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The possible impact of hormonal contraceptive use
on the acquisition or transmission of sexually transmitted infections (STIs),
including HIV, remains an important research question. However, current
knowledge of a potential relationship is insufficient to change family
planning practices.
According to the World Health Organization
medical eligibility criteria for contraceptive use, no restriction
exists for the use of any hormonal contraceptive method for individuals
with a current STI, at increased risk of STIs (for example, having
multiple partners or a partner who has multiple partners), at high risk
of HIV, who are HIV-positive, or who have AIDS.1 Yet,
hormonal contraceptives do not appear to protect against HIV or other
STIs. Thus, while continuing to promote hormonal contraception for
family planning when appropriate, providers should counsel hormonal
contraceptive users who are also at high risk of HIV/STIs to use a
condom during each act of intercourse.
A review of issues related to hormonal
contraceptive use by women who are infected with HIV or are at risk of
infection was held in Washington, DC, USA, in January 2003. Sponsored by
the U.S. National Institute for Child Health and Human Development (NICHD),
the meeting was organized to address HIV-infected and at-risk women's
need for guidance regarding pregnancy prevention, fertility regulation,
and hormone use. The meeting identified the need to better understand:
- Possible interactions between hormonal
contraception and antiretroviral therapy;
- Any relationships between hormonal
contraception and HIV-disease progression;
- Possible effects of hormonal contraception on
HIV-positive women's infectivity; and
- Appropriateness of nonhormonal methods for
HIV-infected or at-risk women.
Meanwhile, research has focused on the following
potential areas of risk:
-
Hormonal use and HIV acquisition: Two
thorough reviews of numerous studies of the risk of HIV acquisition
among women who use hormonal contraceptives have been conducted. One
found a relationship between use of oral contraceptives (OCs) and
HIV acquisition,2 while the other did not.3
Authors of the reviews, however, noted that the quality of such
studies was generally poor4 and their results
inconsistent.5
Few studies of hormonal contraceptive use and HIV acquisition
have been prospective (which would reduce the chance of bias), and
most have had methodological flaws. However, a large prospective
study of the relationship between the use of combined OCs or depot-medroxyprogesterone
acetate (DMPA) and HIV acquisition is being conducted by FHI
researchers and collaborating institutions, and should yield results
in 2004. The study, funded by NICHD, is being conducted in Uganda,
Thailand, and Zimbabwe among some 6,200 HIV-negative, 18- to
35-year-old users of combined OCs, users of DMPA, and women not
using hormonal contraception. Study participants are tested for HIV
every 12 weeks until they have become infected or have been followed
for 15 to 24 months. The study is also designed to determine if the
presence of STIs other than HIV affects the rate of HIV acquisition
among hormonal contraceptive users compared with non-users.
-
Hormonal use and acquisition of other STIs:
Researchers are investigating the effect of hormonal contraceptive
use on the acquisition of STIs (other than HIV), which can have
major health consequences such as infertility, certain cancers, and
other chronic diseases. Infection with STIs (particularly those that
cause genital ulcers) also increases both infectivity of and
susceptibility to HIV.6 A prospective cohort study
involving 948 Kenyan sex workers found that use of oral or
injectable hormonal contraception was associated with susceptibility
to STIs: Users of OCs were at greater risk of acquiring chlamydial
infection and vaginal candidiasis than women not using hormonal
contraception, while women using DMPA had a significantly increased
risk of chlamydial infection.7
Meanwhile, in a prospective study among some
1,000 U.S. women (484 OC users, 151 DMPA users, and 368 controls),
FHI researchers and collaborating institutions found that use of
DMPA — but not OCs — was significantly associated with the risk
of chlamydial and gonococcal infection.8 A substudy of
this larger investigation found that DMPA use was associated with
the risk of acquiring oncogenic human papilloma virus (HPV). OC use,
in contrast, was associated with a decrease in the persistence of
oncogenic HPV infection.9 Oncogenic HPV infection is of
concern because it is associated with increased rates of cervical
cancer.
OC users also had a significantly lower
incidence of HPV infection than non-users in a prospective study
that included, at study entry, 105 HPV-negative, 13- to 21-year-old
U.S. women attending family planning clinics.10 However,
once a persistent HPV infection is established, OCs appear to
provide no protection against, and may even facilitate, progression
to cervical cancer.11 A pooled analysis of data from
eight case control studies conducted by the International Agency for
Research on Cancer showed that prolonged use of OCs (from five to
nine years) among HPV-infected women was associated with up to a
threefold increased risk of cervical cancer. Use for 10 years or
longer was associated with up to a fourfold increased risk of
cervical cancer.12
-
Hormonal use and HIV transmission: A
theoretical concern exists that hormonal contraceptive use by
HIV-infected women might increase shedding of HIV and thus increase
transmission to uninfected partners. A cross-sectional study
evaluating cervical and vaginal secretions of 318 HIV-infected women
attending STI clinics in Mombasa, Kenya, found that cervical
shedding of HIV-infected cells was significantly associated with use
of DMPA and with both low-dose and high-dose OCs.13 But a
prospective study among HIV-positive women attending a family
planning clinic in Mombasa (101 of whom chose to use DMPA; 52,
low-dose combined OCs; seven, high-dose combined OCs; and 50,
progestin-only OCs) detected no increase in cervical shedding of
HIV-infected cells or free virus one and two months after initiation
of hormonal contraception, compared with the period before
initiation.14
To further clarify the matter, FHI
researchers are conducting a prospective study in Zimbabwe and
Uganda, funded by NICHD, of the effect of combined OC or DMPA use on
HIV genital shedding among 140 women with acute or early HIV
infection. The women, who will be compared with HIV-infected women
not using hormonal contraception, are being followed every 12 weeks
for up to four years. Preliminary results are expected in 2004.
Whether hormonal contraceptive use near the time
of HIV infection affects disease progression is also of concern. One
study among 115 HIV-infected Kenyan sex workers found that those using
hormonal contraceptives near the time of HIV acquisition were more
likely to be infected with multiple strains of the virus than women not
using hormones. Infection with multiple strains may be associated with
faster HIV progression.15 Similarly, in a prospective cohort
study of HIV acquisition among 1,337 sex workers in Mombasa — 230 of
whom acquired HIV during follow-up — the use of DMPA and presence of
genital ulcer disease at the time of HIV infection were associated with
a higher viral load set point (the blood level at which the HIV virus
settles about six months after initial infection). The higher the viral
load set point, the faster HIV-related deterioration of the immune
system occurs. Thus, this research finding suggests that DMPA use and
genital ulcer disease may hasten the natural course of HIV infection.16
— Kim Best
References
- World Health Organization. Improving Access to
Quality Care in Family Planning. Medical Eligibility Criteria for
Contraceptive Use. Geneva, Switzerland: World Health
Organization, 2002.
- Wang CC, Kreiss JK, Reilly M. Risk of HIV infection
in oral contraceptive pill users: a meta-analysis. J Acq Immune
Defic Syndr 1999;21(1):51-58.
- Stephenson JM. Systematic review of hormonal
contraception and risk of HIV transmission: when to resist
meta-analysis. AIDS 1998;12(6):545-53.
- Stephenson.
- Stephenson; Wang.
- Eng TR, Butler WT, eds. The Hidden Epidemic.
Confronting Sexually Transmitted Diseases. Washington, DC:
National Academy Press, 1997.
- Baeten JM, Nyange PM, Richardson BA, et al. Hormonal
contraception and risk of sexually transmitted disease acquisition:
results from a prospective study. Am J Obstet Gynecol
2001;185(2):380-85.
- Morrison CS, Bright P, Wong E, et al. Hormonal
contraception, cervical ectopy and the acquisition of cervical
infections. 14th Meeting of the International Society for
Sexually Transmitted Diseases Research, Berlin, Germany, June
24-27, 2001.
- Morrison C, Nanda K, Wong E, et al. Hormonal
contraception and incidence and persistence of high-risk HPV
infection. 20th International Papillomavirus Conference,
Paris, France, October 4-9, 2002.
- Moscicki A-B, Hills N, Shiboski S, et al. Risks for
incident human papillomavirus infection and low-grade squamous
intraepithelial lesion development in young females. JAMA
2001;285(23):2995-3002.
- Brabin L. Interactions of the female hormonal
environment, susceptibility to viral infections, and disease
progression. AIDS Patient Care STDS 2002;16(5):211-21.
- Moreno V, Bosch FX, Muñoz N, et al. Effect of oral
contraceptives on risk of cervical cancer in women with human
papillomavirus infection: the IARC multicentric case-control study. Lancet
2002;359(9312):1085-92.
- Mostad SB, Overbaugh J, DeVange DM, et al. Hormonal
contraception, vitamin A deficiency, and other risk factors for
shedding of HIV-1 infected cells from the cervix and vagina. Lancet
1997;350(9082):922-27.
- McClelland RS, Wang CC, Overbaugh J, et al. The
effect of hormonal contraception on genital shedding of human
immunodeficiency virus type-1. The XIV International Conference
on HIV/AIDS, Barcelona, Spain, July 7-12, 2002.
- Sagar M, Lavreys L, Baeten J, et al. Correlates of
viral diversity in primary HIV-1 infection in women. The Ninth
Conference on Retroviruses and Opportunistic Infections,
Seattle, WA, February 24-28, 2002.
- Lavreys L, Baeten JM, Kreiss JK, et al. Natural
history and covariates of HIV-1 viremia among women in Mombasa,
Kenya. The XIV International Conference on HIV/AIDS,
Barcelona, Spain, July 7-12, 2002.
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