Contraception in HIV prevention trials: injectable hormonal methods more effective?

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Women using injectable (hormonal) contraceptives had a significantly lower rate of pregnancy compared to those using oral contraception in a major HIV prevention study, researchers report in the advance online edition of AIDS.

However, the same study also found that women who used an injectable hormonal contraceptive method were at higher risk of both acquiring and passing on HIV, indicating the dilemma posed for HIV prevention studies and the women who take part in them by the issue of contraception.

Both HIV-positive and negative women who used contraceptive pills were more than twice as likely to become pregnant (aHR: 2.22, p=0.01 and aHR: 2.65, p=0.09, respectively) than those who used injectable contraception.



The result of a statistical test which tells us whether the results of a study are likely to be due to chance and would not be confirmed if the study was repeated. All p-values are between 0 and 1; the most reliable studies have p-values very close to 0. A p-value of 0.001 means that there is a 1 in 1000 probability that the results are due to chance and do not reflect a real difference. A p-value of 0.05 means there is a 1 in 20 probability that the results are due to chance. When a p-value is 0.05 or below, the result is considered to be ‘statistically significant’. Confidence intervals give similar information to p-values but are easier to interpret. 


A chemical messenger which stimulates or suppresses cell and tissue activity. Hormones control most bodily functions, from simple basic needs like hunger to complex systems like reproduction, and even the emotions and mood.


Refers to the mouth, for example a medicine taken by mouth.

inter-quartile range

The spread of values, from the smallest to the largest. The inter-quartile range (IQR) only includes the middle 50% of values and measures the degree of spread of the most common values.


A serodiscordant couple is one in which one partner has HIV and the other has not. Many people dislike this word as it implies disagreement or conflict. Alternative terms include mixed status, magnetic or serodifferent.

The results from this secondary analysis, of a prospective randomised double-blind placebo controlled trial looking at the effect of herpes treatment on HIV transmission, are in keeping with other studies showing injectable contraception is more effective than oral contraception in reducing the likelihood of pregnancy.

Oral contraceptive use significantly reduced the risk of pregnancy among HIV-positive women (aHR: 0.51, p=0.004) but not among HIV-negative women (aHR: 0.64, p=0.3).

Rates of pregnancy were high for both HIV-positive and HIV-negative women (incidence 15.6 and 14.8 per 100 woman-years, respectively). These rates are comparable to other HIV prevention trials as well as in general in sub-Saharan Africa where an estimated one in four (25%) pregnancies is unintended.

Effective contraceptive use in clinical trials looking at new HIV prevention strategies mean minimising protocol-required discontinuation of study products during pregnancy and foetal exposure, note the authors. Recent HIV prevention trials, they add, have required use of an effective contraceptive method to qualify for enrolment.

However, previous previous secondary analyses from the same study have suggested that injectable methods both double the risk of acquiring as well as passing on HIV; and for a woman who is HIV-positive the risk for her to pass on HIV when she is pregnant is also doubled. These analyses, however, are observational, so are inconclusive; some studies support them while others do not.

The association between pregnancy and injectable contraception and HIV transmission may relate to the higher dose of hormones compared to other hormonal contraception methods.

The question of which contraceptive method to use is also of importance for women living with HIV who want to avoid pregnancy. Reducing unwanted pregnancies in women living with HIV is one of the four pillars of the global strategy for prevention of mother-to-child transmission of HIV, yet people living with HIV in sub-Saharan Africa have high levels of unmet need regarding contraceptive advice and supplies.

Reducing unintended pregnancy might also be expected to have an effect on onward transmission of HIV. The Partners in Prevention study also found that pregnancy in women living with HIV doubled the risk of female-to-male HIV transmission.

The authors note that factors identified by other studies as affecting pregnancy rates among African women included younger age, fewer children, living with a male partner and having frequent sex without using condoms.

Yet, few have looked at whether the choice of contraceptive method has an effect upon the incidence of pregnancy in HIV-negative and HIV-positive African women.

Between December 2004 and October 2008, 3408 heterosexual HIV serodiscordant couples were enrolled in the Partners in Prevention HSV/HIV transmission study conducted in 14 sites in seven countries in East and Southern Africa (Botswana, Kenya, Rwanda, South Africa, Tanzania, Uganda and Zambia. The herpes treatment, aciclovir, had no effect on HIV transmission. The authors chose to do a secondary analysis of the findings to determine pregnancy incidence according to the contraceptive method used. (Contraceptive method was not randomly assigned.)

Among the 3354 women - of whom approximately two-thirds were HIV positive and one third HIV negative - the median age was 30. Women had an average of one to two children and reported four (IQR:2-8) sex acts each month. The median follow-up was 1.64 (IQR: 1.21-1.97) and 1.68 (IQR: 1.25-2.00) years for HIV-positive and HIV-negative women, respectively.

Among the very few women using intrauterine devices (IUDs) and implanted contraception, both non-hormonal methods, none became pregnant. These findings add to other reports showing IUD use to be safe and effective in preventing pregnancy among women at risk for HIV, yet its use in sub-Saharan Africa remains very low, note the authors.

“Our data provide additional evidence of the potential for safe and effective long-acting user-independent contraceptive methods to reduce unintended pregnancies among HIV-negative and positive African women.”

Women who relied on their partners to use condoms as the primary contraceptive method in the relationship were around three times more likely to become pregnant than women who used an injectable contraceptive (aHR: 3.39, p<0.001 and aHR: 2.82, p=0.01).

The authors point to qualitative work they have done with serodiscordant couples noting the challenges of consistent and correct condom use, notably for HIV-negative men.

They conclude: “Family planning programmes and HIV prevention trials need innovative way to motivate uptake and sustained use of longer acting less user-dependent contraception for women with or at risk of HIV who do not desire pregnancy and ensure that couples understand the importance of using dual methods for HIV and pregnancy protection.”


Ngure, K et al. Contraceptive method and pregnancy incidence among African women in HIV-1 serodiscordant partnerships. AIDS 25, doi: 10.1097/QAD.0b013e32834f981c, 2011.