A high viral load at the time of starting treatment during pregnancy and a shorter time on antiretroviral therapy (ART) before
delivery continued to place mothers at risk of passing on HIV during the breastfeeding period for at least seven months after giving birth, researchers report in a sub-study
of the Kisumu Breastfeeding Study in Kenya, published in the advance online
edition of the Journal of Acquired Immune
Among this cohort of 434
women, over 80% had an adherence rate equal to or greater than 95%.
Twenty-four infants were infected with HIV during the seven-month study period, with over 50% infected during delivery. Eleven of the mothers of infected infants had a viral load over 10,000 copies/ml. Viral load was linked to vertical (mother-to-child) transmission
at delivery (p = 0.0028), at 14 weeks (p = 0.05) and at 24 weeks after delivery
(p = 0.01).
These findings lend further
support to the World Health Organization’s (WHO) guidelines of starting ART
prophylaxis early, for the greatest reduction in maternal viral load, for the
prevention of mother-to-child transmission (PMTCT).
HIV continues to be one of
the leading causes of death in sub-Saharan Africa, where over half of those
infected are women of reproductive age. ART has had a considerable effect on
reducing death and disease among people with HIV.
Women in sub-Saharan Africa
are often diagnosed during pregnancy and, depending on eligibility criteria (CD4
cell counts), start ART either for their own health or to prevent vertical transmission. For those women not eligible for treatment for their own health, ART throughout
breastfeeding is recommended
for infant protection.
CD4 cell counts and clinical
staging, while imperfect, are used to determine eligibility and treatment
response in resource-poor settings, where viral load monitoring is often
unavailable. CD4 cell counts alone often do not have the sensitivity to detect rising viral load until treatment failure and HIV progression is apparent.
Good adherence is critical to
improve health outcomes, delaying viral resistance as well as preventing transmission to the baby.
Since a high viral load is a
risk factor for transmission, the goal of ART is to reduce viral load to undetectable
levels. So the mother’s health will determine the health and survival of the
With this in mind, the authors
chose to evaluate immunologic response, viral load suppression and adherence
among women receiving ART prophylaxis (consisting of lamivudine/zidovudine and
either nevirapine or nelfinavir) in the Kisumu Breastfeeding Study. They also
looked at other risk factors that affected time to viral load suppression.
The Kisumu Breastfeeding
Study, an open-label clinical trial, enrolled women between July 2003 and
November 2007 to look at the efficacy of, tolerance of, and adherence to, maternal
triple ART for PMTCT up to 24 weeks after delivery.
Women were enrolled into this
sub-study if they had adherence, viral load and CD4 data in at least three time
points during the study period: from 32 to 34 weeks of pregnancy to 24 weeks after
Among the 434 women remaining
in the sub-study, baseline demographic data, trends in CD4 cell count, and viral
load at enrolment, delivery, 14 and 24 weeks after delivery were analysed. Pill
counts, in addition to self-report and drug calendar, determined adherence rates.
Adherence was defined as equal to or above 95%.
Significant improvements in
virological response and immunological status provided solid support for triple
ART for PMTCT in resource-poor settings.
Women with undetectable viral
load at baseline increased from 6 to 79%; women with CD4 cell counts under 250
cells/mm3 decreased from 100 (23%) at baseline to 22 (5%) at 24 weeks after
Most women (84%) were
adherent throughout the study period.
There were no significant
differences in the proportion of women who achieved undetectable viral load at
24 weeks after delivery based on CD4 cell count categories.
However, the authors note
their findings showed the importance of timing of maternal ART for PMTCT. The
longer the women were on treatment before delivery the greater the chance of
undetectable viral load: 35, 54, 71
and 81% of the women on ART for under 2 weeks, 2 to 4 weeks, 4 to 6 weeks and over 6 weeks, respectively, before delivery achieved undetectable viral load.
Since the intervention began
in the third trimester, it is not surprising that a longer time on ART increased
the possibility of undetectable viral load at delivery, they add.
More women achieved an
undetectable viral load on a nelfinavir-based ART regimen, compared to a nevirapine-based ART
regimen, and in a shorter time frame. At delivery 58% (130/226) of women on a
nevirapine-based ART regimen compared to 82% (139/170) of women on a
nelfinavir-based ART regimen achieved undetectable viral load.
The difference between the
two regimens remained after controlling for baseline CD4 cell counts, baseline
viral load and time on treatment (OR=2.02, 95% CI: 1.16-3.54, p=0.014).
While adherence is linked to
viral suppression, the authors note that in a subset of women with CD4 cell
counts above 250 cells/mm3 there was no correlation between
adherence and viral suppression. So the authors question how much adherence is
needed for viral suppression and how accurate are the measures used for
assessing adherence? Or perhaps, they add, some women achieved undetectable
viral load between tests and then rebounded within the same interval.
While close to 70% had
increased CD4 cell counts equal to or above 500 cells/mm3 at 14
weeks, the proportion did not change at 24 weeks. This would suggest, note the
authors, an immunological response to ART can be assessed as soon as 14 weeks
after starting treatment.
The original study was
designed to look at nevirapine-based ART for PMTCT and was later modified to
include nelfinavir-based ART in some women. So the finding that
nelfinavir-based ART improved virologic response is, the authors point out, an
unplanned secondary analysis and the results are considered preliminary.
This study shows viral load
remains a risk factor for MTCT. The findings suggest, the authors note,
possibly more women would have achieved undetectable viral load by delivery had
they started ART earlier. As such, these findings have important implications for PMTCT
during pregnancy and delivery.
The authors conclude that: “to
ensure long term success of PMTCT which involves extended use of ART, we must
identify feasible and reliable tools to assess adherence and provide real-time
interventions to support optimal adherence among these HIV-infected women”.