Hormonal contraception and the risk of HIV acquisition
Polly Clayden, HIV i-Base
Combined oral contraceptives (COC) and depot-medroxyprogesterone acetate (DMPA) are among the most widely used family planning methods across the world. Use of hormonal contraception, and especially DMPA, is increasing rapidly in many resource limited settings where the prevalence of HIV and other sexually transmitted infections (STI) is high.
Previous studies have examined the effect on the acquisition of HIV of hormonal contraception with conflicting results.
Findings from a study conducted by the Hormonal Contraception and the Risk of HIV Acquisition (HC-HIV) Study Group, to evaluate the effect of COC and DMPA on HIV acquisition and any effects of other sexually transmitted infections (STIs), were published in the 2 January edition of AIDS.
This was a prospective study conducted in Uganda, Zimbabwe, and Thailand between November 1999 and January 2004.
Women were aged 18-35 years, HIV negative, sexually active, not pregnant, had not injected drugs or had a blood transfusion in the prior 3 months. They had been using either no hormonal contraception (non-HC); COC (low-dose pills containing 30ug ethinylestradiol and 150ug levonorgestrel) or DMPA (150mg administered every 12 weeks) for at least 3 months and intended to continue use for the following year.
At screening women received pretest HIV counseling and provided blood for testing for HIV, syphilis, and herpes simplex virus 2 (HSV-2).
Women had a standardised interview to evaluate sexual behavior, reproductive health and contraceptive history; a physical (including gynaecological) examination; and samples were taken to be tested for chlamydia, gonorrhoea, trichomonas vaginalis, candida, and bacterial vaginosis.
The women had follow up visits every 12 weeks for 15-24 months. Women with abnormal Pap smears were referred for colposcopy. The analysis includes women for whom there was at least one follow up visit with HIV test results.
The primary endpoint was defined as the date of the first positive HIV result.
The study screened 10, 082 women from Uganda, Zimbabwe, and Thailand. Of this group 2425 women (24%) were HIV positive (16.4% in Uganda, 38.1% in Zimbabwe, 2.1% in Thailand) and therefore not eligible. Another additional 1548 women were ineligible for other reasons.
A total of 6109 women participated in the study: 2235 in Uganda, 2296 in Zimbabwe, and 1578 in Thailand.
Data from Thailand was excluded because of few (n=4) HIV infections, as was data from women without follow-up or those exclusively using non-study methods. Data from 4439 African women were included.
The investigators reported at baseline, 34.7% participants used COC, 34.2% used DMPA and 31.1% were in the non-HC group (84% used condoms, 13% practiced withdrawal, 10% used the rhythm method, 3% were sterilised, and 5% used another non-HC method).
Median age of the women in the study was 25 years and most lived with a partner. Few women reported multiple sex partners, commercial sex or sex while using alcohol or drugs. Less than half reported recent condom use.
The majority of women (67%) did not change contraceptive methods during the study. The investigators reported that STI symptoms and risky sexual behavior were higher among women using non-HC than among hormonal contraceptive users but not common in either group. More women using non-HC than hormonal contraception users had a primary partner with high-risk characteristics (48% versus 36%, p< 0.001).
Over the study period there were 213 HIV infections, giving an incidence rate of 2.75/100 woman-years. 4.07/100 woman-years in Zimbabwe and 1.55/100 woman-years in Uganda. HIV incidence among the COC, DMPA, and non-HC groups was 2.59, 3.11, and 2.55/100 woman-years respectively.
In multivariate analysis the investigators found no significant association with either COC or DMPA use and risk of HIV acquisition (COC: HR, 0.99; 95% CI, 0.69-1.42; DMPA: HR, 1.25; 95% CI, 0.89-1.78).
When they compared the effect of DMPA or COC use on the risk of HIV acquisition they found no statistically significant in the risk of HIV acquisition (HR, 1.26; 95% CI, 0.92-1.74) between the two hormonal contraception methods.
They reported a significant association between hormonal contraception and study site (p = 0.015). For COC use HR: 0.78 (95% CI, 0.51-1.20) in Zimbabwe vs 1.43 (95% CI, 0.71-2.86) in Uganda. For DMPA use HR: 0.97 (95% CI, 0.65-1.45) in Zimbabwe vs 1.81 (95% CI, 0.93-3.56) in Uganda.
Of the STIs investigated only HSV-2 infection at enrolment significantly influenced the effect of hormonal contraception on HIV acquisition (p = 0.003). They found that HIV incidence was higher among HSV-2-positive participants (52%) than HSV-2-negative participants (48%) at enrolment. This effect was across contraceptive groups and was especially strong for the non-HC group.
Among women HSV-2-positive at enrolment, after adjustment neither COC nor DMPA use increased HIV risk,
However HIV acquisition risk was significantly higher for both COC (HR, 2.48; 95% CI, 0.82-7.53) and DMPA (HR, 4.96; 95% CI, 1.73-14.20) users who were HSV-2 negative.
The investigators wrote: Our findings concerning HSV-2-negative participants have not been evaluated by other studies The modifying role of HSV-2 serostatus reported here merits further investigation.
Concerning the lack of effect of hormonal contraception on HIV acquisition they concluded: This provides reassurance for women in a setting of moderate and high HIV prevalence who need effective contraception; that any increased overall risk associated with hormonal contraception is, at most, modest.
Regardless, our findings should reinforce efforts to counsel all women at risk of HIV infection to use condoms consistently and correctly to prevent HIV acquisition. They added.
Morrison CS, Richardson BA; Mmiro F et al. Hormonal contraception and the risk of HIV acquisition. AIDS: Volume 21(1) 2 January 2007 p 85-95.