Questions and answers: study of hormonal contraceptive use and HIV acquisition.
Worldwide, about 84 million women currently married or in union use combined oral contraceptives (COCs) and about 24 million such women use the injectable depot-medroxyprogesterone acetate (DMPA). Many other women not currently married or in union also use these contraceptive methods. (1)
What are COCs?
Most oral contraceptives contain both progestin and estrogen and thus are called combined oral contraceptives. The COCs used in this study were low dose (30 micrograms estrogen, 150 micrograms levonorgestrel) monophasic pills.
What is DMPA?
DMPA, known commercially as Depo Provera, is a synthetic form of the natural hormone progesterone. The most widely used injectable contraceptive, it is among the most effective methods of contraception, with typical one-year pregnancy rates of 0.4 percent or lower. DMPA is injected intramuscularly at a dose of 150 milligrams every three months. This decreases the risk of missed doses, such as missing a daily oral contraceptive pill.
Were the pills and injectables used in this study the same as those used in the United States?
The COCs used in this study (Lo-Femenal and Microgynon) are what many women in the United States and other developed countries most commonly use. Similarly, the DMPA used in this study is the same as that used in the United States and in many countries throughout the world.
Are other injectables safe to use?
The World Health Organization's (WHO's) Medical Eligibility Criteria for Contraceptive Use currently recommends that women at risk of HIV infection may use all injectables with no restrictions. (2)
Another progestin-only injectable contraceptive is norethisterone enanthate (NETEN), known commercially as Noristerat or Norigest. It differs from DMPA in that it contains a different progestin and is administered every two months at a dose of 200 milligrams. Two combined progestin-estrogen injectable contraceptives, known commercially as Cyclofem and Mesigyna, are administered monthly. Determining whether the differences in dose or types of hormones in these injectables might result in different effects on HIV acquisition would require further research.
(Of note, a recently completed secondary analysis of data collected as part of another study found that use of COCs, NET-EN, or DMPA by South African women from the general population was not associated with increased risk of HIV infection. (3))
Could hormonal contraceptives with different dosages of progestins and estrogens than those used by participants in this study pose different risks of HIV acquisition?
Formulations similar to those used in this study are likely to have similar effects. However, more research is needed to investigate this possibility.
Why were Uganda, Zimbabwe, and Thailand selected for this study?
The use of hormonal contraception had to be tested among the populations most likely to benefit from the study results, such as those in sub-Saharan Africa, where more than 80 percent of all HIV infections worldwide among women occur. Also, the study needed to be conducted where the incidence of heterosexual HIV transmission and exposure to the virus was high enough to determine whether hormonal contraceptive use had any impact on HIV acquisition. (Although Thailand's HIV incidence rate turned out to be too low to produce useful results, HIV incidence rates in both African countries were high enough for this study to produce results. Of the 217 HIV infections that occurred during follow-up, 214 were in the two African countries.) In addition, all three countries in this study had a variety of contraceptive methods from which women could choose, allowing researchers to study large numbers of both injectable contraceptive users and oral contraceptive users. In all three settings, both U.S. and in-country investigators were interested in conducting this research and had the expertise and infrastructure to do so. Finally, these sites were part of an international network of sites participating in HIV prevention studies.
Why was the study conducted primarily among family planning clients?
The study was conducted primarily among family planning clients because they are more likely than other women to use hormonal contraception and because it is important to know whether that use increases their risk of HIV acquisition. Also, family planning clients are at relatively low risk of HIV infection. In contrast, many previous analyses of hormonal contraceptive use and HIV acquisition came from studies conducted among women at high risk for HIV infection: commercial sex workers or women seeking medical care for sexually transmitted infections (STIs).
What was done to safeguard the rights of women participating in the study?
The study was designed according to the most rigorous international ethical standards. It was reviewed and approved by the U.S. National Institutes of Health (NIH) and by 12 institutional review and human protection boards in the United States and participating countries.
* All study participants voluntarily agreed to take part in the study, and the study's prospective cohort design allowed them to continue using their voluntarily chosen contraceptive method. Before the trial began, they were counseled on what the study required of them, as well as the potential risks and benefits of study participation. They were also counseled that they were not obligated to participate and could stop participating at any time.
* Staff emphasized that the effects of hormonal contraceptive use on HIV acquisition--beneficial or harmful--were unknown.
* Everything possible was done to eliminate the possibility that study participants would be exposed to HIV infection. At each regularly scheduled 12-week visit during the study, counselors provided study participants with information on HIV transmission and prevention.
* The use of condoms with all sexual partners was emphasized for protection from HIV. Counseling also included condom negotiation skills, skills-building in partner communication, and demonstration and practice with models of the correct application of condoms. Finally, free condoms were provided.
In addition, highly sensitive tests were used to detect STIs at each study visit. Participants were contacted and treated free of charge for any detected STI, thus reducing the risk of HIV acquisition.
How were the women who became infected with HIV during the study cared for?
All HIV-infected women were encouraged to continue to return for study follow-up visits and were provided their contraceptive methods of choice. Such women were counseled to use condoms consistently, told about the implications of becoming pregnant while HIV-infected, and advised that they should bring their partners for HIV testing and counseling. All participants who became infected with HIV during the study were extensively counseled and given referrals to medical services and to research studies that provided HIV care and treatment. They were also referred to local support groups that offer HIV-related psychological and social services.
In addition, women in Uganda and Zimbabwe (where almost all of the HIV infections occurred) who became HIV-infected during the study were offered the opportunity to enroll in a follow-on study of HIV-infected women. Women in that study received counseling about condom use, reduction in transmission risk, and health maintenance; their choice of contraceptive method and free condoms; diagnosis and treatment for STIs; access to a support group for HIV-infected women and to HIV support counseling; referrals for other HIV support services; referral to an HIV-experienced health care provider (as needed); antiretroviral drug therapy and prophylaxis for pneumonia or tuberculosis, if medically indicated; treatment for malaria and other common infections; Pap smears; daily multivitamins and iron; and referral for treatment to prevent mother-to-child transmission of HIV.
What further analyses can we expect?
Various ancillary studies and secondary analyses will be conducted, ultimately helping international normative bodies set evidence-based standards for the provision of hormonal contraception in countries with high HIV prevalence.
Ancillary studies and secondary analyses will look at whether hormonal contraceptive use is associated with:
1) bacterial vaginosis
2) herpes simplex virus (HSV)
3) chlamydial and gonoccocal infection
They will also evaluate the subsequent impact of these STIs on HIV acquisition. Whether hormonal contraceptive use is associated with human papillomavirus will also be examined.
In addition, ancillary studies among women who become HIV-infected will examine hormonal contraceptive use and its relationship with:
1) genital shedding of HIV (and thus possible HIV transmission to male partners)
2) HIV viral set point (HIV level in the blood after the immune system's initial response to the virus), progression of HIV infection, and clinical manifestations of HIV/AIDS
3) antiretroviral drug therapy Finally, the study's findings related to HIV risk among HSV-negative hormonal contraceptive users will be further analyzed.
(1) Population Reference Bureau (PRB). Family Planning Worldwide: 2002 Data Sheet, wall chart. Washington, DC: PRB, 2002. Available: www.prb.org/pdf/FamPlanWorldwide_Eng.pdf.
(2) World Health Organization (WHO). Improving Access to Quality Care in Family Planning: Medical Eligibility Criteria for Contraceptive Use. Third Edition. Geneva, Switzerland: WHO, 2004. Available: http://www.who.int/reproductivehealth/publications/mec/.
(3) Myer L, Denny L, Wright T, et al. Prospective study of hormonal contraception and women's risk of HIV infection in South Africa. Int J Epidemiol December 14, 2006 [electronic publication ahead of print].
|Printer friendly Cite/link Email Feedback|
|Date:||Jun 22, 2007|
|Previous Article:||Why this study is unique.|
|Next Article:||Research implications for users and providers.|