Commentary: Antiretroviral treatment for pregnant

and breastfeeding women the shifting paradigm

Landry Tsaguea and Elaine J. Abramsb

AIDS 2014, 28 (Suppl 2):S119S121

Keywords: antiretroviral treatment, HIV infection, mother-to-child

transmission, pregnancy

The global community has called for the elimination of
new HIV infections among children by 2015 and keeping
their mothers alive [1]. Though viewed by some as
overly optimistic and aspirational, this call to action has
generated unprecedented momentum and transformed
the global dialogue around prevention of mother-to-child
HIV transmission (PMTCT) to emphasize efficiency,
effectiveness and measurable impact of efforts to prevent
new pediatric HIV infections. The 2013 WHO guide-
lines for the use of antiretroviral drugs in pregnant and
breastfeeding women also represent a major paradigm
shift from previous recommendations for PMTCT in low
and middle-income settings (Table 1) [2].
For the first time, the ART strategy for pregnant women
is fully harmonized with the recommended first-line
regimen for nonpregnant adults (once-daily tenofovir
lamivudine/efavirenz emtracitabine). And, perhaps,
more dramatically, the PMTCT regimen will no longer
be determined by the womans health status. Rather, all
women, irrespective of CD4 T-cell count or clinical
stage, will initiate standard first-line ART to reduce
the risk of HIV transmission to the child and to her
uninfected partners. For programmatic and operational
reasons, particularly in generalized HIV epidemics,
all pregnant and breastfeeding women with HIV should
initiate ART as lifelong treatment (the option B
approach), whereas in some countries, for women not
eligible for ART for their own health, consideration can
be given to stopping the antiretroviral drug regimen
after the period of MTCT risk has ceased (option B) [2].
Using pregnancy status as the sole criterion to initiate
ART represents a substantial change from previous
PMTCT guidance, which traditionally recommended
different antiretroviral regimens (prophylaxis vs. treat-
ment) on the basis of maternal health status and vertical
transmission risk. This simplified approach initiation of
the tenofovir lamivudine/efavirenz emtracitabine
for all pregnant and breastfeeding women and, for
most, continuation as lifelong treatment furthers
the notion of treatment as prevention, which has been
the basic tenet of PMTCT, and should dramatically
expand access to ART among pregnant and breastfeeding
women.
Over the past decade, there has been a progressive
increase in antiretroviral drug use for PMTCT, from
single-dose nevirapine, to short-course prophylaxis, to,
in 2010 [3], a stratified approach with lifelong ART for
eligible pregnant women and, for healthier women,
a prophylaxis regimen of either twice-daily zidovudine
during pregnancy and daily daily nevirapine to their
infants during breastfeeding (option A), or maternal triple
antiretroviral drug through breastfeeding (option B). And
although thought to be highly and equally efficacious
regimens for preventing transmission, implementation
in the field has been fraught with complexity. Few
low and middle-income countries have been successful
in efforts to scale up these antiretroviral regimens [4],
particularly to identify and treat ART-eligible women
who are at highest risk for both HIV disease progression
and MTCT during pregnancy and breastfeeding [5].
In 2012, among pregnant women who needed ART
for their own health, less than 50% received it in
10 priority countries for the elimination of mother-to-
child transmission Global Plan [4]. By eliminating
the need for CD4 T-cell count determination to
identify treatment eligibility, and with the use of the
same once-daily regimen for all pregnant women as
in nonpregnant adults, option B simplifies program
implementation, and as demonstrated in Malawi [6],
where the approach was innovated, should substantially
improve ART uptake among pregnant and breastfeeding
women [7].

a
UNICEF, Lusaka, Zambia, and bICAP, Mailman School of Public Health, and College of Physicians & Surgeons, Columbia
University, New York, New York, USA.
Correspondence to Elaine J. Abrams, MD, ICAP, Mailman School of Public Health, 722 W168th Street, New York, NY 10032,
USA.
Tel: +1 212 342 0543; e-mail: eja1@columbia.edu

DOI:10.1097/QAD.0000000000000234

ISSN 0269-9370 Q 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins S119
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S120 AIDS 2014, Vol 28 (Suppl 2)

Table 1. Summary of recommendations for use of antiretroviral drugs for pregnant and breastfeeding women and HIV-exposed infants in the
2013 WHO guidelines [2].

Strength of Recommendation/
Recommendation Quality of evidence

All pregnant and breastfeeding women with HIV should initiate triple ARVs, which Strong recommendation, moderate-quality
should be maintained at least for the duration of mother-to-child transmission risk. evidence
Women meeting treatment eligibility criteria should continue lifelong ART
For programmatic and operational reasons, particularly in generalized epidemics, Conditional recommendation, low-quality
all pregnant and breastfeeding women infected with HIV should initiate ART as evidence
lifelong treatment
In some countries, for women who are not eligible for ART for their own health, Conditional recommendation, low-quality
consideration can be given to stopping the ARV regimen after the period of evidence
mother-to-child transmission risk has ceased

First-line ART should consist of two nucleoside reverse-transcriptase inhibitors (NRTIs) Strong recommendation, moderate-quality
plus a non-nucleoside reverse-transcriptase inhibitor (NNRTI) tenofovir evidence
lamivudine/efavirenz emtracitabine as a fixed-dose combination, (FDC)
is recommended option for ART initiation

Viral load is recommended as the preferred approach to diagnose and confirm ARV Strong recommendation, low-quality
treatment failure evidence
If viral load is not available, CD4 and clinical monitoring should be used to diagnose Strong recommendation, moderate-quality
treatment failure evidence

Infants of mothers who are receiving ART and breast feeding should receive 6 weeks Strong recommendation, low to moderate-quality
of infant prophylaxis with daily nevirapine; Infants receiving replacement evidence for breastfeeding infants; low quality
feeding should receive 46 weeks of infant prophylaxis with daily nevirapine of evidence for infants receiving only
(or twice daily AZT); Prophylaxis should begin at birth or when the exposure replacement feeding
is recognized postpartum

Historically, the PMTCT community has been moderately
conservative in recommended approaches and regimens,
balancing risk of transmission, maternal health concerns,
and safety of drugs for mother and fetus. There has been
particular reluctance to use emtracitabine during preg-
nancy, given teratogenic effects observed in primates
exposed in utero to emtracitabine, several reports of neural
tube and other central nervous system defects in children
with first trimester exposure [8], and an US Food and Drug
Administration (FDA) pregnancy category D classification
[9]. Given other drug options, emtracitabine was generally
avoided for pregnant women and women considering
pregnancy. However, emtracitabine use has increased over
the past years in nonpregnant adult populations in low and
middle-income settings and in 2010 WHO-recommended
tenofovir lamivudine/efavirenz emtracitabine as
first-line ART regimen for adults [3]. Given high rates of
unintended pregnancy and late entry into antenatal care in
many countries, this recommendation paved the way for
increased emtracitabine use during pregnancy.
Although data on both emtracitabine and tenofovir use in
pregnant women remain limited, more data have become
available since 2010 and provide increased reassurance
around safety of the recommended regimen for use during
pregnancy and breastfeeding [1012]. In June 2012,
WHO issued a technical update on emtracitabine use
during pregnancy delineating the clinical and program-
matic risks and benefits and concluding that the
balance favored inclusion of emtracitabine as part of the
preferred first-line ART regimen for pregnant women
[13]. Harmonizing the available fixed dose combination
tenofovir lamivudine/efavirenz emtracitabine as
first-line treatment for adults and all pregnant women
including those with higher CD4 T-cell counts was a
logical next step. Emtracitabine was further preferred
over nevirapine given concerns about the increased
risk of maternal hepatotoxicity of nevirapine in this group
[14,15].
The following article by Ford et al. provides additional
evidence of the safety of emtracitabine in pregnancy
for women with HIV [16]. This is the third updated
systematic review and meta-analysis, including data from
the Antiretroviral Pregnancy Registry. Overall, there
were 44 congenital anomalies reported among 1995 live
births to women receiving emtracitabine in the first
trimester. The authors found no increase in overall birth
defects and no elevated signal for emtracitabine compared
with other antiretroviral drug exposures in pregnancy
[relative risk 0.78; 95% confidence interval (CI) 0.56
1.09]. With one identified neural tube defect, the
estimated prevalence from the systematic review conti-
nues to be approximately 7 per 10 000 population
(0.07%), which is comparable to the estimates of 0.1% in
the general population. Although a much larger sample
size is needed to definitively rule out a two-fold
increase in low-incidence birth defects, these findings
are reassuring.
Similarly, concerns linger around tenofovir use during
pregnancy. In adult and pediatric populations, tenofovir

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 Antiretroviral treatment for pregnant and breastfeeding women Tsague and Abrams
has been associated with renal dysfunction and bone
density loss. Findings from several studies of infants with
in-utero tenofovir exposure suggest no increase in poor
pregnancy outcomes or congenital defects [12,17,18].
Studies are currently underway to formally evaluate
tenofovir exposure on a variety of infant outcomes
including growth and bone mineral content.
Any antiretroviral drug use during pregnancy is not
without risk to the fetus, but when balanced against the
benefits of preventing infant infection and treating
maternal HIV disease, ART use appears to be highly
favorable. Operational and programmatic imperatives
further support the choice of once-daily tenofovir
lamivudine/efavirenz emtracitabine as the first-line
regimen for pregnant and breastfeeding women. It will be,
however, critical to continue to monitor outcomes and
confirm the findings of Ford et al., as these drugs are more
widely used in pregnant and breastfeeding populations.
Over the past decade, the ART scale-up in low and middle-
income countries has met with unprecedented success.
More than 9.7 million people have initiated ART and an
estimated 5.5 million AIDS-related deaths have been
averted in low and middle-income countries [4].
Unfortunately, pregnant women have been somewhat
marginalized and under-represented among those on ART
[19]. Option B/B offers a unique opportunity to achieve
equity for this population, but it will require thoughtful
investment investments in the health systems in which
women and children receive PMTCT and other health
services, as well as investments to transform PMTCT
services into ART programs prepared to engage in lifetime
ART care for this population [20]. The WHO 2013
guidelines for the use of antiretroviral drugs for treating and
preventing HIV infection provides a platform and a catalyst
to effectively prevent new pediatric HIV infections and
keep mothers alive, but it remains up to the global
community to ensure that these aspirations are realized.
Acknowledgements
Conflicts of interest
Dr. Abrams was the co-chair of the maternal-child group
for the WHO 2013 guidelines. Dr. Tsague was a member
of the maternal-child group for the WHO 2013 guidelines.
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