Repeated administration of high-dose depot medroxyprogesterone acetate does not alter SHIVSF 162p3 viral kinetics and tenofovir pharmacokinetics when delivered via intravaginal rings

Priya Srinivasan, Jining Zhang, Chuong T. Dinh, Ryan S. Teller, Janet M. McNicholl, Patrick F. Kiser, Betsy Herold, James M. Smith

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background: Intravaginal rings (IVR) for HIV prevention will likely be used by women on depot medroxyprogesterone acetate (DMPA) hormonal contraception. We used pigtailed macaques to evaluate the effects of DMPA on tenofovir disoproxil fumarate (TDF) IVR pharmacokinetics and viral shedding. Methods: Mucosal tenofovir (TFV) levels were compared in SHIVSF 162p3-negative DMPA-treated (n=4) and normally cycling (n=6) macaques receiving TDF IVRs. Plasma viremia and vaginal shedding were determined in groups of SHIVSF 162p3-positive DMPA-treated (n=6) and normally cycling (n=5) macaques. Results: Similar median vaginal fluid TFV concentrations were observed in the DMPA-treated and cycling macaques over 4 weeks (1.2×105 and 1.1.×105 ng/mL, respectively). Median plasma viremia and vaginal shedding AUC of the DMPA-treated (2.73×107 and 8.15×104 copies/mL, respectively) and cycling macaques (3.98×107 and 1.47×103 copies/mL, respectively) were statistically similar. Conclusions: DMPA does not affect TDF IVR pharmacokinetics or SHIV shedding.

Original languageEnglish (US)
Pages (from-to)129-136
Number of pages8
JournalJournal of Medical Primatology
Volume46
Issue number4
DOIs
StatePublished - Aug 1 2017

Fingerprint

Tenofovir
medroxyprogesterone
Medroxyprogesterone Acetate
pharmacokinetics
Macaca
Pharmacokinetics
acetates
kinetics
dosage
Viremia
viremia
Virus Shedding
Macaca nemestrina
contraception
viral shedding
Contraception
Area Under Curve

Keywords

  • DMPA and HIV
  • mucosal HIV shedding
  • nonhuman primates
  • SHIV
  • tenofovir pharmacokinetics

ASJC Scopus subject areas

  • Animal Science and Zoology
  • veterinary(all)

Cite this

Repeated administration of high-dose depot medroxyprogesterone acetate does not alter SHIVSF 162p3 viral kinetics and tenofovir pharmacokinetics when delivered via intravaginal rings. / Srinivasan, Priya; Zhang, Jining; Dinh, Chuong T.; Teller, Ryan S.; McNicholl, Janet M.; Kiser, Patrick F.; Herold, Betsy; Smith, James M.

In: Journal of Medical Primatology, Vol. 46, No. 4, 01.08.2017, p. 129-136.

Research output: Contribution to journalArticle

Srinivasan, Priya ; Zhang, Jining ; Dinh, Chuong T. ; Teller, Ryan S. ; McNicholl, Janet M. ; Kiser, Patrick F. ; Herold, Betsy ; Smith, James M. / Repeated administration of high-dose depot medroxyprogesterone acetate does not alter SHIVSF 162p3 viral kinetics and tenofovir pharmacokinetics when delivered via intravaginal rings. In: Journal of Medical Primatology. 2017 ; Vol. 46, No. 4. pp. 129-136.
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abstract = "Background: Intravaginal rings (IVR) for HIV prevention will likely be used by women on depot medroxyprogesterone acetate (DMPA) hormonal contraception. We used pigtailed macaques to evaluate the effects of DMPA on tenofovir disoproxil fumarate (TDF) IVR pharmacokinetics and viral shedding. Methods: Mucosal tenofovir (TFV) levels were compared in SHIVSF 162p3-negative DMPA-treated (n=4) and normally cycling (n=6) macaques receiving TDF IVRs. Plasma viremia and vaginal shedding were determined in groups of SHIVSF 162p3-positive DMPA-treated (n=6) and normally cycling (n=5) macaques. Results: Similar median vaginal fluid TFV concentrations were observed in the DMPA-treated and cycling macaques over 4 weeks (1.2×105 and 1.1.×105 ng/mL, respectively). Median plasma viremia and vaginal shedding AUC of the DMPA-treated (2.73×107 and 8.15×104 copies/mL, respectively) and cycling macaques (3.98×107 and 1.47×103 copies/mL, respectively) were statistically similar. Conclusions: DMPA does not affect TDF IVR pharmacokinetics or SHIV shedding.",
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T1 - Repeated administration of high-dose depot medroxyprogesterone acetate does not alter SHIVSF 162p3 viral kinetics and tenofovir pharmacokinetics when delivered via intravaginal rings

AU - Srinivasan, Priya

AU - Zhang, Jining

AU - Dinh, Chuong T.

AU - Teller, Ryan S.

AU - McNicholl, Janet M.

AU - Kiser, Patrick F.

AU - Herold, Betsy

AU - Smith, James M.

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N2 - Background: Intravaginal rings (IVR) for HIV prevention will likely be used by women on depot medroxyprogesterone acetate (DMPA) hormonal contraception. We used pigtailed macaques to evaluate the effects of DMPA on tenofovir disoproxil fumarate (TDF) IVR pharmacokinetics and viral shedding. Methods: Mucosal tenofovir (TFV) levels were compared in SHIVSF 162p3-negative DMPA-treated (n=4) and normally cycling (n=6) macaques receiving TDF IVRs. Plasma viremia and vaginal shedding were determined in groups of SHIVSF 162p3-positive DMPA-treated (n=6) and normally cycling (n=5) macaques. Results: Similar median vaginal fluid TFV concentrations were observed in the DMPA-treated and cycling macaques over 4 weeks (1.2×105 and 1.1.×105 ng/mL, respectively). Median plasma viremia and vaginal shedding AUC of the DMPA-treated (2.73×107 and 8.15×104 copies/mL, respectively) and cycling macaques (3.98×107 and 1.47×103 copies/mL, respectively) were statistically similar. Conclusions: DMPA does not affect TDF IVR pharmacokinetics or SHIV shedding.

AB - Background: Intravaginal rings (IVR) for HIV prevention will likely be used by women on depot medroxyprogesterone acetate (DMPA) hormonal contraception. We used pigtailed macaques to evaluate the effects of DMPA on tenofovir disoproxil fumarate (TDF) IVR pharmacokinetics and viral shedding. Methods: Mucosal tenofovir (TFV) levels were compared in SHIVSF 162p3-negative DMPA-treated (n=4) and normally cycling (n=6) macaques receiving TDF IVRs. Plasma viremia and vaginal shedding were determined in groups of SHIVSF 162p3-positive DMPA-treated (n=6) and normally cycling (n=5) macaques. Results: Similar median vaginal fluid TFV concentrations were observed in the DMPA-treated and cycling macaques over 4 weeks (1.2×105 and 1.1.×105 ng/mL, respectively). Median plasma viremia and vaginal shedding AUC of the DMPA-treated (2.73×107 and 8.15×104 copies/mL, respectively) and cycling macaques (3.98×107 and 1.47×103 copies/mL, respectively) were statistically similar. Conclusions: DMPA does not affect TDF IVR pharmacokinetics or SHIV shedding.

KW - DMPA and HIV

KW - mucosal HIV shedding

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