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Depo-Provera and HIV


The Issue

Injectable contraceptives like Depo-Provera increase the risk of HIV transmission. A recent meta-analysis conducted in collaboration with the Population Research Institute reviewed a total of 24 studies published in peer-reviewed journals and found a significant increased risk of acquiring HIV when using Depo-Provera and other injectables.

Injectable contraceptives are commonly used worldwide, particularly in Sub-Saharan Africa where the prevalence of HIV remains high. International aid programs that are providing DMPA contraceptives to areas with high HIV prevalence may be contributing to the spread of AIDS.

What is Depo-Provera and DMPA?

Depo-Provera is a pharmaceutical brand owned by Pfizer, Inc. and is the most widely used injectable contraceptive worldwide. Depot medroxyprogesterone acetate, or DMPA, is the active ingredient in Depo-Provera and in other popular DMPA injectables including Depo Sub-Q Provera 104, Sayana Press, and a number of other brands.

DMPA injectables prevent pregnancy for three months. Studies have shown, however, that Depo-Provera can delay a return to fertility for much longer, up to 31 months.i

DMPA injectables are administered as an intramuscular or subcutaneous injection. DMPA consists of large doses of artificial steroids that prevent follicular maturation and ovulation. DMPA has been noted to maintain thick cervical mucus which prevents fertilization. DMPA also causes endometrial thinning which makes the uterine lining hostile to blastocyst implantation in the event that an egg does becomes fertilized.

What Is the Associated Risk of Acquiring HIV with DMPA?

A recent meta-analysis, Brind, et al. (2015), conducted in collaboration with the Population Research Institute, found that the associated risk of acquiring HIV with DMPA usage was significantly higher than for women who did not use DMPA based injectable contraceptives. DMPA was found to increase women’s risk of contracting HIV by 49% compared to women not using steriodal (hormonal) contraceptives (HR = 1.49, 95% CI 1.28-1.73). Over 88% of cross-sectional studies and over 75% of longitudinal studies observed a positive association between HIV acquisition and DMPA use.

These findings were confirmed in earlier, less precise studies comparing the risk of DMPA compared to the general population. Less precise non-prospective studies found that DMPA increased the risk of HIV transmission by over 40% (OR=1.41, 95% CI 1.15-1.73).

These findings are confirmed in two other meta-analyses published that were also published in 2015. Ralph, et al. (2015) in Lancet Infectious Diseases found a pooled hazard ratio of 1.40, 95% CI 1.16-1.69 among DMPA users. Morrison, et al. (2015) in PLoS Medicine also found similar results with an adjusted hazard ratio of 1.50, 95% CI 1.24-1.83 for DMPA. All three meta-analyses found that the risk of acquiring HIV with DMPA is 40-50% higher than the comparison group.

“Risk of HIV Infection in Depot-Medroxyprogesterone Acetate (DMPA) Users: A Systematic Review and Meta-Analysis”
Joel Brind, Ph.D.; Steven J. Condly, Ph.D.; Steven W. Mosher, M.S., M.A.; Anne R. Morse, B.A.; and Jennifer Kimball, Be.L.
Volume 30, Issue 2, Article 2

Figure 1: Hazards of HIV Acquisition with Depot Medroxyprogesterone Acetate: Pooled Hazard Ratio

Figure 1

How Does DMPA Increase the Risk of HIV Acquisition?

Researchers are not entirely certain why women who use DMPA injectables contract HIV at higher rates than the general population. A number of likely mechanisms of action have been proposed.

DMPA is an artificial steroid made to mimic the effects of natural endogenous progesterone, a hormone that helps regulate the menstrual cycle and is crucial during pregnancy for the health of the fetus. One of the effects of progesterone is to attenuate the immune system’s inflammatory response to allow the body to accept the embryo during pregnancy. This attenuation of the immune system could also make it easier for the HIV virus to cause an infection.

Studies have shown that, unlike endogenous progesterone, DMPA has an affinity not only for the progesterone receptor, but also the glucocorticoid receptor (GR) and the androgen receptor.ii MPA has been found to mediate the upregulation or downregulation of various pro-inflammatory and anti-inflammatory cytokines and chemokines through, as some studies have found, MPA’s affinity for the GR.iii

One study found that, in the presence of concentrations of MPA in similar to serum levels of MPA found in women after receiving a DMPA injection, MPA significantly increases transcytosis of HIV across genital epithelial cells in vitro.iv Epithelial layers in the genital tract are crucial preventing the HIV virus from reaching stromal tissues where active infection of target leukocytes such as CD4+ T cells and macrophages is easily effected. T cells cultured in epithelial cells challenged with a CRCX4-tropic strain of HIV and treated with MPA have been observed in vitro to produce significantly higher levels of HIV viral replication than estradiol treated cells.v

What Has Been the Response among Government Agencies Involved in International Aid Programs, the U.N., and NGOs that Promote DMPA Contraception Overseas?

International Aid Programs and non-governmental organizations (NGOs) have largely ignored the recent evidence suggesting a strong association between DMPA and HIV acquisition. In spite of the evidence indicating an associated risk, government agencies and NGOs continue to provide over $75 million USD per year in DMPA injectables, mostly to Sub-Saharan African countries.

Figure 2 shows the expenditures by the top seven government agencies and NGOs involved in external procurement of contraceptives as reported to the United Nations Population Fund (UNFPA). Figure 2 shows the level of funding in U.S. dollars for injectable contraceptives. It is estimated that over 70% of injectable contraceptives procured by government and U.N. agencies and NGOs are DMPA based injectables.

Figure 2: Government Agency and NGO Annual Expenditures on Injectable Contraceptives*,1





United Nations Population Fund (UNFPA)





United States Agency for International Development (USAID)





Department for International Development (DFID )





International Planned Parenthood Federation (IPPF)





KfW (Kreditanstalt für Wiederaufbau)





Marie Stopes International (MSI)





Population Services International (PSI)










*Includes figures for Norethisterone, Estradiol, and other non-DMPA based injectables

NA—data not available

1. Source: UNFPA, External Procurement Support Reports, 2010–2013.

Figure 3: Funding for Injectable Contraceptives Worldwide, 2000–2013

Figure 3

International external procurement of injectable contraceptives have been shipped primarily to Sub-Saharan African countries, some 70% vi of all externally procured injectables worldwide from 2012–2013.

Figure 4: External Procurement of Injectable Contraceptives in Sub-Saharan Africa and Worldwide, 2012–2013

Figure 4


The United Nations Population Fund (UNFPA) and the United States Agency for International Development (USAID) have been the two biggest players in procuring DMPA based injectable contraceptives in developing countries. Figure 5 shows the number of doses of injectable contraceptives provided through USAID in Sub-Saharan African countries each year since 2000. Recently USAID has been behind efforts in promoting Sayana Press, a Uniject system DMPA injectable intended for self-administration for one-time use as a subcutaneous injection.

Figure 5: Number of Doses of Injectable Contraceptives Provided by USAID in Sub-Saharan Africa, 2000–2014

Figure 5

From 2012–2013, international aid programs and NGOs shipped over 130 million vials, ampoules, and syringes for injectable contraceptives to Sub-Saharan African countries.vii Figure 6 shows the external procurement of injectable contraceptives to select countries with a high prevalence of HIV. To compare, the median estimated percentage of adults (15–49 years of age) living with HIV in the United Kingdom in 2013 was 0.3% according to the World Health Organization (WHO).

Figure 6: Distribution of Injectable Contraceptives to Select Countries with High Prevalence of HIV, 2012–2013

Quantity of injectable contraceptives shipped, 2012–20131

Median Estimated Percentage of Persons, 15–49, Living with HIV, 20132

Estimated Number of Persons, 15–49, Living with HIV, 20132,3

Avg. Number of Injectable Contraceptive Doses per Woman, 15–49, 2012–20133




170,000 – 180,000





230,000 – 260,000





1,000,000 – 1,200,000





830,000 – 930,000





1,100,000 – 1,400,000





710,000 – 800,000





1,100,000 – 1,300,000





1,200,000 – 1,400,000





2,400,000 – 2,800,000





140,000 – 170,000





98,000 – 110,000





490,000 – 630,000


Democratic Republic of the Congo



290,000 – 420,000





44,000 – 53,000


1) UNFPA, External Procurement Support Reports, 2012–2013 2) WHO, 2013 3) Figures based on United Nations, Department of Economic and Social Affairs, Population Division (2015). World Population Prospects: The 2015 Revision

Figure 7: Government Agency and NGO Annual Expenditures on Injectable Contraceptives in Africa

Figure 7

Figure 8: Prevalence of HIV in Africa among Adults (15–49)

Figure 8

The Solution

At present, the research clearly indicates that women exposed to DMPA in developing countries and in regions where HIV prevalence remains high are placed at a significantly greater risk of contracting HIV. Those involved with decision making in international aid programs should take note of the strong association between DMPA and HIV and should consider the evidence on the issue when planning and implementing aid programs. In the interest of public health, government agencies and the UNFPA should cease providing funding for DMPA injectable contraceptives at least until or unless it can be proven that DMPA does not place women at a greater risk of acquiring HIV.

In light of the evidence, the World Health Organization should revise its current recommendation that DMPA be provided without restriction (MEC Category 1), even to women at risk of contracting HIV. The WHO’s denial of an association between HIV and DMPA is contrary to what the data shows. The failure on the part of the WHO to recommend that women be provided with accurate information as to the risks associated with DMPA is inexcusable.

Those considering using DMPA, especially in high risk scenarios, should be warned of the associated risks of contracting HIV. The WHO’s recommendation for the provision of condoms, among even serodiscordant couples who choose DMPA, is irresponsible and provides couples with a false sense of security. Ralph, et al. (2015) found an increased risk of HIV acquisition even when accounting for condom use. Condoms frequently fail and typical use is much less than consistent, especially in developing regions and among the young. The promotion of condoms and injectable contraceptives are contrary to the cultural sensitivities and beliefs among significant minorities in Sub-Saharan Africa. Continued promotion in these contexts is intrusive and culturally insensitive.

AIDS and HIV prevalence remains high throughout much of Sub-Saharan Africa and the continued promotion of DMPA injectable contraceptives, without informing women of the significant risks involved in their use, constitutes a violation of human rights.

i See Full Prescribing Information for DEPO-PROVERA CI.

ii Africander, et al. (2011)

iii Govender, et al. (2014)

iv Ferreira, et al. (2015)

v Ferreira, et al. (2015)

vi Assuming figures in UNFPA, Contraceptives and Condoms for Family Planning and STI & HIV Prevention: External Procurement Report, 2012 & 2013.

vii UNFPA, Contraceptives and Condoms for Family Planning and STI & HIV Prevention: External Procurement Report, 2012 & 2013.


Africander D, Louw R, Verhoog N, Noeth D, Hapgood JP. Differential regulation of endogenous pro-inflammatory cytokine genes by medroxyprogesterone acetate and norethisterone acetate in cell lines of the female genital tract. Contraception. 2011; 84(4): 423-35. doi: 10.1016/j.contraception.2011.06.006.

Brind, Joel, Steven Condly, Steven W. Mosher, Anne Morse, Jennifer Kimball. “Risk of HIV infection in depot-medroxyprogesterone acetate (DMPA) users: a systematic review and meta-analysis.” Issues in Law & Medicine 30, no.2 (2015): 129–139.

Ferreira VH, Dizzell S, Nazli A, Kafka JK, Mueller K, Nguyen PV, Tremblay MJ, Cochrane A, Kaushic C. Medroxyprogesterone acetate regulates HIV-1 uptake and transcytosis but not replication in primary genital epithelial cells, resulting in enhanced T-cell infection. The Journal of Infectious Diseases. 2015; 211:1745–1756.

Govender Y, Avenant C, Verhoog NJD, Ray RM, Grantham NJ, Africander D, and Hapgood JP. The Injectable-Only Contraceptive Medroxyprogesterone Acetate, Unlike Norethisterone Acetate and Progesterone, Regulates Inflammatory Genes in Endocervical Cells via the Glucocorticoid Receptor. PLoS One. 2014; 9(5): e96497. doi: 10.1371/journal.pone.0096497.

Huijbregts, Richard P. H., E. Scott Helton, Katherine G. Michel, Steffanie Sabbaj, Holly E. Richter, Paul A. Goepfert, Zdenek Hel. “Hormonal contraception and HIV-1 infection: medroxyprogesterone acetate suppresses innate and adaptive immune mechanisms.” Endocrinology 154, no. 3 (2013): 1282-1295. doi: 10.1210/en.2012-1850.

Marx, P. A., A. I. Spira, A. Gettie, P. J. Dailey, R. S. Veazey, A. A. Lackner, C. J. L., C. J. Miller, L. E. Claypool, D. D. Ho, N. J. Alexander. “Progesterone implants enhance SIV vaginal transmission and early virus load.” Nature Medicine 2, no. 10 (1996): 1084-1089.

Morrison, Charles S., Pai-Lien Chen, Cynthia Kwok, Jared M. Baeten, Joelle Brown, Angela M. Crook, Lut Van Damme, Sinead Delany-Moretlwe, Suzanna C. Francis, Barbara A. Friedland, Richard J. Hayes, Renee Heffron, Saidi Kapiga, Quarraisha Abdool Karim, Stephanie Karpoff, Rupert Kaul, R. Scott McClelland, Sheena McCormack, Nuala McGrath, Landon Myer, Helen Rees, Ariane van der Straten, Deborah Watson-Jones, Janneke H. H. M. van de Wijgert, Randy Stalter, Nicola Low. “Hormonal contraception and the risk of HIV acquisition: an individual participant data meta-analysis.” PLoS Medicine 12, no. 1 (2015). doi:10.1371/journal.pmed.1001778.

Mosher, Steven W. Population Control: Real Costs, Illusory Benefits. (New Brunswick: Transaction Publishers, 2009).

Namibia Ministry of Health and Social Services (MoHSS) and ICF International. The Namibia Demographic and Health Survey 2013. (Windhoek, Namibia & Rockville, Maryland, USA: MoHSS and ICF International, 2014).

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