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

Radzio, Jessicaa; Hanley, Krisztinab; Mitchell, Jamesa; Ellis, Shanona; Deyounks, Franka; Jenkins, Leecresia T.a; Hanson, Debraa; Heneine, Walida; García-Lerma, J. Gerardoa

doi: 10.1097/QAD.0000000000000294
Basic Science

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 3 mg 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.

aLaboratory Branch, Division of HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention

bDepartment of Pathology, Emory University, Atlanta, Georgia, USA.

Correspondence to J. Gerardo Garcia-Lerma, Laboratory Branch, Division of HIV/AIDS Prevention, MS G45, 1600 Clifton Road, Atlanta, GA 30329, USA. Tel: +1 404 639 4987; fax: +1 404 639 1174; e-mail: GGarcia-Lerma@cdc.gov

Received 11 December, 2013

Revised 17 April, 2014

Accepted 26 April, 2014

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© 2014 Lippincott Williams & Wilkins, Inc.