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KEYWORDS Summary In 2012, 3.3 million children were living with HIV (Human Immunodeficiency virus),
HIV; of whom 260,000 were new infections. Prevention of mother to child transmission is vital in
Mother; reducing HIV-related child mortality and morbidity. With intervention the risk of transmission
Child; can be as low as 1% and without it, as high as 45%. The WHO (World Health Organisation) rec-
Transmission; ommends a programmatic approach to the prevention of perinatal HIV transmission and has
Prevention; withdrawn option A and introduced option Bþ. This recommends that all HIV positive pregnant
Perinatal; and breastfeeding women receive lifelong triple ARV (antiretroviral) from the point of diag-
Pregnancy; nosis. The infant would then receive 4e6 weeks of ART (antiretroviral therapy) (NVP, nevira-
Anti-retroviral therapy pine or AZT, Zidovudine) regardless of the feeding method. Where resources are not limited
an individualised approach can be adopted. Worldwide, health care needs to be accessible
and HIV testing performed in pregnancy and followed up in a robust but socially sensitive
way so that treatment can be initiated appropriately. In either setting the risk of transmission
is never zero and countries need to decide for themselves what is the most practical and sus-
tainable approach for their setting, so that the maximum impact on maternal and child mor-
tality and morbidity can be achieved.
ª 2014 Published by Elsevier Ltd on behalf of The British Infection Association.
The global picture children were newly infected with HIV in these countries
in 2012.1 Children living with HIV in low and middle income
countries, eligible for ART are less likely than adults to
It is estimated that 35.3 million people are living with HIV
receive it, with ART coverage being 34% for children and
worldwide, with 25 million living in sub-saharan Africa.1 3.3
64% for adults in 2012.2 Prevention of mother to child trans-
million children are living with HIV, of whom 260,000 were
mission is key to reducing the HIV-related child mortality
new infections in 2012.1 In the 22 priority countries in the
and morbidity (see Table 1).
Global Plan, coverage of ART amongst pregnant women
living with HIV reached 62% and approximately 230,000
http://dx.doi.org/10.1016/j.jinf.2014.07.018
0163-4453/ª 2014 Published by Elsevier Ltd on behalf of The British Infection Association.
Mother to child transmission of HIV S57
cells/mm3)
Option Aa Triple ARVs starting as soon as diagnosed, Antepartum: AZT starting as early as 14 Daily NVP from birth
continued for life weeks gestation until 1 week after
Intrapartum: at onset of labour, single-dose cessation of all
NVP and first dose of AZT/3TC breastfeeding; or, if not
Postpartum: daily AZT/3TC through 7 days breastfeeding or if
postpartum mother is on treatment,
through age 4e6 weeks
Option Ba Same initial ARVs for bothb: Daily NVP or AZT from
Triple ARVs starting as soon as diagnosed, Triple ARVs starting as early as 14 weeks birth through age 4e6
continued for life gestation and continued intrapartum and weeks regardless of
through childbirth if not breastfeeding or infant feeding method
until 1 week after cessation of all
breastfeeding
Option Bþ Same for treatment and prophylaxisb: Daily NVP or AZT from
Regardless of CD4 count, triple ARVs starting as soon as diagnosed,c continued for life birth through age 4e6
weeks regardless of
infant feeding method
From UNICEF. Options B and Bþ: key considerations for countries to implement an equity-focussed approach. Eliminating new HIV
infections among children and keeping mothers living with HIV alive and well; July 2012.5
Note: “Triple ARVs” refers to the use of one of the recommended 3-drug fully suppressive treatment options. For the drug abbreviations
in the table: AZT (azidothymidine, zidovudine [ZDV]); NVP (nevirapine); 3TC (lamivudine).
a
Recommended in WHO 2010 PMTCT guidelines; single dose NVP and AZT þ 3TC intrapartum and postpartum tail can be omitted if the
mother received more than 4 weeks of AZT during pregnancy; in this case continue maternal AZT twice daily during labour and stop at
delivery.
b
True only for EFV-based first-line ART; NVP-based ART not recommended for prophylaxis (CD4 >350).
c
Formal recommendations for Option Bþ have not been made, but presumably ART would start at diagnosis.
Without intervention the risk of MTCT (mother to child on the nature of their epidemic. For example, the Western
transmission) ranges from 20 to 45%.3 In non-breastfeeding Pacific, South East Asia and the Americas focus on the dual
populations, with specific interventions the risk of MTCT elimination of HIV and congenital syphilis, whereas Eastern
can be as low as less than 1% and as low as 2e5% in breast- Europe targets the IV drug users and their partners as a pri-
feeding populations.4 Target 3 of the United Nations ority population for improving PMTCT (prevention of
Programme on HIV/AIDS (UNAIDS) goals for 2015 is to elim- mother to child transmission).4 In 2010 the Pan American
inate new HIV infections amongst children by 90% and to Health Organisation and UNICEF (United Nation’s Interna-
substantially reduce AIDS related maternal deaths by tional Children’s Emergency Fund) developed strategies
50%.3,5 The millennium development goal 4 is to reduce for the advancement of elimination of MTCT of HIV and
the under 5 mortality by two thirds by 2015.4 Goal 5 aims congenital syphilis.6 The aim was to reduce new paediatric
to reduce maternal mortality by three quarters and have cases of HIV to 0.3 per 1000 live births and to reduce
universal access to reproductive health by 2015.6 Millen- congenital syphilis to 0.5 cases per 1000 live births by pro-
nium Goal 6 aims for the number of new HIV infections to moting the integration of HIV, sexual and reproductive
have halved by 2015 and for there to be universal access health, paediatric, family and community health services.6
to treatment by 2010.4 In the context of the UNAIDS goals It aims to ensure that women have access to rapid diagnos-
and the millennium development goals we are in a critical tics for both HIV and syphilis and to treatments and moni-
position to assess current progress and recommit to toring. Studies in nine European countries found that HIV
advance our success in tackling this issue both on national prevalence in women IVDU (intravenous drug users) was
and international levels. 50% higher than among male IVDU.8 MTCT was also found
In 2011 the countries with the lowest estimated to be 42% higher in this female group when compared to
coverage of the most effective regimen were North Africa HIV positive mothers who were not drug users, in the
and the middle east (9%), west and central Africa (26%) and Ukraine.8 One step towards combating this problem is the
East, South and South east Asia (20%).7 This compares with integration of antenatal services with drug treatment
Europe and central Asia (95%) and sub-Saharan Africa services.8
(58%).7 There has been a steady decline of 24% in MTCT in So whilst data showing downwards trends is encouraging
sub-Saharan Africa from 2009e2011.7 There were modest we need to ensure that all pregnant women living with HIV
declines in the Caribbean and Oceania, with North Africa have safe and simple access to ART, with prime focus on
and the Middle East yet to show any decline.7 However those living in the hardest to reach settings. This refers to
different countries will have different priorities depending both the difficult to reach geographical and social
S58 J. Stevens, H. Lyall
environments (ie. marginalised populations). This, coupled where the mother is on ART, or the infant is on pre-
with fragile health care systems heightens the vulnerability exposure prophylaxis.10,11 Therefore in such settings PMTCT
of these women and increases the risks that they are programmes should be designed around breastfeeding
exposed to, which in turn, impact upon their children. The which is the most appropriate way to safely feed infants.10
answer is multi-faceted but requires flexible, practical and The combined effect of maternal ART and infant post
innovative solutions. exposure prophylaxis has been adopted into programmes in
Africa to reduce MTCT, and so despite breastfeeding the
risk of transmission is 1e2%, this compares to the UK where
Timing of mother to child transmission the risk of transmission is as low as 0.1% with maternal ART
and formula feeding.
MTCT occurs as a continuum across three time periods; in-
utero (10%), perinatal (15%) and postnatally through
breastfeeding (10%) [3]. Maternal risk factors include; The programmatic approach
plasma viral load, CD4 count and the stage of HIV disease.
The risk of transmission ranges from 1% with a viral load of The three main objectives of the WHO in their 2010e2015
less than 400 to 32% with a viral load of 100,000.9 At deliv- PMTCT strategic vision is to accelerate global and national
ery risk factors include: mode of delivery, premature deliv- scale-up of effective and comprehensive PMTCT services, to
ery, duration of membrane rupture and infection in the improve the quality and demonstrate the public health
birth canal.9 Post natal risk factors include mixed feeding impact of PMTCT services and to strengthen the linkages
and mastitis.9 Interventions for MTCT can be targeted to between maternal, newborn and child health services,
these three time periods and can either take a program- reproductive health services and HIV related services to
matic or individualised approach (Fig. 1). reduce overall maternal and child mortality.4
Preventative interventions need to be considered within The WHO emphasizes the importance of all HIV infected
the context of the environment of the mothereinfant pair. women having access to life-long treatment if they are
In resource poor settings, cessation of breastfeeding is clinically or immunologically eligible for it. For those
deemed unsafe as the risks of gastroenteritis and malnu- pregnant women who did not require it for their own health
trition from early weaning outweigh the risk of transmission there were two options; A and B, see Table (Table 2).4 In
of HIV. Termination of breastfeeding before 6 months of 2010 a further option, Bþ was introduced which advocates
age increases the risk of gastro-enteritis and associated life-long treatment for all HIV positive pregnant or breast-
morbidity and mortality as well as increasing the risk of feeding women, irrespective of their clinical stage or CD4
malnutrition in the absence of safe and nutritious feeding count.4,5
alternatives.10 Recent randomised controlled studies have In June 2013, WHO issued new guidance which now
demonstrated the low risk of breast milk transmission excludes option A and recommends one simplified triple
Figure 1 MCT rates in diagnosed women in UK and Ireland 2000e2011. From Townsend CL, Byrne L, Cortina-Borja M, Thorne C, de
Ruiter A, Lyall H, Taylor GP, Peckham CS, Tookey P. Earlier initiation of ART and further decline in mother to child transmission
rates 2000e2011. AIDS, 2014;28 (7):1049e57.22
Mother to child transmission of HIV S59
regimen for all pregnant women irrespective of their CD4 meet the immunological or clinical criteria for ART would
count (option Bþ), this would then continue lifelong for all have an advantageous affect on their health (65% reduced
or just for those who meet the eligibility criteria (option risk of contracting TB whilst on ART irrespective of CD4
B).12 This decision was made on the evidence that whilst tri- count7) and may reduce drug resistance if they are not
als have shown similar efficacy between Option A and B, the starting and stopping ART regularly, especially in areas of
complexities of the former have hindered the up-scaling of high birth rates.9 It also reinforces the message that ART
PMTCT in many low-resource countries.12 Countries have is intended for lifelong treatment and therefore may
to make a programmatic choice between ‘option B’ and improve compliance.9
‘Bþ’, as there is not yet the evidence to detail the overall
impact of lifelong treatment in this scenario.12 Countries Feedback from the field
that have the capacity to monitor CD4 count, with concen-
trated epidemics and where the option of alternative Results from Malawi where option Bþ has been imple-
feeding is safe, option B may still be considered (Table 1).12 mented since the third quarter of 2011, show that there has
This WHO programmatic update 2012, suggests that been a dramatic increase in the number of new ART
option B and specifically Bþ are preferable over option initiations in pregnant women from the 4th quarter of
A.13 Both B and Bþ start women on a triple ARV regimen 2011 through to 2012. Numbers rose from 1 new initiation
which carries more assurance that those eligible for treat- per quarter (5% of all new initiations) to 11 per quarter
ment will get a fully suppressive regimen. The ability to (35%).7 Of those who initiated ART in the third quarter of
use the same regimen for ART and PMTCT simplifies drug 2011 77% remained on treatment, of the 23% that discontin-
forecasting, procurement, supply and stock monitoring ued; 94% were lost to follow-up, 3% died and 3% decided to
and is less confusing for the women.13 Option Bþ has stop treatment.14 ART and PMTCT programmes were com-
several advantages such as not requiring CD4 counts to bined and administered by nurses at primary health facil-
determine eligibility for ART or to decide whether or ities where women and children were already accessing
when to stop once the risk of MTCT is over.5,13 It also offers health care; helping to target the hard to reach areas and
protection for future pregnancies by remaining on ART from reducing stigma.5 This could in turn encourage compliance
conception as well as offering ongoing protection to sero- and adherence. So revising the national guidelines, moni-
discordant couples.5,13 Early treatment before women toring and evaluation systems, the supply chain and human
resources strategies they made significant steps in With an individualised approach MTCT rates in UK and
providing an effective, equitable service with a broad Ireland have also shown a steady decline over the last 11
health impact.5 years to 0.5% overall in 2010e2011 (Fig. 1).15
If the HIV test is declined at antenatal screening it
Cost should be offered at subsequent visits and if still declined
at delivery, the infant should be tested at birth.11 For those
late bookers or those un-booked in labour a point of care
The WHO anticipate B and Bþ to be more cost effective
test should be offered. A rapid result, if positive, enables
than A, as first line once daily regimens are less costly now.5
initiation of intrapartum ART, infant PEP (post-exposure
The regimen recommended is Tenofavir, lamivudine or em-
prophylaxis), avoidance of breastfeeding and infant co-
tricitabine and efavirenz, (for ART and PMTCT). It is avail-
trimoxazole prophylaxis (whilst awaiting the infant HIV
able as a single pill, fixed-dose combination and currently
diagnostic results).11
costs $180 per year with declines anticipated.13 Recent
Baseline resistance testing should be undertaken before
pharmacokinetic data is reassuring on the use of efavirenz
starting ART. Vaginal delivery is the preferred delivery
in pregnancy but continued pharmacovigilence is essential.
option if the viral load is undetectable (<50 copies/ml) by
Simple regimens are needed for the best chance of
36 weeks.11
success.15
20. European mode of delivery collaboration 1999; elective following effective pregnancy interventions in the UK and
caesarean-section versus vaginal delivery in prevention of ver- Ireland 2000e2006. AIDS 2008;22(8):973e81.
tical HIV-1 transmission: a randomised clinical trial. Lancet 22. Townsend CL, Byrne L, Cortina-Borja M, Thorne C, de Ruiter A,
1999;353:1035e9. Lyall H, et al. Earlier initiation of ART and further decline in
21. Townsend CL, Cortina-Borja M, Peckham CS, de Ruiter A, Lyall H, mother to child transmission rates 2000e2011. AIDS 2014;
Tookey PA, et al. Low rates of mother to child transmission of HIV 28(7):1049e57.