No significant link between injectable contraceptives and HIV risk, but questions still remain

Two studies presented at the International Microbicides Conference this week failed to completely dispel the association between injectable contraceptives and an increased risk of acquiring HIV.

The field of HIV prevention was thrown into confusion last year when a large international study found that women taking hormonal contraceptives appeared to have twice the risk of acquiring HIV or, if they were already HIV positive, of transmitting it. Later studies confirmed that the risk appeared to be restricted to injectable contraceptives. To add further confusion to the scene, a large South African study published this January found no significant link between hormonal contraceptives and HIV and a study presented at the Conference on Retroviruses and Opportunistic Infections (CROI) in March found only a marginally significant association. This left global public health organisations such as the World Health Organization (WHO) faced with a dilemma, especially as the most widely used injectable contraceptive, depot medroxy-progesterone acetate (DMPA, Depo-Provera) is the most commonly used contraceptive in Africa. Would more lives be saved if they told women not to use DMPA and therefore fewer became HIV positive? Or would more women (and children) then die as a result of deaths during childbirth and infancy?

A new analysis presented at Microbicides 2012 found that, compared with women not using any hormonal contraception, the HIV infection rate was not significantly raised in women taking DMPA, although they did have a nearly significantly higher risk of infection than women taking oral contraceptive pills. It was found that genital herpes (HSV-2) infection may also be a part of this story, with a particularly raised risk of HIV infection in women who were both HSV-2 positive and used DMPA.

This analysis was of 3087 women who took part in HPTN 035, a large multi-country trial of the candidate microbicide PRO2000 that reported in February 2009. The women had a mean age of 26 and 62% were married. Seven out of every ten were using some form of hormonal contraception, with 51% using DMPA and 21% oral contraceptive pills. Thirteen per cent relied on condoms for contraception, 5% had been sterilised and 9% used no contraception.

However, patterns of contraception use varied widely according to study centre. In centres in Malawi, for instance, two-thirds of the women were using DMPA and only 8% oral contraceptives, whereas in Harare, Zimbabwe, 72% of women were taking oral contraceptives. Similarly, condom used ranged from 2% in Harare to 27% in Durban in South Africa.

After a mean 1.7 years of follow-up, annual HIV incidence in study participants was 4%, ranging from 9% in Hlabisa in KwaZulu Natal to 1.4% in Lilongwe, Malawi, while pregnancy incidence was 11.5% a year overall.

HIV incidence in DMPA users overall was 4.27% a year and this was not statistically different from mean incidence (hazard ratio, 1.42, 95% confidence interval 0.78-2.58). HIV incidence in oral contraceptive users was also not significantly different from the mean (hazard ratio 0.86, 95% confidence interval 0.41-1.83).

Certain STIs were associated with higher risk of HIV: women with gonorrhoea were six times more likely to acquire HIV. There was a particularly strong likelihood of HIV acquisition in women who had HSV-2 and were on DMPA: they were 8.2 times more likely to acquire HIV, though this just failed to reach statistical significance (p=0.07). It is not known if this risk is associated with already having HSV-2, or whether HIV acquisition is associated with HSV-2 acquisition. Further analyses are being done.

Meanwhile, another study also found a similarly raised risk of HIV infection of women taking hormonal contraceptives (not, in this study, differentiated between oral and injectable users). In a study of 606 women taking part in a microbicides feasibility study, 45% of the women were using hormonal contraceptives and, of these, 86% were using injectable ones. HIV incidence was raised 40% in women taking hormonal contraceptives but this was not statistically significant (p=0.32).

Overall, the doubling of HIV risk found in women taking injectable contraceptives in last year's study has not been upheld. Yet studies continue to show a slightly increased risk for women taking DMPA which is not, due to the numbers involved, statistically significant. For now the question as to whether injectable contraceptives increase HIV risk remains open.