Hormonal contraceptives increase cervical infections in HIV-positive women: implications for disease progression and HIV transmission

A ten-year prospective study of HIV-positive Kenyan sex workers has found that the use of hormonal contraceptives is associated with a significantly increased risk of cervical chlamydial infection and cervicitis, even after controlling for demographic factors and sexual behaviour. The results are published in the November 5^th issue of the journal, AIDS.

Until now, it has not been established if the use by HIV-positive women of hormonal contraceptive methods that include injectable progesterone (DMPA) or oral pills increases the risk of sexually transmitted infections (STIs), although an association has been found in HIV-negative women. However, previous studies reported from the same research group have found that hormonal contraceptives are associated with an increased risk of HIV infection and an increase in HIV shedding from the cervix.

The study included 242 HIV-positive women with a median duration of HIV infection of 35 months over a total of 799 person-years of follow-up. At some point after HIV infection, 104 women (43%) used DMPA (depot medoxyprogestoerone acetate) and 54 (22%) used oral contraceptive pills.

During follow-up, there were 26 cases of infection with Chlamydia trachomatis (incidence 7.7 cases per 100 person-years), 119 cases of Neisseria gonorrhoeae (14.9 cases per 100 person-years) and 193 cases of non-specific cervicitis (24.2 cases per 100 person-years). The investigators note that since their lab used relatively insensitive methods of chlamydia and gonorrhoea detection, it is likely that many of the cases of non-specific cervicitis were caused by one or both of these infections.

The investigators found that, compared to women who used no hormonal contraceptive method, the women using DMPA had a threefold increased incidence of cervical chlamydial infection (p=0.02) and a 1.6-fold increased incidence of non-specific cervicitis (p=0.03); and the women using oral contraceptive pills had more than double the increased incidence of non-specific cervicitis (p=0.03). The use of hormonal contraceptives was not associated with an increased incidence of gonorrhoea infection, however.

In order to adjust for possible confounding factors, including demographic characteristics and/or sexual behaviour (including condom use), the investigators used multivariate analysis to assess the relationship between hormonal contraceptive use and STIs. Here, again, DMPA was associated with a threefold increased risk of chlamydia and 1.6-fold increased risk of non-specific cervicitis. The use of contraceptive pills was found be associated with more than double the risk of both chlamydia and non-specific urethritis.

The authors note that there are both biological and epidemiological data to support their findings, including animal model studies which have suggested that progesterone enhances both susceptibility to, and persistence of, genital chlamydial infections; a meta-analysis also found a doubling of the risk of chlamydial infection in HIV-negative users of the oral contraceptive pill.

Since cervical STIs, including chlamydia and non-specific cervicitis, increase HIV shedding in cervical secretions, this study suggests that women taking hormonal contraceptives are at increased risk of passing on HIV to their sexual partners if barrier contraceptive methods are not also used. Since STIs also increase HIV viral load, and are associated with pelvic inflammatory disease, this could lead to increased illness and a more rapid course of HIV disease, particularly if, as was the case in this cohort, anti-HIV therapy is unavailable.

The authors conclude that, “HIV positive women using hormonal contraception may be at increased risk of cervical infections. This may translate into increased infectiousness and excess morbidity. HIV-1-seropositive women should be counselled about the importance of consistent condom use to prevent STI acquisition, especially those using hormonal contraception.”