Journal of Infection (2014) 69, S56eS62
www.elsevierhealth.com/journals/jinf
Mother to child transmission of HIV: What works and how much is enough? Jennifer Stevens, Hermione Lyall* St Mary’s Hospital, Praed Street, London W2 1NY, UK Accepted 18 July 2014 Available online 17 October 2014
KEYWORDS HIV; Mother; Child; Transmission; Prevention; Perinatal; Pregnancy; Anti-retroviral therapy
Summary In 2012, 3.3 million children were living with HIV (Human Immunodeficiency virus), of whom 260,000 were new infections. Prevention of mother to child transmission is vital in reducing HIV-related child mortality and morbidity. With intervention the risk of transmission can be as low as 1% and without it, as high as 45%. The WHO (World Health Organisation) recommends a programmatic approach to the prevention of perinatal HIV transmission and has withdrawn option A and introduced option Bþ. This recommends that all HIV positive pregnant and breastfeeding women receive lifelong triple ARV (antiretroviral) from the point of diagnosis. The infant would then receive 4e6 weeks of ART (antiretroviral therapy) (NVP, nevirapine 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 sustainable approach for their setting, so that the maximum impact on maternal and child mortality and morbidity can be achieved. ª 2014 Published by Elsevier Ltd on behalf of The British Infection Association.
The global picture It is estimated that 35.3 million people are living with HIV worldwide, with 25 million living in sub-saharan Africa.1 3.3 million children are living with HIV, of whom 260,000 were new infections in 2012.1 In the 22 priority countries in the Global Plan, coverage of ART amongst pregnant women living with HIV reached 62% and approximately 230,000
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 receive it, with ART coverage being 34% for children and 64% for adults in 2012.2 Prevention of mother to child transmission is key to reducing the HIV-related child mortality and morbidity (see Table 1).
* Corresponding author. Tel.: þ44 0203 3121013. E-mail addresses: [email protected] (J. Stevens), [email protected] (H. Lyall). 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 Table 1
S57
WHO recommendations for prevention of mother to child transmission 2012. Woman receives:
Infant receives:
Treatment (for CD4 count 350 cells/mm ) Prophylaxis (for CD4 count > 350 cells/mm3) 3
Option Aa Triple ARVs starting as soon as diagnosed, continued for life
Option Ba Same initial ARVs for bothb: Triple ARVs starting as soon as diagnosed, continued for life
Antepartum: AZT starting as early as 14 weeks gestation Intrapartum: at onset of labour, single-dose NVP and first dose of AZT/3TC Postpartum: daily AZT/3TC through 7 days postpartum
Triple ARVs starting as early as 14 weeks gestation and continued intrapartum and through childbirth if not breastfeeding or until 1 week after cessation of all breastfeeding
Option Bþ Same for treatment and prophylaxisb: Regardless of CD4 count, triple ARVs starting as soon as diagnosed,c continued for life
Daily NVP from birth until 1 week after cessation of all breastfeeding; or, if not breastfeeding or if mother is on treatment, through age 4e6 weeks Daily NVP or AZT from birth through age 4e6 weeks regardless of infant feeding method
Daily NVP or AZT from 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 transmission) ranges from 20 to 45%.3 In non-breastfeeding populations, with specific interventions the risk of MTCT can be as low as less than 1% and as low as 2e5% in breastfeeding populations.4 Target 3 of the United Nations Programme on HIV/AIDS (UNAIDS) goals for 2015 is to eliminate new HIV infections amongst children by 90% and to substantially reduce AIDS related maternal deaths by 50%.3,5 The millennium development goal 4 is to reduce the under 5 mortality by two thirds by 2015.4 Goal 5 aims to reduce maternal mortality by three quarters and have universal access to reproductive health by 2015.6 Millennium Goal 6 aims for the number of new HIV infections to have halved by 2015 and for there to be universal access to treatment by 2010.4 In the context of the UNAIDS goals and the millennium development goals we are in a critical position to assess current progress and recommit to advance our success in tackling this issue both on national and international levels. In 2011 the countries with the lowest estimated coverage of the most effective regimen were North Africa and the middle east (9%), west and central Africa (26%) and East, South and South east Asia (20%).7 This compares with Europe and central Asia (95%) and sub-Saharan Africa (58%).7 There has been a steady decline of 24% in MTCT in sub-Saharan Africa from 2009e2011.7 There were modest declines in the Caribbean and Oceania, with North Africa and the Middle East yet to show any decline.7 However different countries will have different priorities depending
on the nature of their epidemic. For example, the Western Pacific, South East Asia and the Americas focus on the dual elimination of HIV and congenital syphilis, whereas Eastern Europe targets the IV drug users and their partners as a priority population for improving PMTCT (prevention of mother to child transmission).4 In 2010 the Pan American Health Organisation and UNICEF (United Nation’s International Children’s Emergency Fund) developed strategies for the advancement of elimination of MTCT of HIV and congenital syphilis.6 The aim was to reduce new paediatric cases of HIV to 0.3 per 1000 live births and to reduce congenital syphilis to 0.5 cases per 1000 live births by promoting the integration of HIV, sexual and reproductive health, paediatric, family and community health services.6 It aims to ensure that women have access to rapid diagnostics for both HIV and syphilis and to treatments and monitoring. Studies in nine European countries found that HIV prevalence in women IVDU (intravenous drug users) was 50% higher than among male IVDU.8 MTCT was also found to be 42% higher in this female group when compared to HIV positive mothers who were not drug users, in the Ukraine.8 One step towards combating this problem is the integration of antenatal services with drug treatment services.8 So whilst data showing downwards trends is encouraging we need to ensure that all pregnant women living with HIV have safe and simple access to ART, with prime focus on those living in the hardest to reach settings. This refers to both the difficult to reach geographical and social
S58 environments (ie. marginalised populations). This, coupled with fragile health care systems heightens the vulnerability of these women and increases the risks that they are exposed to, which in turn, impact upon their children. The answer is multi-faceted but requires flexible, practical and innovative solutions.
Timing of mother to child transmission MTCT occurs as a continuum across three time periods; inutero (10%), perinatal (15%) and postnatally through breastfeeding (10%) [3]. Maternal risk factors include; plasma viral load, CD4 count and the stage of HIV disease. The risk of transmission ranges from 1% with a viral load of less than 400 to 32% with a viral load of 100,000.9 At delivery risk factors include: mode of delivery, premature delivery, duration of membrane rupture and infection in the birth canal.9 Post natal risk factors include mixed feeding and mastitis.9 Interventions for MTCT can be targeted to these three time periods and can either take a programmatic or individualised approach (Fig. 1). Preventative interventions need to be considered within the context of the environment of the mothereinfant pair. In resource poor settings, cessation of breastfeeding is deemed unsafe as the risks of gastroenteritis and malnutrition from early weaning outweigh the risk of transmission of HIV. Termination of breastfeeding before 6 months of age increases the risk of gastro-enteritis and associated morbidity and mortality as well as increasing the risk of malnutrition in the absence of safe and nutritious feeding alternatives.10 Recent randomised controlled studies have demonstrated the low risk of breast milk transmission
J. Stevens, H. Lyall where the mother is on ART, or the infant is on preexposure prophylaxis.10,11 Therefore in such settings PMTCT programmes should be designed around breastfeeding which is the most appropriate way to safely feed infants.10 The combined effect of maternal ART and infant post 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 the risk of transmission is as low as 0.1% with maternal ART and formula feeding.
The programmatic approach The three main objectives of the WHO in their 2010e2015 PMTCT strategic vision is to accelerate global and national scale-up of effective and comprehensive PMTCT services, to improve the quality and demonstrate the public health impact of PMTCT services and to strengthen the linkages between maternal, newborn and child health services, reproductive health services and HIV related services to reduce overall maternal and child mortality.4 The WHO emphasizes the importance of all HIV infected women having access to life-long treatment if they are clinically or immunologically eligible for it. For those pregnant women who did not require it for their own health there were two options; A and B, see Table (Table 2).4 In 2010 a further option, Bþ was introduced which advocates life-long treatment for all HIV positive pregnant or breastfeeding women, irrespective of their clinical stage or CD4 count.4,5 In June 2013, WHO issued new guidance which now 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 Table 2
S59
BHIVA recommendations for ART in pregnancy 2012.
Mother requires ART for herself
Mother requires ART for PMTCT only
Late presenter not on ART
Elite controllers
Nucleoside backbone Zidovudine/lamivudine Abacavir/lamivudine Tenofavir/emtricitabine Third agent Efavirenz or Nevirapine OR boosted protease inhibitor Special considerations Darunavir needs twice daily dosing. Consider 3rd trimester TDM if on tenofovir and atazanavir.
Commence by 24 weeks gestation Nucleoside backbone Zidovudine/lamivudine Abacavir/lamivudine Tenofavir/emtricitabine Third agent Preferably boosted PI Special considerations Zidovudine monotherapy þ C-section if VL < 10,000 þ CD4>350 Start ART by week 14 if VL > 30,000 Start earlier if >100,000
Commence ART immediately if > 28weeks gestation VL > 100,000/unknown use raltegravir in 3 or 4 drug regimen. Presenting in term labour: stat dose Nevirapine þ zidovudine, lamivudine and raltegravir. If in preterm labour consider double dose tenofavir to further load baby, especially if unable to feed.
CD4>350, VL < 50: Zidovudine monotherapy or ART.
From British HIV association guidelines for the management of HIV infection in pregnant women, 2012. HIV Med 2012;13 (Suppl. 2):87e157.11
regimen for all pregnant women irrespective of their CD4 count (option Bþ), this would then continue lifelong for all or just for those who meet the eligibility criteria (option B).12 This decision was made on the evidence that whilst trials have shown similar efficacy between Option A and B, the complexities of the former have hindered the up-scaling of PMTCT in many low-resource countries.12 Countries have to make a programmatic choice between ‘option B’ and ‘Bþ’, as there is not yet the evidence to detail the overall impact of lifelong treatment in this scenario.12 Countries that have the capacity to monitor CD4 count, with concentrated epidemics and where the option of alternative feeding is safe, option B may still be considered (Table 1).12 This WHO programmatic update 2012, suggests that option B and specifically Bþ are preferable over option A.13 Both B and Bþ start women on a triple ARV regimen which carries more assurance that those eligible for treatment will get a fully suppressive regimen. The ability to use the same regimen for ART and PMTCT simplifies drug forecasting, procurement, supply and stock monitoring and is less confusing for the women.13 Option Bþ has several advantages such as not requiring CD4 counts to determine eligibility for ART or to decide whether or when to stop once the risk of MTCT is over.5,13 It also offers protection for future pregnancies by remaining on ART from conception as well as offering ongoing protection to serodiscordant couples.5,13 Early treatment before women
Table 3
meet the immunological or clinical criteria for ART would have an advantageous affect on their health (65% reduced risk of contracting TB whilst on ART irrespective of CD4 count7) and may reduce drug resistance if they are not starting and stopping ART regularly, especially in areas of high birth rates.9 It also reinforces the message that ART is intended for lifelong treatment and therefore may improve compliance.9
Feedback from the field Results from Malawi where option Bþ has been implemented since the third quarter of 2011, show that there has been a dramatic increase in the number of new ART initiations in pregnant women from the 4th quarter of 2011 through to 2012. Numbers rose from 1 new initiation per quarter (5% of all new initiations) to 11 per quarter (35%).7 Of those who initiated ART in the third quarter of 2011 77% remained on treatment, of the 23% that discontinued; 94% were lost to follow-up, 3% died and 3% decided to stop treatment.14 ART and PMTCT programmes were combined and administered by nurses at primary health facilities where women and children were already accessing health care; helping to target the hard to reach areas and reducing stigma.5 This could in turn encourage compliance and adherence. So revising the national guidelines, monitoring and evaluation systems, the supply chain and human
BHIVA recommendations for stopping ART postpartum 2012.
Clinical scenario
Duration of treatment
AIDS defining illness/CD4 500 þ no discordance þ no hepatitis co-infection
Continue as per adult treatment guidelines Continue as per adult treatment guidelines Continue as per adult treatment guidelines Discontinue treatment
From British HIV association guidelines for the management of HIV infection in pregnant women, 2012. HIV Med 2012;13 (Suppl. 2):87e157.11
S60 resources strategies they made significant steps in providing an effective, equitable service with a broad health impact.5
Cost The WHO anticipate B and Bþ to be more cost effective than A, as first line once daily regimens are less costly now.5 The regimen recommended is Tenofavir, lamivudine or emtricitabine and efavirenz, (for ART and PMTCT). It is available as a single pill, fixed-dose combination and currently costs $180 per year with declines anticipated.13 Recent pharmacokinetic data is reassuring on the use of efavirenz in pregnancy but continued pharmacovigilence is essential. Simple regimens are needed for the best chance of success.15
Early concerns However, option Bþ does raise questions around how to guarantee long term adherence, retention in treatment, safe transition to HIV care from antenatal care, development of drug resistance, increased drug exposure to the foetus and newborn, sustainability of service delivery in fragile primary care settings and the ongoing acceptability to women.13 Continued application and reflection of and on this programme will in time reveal resolutions to these questions.
Infant feeding The 2010 guidelines for infant feeding have not changed in the updated WHO 2013 guideline document.12 In countries where breastfeeding with the mother on ART and the infant receiving prophylaxis is considered the safest approach to ensuring survival of the newborn, mothers should exclusively breastfeed for the first 6 months of life and continue breastfeeding through weaning until 12 months of life.12 They can stop when a safe alternative is guaranteed after this age.12
The individualised approach The UK and Ireland adopt an individualised approach to PMTCT, but it is not without its own complications and the risk of MTCT still is not totally eliminated. Reasons for this are drug resistance, poor maternal adherence to treatment, late presenters in pregnancy and sero-conversion in pregnancy. Tables 2 and 3 give details of the British HIV Association guidelines for the individualised management of HIV in pregnancy.11 In the UK and Ireland, from 2005 onwards more than 95% of women living with HIV are diagnosed antenatally through universal antenatal screening.15 This compares to a 30% antenatal diagnosis in the early 90s. Over the last 14 years, a higher proportion of women are being diagnosed before their current pregnancy rather than during it.15 Plus, a higher proportion of women are on ART at conception due to a prior diagnosis rather than being HIV positive but not on ART at conception.16
J. Stevens, H. Lyall With an individualised approach MTCT rates in UK and Ireland have also shown a steady decline over the last 11 years to 0.5% overall in 2010e2011 (Fig. 1).15 If the HIV test is declined at antenatal screening it 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 test should be offered. A rapid result, if positive, enables initiation of intrapartum ART, infant PEP (post-exposure prophylaxis), avoidance of breastfeeding and infant cotrimoxazole prophylaxis (whilst awaiting the infant HIV diagnostic results).11 Baseline resistance testing should be undertaken before starting ART. Vaginal delivery is the preferred delivery option if the viral load is undetectable (
www.elsevierhealth.com/journals/jinf
Mother to child transmission of HIV: What works and how much is enough? Jennifer Stevens, Hermione Lyall* St Mary’s Hospital, Praed Street, London W2 1NY, UK Accepted 18 July 2014 Available online 17 October 2014
KEYWORDS HIV; Mother; Child; Transmission; Prevention; Perinatal; Pregnancy; Anti-retroviral therapy
Summary In 2012, 3.3 million children were living with HIV (Human Immunodeficiency virus), of whom 260,000 were new infections. Prevention of mother to child transmission is vital in reducing HIV-related child mortality and morbidity. With intervention the risk of transmission can be as low as 1% and without it, as high as 45%. The WHO (World Health Organisation) recommends a programmatic approach to the prevention of perinatal HIV transmission and has withdrawn option A and introduced option Bþ. This recommends that all HIV positive pregnant and breastfeeding women receive lifelong triple ARV (antiretroviral) from the point of diagnosis. The infant would then receive 4e6 weeks of ART (antiretroviral therapy) (NVP, nevirapine 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 sustainable approach for their setting, so that the maximum impact on maternal and child mortality and morbidity can be achieved. ª 2014 Published by Elsevier Ltd on behalf of The British Infection Association.
The global picture It is estimated that 35.3 million people are living with HIV worldwide, with 25 million living in sub-saharan Africa.1 3.3 million children are living with HIV, of whom 260,000 were new infections in 2012.1 In the 22 priority countries in the Global Plan, coverage of ART amongst pregnant women living with HIV reached 62% and approximately 230,000
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 receive it, with ART coverage being 34% for children and 64% for adults in 2012.2 Prevention of mother to child transmission is key to reducing the HIV-related child mortality and morbidity (see Table 1).
* Corresponding author. Tel.: þ44 0203 3121013. E-mail addresses: [email protected] (J. Stevens), [email protected] (H. Lyall). 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 Table 1
S57
WHO recommendations for prevention of mother to child transmission 2012. Woman receives:
Infant receives:
Treatment (for CD4 count 350 cells/mm ) Prophylaxis (for CD4 count > 350 cells/mm3) 3
Option Aa Triple ARVs starting as soon as diagnosed, continued for life
Option Ba Same initial ARVs for bothb: Triple ARVs starting as soon as diagnosed, continued for life
Antepartum: AZT starting as early as 14 weeks gestation Intrapartum: at onset of labour, single-dose NVP and first dose of AZT/3TC Postpartum: daily AZT/3TC through 7 days postpartum
Triple ARVs starting as early as 14 weeks gestation and continued intrapartum and through childbirth if not breastfeeding or until 1 week after cessation of all breastfeeding
Option Bþ Same for treatment and prophylaxisb: Regardless of CD4 count, triple ARVs starting as soon as diagnosed,c continued for life
Daily NVP from birth until 1 week after cessation of all breastfeeding; or, if not breastfeeding or if mother is on treatment, through age 4e6 weeks Daily NVP or AZT from birth through age 4e6 weeks regardless of infant feeding method
Daily NVP or AZT from 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 transmission) ranges from 20 to 45%.3 In non-breastfeeding populations, with specific interventions the risk of MTCT can be as low as less than 1% and as low as 2e5% in breastfeeding populations.4 Target 3 of the United Nations Programme on HIV/AIDS (UNAIDS) goals for 2015 is to eliminate new HIV infections amongst children by 90% and to substantially reduce AIDS related maternal deaths by 50%.3,5 The millennium development goal 4 is to reduce the under 5 mortality by two thirds by 2015.4 Goal 5 aims to reduce maternal mortality by three quarters and have universal access to reproductive health by 2015.6 Millennium Goal 6 aims for the number of new HIV infections to have halved by 2015 and for there to be universal access to treatment by 2010.4 In the context of the UNAIDS goals and the millennium development goals we are in a critical position to assess current progress and recommit to advance our success in tackling this issue both on national and international levels. In 2011 the countries with the lowest estimated coverage of the most effective regimen were North Africa and the middle east (9%), west and central Africa (26%) and East, South and South east Asia (20%).7 This compares with Europe and central Asia (95%) and sub-Saharan Africa (58%).7 There has been a steady decline of 24% in MTCT in sub-Saharan Africa from 2009e2011.7 There were modest declines in the Caribbean and Oceania, with North Africa and the Middle East yet to show any decline.7 However different countries will have different priorities depending
on the nature of their epidemic. For example, the Western Pacific, South East Asia and the Americas focus on the dual elimination of HIV and congenital syphilis, whereas Eastern Europe targets the IV drug users and their partners as a priority population for improving PMTCT (prevention of mother to child transmission).4 In 2010 the Pan American Health Organisation and UNICEF (United Nation’s International Children’s Emergency Fund) developed strategies for the advancement of elimination of MTCT of HIV and congenital syphilis.6 The aim was to reduce new paediatric cases of HIV to 0.3 per 1000 live births and to reduce congenital syphilis to 0.5 cases per 1000 live births by promoting the integration of HIV, sexual and reproductive health, paediatric, family and community health services.6 It aims to ensure that women have access to rapid diagnostics for both HIV and syphilis and to treatments and monitoring. Studies in nine European countries found that HIV prevalence in women IVDU (intravenous drug users) was 50% higher than among male IVDU.8 MTCT was also found to be 42% higher in this female group when compared to HIV positive mothers who were not drug users, in the Ukraine.8 One step towards combating this problem is the integration of antenatal services with drug treatment services.8 So whilst data showing downwards trends is encouraging we need to ensure that all pregnant women living with HIV have safe and simple access to ART, with prime focus on those living in the hardest to reach settings. This refers to both the difficult to reach geographical and social
S58 environments (ie. marginalised populations). This, coupled with fragile health care systems heightens the vulnerability of these women and increases the risks that they are exposed to, which in turn, impact upon their children. The answer is multi-faceted but requires flexible, practical and innovative solutions.
Timing of mother to child transmission MTCT occurs as a continuum across three time periods; inutero (10%), perinatal (15%) and postnatally through breastfeeding (10%) [3]. Maternal risk factors include; plasma viral load, CD4 count and the stage of HIV disease. The risk of transmission ranges from 1% with a viral load of less than 400 to 32% with a viral load of 100,000.9 At delivery risk factors include: mode of delivery, premature delivery, duration of membrane rupture and infection in the birth canal.9 Post natal risk factors include mixed feeding and mastitis.9 Interventions for MTCT can be targeted to these three time periods and can either take a programmatic or individualised approach (Fig. 1). Preventative interventions need to be considered within the context of the environment of the mothereinfant pair. In resource poor settings, cessation of breastfeeding is deemed unsafe as the risks of gastroenteritis and malnutrition from early weaning outweigh the risk of transmission of HIV. Termination of breastfeeding before 6 months of age increases the risk of gastro-enteritis and associated morbidity and mortality as well as increasing the risk of malnutrition in the absence of safe and nutritious feeding alternatives.10 Recent randomised controlled studies have demonstrated the low risk of breast milk transmission
J. Stevens, H. Lyall where the mother is on ART, or the infant is on preexposure prophylaxis.10,11 Therefore in such settings PMTCT programmes should be designed around breastfeeding which is the most appropriate way to safely feed infants.10 The combined effect of maternal ART and infant post 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 the risk of transmission is as low as 0.1% with maternal ART and formula feeding.
The programmatic approach The three main objectives of the WHO in their 2010e2015 PMTCT strategic vision is to accelerate global and national scale-up of effective and comprehensive PMTCT services, to improve the quality and demonstrate the public health impact of PMTCT services and to strengthen the linkages between maternal, newborn and child health services, reproductive health services and HIV related services to reduce overall maternal and child mortality.4 The WHO emphasizes the importance of all HIV infected women having access to life-long treatment if they are clinically or immunologically eligible for it. For those pregnant women who did not require it for their own health there were two options; A and B, see Table (Table 2).4 In 2010 a further option, Bþ was introduced which advocates life-long treatment for all HIV positive pregnant or breastfeeding women, irrespective of their clinical stage or CD4 count.4,5 In June 2013, WHO issued new guidance which now 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 Table 2
S59
BHIVA recommendations for ART in pregnancy 2012.
Mother requires ART for herself
Mother requires ART for PMTCT only
Late presenter not on ART
Elite controllers
Nucleoside backbone Zidovudine/lamivudine Abacavir/lamivudine Tenofavir/emtricitabine Third agent Efavirenz or Nevirapine OR boosted protease inhibitor Special considerations Darunavir needs twice daily dosing. Consider 3rd trimester TDM if on tenofovir and atazanavir.
Commence by 24 weeks gestation Nucleoside backbone Zidovudine/lamivudine Abacavir/lamivudine Tenofavir/emtricitabine Third agent Preferably boosted PI Special considerations Zidovudine monotherapy þ C-section if VL < 10,000 þ CD4>350 Start ART by week 14 if VL > 30,000 Start earlier if >100,000
Commence ART immediately if > 28weeks gestation VL > 100,000/unknown use raltegravir in 3 or 4 drug regimen. Presenting in term labour: stat dose Nevirapine þ zidovudine, lamivudine and raltegravir. If in preterm labour consider double dose tenofavir to further load baby, especially if unable to feed.
CD4>350, VL < 50: Zidovudine monotherapy or ART.
From British HIV association guidelines for the management of HIV infection in pregnant women, 2012. HIV Med 2012;13 (Suppl. 2):87e157.11
regimen for all pregnant women irrespective of their CD4 count (option Bþ), this would then continue lifelong for all or just for those who meet the eligibility criteria (option B).12 This decision was made on the evidence that whilst trials have shown similar efficacy between Option A and B, the complexities of the former have hindered the up-scaling of PMTCT in many low-resource countries.12 Countries have to make a programmatic choice between ‘option B’ and ‘Bþ’, as there is not yet the evidence to detail the overall impact of lifelong treatment in this scenario.12 Countries that have the capacity to monitor CD4 count, with concentrated epidemics and where the option of alternative feeding is safe, option B may still be considered (Table 1).12 This WHO programmatic update 2012, suggests that option B and specifically Bþ are preferable over option A.13 Both B and Bþ start women on a triple ARV regimen which carries more assurance that those eligible for treatment will get a fully suppressive regimen. The ability to use the same regimen for ART and PMTCT simplifies drug forecasting, procurement, supply and stock monitoring and is less confusing for the women.13 Option Bþ has several advantages such as not requiring CD4 counts to determine eligibility for ART or to decide whether or when to stop once the risk of MTCT is over.5,13 It also offers protection for future pregnancies by remaining on ART from conception as well as offering ongoing protection to serodiscordant couples.5,13 Early treatment before women
Table 3
meet the immunological or clinical criteria for ART would have an advantageous affect on their health (65% reduced risk of contracting TB whilst on ART irrespective of CD4 count7) and may reduce drug resistance if they are not starting and stopping ART regularly, especially in areas of high birth rates.9 It also reinforces the message that ART is intended for lifelong treatment and therefore may improve compliance.9
Feedback from the field Results from Malawi where option Bþ has been implemented since the third quarter of 2011, show that there has been a dramatic increase in the number of new ART initiations in pregnant women from the 4th quarter of 2011 through to 2012. Numbers rose from 1 new initiation per quarter (5% of all new initiations) to 11 per quarter (35%).7 Of those who initiated ART in the third quarter of 2011 77% remained on treatment, of the 23% that discontinued; 94% were lost to follow-up, 3% died and 3% decided to stop treatment.14 ART and PMTCT programmes were combined and administered by nurses at primary health facilities where women and children were already accessing health care; helping to target the hard to reach areas and reducing stigma.5 This could in turn encourage compliance and adherence. So revising the national guidelines, monitoring and evaluation systems, the supply chain and human
BHIVA recommendations for stopping ART postpartum 2012.
Clinical scenario
Duration of treatment
AIDS defining illness/CD4 500 þ no discordance þ no hepatitis co-infection
Continue as per adult treatment guidelines Continue as per adult treatment guidelines Continue as per adult treatment guidelines Discontinue treatment
From British HIV association guidelines for the management of HIV infection in pregnant women, 2012. HIV Med 2012;13 (Suppl. 2):87e157.11
S60 resources strategies they made significant steps in providing an effective, equitable service with a broad health impact.5
Cost The WHO anticipate B and Bþ to be more cost effective than A, as first line once daily regimens are less costly now.5 The regimen recommended is Tenofavir, lamivudine or emtricitabine and efavirenz, (for ART and PMTCT). It is available as a single pill, fixed-dose combination and currently costs $180 per year with declines anticipated.13 Recent pharmacokinetic data is reassuring on the use of efavirenz in pregnancy but continued pharmacovigilence is essential. Simple regimens are needed for the best chance of success.15
Early concerns However, option Bþ does raise questions around how to guarantee long term adherence, retention in treatment, safe transition to HIV care from antenatal care, development of drug resistance, increased drug exposure to the foetus and newborn, sustainability of service delivery in fragile primary care settings and the ongoing acceptability to women.13 Continued application and reflection of and on this programme will in time reveal resolutions to these questions.
Infant feeding The 2010 guidelines for infant feeding have not changed in the updated WHO 2013 guideline document.12 In countries where breastfeeding with the mother on ART and the infant receiving prophylaxis is considered the safest approach to ensuring survival of the newborn, mothers should exclusively breastfeed for the first 6 months of life and continue breastfeeding through weaning until 12 months of life.12 They can stop when a safe alternative is guaranteed after this age.12
The individualised approach The UK and Ireland adopt an individualised approach to PMTCT, but it is not without its own complications and the risk of MTCT still is not totally eliminated. Reasons for this are drug resistance, poor maternal adherence to treatment, late presenters in pregnancy and sero-conversion in pregnancy. Tables 2 and 3 give details of the British HIV Association guidelines for the individualised management of HIV in pregnancy.11 In the UK and Ireland, from 2005 onwards more than 95% of women living with HIV are diagnosed antenatally through universal antenatal screening.15 This compares to a 30% antenatal diagnosis in the early 90s. Over the last 14 years, a higher proportion of women are being diagnosed before their current pregnancy rather than during it.15 Plus, a higher proportion of women are on ART at conception due to a prior diagnosis rather than being HIV positive but not on ART at conception.16
J. Stevens, H. Lyall With an individualised approach MTCT rates in UK and Ireland have also shown a steady decline over the last 11 years to 0.5% overall in 2010e2011 (Fig. 1).15 If the HIV test is declined at antenatal screening it 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 test should be offered. A rapid result, if positive, enables initiation of intrapartum ART, infant PEP (post-exposure prophylaxis), avoidance of breastfeeding and infant cotrimoxazole prophylaxis (whilst awaiting the infant HIV diagnostic results).11 Baseline resistance testing should be undertaken before starting ART. Vaginal delivery is the preferred delivery option if the viral load is undetectable (
