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 C. Herold; James M. Smith

doi:10.1111/jmp.12299

Repeated administration of high-dose depot medroxyprogesterone acetate does not alter SHIV_SF _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 C. Herold, James M. Smith^*

^*Corresponding author for this work

Biomedical Engineering

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

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 SHIV_SF _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 SHIV_SF _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 language	English (US)
Pages (from-to)	129-136
Number of pages	8
Journal	Journal of Medical Primatology
Volume	46
Issue number	4
DOIs	https://doi.org/10.1111/jmp.12299
State	Published - Aug 2017

Keywords

DMPA and HIV
SHIV
mucosal HIV shedding
nonhuman primates
tenofovir pharmacokinetics

ASJC Scopus subject areas

Animal Science and Zoology
veterinary(all)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1111/jmp.12299

Cite this

Srinivasan, P., Zhang, J., Dinh, C. T., Teller, R. S., McNicholl, J. M., Kiser, P. F., Herold, B. C., & Smith, J. M. (2017). Repeated administration of high-dose depot medroxyprogesterone acetate does not alter SHIV_SF _162p3 viral kinetics and tenofovir pharmacokinetics when delivered via intravaginal rings. Journal of Medical Primatology, 46(4), 129-136. https://doi.org/10.1111/jmp.12299

@article{d4c19bbce0e34c92acac9c6db98078f1,

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

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.",

keywords = "DMPA and HIV, SHIV, mucosal HIV shedding, nonhuman primates, tenofovir pharmacokinetics",

author = "Priya Srinivasan and Jining Zhang and Dinh, {Chuong T.} and Teller, {Ryan S.} and McNicholl, {Janet M.} and Kiser, {Patrick F.} and Herold, {Betsy C.} and Smith, {James M.}",

note = "Funding Information: Funding information This study was supported by U19AI03461. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of the NIH or the Centers for Disease Control and Prevention. We acknowledge the following members of the CDC DHAP Laboratory Branch/Preclinical Evaluation Team for their contributions to our non-human primate research: David Garber, James Mitchell, Leecresia Jenkins, Frank Deyounks, Shanon Ellis, and Kristen Kelley for animal technical assistance. We also gratefully acknowledge Chou-Pong Pau at the CDC DHAP Laboratory Branch/Analytical Chemistry Team for drug analyses of PK samples. Publisher Copyright: {\textcopyright} 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd",

year = "2017",

month = aug,

doi = "10.1111/jmp.12299",

language = "English (US)",

volume = "46",

pages = "129--136",

journal = "Journal of Medical Primatology",

issn = "0047-2565",

publisher = "Blackwell Munksgaard",

number = "4",

}

Srinivasan, P, Zhang, J, Dinh, CT, Teller, RS, McNicholl, JM, Kiser, PF, Herold, BC & Smith, JM 2017, 'Repeated administration of high-dose depot medroxyprogesterone acetate does not alter SHIV_SF _162p3 viral kinetics and tenofovir pharmacokinetics when delivered via intravaginal rings', Journal of Medical Primatology, vol. 46, no. 4, pp. 129-136. https://doi.org/10.1111/jmp.12299

Repeated administration of high-dose depot medroxyprogesterone acetate does not alter SHIV_SF _162p3 viral kinetics and tenofovir pharmacokinetics when delivered via intravaginal rings. / Srinivasan, Priya; Zhang, Jining; Dinh, Chuong T. et al.
In: Journal of Medical Primatology, Vol. 46, No. 4, 08.2017, p. 129-136.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

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 C.

AU - Smith, James M.

N1 - Funding Information: Funding information This study was supported by U19AI03461. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of the NIH or the Centers for Disease Control and Prevention. We acknowledge the following members of the CDC DHAP Laboratory Branch/Preclinical Evaluation Team for their contributions to our non-human primate research: David Garber, James Mitchell, Leecresia Jenkins, Frank Deyounks, Shanon Ellis, and Kristen Kelley for animal technical assistance. We also gratefully acknowledge Chou-Pong Pau at the CDC DHAP Laboratory Branch/Analytical Chemistry Team for drug analyses of PK samples. Publisher Copyright: © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

PY - 2017/8

Y1 - 2017/8

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 - SHIV

KW - mucosal HIV shedding

KW - nonhuman primates

KW - tenofovir pharmacokinetics

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U2 - 10.1111/jmp.12299

DO - 10.1111/jmp.12299

M3 - Article

C2 - 28748662

AN - SCOPUS:85025842713

SN - 0047-2565

VL - 46

SP - 129

EP - 136

JO - Journal of Medical Primatology

JF - Journal of Medical Primatology

IS - 4

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