A DMPA (Depot Medroxyprogesterone Acetate) Dose that Models Human Use and its Effect on Vaginal SHIV Acquisition Risk
Published Date:Aug 1 2016
Source:J Acquir Immune Defic Syndr. 72(4):363-371.
Pubmed Central ID:PMC4930010
Funding:CC999999/Intramural CDC HHS/United States
Y01 AI000681-02/AI/NIAID NIH HHS/United States
Hormonal contraception with DMPA may increase HIV acquisition risk, but observational human studies are inconclusive, and animal models can help investigate this risk. Here we test the impact of a low DMPA dose, designed to resemble human contraceptive use, on SHIV acquisition risk in pigtail macaques (Macaca nemestrina).
Macaques metabolize DMPA faster than humans. We previously identified a per-weight DMPA dose and administration frequency that achieves long-lasting suppression of ovulation in macaques. Eight macaques were given 1.5 mg/kg DMPA monthly, while eleven were untreated controls. For comparison, women receive 150 mg (approximately 2 mg/kg) every 3 months. We exposed monkeys to 20 sub-optimal SHIV challenges, designed to slowly infect half of controls and allow increased infection in the DMPA group.
It took a median 5.5 viral challenges to infect DMPA-treated macaques, and 9 challenges for controls (p=0.27; exact conditional logistic regression). The exact odds ratio was 2.2 (CI 0.6 – 8.3). Ovulation was suppressed, and the vaginal epithelium was thinned after DMPA-treatment in all animals (mean 30 and 219 micrometers in DMPA-treated and control macaques, respectively, p=0.03, t-test using the Satterthwaite degrees-of-freedom approximation).
SHIV infections in DMPA treated macaques were 2.2 times those of controls, but this was not statistically significant. The result is remarkably similar to studies of human DMPA use, which have shown HIV risk increases of a similar magnitude and of variable significance. Taken together with previous studies of higher DMPA doses in macaques, the results suggest a dose-dependent effect of DMPA on SIV or SHIV acquisition.
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