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


METHODS
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).


CONCLUSIONS
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.
Jessica
J
Radzio
Krisztina
K
Hanley
James
J
Mitchell
Shanon
S
Ellis
Frank
F
Deyounks
Leecresia T
LT
Jenkins
Debra
D
Hanson
Walid
W
Heneine
J Gerardo
JG
García-Lerma
D000818:Animals; D003271:Contraceptive Agents, Female / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D008254:Macaca nemestrina; D017258:Medroxyprogesterone Acetate / Q000008:administration & dosage* / Q000009:adverse effects; D009092:Mucous Membrane / Q000821:virology*; D010949:Plasma / Q000737:chemistry / Q000821:virology*; D012367:RNA, Viral / Q000097:blood; D015302:Simian Immunodeficiency Virus / Q000302:isolation & purification*; D014766:Viremia; D017201:Virus Shedding / Q000187:drug effects*
D003271:Contraceptive Agents, Female; D012367:RNA, Viral; D017258:Medroxyprogesterone Acetate