglish (US)
Pages (from-to)1431-1439
Number of pages9
JournalAIDS
Volume28
Issue number10
DOIs
StatePublished - Jun 19 2014

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Macaca nemestrina
Virus Shedding
Medroxyprogesterone Acetate
Viremia
HIV
Macaca

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

Radzio-Basu, Jessica Ann ; Hanley, Krisztina ; Mitchell, James ; Ellis, Shanon ; Deyounks, Frank ; Jenkins, Leecresia T. ; Hanson, Debra ; Heneine, Walid ; García-Lerma, J. Gerardo. / Physiologic doses of depot-medroxyprogesterone acetate do not increase acute plasma simian HIV viremia or mucosal virus shedding in pigtail macaques. In: AIDS. 2014 ; Vol. 28, No. 10. pp. 1431-1439.
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title = "Physiologic doses of depot-medroxyprogesterone acetate do not increase acute plasma simian HIV viremia or mucosal virus shedding in pigtail macaques",
abstract = "OBJECTIVE:: Epidemiologic studies remain inconclusive on whether the injectable contraceptive depot-medroxyprogesterone acetate (DMPA) increases mucosal HIV shedding and transmissibility. Nonhuman primate models may help to determine the effects of DMPA on acute HIV replication. DESIGN:: We defined a physiologic dose of DMPA in macaques and assessed the impact of DMPA on acute simian HIV (SHIV) replication. METHODS:: Pigtail macaques received 1-30 mg of DMPA intramuscularly followed by measurements of progesterone and medroxyprogesterone acetate (MPA). Vaginal epithelial thickness, number of cell layers and density of intraepithelial CD3 cells were measured. The effect of DMPA on SHIV viremia and genital virus shedding was investigated in six pigtail macaques infected during monthly treatment cycles with 3 mg DMPA. Six DMPA-untreated macaques were controls. RESULTS:: Plasma MPA concentrations directly correlated with changes in epithelial thickness (correlation =0.84; P<0.001) and density of intraepithelial CD3 cells (correlation=0.41; P=0.02). A 3mg DMPA dose recapitulated plasma MPA concentrations and changes in vaginal epithelial thickness seen in women. DMPA-treated and untreated macaques showed similar peak plasma viremia and RNA area under the curve values over 12 weeks (P=0.94), although treated macaques had higher odds of having virus being detected in plasma (odds ratio 6.6, P=0.02). Rectal and vaginal virus shedding was similar between treated and untreated macaques (P=0.72 and P=0.53, respectively). CONCLUSION:: In this pigtail macaque model of DMPA and vaginal SHIV infection, we found little or no effect of DMPA on plasma viremia and mucosal virus shedding during acute infection. These results do not support a role of DMPA in increasing mucosal HIV shedding.",
author = "Radzio-Basu, {Jessica Ann} and Krisztina Hanley and James Mitchell and Shanon Ellis and Frank Deyounks and Jenkins, {Leecresia T.} and Debra Hanson and Walid Heneine and Garc{\'i}a-Lerma, {J. Gerardo}",
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Radzio-Basu, JA, Hanley, K, Mitchell, J, Ellis, S, Deyounks, F, Jenkins, LT, Hanson, D, Heneine, W & García-Lerma, JG 2014, 'Physiologic doses of depot-medroxyprogesterone acetate do not increase acute plasma simian HIV viremia or mucosal virus shedding in pigtail macaques', AIDS, vol. 28, no. 10, pp. 1431-1439. https://doi.org/10.1097/QAD.0000000000000294

Physiologic doses of depot-medroxyprogesterone acetate do not increase acute plasma simian HIV viremia or mucosal virus shedding in pigtail macaques. / Radzio-Basu, Jessica Ann; Hanley, Krisztina; Mitchell, James; Ellis, Shanon; Deyounks, Frank; Jenkins, Leecresia T.; Hanson, Debra; Heneine, Walid; García-Lerma, J. Gerardo.

In: AIDS, Vol. 28, No. 10, 19.06.2014, p. 1431-1439.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Physiologic doses of depot-medroxyprogesterone acetate do not increase acute plasma simian HIV viremia or mucosal virus shedding in pigtail macaques

AU - Radzio-Basu, Jessica Ann

AU - Hanley, Krisztina

AU - Mitchell, James

AU - Ellis, Shanon

AU - Deyounks, Frank

AU - Jenkins, Leecresia T.

AU - Hanson, Debra

AU - Heneine, Walid

AU - García-Lerma, J. Gerardo

PY - 2014/6/19

Y1 - 2014/6/19

N2 - OBJECTIVE:: Epidemiologic studies remain inconclusive on whether the injectable contraceptive depot-medroxyprogesterone acetate (DMPA) increases mucosal HIV shedding and transmissibility. Nonhuman primate models may help to determine the effects of DMPA on acute HIV replication. DESIGN:: We defined a physiologic dose of DMPA in macaques and assessed the impact of DMPA on acute simian HIV (SHIV) replication. METHODS:: Pigtail macaques received 1-30 mg of DMPA intramuscularly followed by measurements of progesterone and medroxyprogesterone acetate (MPA). Vaginal epithelial thickness, number of cell layers and density of intraepithelial CD3 cells were measured. The effect of DMPA on SHIV viremia and genital virus shedding was investigated in six pigtail macaques infected during monthly treatment cycles with 3 mg DMPA. Six DMPA-untreated macaques were controls. RESULTS:: Plasma MPA concentrations directly correlated with changes in epithelial thickness (correlation =0.84; P<0.001) and density of intraepithelial CD3 cells (correlation=0.41; P=0.02). A 3mg DMPA dose recapitulated plasma MPA concentrations and changes in vaginal epithelial thickness seen in women. DMPA-treated and untreated macaques showed similar peak plasma viremia and RNA area under the curve values over 12 weeks (P=0.94), although treated macaques had higher odds of having virus being detected in plasma (odds ratio 6.6, P=0.02). Rectal and vaginal virus shedding was similar between treated and untreated macaques (P=0.72 and P=0.53, respectively). CONCLUSION:: In this pigtail macaque model of DMPA and vaginal SHIV infection, we found little or no effect of DMPA on plasma viremia and mucosal virus shedding during acute infection. These results do not support a role of DMPA in increasing mucosal HIV shedding.

AB - OBJECTIVE:: Epidemiologic studies remain inconclusive on whether the injectable contraceptive depot-medroxyprogesterone acetate (DMPA) increases mucosal HIV shedding and transmissibility. Nonhuman primate models may help to determine the effects of DMPA on acute HIV replication. DESIGN:: We defined a physiologic dose of DMPA in macaques and assessed the impact of DMPA on acute simian HIV (SHIV) replication. METHODS:: Pigtail macaques received 1-30 mg of DMPA intramuscularly followed by measurements of progesterone and medroxyprogesterone acetate (MPA). Vaginal epithelial thickness, number of cell layers and density of intraepithelial CD3 cells were measured. The effect of DMPA on SHIV viremia and genital virus shedding was investigated in six pigtail macaques infected during monthly treatment cycles with 3 mg DMPA. Six DMPA-untreated macaques were controls. RESULTS:: Plasma MPA concentrations directly correlated with changes in epithelial thickness (correlation =0.84; P<0.001) and density of intraepithelial CD3 cells (correlation=0.41; P=0.02). A 3mg DMPA dose recapitulated plasma MPA concentrations and changes in vaginal epithelial thickness seen in women. DMPA-treated and untreated macaques showed similar peak plasma viremia and RNA area under the curve values over 12 weeks (P=0.94), although treated macaques had higher odds of having virus being detected in plasma (odds ratio 6.6, P=0.02). Rectal and vaginal virus shedding was similar between treated and untreated macaques (P=0.72 and P=0.53, respectively). CONCLUSION:: In this pigtail macaque model of DMPA and vaginal SHIV infection, we found little or no effect of DMPA on plasma viremia and mucosal virus shedding during acute infection. These results do not support a role of DMPA in increasing mucosal HIV shedding.

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JF - AIDS

SN - 0269-9370

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