Efforts to achieve "virtual elimination" of new HIV infections in infants by 2015 could prove highly challenging, according to computer modelling of the situation in Zimbabwe, one of the most seriously HIV-affected countries in southern Africa.
a validated computer simulation model of a cohort of HIV-infected, pregnant or breastfeeding
women in Zimbabwe, researchers found that even with a 95% uptake of the World
Health Organization’s (WHO) 2010 prevention of mother-to-child (PMTCT) guidelines, projected transmission risks (6.1 to 7.7%)
would still exceed those set for WHO’s goal of
“virtual elimination” of paediatric HIV (defined as a mother-to-child-transmission
risk of less than 5%).
analysis, published in the 10 January edition of PLoS Medicine, looked at the
effectiveness of three PMTCT treatment regimens:
single-dose nevirapine (sdNVP)
WHO's Option A regimen: zidovudine during pregnancy and sdNVP at delivery and infant
nevirapine throughout breastfeeding in women with advanced illness
B regimen: triple ART during pregnancy and breastfeeding and lifelong ART for women
with advanced illness.
These were studied at four different levels of uptake of PMTCT services
(36, 56, 80 and 95%, corresponding to reported national 2008, 2009 rates and
WHO target and optimal rates, respectively).
authors found that increased uptake of PMTCT services played a significant role
in reducing MTCT, even in times of economic hyperinflation; uptake from 2008 to
2009 increased from 36 to 56%, with a corresponding decrease in MTCT from 20.3
the 2009 national programme of sdNVP with Option A (at the corresponding
reported uptake of 56%), was projected to reduce the estimated transmission risk
from 18% to 14.4%, or 13.4% with Option B, they add. Both options are more
effective than increasing sdNVP coverage to 80% (which has a MTCT risk of 15.4%).
planned implementation of Option A in Zimbabwe, like many other sub-Saharan
African countries where prolonged breastfeeding is common, could significantly
reduce infant HIV infection, compared to the 2009 national programme of sdNVP.
the United States and Europe, the availability of antiretroviral therapy during
pregnancy and avoidance of breastfeeding among HIV-infected women has led to
the near elimination of paediatric HIV.
can be passed from the mother to the child during pregnancy, labour and
delivery, or breastfeeding. Without treatment, approximately 30% of infants will
be infected during pregnancy or delivery, and an estimated 5 to 20% during
settings where breastfeeding is the norm and replacement feeding is not an option,
recent studies have shown that the provision of maternal ARV during
breastfeeding can reduce MTCT to between 1 and 5%.
a consequence, WHO, among others, made “virtual elimination” of paediatric HIV a
new target and accordingly released new guidelines in 2010 comprising options A
many women are lost to care at any point along what is known as the PMTCT
receiving antenatal care
having an HIV test and getting the results
being assessed for ART eligibility
having a CD4 cell count test and timely receipt of
availability of ART
help with adherence
receiving postnatal care.
an estimated 53% of pregnant women got any kind of treatment for PMTCT in 2009,
resulting in around 400,000 infants newly infected with HIV; over 90% were in
the difficulties of enrolling and keeping women in care at any step of the
PMTCT cascade, the effectiveness of Options A or B is unknown.
the authors chose to expand a simulated model of MTCT to include all the steps,
projecting the level of PMTCT uptake, the drug regimens, and length of
breastfeeding necessary, to reach “virtual elimination” in Zimbabwe.
model simulated a cohort of two populations of HIV-infected pregnant and
breastfeeding women, with a mean age of 24, a mean CD4 cell count of 451cells/mm3, and a breastfeeding period of 12 months. The cohort was followed from first antenatal visit to two years after giving birth.
1 included women already HIV-infected at their first antenatal visit. Cohort 2 included
all women getting pregnant each year in Zimbabwe (392,460) with an HIV
prevalence of 16% at the first antenatal visit and HIV incidence of 1% during late
pregnancy and breastfeeding. Cohort 1 was nested within Cohort 2. Cohort 1 was
analysed to project MTCT rates and Cohort 2 to project the proportion and
number of infants to become HIV-infected in an annual birth cohort.
primary outcome was MTCT risk at weaning. The authors looked at improvements in
two measures of PMTCT care: more effective regimens and improved uptake of the
authors note their findings are consistent with previous analyses (using
different modelling methodologies) that suggest that “virtual elimination” will
require massive scale-up of PMTCT services.
authors stress that, regardless of whether sdNVP was replaced with Option A or B,
it is the level of PMTCT uptake that has the greatest effect on MTCT rates.
note that, once 56% uptake is reached with Option A, increasing this to 80% results in
an MTCT risk of 10.5%, with better outcomes than if Option A were replaced with
Option B at current levels of 56% (an MTCT risk of 13.4%).
analysis depends on the effectiveness of each ART regimen, note the authors,
adding that Option B may not be better than Option A for PMTCT; no randomised comparisons
have been reported. Studies suggest that both options are equally efficacious
in women with CD4 cell counts over 350 cells/mm3, in line with WHO’s
strong recommendation for both options.
cite the anticipated results of the IMPAACT/PROMISE study, a multinational
clinical trial comparing these regimens in women with CD4 cell counts over 350
cells/mm3 which will, importantly, inform policy decisions around
Options A and B.
noted, increased uptake of PMTCT services reduced projected MTCT risk. This happens,
the authors add, by improving the proportion of ART-eligible women who get ART,
including the greater availability of CD4 testing and timely receipt of results, or by providing triple-drug ART.
shorter breastfeeding periods can contribute to reduced MTCT, the absence of clean water
and availability of infant formula make this impractical in many resource-poor
specific step in the cascade where uptake varied did not affect MTCT risk at
4 to 6 weeks. However, the proportion of mother-infant pairs linked in to postnatal
care had a considerable effect on twelve-month MTCT risk.
authors suggest promotion of high levels of access to postnatal care and
adherence to ARV during breastfeeding is critical.
of the study included computer model simplification of complex biological and operational
processes; data from multiple sources was combined.
meet this challenging and critical goal of “virtual elimination” in Zimbabwe,
or in other resource-poor settings with a high HIV prevalence and prolonged
breastfeeding, a national programme using either Option A or B must be
implemented, together with strategies to improve access to PMTCT services (to
close to 100%), to retain women in care, and to support medication adherence
throughout pregnancy and breastfeeding, the authors conclude.