A two-year, seven-country study has concluded that women using hormonal contraceptives, particularly injectable forms, are at a greater risk both of acquiring HIV themselves and of passing it on to a male sexual partner. Presenting the results to the International AIDS Society conference (IAS 2011) in Rome yesterday, Renee Heffron of the University of Washington said that strategies are needed to improve access to and uptake of lower-dose contraceptives and non-hormonal methods – such as IUDs, implants, patches or combination injectables.
The new study will be considered alongside the findings of a number of other studies that have also found an association between hormonal contraceptive use and HIV infection in women. However, this link has not been found consistently in all research. Most notably, a five-year study conducted with 6109 women in Zimbabwe, Uganda and Thailand found that neither the combined oral contraceptive pill nor DMPA (Depo-Provera) injections were associated with HIV infection.
The new findings are also notable for their investigation of the effect of contraceptive use on onward transmission to men – a previously unexplored area.
"It’s clear that the benefits of effective hormonal contraception are unequivocal – especially when you think about maternal mortality – and the risk of HIV infection really needs to be balanced with these benefits" Renee Heffron
The data come from an analysis of 3790 serodiscordant couples (i.e. 7580 people) in South Africa, Botswana, Zambia, Tanzania, Uganda, Kenya and Rwanda. In two-thirds of the couples, the female partner was HIV-positive, in one-third, the man.
The couples were recruited either as part of the Partners in Prevention cohort or for the Couples Observational Study (a study of immune correlates of HIV protection). Every three months, data were recorded on contraceptive use and sexual behaviour. HIV-negative partners were tested for HIV at the same frequency; only seroconversions that were determined by gene sequencing to have been acquired from the study partner were included in the analysis.
Most couples were married and had at least one child together, on average. At enrolment around a quarter of couples reported having unprotected sex in the last month. A quarter of couples experienced a pregnancy during the two-year study.
HIV acquisition in women
Overall, 21% of HIV-negative women used hormonal contraception at least once during the study period. Injectable contraception was used at least once by 16% of women and oral contraception was used at least once by 7% of women.
Of the 1314 HIV-negative women, 73 acquired HIV. Incidence among women using contraception was 6.61 per 100 person-years, compared to 3.78 per 100 person-years among women not using contraception.
After adjusting for confounding factors in multivariate analysis, women using any hormonal method had twice the risk of acquiring HIV as other women (hazard ratio 1.98, 95% confidence interval 1.06 – 3.68).
An analysis of women using injectable methods gave similar results. However, the findings were not statistically significant for women using oral contraceptives – this may be because fewer women in the study used oral methods, so there was not statistical power.
HIV transmission to men
Of the HIV-negative men, one-third of their female partners used hormonal contraception at least once during the study. Injectable contraception was used by 27% and oral contraception by 9%.
Of the 2476 men, 59 acquired HIV from their primary partner during the study. HIV incidence in the partners of hormonal contraceptive users was 2.61 per 100 person-years, compared to 1.51 per 100 person-years among men whose partners did not use contraception.
After statistical adjustment, men whose partners used any form of hormonal contraceptive had twice the risk of acquiring HIV as other men (hazard ratio 1.97, 95% confidence interval 1.12 – 3.45).
Again, the findings in relation to injectables were very similar, whereas those in relation to oral contraceptives were not statistically significant.
A possible mechanism for the increased transmission from women to men is that users of hormonal contraceptives had higher levels of genital HIV viral load than other women.
An examination of genital samples from 1691 women – with the figures adjusted for blood viral load and CD4 count – found that women using hormonal contraception were more likely to have detectable genital viral loads and a greater quantity – by 0.14 logs. The difference was driven by injectable users who had a 67% increased odds of having a detectable genital viral load compared to non-users.
“It’s clear that the benefits of effective hormonal contraception are unequivocal – especially when you think about maternal mortality – and the risk of HIV infection really needs to be balanced with these benefits,” researcher Renee Heffron said.
She recommended that women and couples should be counselled about both the HIV risks and the importance of dual contraception – condom use in conjunction with hormonal contraceptive use.
Ward Cates of Family Health International and Professor Helen Rees of the Wits Reproductive Health and HIV Institute both commented that the findings underline the relevance of the intrauterine device (IUD) as a contraceptive choice for women in high-prevalence settings.
Rees noted that the South African policy on contraception was in the process of being revised and would take these findings into account. "The entire policy is being written in the context of HIV, because there is no such thing as a pocket of HIV in our setting," she said.
She noted that, while current thinking was that lower-dose hormonal methods would be safer, this has not actually been empirically tested. She called for randomised controlled trials, which would not be subject to the challenges of bias and confounding factors found in all observational studies (including the one described here).
She also commented that establishing the safety of hormonal methods is particularly important in the light of moves to develop multipurpose health technologies – such as microbicides and vaginal rings – which could simultaneously prevent unwanted pregnancy, HIV infection and other sexually transmitted infections.
Heffron R et al. Hormonal contraceptive use and risk of HIV-1 transmission: a prospective cohort analysis. Sixth International AIDS Conference, Rome, abstract WEAX020620, 2011.