Pregnancy increased the risks
of female-to-male HIV transmission twofold among over 3300 serodiscordant
couples from seven African countries, Nelly R Mugo and colleagues reported in a
prospective study published in the advance online edition of AIDS.
The risks of becoming
infected with HIV during pregnancy increased at the same rate. However, this was
partly explained by other factors, including unprotected sex.
Women now account for 60% of
HIV infections in adults in sub-Saharan Africa. Many African countries with
high HIV prevalence also have high fertility rates and often women are pregnant
for a considerable proportion of their adult lives.
Pregnancy brings biological
and behavioural changes that may make a woman more susceptible to getting HIV,
as well as making her more infectious, so increasing the risks of transmission.
To date, limited prospective studies
have found inconsistent results, showing either an increased risk or no elevated
risk of acquiring HIV during pregnancy. However, evidence shows that women
infected during their pregnancy have a high rate of HIV transmission to their
The authors note one study
which showed increased HIV shedding in genital secretions during pregnancy,
suggesting increased infectiousness, yet no prospective study has looked
specifically at pregnancy as a risk factor for female-to-male transmission.
The authors chose to look at
the association between pregnancy and the risks of getting HIV, as well as the
risks of transmitting HIV from females to males, in a secondary analysis of a prospective
study of African HIV serodiscordant couples.
From November 2004 to April
2007, 3408 HIV serodiscordant couples from Botswana, Kenya, Rwanda, South
Africa, Tanzania, Uganda and Zambia were enrolled in the Partners in Prevention
HSV-2/HIV transmission study, a randomised, placebo-controlled, clinical trial
of aciclovir as herpes simplex virus-2 (HSV-2) suppressive therapy for the
prevention of HIV transmission. Aciclovir did not decrease HIV transmission
risk within the couples.
Of the 3321 couples in the
analysis, about a third (1085) included an HIV-positive male partner and the
remaining two-thirds (2236) included an HIV-positive female partner. Eligibility included being
over 18 years of age, having three or more episodes of vaginal intercourse in
the three months before screening, and having the intention of remaining a
HIV-positive partners were
positive for HSV-2, had CD4 cell counts over 250 cells/mm3 and were
not taking antiretrovirals. HIV-positive women pregnant at the time of screening were
excluded from the study. Women who became pregnant stopped the study medication
until the end of pregnancy. Pregnant HIV-negative women were included, as were
those who became pregnant during follow-up.
HIV-positive partners were
seen monthly, and HIV-negative partners were seen every three months. Sexual
behaviour data including condom use was recorded at each visit, as was
services included individual and couple HIV-risk-reduction counselling,
quarterly syndromic management of sexually transmitted infections, STI treatment and
The majority were married and
living together. Median CD4 cell count was 461 cells/mm3. The
couples were followed for up to 24 months; median time for HIV-negative and
HIV-positive partners was 20.9 months (IQR: 15.6-24.1) and 19.9 months (IQR:
Of the 61 HIV seroconversions
among women, close to 30% (17) happened during pregnancy. HIV incidence during
pregnancy was 7.35 per 100 person years compared to 3.01 per 100 person years during
non-pregnant periods, (HR: 2.34, 95% CI:
1.33-4.09, p=0.003). Risk was high during both early and late pregnancy.
However, in multivariate analysis after controlling for age, contraceptive use
and unprotected sex, the effect of pregnancy on HIV risk was not statistically
Of the 58 HIV transmissions
to men, 12 (20.7%) happened during pregnancy. The incidence of female-to-male
transmission was 3.46 per 100 person-years during pregnancy, compared to 1.58
per 100 person-years when the female partner was not pregnant. This was
statistically significant (HR 2.31, p=0.01) and remained significant after
adjusting for confounding factors (HR.2.47, p=0.01).
The authors underscore the
public health importance of these new findings showing pregnancy increases the
risk of female-to-male transmission twofold. New strategies, they add, are needed “to strengthen family planning and
maternal health services for women with and at risk for HIV in order to reduce
unwanted pregnancies and avert HIV transmission to pregnant women and from
pregnant women to their infants and partners”.
Strengths of the study
include a large sample size and multinational cohort. The study also
established a genetic viral linkage of transmitted HIV within partnerships, so
minimising the potential for misclassification of female-to-male transmission.
The authors note their
findings can be generalised; all participants were co-infected with HSV-2, as
are over 80% of all HIV-positive adults in sub-Saharan Africa.
The authors conclude
increased risk for HIV female-to-male transmission during pregnancy requires
“further studies to understand the possible biologic mechanisms that may
explain this finding”. They add: “Prenatal couples' HIV counselling and testing,
implementation of repeat HIV testing in pregnancy, and earlier initiation of
combination ART should become part of routine antenatal care to protect
mothers, infants and male partners from HIV.”