Novel contraceptive method preventing HIV transmission and unwanted pregnancy

A recent (2014) publication by Kiser et. al. in the Public Library of Science: One (PLOS ONE) showed promising results for a new contraceptive device, in the form of a intra-vaginal ring, which is able to prevent unwanted pregnancies and the transmission of HIV (Human-Immunodeficiency Virus). Once in the vagina it secretes two separate drugs, levonorgestrel and Tenofovir for a period of 90days. These drugs work independently to stop unwanted pregnancy and HIV transmission. 

Tenofovir is an anti-retroviral drug commonly used in treatment of HIV infection. It belongs to the class of drugs known as nucleoside reverse transcriptase inhibitors (NRTIs). Tenofovir stops HIV from reproducing in the human host cells by inhibiting its ability to insert its viral genome into our human genome [More information on this pathway here]. Thus the virus is unable to reproduce and the infection is transient; by the same mechanism Tenofovir also blocks genital herpes virus (HSV-2) infection.

Levonorgestrel is a drug commonly known as 'the morning after pill'. It is generally taken orally within 72 of unprotected sex to avoid unwanted pregnancy (with a time-dependent decrease in efficacy). Recently it has shown efficacy as a pregnancy prophylactic in women, as it prevents unwanted pregnancies when applied to in the vagina at 20ug/day by intra-vaginal rings in women. 

Kiser et. al. have combined the two drugs into one ring. Both drugs are secreted at clinically appropriate levels for 90 days, meaning that to be protected year round women would have to change their rings quarterly. While this study was only a test of efficacy of the drugs in rabbits, translation to human medicine is promising due to previous successes of levonorgestrel-secreting intra-vaginal rings.

Why Do We Care?

According to the WHO one of leading causes of death in low and middle-income countries of women aged 15-19 years is from complications arising from pregnancy and childbirth. These same women are also 50% more likely to have stillbirths than mothers over 20 years old. The use of contraception to prevent early pregnancy could improve the individual's life span and quality of life.. 

Physical and social barriers to contraception are present throughout the world, but are especially prevalent in the developing world. 2014 WHO contraceptive guidelines indicate that as many as 222 million women who want access to contraception do not have it. This is most common in vulnerable populations (the poor, those living with HIV, people in low and middle income countries). The reasons are many, but are often are due to lack of contraceptive availability and the cultural practices around contraception. Senior author on these WHO guidelines Dr Marleen Temmerman speaks out about the what it can be like to seek contraception with these social pressures:

"Many women are coerced in their decision to be pregnant or not to be pregnant by their family, their father, the mother, the husband, the mother-in-law, the society, the community, by cultural and religious obstacles. But sometimes also by the governments, who are forcing tubal ligation, forcing sterilization onto some women and not giving access to others." (Dr. Temmerman, WHO)

The potential advantage of the device being trialed by Kiser et. al. is that it may provide some more autonomy and self-determination for women seeking birthing control. Once the product has been inserted intra-vaginally there is no outward notification of contraception, potentially alleviating social pressures on the woman whilst simultaneously providing protection. Nevertheless, despite the development of effective, discreet contraceptives, the social and cultural paradigms of contraceptive use need to be shifted to ensure viable use of contraception in 'at risk' sub-populations.

"It is not just about increasing [access], it’s also about increasing knowledge. It is vital for women—and men—to understand how contraception works, be offered a choice of methods, and be happy with the method they receive.” (Dr. Temmerman, WHO)

In 2011 there were 34 million people living with HIV globally, 1.7 million of which died from Acquired Immunodeficiency Syndrome (AIDS)-related illnesses. Unfortunately the prevalence of HIV is generally higher amongst people from lower socio-economic areas, often in developing countries (see figure below), perhaps due to inadequate contraception access.

Prevalence of HIV by WHO region, 2011. http://www.who.int/gho/hiv/en/

Whlist pre-exposure prophalactics (PrEP) are available (taken prior to exposure, they reduce the risk of HIV infection) in addition to preventative barrier methods, the benefits of use are minimal due to difficulties in drug adherence and inadequate access. While this intra-vaginal ring reduces adherence problems by supplying the dose directly for up to three months, accessibility to these 'at risk' populations remains unclear.  

In the developed world HIV transmission and unwanted pregnancies still contribute an incredibly significant burden on people (social and cultural stigma, financial cost, relationship deterioration) and the healthcare system (extensive financial burden). Kiser et al's rings can be directly compared to the implantable, etonogestrel containing, 'Implanon' contraceptive, yet it has the additional advantage of providing resistance to HIV infection. This would allow discordant couples (where one partner is HIV positive and the other is negative) to have 'unprotected' sex without transmitting the virus and having unplanned pregnancies.  

Limitations

Primarily the applicability of this study is limited by the fact that so far efficacy has only been shown in rabbits. Further research is needed to show the same levels of prevention in human females. 

Secondarily the new contraceptive method fails to address other sexually transmitted infections (STIs) such as hepatitis viruses, syphilis and chlamydia. Condoms remain the best method to prevent STIs and unwanted pregnancies (with an estimated 99% protection rate if used properly). 

Summary

The amalgamation of a preventative device for both unwanted pregnancy and HIV transmission by Kiser and colleagues provides a novel method to tackle these related problems; further research is necessary to establish efficacy in human females. In the future, the intra-vaginal ring  may allow discordant couples to practice safe unprotected sex. Use of this contraceptive device in the developing world may provide protection for women in social structures that do not openly support contraceptive use, thereby reducing HIV infection within these high-risk groups and subsequently in the developed world. It is evident that access to novel contraceptive methods is simply not enough; sexual education is a necessity in changing social and cultural practices around contraceptive use.