The technical review did not consider the studies presented
The first study was a data analysis of the relationship
between oral and injectable hormonal contraceptive use and HIV acquisition in
the Methods for Improving Reproductive Health in Africa (MIRA) trial, a large
trial that evaluated the use of diaphragm and lubricant gel in the prevention
of HIV infection among women in sub-Saharan Africa. The trial was not
specifically designed to evaluate the effect of hormonal contraception on HIV
The trial recruited sexually active women who were followed
for up to two years and the analysis presented to the conference reported on
4866 women. Participants underwent pregnancy testing and screening for HIV and
for sexually transmitted infections at quarterly visits. A total of 274 women
became infected with HIV during the study.
The investigators evaluated the risk of HIV infection according
to contraceptive type among non-pregnant women in the study, compared to women
who did not use a hormonal contraceptive. The contraceptive methods were
classified as follows:
- Combined oral contraceptive
- Progestin-only pills
- Injectable hormonal
contraceptives (DMPA or NET-En)
- Non-hormonal methods (no
contraception, condoms, withdrawal, traditional methods, etc)
The investigators used several statistical approaches to
their analysis. The analysis found no increase in the risk of HIV infection in
women who used combined oral contraceptives (adjusted hazard ratio 0.88, 95%
confidence interval 0.59-1.32) or progestin-only contraceptive pills (aHR 1.02,
95% CI 0.58-1.81) in any of their analyses.
The results for injectable hormonal contraception depended
on the analysis technique. Using a Cox proportional hazards model, women who
used injectable contraceptives were at 37% higher risk of HIV infection
(aHR 1.37, 95% CI 1.01-1.86, p = 0.04).
However, when the two types of injectable contraceptive
were analysed as separate categories, neither were associated with an increased
risk of HIV infection.
However the result for injectable hormonal contraception depended
on the statistical method used to control for confounding factors. A method
which better controlled for factors which might vary over time and confound the
association between hormonal contraception and HIV risk, such as the level of
condom use, found no significant increase in the risk of infection among women using
injectable hormonal contraception (aOR = 1.16 95% CI 0.97-1.53).
The use of a causal inference technique to examine the ‘direct
effects’ of injectable hormonal contraception – a statistical technique which simulated what
would happen in a hypothetical randomised trial of contraceptive methods where
women were constrained from using condoms – showed a similar increased risk of
injectable hormonal contraception as the Cox model.
Sandra McCoy of the University of California at Berkeley,
presenting the results, concluded that the findings underscore the continued
importance of dual protection for women at high risk of HIV infection who use
injectable hormonal contraception – which in many settings in sub-Saharan
Africa could apply to the vast majority of women using this contraceptive
method. She also noted that the variability in the results by statistical
analysis method highlights the importance of adequately controlling for
confounding (e.g., other factors that might explain the results).
The second study looked at the risk of HIV disease
progression according to contraceptive type among HIV-positive women enrolled
in the Partners in Prevention study, a large trial which evaluated the effect
of acyclovir treatment for the herpes virus HSV-2 on the risk of HIV
transmission in HIV-serodiscordant partnerships in sub-Saharan Africa.
Some evidence of a negative effect of hormonal
contraception has been reported in one study, although a large
cohort study of over 4500 women failed to find an increased risk, and the
WHO technical review on hormonal contraception noted that a total of ten
studies have now failed to find any increased risk of disease progression.
Nevertheless the technical review concluded that because of limitations in the
design of these studies, the overall body of evidence on hormonal contraception
is 'weak' and in need of improvement.
The analysis of the Partners in Prevention study looked at
the relationship between contraceptive usage and disease progression in 2236
women recruited to the study in southern and eastern Africa. Hormonal
contraception of some form was being used by 18.7% of HIV-positive women at the
beginning of the study, and in the majority of cases they were using an
injectable hormonal contraceptive. (A separate analysis of this study, recently reported,
showed that women who used an injectable method, among the study population as a
less likely to become pregnant but more
likely to become infected with HIV.)
Disease progression was evaluated by two measures:
- Any one of the following: death
for any reason apart from trauma or accident; the need to start antiretroviral
therapy due to CD4 cell decline or clinical illness as indicated in guidelines;
or a CD4 cell decline below 200 cells/mm3
- A CD4 cell decline below 500
cells/mm3 in women who became infected during the study.
The disease progression rate observed in women with HIV at
baseline was 11.5 events per 100 person-years of follow-up, and 377 events were
observed during the study.
The rate of disease progression was significantly lower
among women using a hormonal contraceptive of any type when compared to women
not using hormonal contraception (aHR 0.75, 95% CI 0.56-0.99, p = 0.03). There
was no significant difference between women using injectable and non-injectable
A similar association was seen in women who became infected
with HIV during the study; those who used any hormonal contraceptive method
were around 75% less likely to experience a CD4 cell decline below 500
cells/mm3 (aHR 0.26, 95% CI0.07-0.97, p = 0.05).