By Liz Highleyman

Some past research has suggested that hormonal contraceptives - such as combination estrogen/progestin pills and the depot medroxyprogesterone acetate (Depo-Provera) injection - may facilitate acquisition of HIV and other sexually transmitted infections, but data so far have been inconclusive.

To explore this issue, researchers with the international Hormonal Contraception and the Risk of HIV Acquisition Study Group conducted a prospective cohort study that enrolled 6109 HIV negative women, aged 18-35 years, at family planning clinics in Thailand, Uganda, and Zimbabwe between 1999 and 2004. About one-third (34.7%) used low-dose pills containing ethinyl estradiol and levonorgestrel, 34.2% used Depo-Provera, and 31.1% used non-hormonal forms of contraception (e.g., condoms, sterilization, withdrawal).

Estrogen Pill

Participants received HIV antibody tests every 3 months for 15-24 months. The risk of HIV acquisition with different contraceptive methods was assessed. More than 200 out of a total of 4531 women were newly infected with HIV in the 2 African countries; there were only 4 new HIV infections among the 1578 women at the Thai sites, which did not allow for statistical analysis.

Results

• HIV infection occurred in 213 out of 4439 African participants with adequate follow-up data (2.75 per 100 person-years combined; 4.07 in Zimbabwe and 1.55 in Uganda).

• Women who used hormonal contraceptives reported more frequent sexual intercourse (36% vs 28% reporting at least 15 acts per month; P < 0.001) and were less likely to report consistent condom use (51% versus 13% of visit segments; P < 0.001).

• HIV incidence in the oral contraceptive, Depo-Provera, and non-hormonal contraception groups was 2.59, 3.11, and 2.55 per 100 person years, respectively.

• Factors associated with HIV acquisition were younger age (P = 0.001), women's behavioral risk (P = 0.002), partner's behavioral risk (P < 0.001), and not living with a partner (P = 0.008).

• Overall, neither combination oral contraceptives (HR 0.99; 95% CI 0.69-1.42) nor Depo-Provera (HR 1.25; 95% CI 0.89-1.78) was associated with increased risk of HIV acquisition.

• This pattern also held true for participants with most types of cervical or vaginal infections (trichomonas, bacterial vaginosis, candidiasis, chlamydia, gonorrhea).

• The absolute risk of HIV acquisition was higher among participants who were seropositive for herpes simplex virus 2 (HSV-2) (52% versus 48%; P = 0.003).

• Among HSV-2 negative women, both combination oral contraceptives (HR 2.85; 95% CI 1.39-5.82) and Depo-Provera (HR 3.97; 95% CI 1.98-8.00) were associated with a higher risk of HIV acquisition compared with women who did not use hormonal contraceptives.

Conclusion

"No association was found between hormonal contraceptive use and HIV acquisition overall," the authors concluded. "This is reassuring for women needing effective contraception in settings of high HIV prevalence."

However, they added, "hormonal contraceptive users who were HSV-2 seronegative had an increased risk of HIV acquisition." Because "a solid biological explanation for our finding among the HSV-2-negative women is elusive," they said that additional research is needed to confirm and explain this finding.

In their discussion, the researchers suggested that hormonal contraceptives and HSV-2 infection may both disrupt the genital epithelium, but that HSV-2 may have a greater effect that overshadows that of contraceptives. Alternatively, "HSV-2-negative status may be a marker for other variables that may interact with hormonal contraception, placing certain women at increased risk of HIV infection." They noted that their study could not rule out an increased risk of HIV acquisition with hormonal contraceptives among women already at higher risk, such as commercial sex workers.

In an accompanying editorial, Marc Bulterys, MD, from the Centers for Disease Control and Prevention and colleagues said the findings concerning HSV-2 were "unexpected." While they agreed that the results from this study are reassuring, they stressed that family planning programs should include HIV prevention.

"Sexual activity leads to transmission of both sperm and microorganisms," they wrote. "Any fertility regulation counseling must be coupled with condom promotion and counseling about HIV and prevention and treatment of sexually transmitted infections."

Family Health International, Research Triangle Park, NC; University of Washington, Fred Hutchinson Cancer Research Center, Children's Hospital and Regional Medical Center, Seattle, WA; Makerere University, Kampala, Uganda; University of Zimbabwe, Harare, Zimbabwe; Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD; National Institutes of Health, Department of Health and Human Services, Bethesda, MD; University of California at San Francisco, San Francisco, CA; Chiang Mai University, Chiang Mai, Thailand; Case Western Reserve University, Cleveland, OH.

1/12/07

References

C S Morrison, B A Richardson, F Mmiro (Hormonal Contraception and the Risk of HIV Acquisition Study Group). Hormonal contraception and the risk of HIV acquisition. AIDS 21(1): 85-95.

M Bulterys, D Smith, A Chao, H Jaffe. Hormonal contraception and incident HIV-1 infection: new insight and continuing challenges. AIDS 21(1): 97-99.