Contraceptive jab 'linked to increased HIV risk'

“Contraceptive injections moderately increase a woman’s risk of becoming infected with HIV,” The Guardian reports.

The headline was prompted by an analysis of 12 studies that looked at whether the use of hormonal contraception, such as the oral contraceptive pill, increases the risk of contracting HIV.

All of the studies involved were conducted in sub-Saharan Africa in low- and middle-income countries.

Researchers found a link between a common injectable form of contraception called depot medroxyprogesterone acetate (Depo-Provera) and the risk of HIV. No link was found with other types of hormonal contraception.

But these results do not prove the depot injection directly increases the risk of HIV. The studies included varied in their design and methods, and have several potential sources of bias.

Any link could be down to behavioural patterns rather than medical reasons. For example, women who know they have an effective long-term contraceptive may forget about the risks of sexually transmitted infections.

Hormonal contraception, including injections or oral tablets, can be an extremely effective form of contraception. But it won’t protect you against sexually transmitted infections.

It is worth discussing with your health professional and making sure you are using the method that is most effective, convenient and safest for you, depending on your circumstances.  

Where did the story come from?

The study was carried out by researchers from the University of California and received no financial support.

It was published in the peer-reviewed medical journal, The Lancet.

The Mail Online correctly reports the main findings of this study, but would benefit from highlighting that the findings do not prove a causal association between the depot injection and HIV risk, a point clearly made by the researchers in the original publication.

The Guardian’s reporting of the study is more measured and highlights how for women in poorer countries, an unwanted pregnancy may pose a greater threat to health and wellbeing than HIV. Rates of maternal death occurring during or shortly after pregnancy remain high in many sub-Saharan countries.

What kind of research was this?

This was a systematic review that aimed to search the global literature to find studies examining whether the use of hormonal contraception, such as the oral contraceptive pill or contraceptive injections, increase the risk of contracting HIV.

The researchers say previous study into whether there could be an associated risk has been inconsistent. They pooled the results of different studies in a meta-analysis.

A systematic review and meta-analysis is the best way of identifying and looking at all evidence that has addressed the particular question of interest.

But this type of research is always going to have some limitations reflecting the strength and quality of the underlying studies being reviewed.

It is unlikely a trial would be conducted that would allocate women to hormonal contraception or not, purely to see if this increased their risk of getting HIV.

Instead, the studies are likely to be observational or trials that have primarily been investigating other things.

This means there is potential that associations are being influenced by confounders. In short, other factors linked to contraceptive use, such as lifestyle behaviours, are themselves influencing the risk of HIV, rather than contraceptives directly. 

What did the research involve?

The researchers built on the findings of a previous 2012 World Health Organization (WHO) review.

For the current review, they searched one literature database for English-language articles published from December 2011 onwards that included the terms “hormonal contraception”, “HIV/acquisition”, “injectables”, “progestin”, and “oral contraceptive pills”.

They included studies that assessed hormonal contraceptives, included women without HIV at the study start, and were prospective in nature (following people over time).

Eligible studies were also required to have followed up at least 70% of their participants, have adjusted at least for a woman’s age and condom use (to try to minimise confounding from these factors), and been conducted in a low- or middle-income country.

Separate researchers individually assessed the methods and quality of the eligible studies, and extracted data.

What were the basic results?

A total of 12 studies met the criteria for being included. All of these studies were conducted in low- or middle-income African countries.

They included large numbers of women, from between 400 to more than 8,000, and lasted between one and three years.

Three studies were observational studies designed specifically to examine the contraception-HIV connection.

The remaining studies included women taking part in trials investigating interventions for HIV prevention, often antivirals.

One trial involved women taking possible preventative treatment for cervical cancer.

Two studies included women at high risk of HIV: commercial sex workers or women whose partner was HIV positive.

The remaining studies included women in the general population. The women’s ages ranged from about 25 to 40 years.

Ten of the studies included women taking oral hormonal contraception (either combined pill or progestogen only), while in 10 studies women were taking the injectable progestogen depot medroxyprogesterone acetate.

In the remaining five they were taking another type of injectable progestogen (norethisterone enanthate).

Most trials compared this with a non-hormonal method of contraception or no method of contraception at all.

Pooled results of 10 studies of depot medroxyprogesterone acetate found it was associated with a 40% increased risk of HIV (hazard ratio [HR] 1.40, 95% confidence interval [CI] 1.16 to 1.69).

This risk was slightly lower when restricted to the eight studies of women in the general population (pooled HR 1.31, 95% CI 1.10 to 1.57).

There was no evidence of an increased risk of HIV in women taking the other injectable progestogen, norethisterone enanthate (pooled HR 1.10, 0.88 to 1.37).

Pooled analysis of 10 studies did not find the use of oral contraceptive pills increased the risk of HIV (HR 1.00, 0.86 to 1.16).

How did the researchers interpret the results?

The researchers concluded their findings “show a moderate increased risk of HIV acquisition for all women using depot medroxyprogesterone acetate, with a smaller increase in risk for women in the general population.

“Whether the risks of HIV observed in our study would merit complete withdrawal of depot medroxyprogesterone acetate needs to be balanced against the known benefits of a highly effective contraceptive.”

Conclusion

This is a well-conducted systematic review that has aimed to identify all studies investigating the possible link between hormonal contraceptive use and HIV.

It did not find an association between HIV risk and oral contraceptive use (the combined pill, also known as “the pill”, or the progestogen-only “mini-pill”).

But it did find an increased risk of HIV in 10 studies where women used the commonly used injectable form of contraception, depot medroxyprogesterone acetate (UK brand name Depo-Provera). The depot injection provides effective contraception for three months.

The other injectable progestogen contraceptive (UK brand name Noristerat) was not associated with this risk, although only five studies looked at this type of contraception.

The review benefits from its strict inclusion criteria, only including prospective studies that followed up at least 70% of their participants and adjusted for the women’s age and condom use.

However, the possibility of selection bias and confounding from other factors still cannot be ruled out.

Only three out of the 12 studies directly set out to look at whether hormonal contraceptive use was linked to HIV. And these were still observational studies, meaning the women chose their method of contraception.

The remaining studies were trials investigating preventative treatments for HIV or cervical cancer, so they were not designed to look for this association.

As women in all of the 12 included studies were selecting their own contraceptive use, this could mean there are other differences (such as health and lifestyle) between the women who chose to use this form of contraception and those who chose to use non-hormonal methods.

This could mean the contraception may not have been the sole or direct cause of the link seen.

Two of the studies also included high-risk women, such as commercial sex workers or women whose partner was HIV positive.

Exclusion of these two studies did decrease the association between depot injection use and HIV, although the link remained statistically significant.

As the researchers themselves acknowledge, the studies they included “are inherently prone to bias and cannot be used to address whether the association between hormonal contraception and HIV is causal”.

This lack of proof of a direct causal association is a key point to bear in mind for this review.

Other important limitations the authors raise are the potential for publication bias – only studies finding significant results were published.

As the authors also say, it is difficult for them to be sure of the timing of contraception use in relation to subsequent HIV infection.

Although the studies included contraceptive methods that are used in the UK, none of these studies were UK-based and all were conducted in sub-Saharan Africa.

When considering the increase in risk of HIV, we need to remember the prevalence of HIV in these countries is much higher than it is the UK. Therefore, the baseline risk of acquiring HIV in these countries is already much higher than that in the UK.

The 40% risk increase with the depot injection is a relative increase of what would comparatively be a very small baseline risk in the UK.

Contraceptive injections such as Depo-Provera are extremely effective – estimated to have a failure rate of less than one in 330 – but, like any form of hormonal contraception, they do not provide protection against sexually transmitted infections.

Only condoms protect against HIV and other sexually transmitted infections, such as chlamydia and genital warts.

It is worth discussing with your health professional and making sure you are using the method that is most effective, convenient and safest for you, depending on your circumstances. 

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.

Links To The Headlines

Contraceptive injection raises risk of HIV, research warns. The Guardian, January 9 2015

Women on the contraceptive jab have a greater risk of contracting HIV than those using other forms of birth control or NONE at all. Mail Online, January 9 2015

Links To Science

Ralph LJ, McCoy SI, Shu K, et al. Hormonal contraceptive use and women’s risk of HIV acquisition: a meta-analysis of observational studies. The Lancet Infectious Diseases. Published online January 9 2015