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Guidelines for the perinatal management of HIV infection 2019

Guideline Writing Group.

On behalf of Mersey, Cheshire & North Wales HIV Managed Care Network

27th February 2019

GUIDELINES WRITING GROUP

Dr R Thomson-Glover (Consultant in GUM) St Helens and Knowsley NHS Trust

Dr S Aston (Specialist Registrar in ID) Dr E Clarke (Consultant in GUM) Dr M Chaponda (Consultant in ID) Prof S H Khoo (Consultant in ID) Ms E Railton (Clinical Nurse Specialist)

Royal Liverpool & Broadgreen University Hospitals NHS Trust

Dr A Riordan (Consultant in Paediatric ID) Dr D Porter (Consultant in Paediatric ID) Ms C Benson (Paediatric ID Specialist Nurse)

Alder Hey Children’s NHS Foundation Trust

Dr K Jiliani (Consultant Obstetrician) Mrs H Longworth (Antenatal & Newborn Screening Coordinator)

Liverpool Women’s Hospital NHS Foundation Trust

Correspondence to: Dr E Clarke (emily.a.clarke@rlbuht.nhs.uk) Dr R Thomson-Glover (Rebecca.ThomsonGlover@sthk.nhs.uk) Dr M Chaponda (Mas.Chaponda@rlbuht.nhs.uk)

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Contents

1. Introduction 3 1.1. Background 3 1.2. Purpose 4 1.3. Sources of recommendations 4 1.4. Changes from previous version 5

2. The perinatal care plan 5 2.1. Electronic database at Royal Liverpool University Hospital 5 2.2. Pharmacy aspects 6 2.3. Infection control 6

3. Maternal antenatal HIV care 6 3.1. Antenatal screening 6 3.2. General principles of HIV management 6 3.3. Baseline assessment 7 3.4. Monitoring during pregnancy 8 3.5. When to start cART during pregnancy 8 3.6 What cART to start during pregnancy 8 3.7 Managing the risks and complications of treatment 10

4. Antenatal obstetric management 10 4.1. Overview of assessment and monitoring 10 4.2. Preparations for delivery 11 4.3. Mode of delivery 11

5. Care during labour and delivery 11 5.1. Planned vaginal delivery 11 5.2. Coordination of care 12 5.3. Management of pre-labour spontaneous rupture of membranes 12 5.4. Intrapartum zidovudine 12 5.5. New HIV diagnosis presenting in labour 12 5.6. Maternal care 13

6. Post-natal care 13 6.1. Neonatal care 13 6.2. Infant feeding 13 6.3. Diagnosis of HIV transmission to the infant 14 6.4. Discharge from hospital 14 6.5. Immunisations 15 6.6. Maternal post-natal management 15

7. Infant post-exposure prophylaxis 15 7.1. Risk assessment 15 7.2. Zidovudine monotherapy 16 7.3. Combination post-exposure prophylaxis 16 7.4. ART prescribing and administration advice 17 7.5. Co-trimoxazole prophylaxis 17

8. Antiretroviral therapy management plan under various scenarios 18

References 20

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Appendices

APPENDIX 1 - Perinatal Care Plan

APPENDIX 2 - Contacts: Local, Regional and National

APPENDIX 3 - How to give HIV drugs during delivery and to the baby

3.1 Zidovudine infusion (MOTHER)

3.2 Zidovudine infusion (BABY)

3.3 Zidovudine oral syrup (BABY)

3.4 Nevirapine oral suspension (BABY)

3.5 Lamivudine oral solution (BABY)

3.6 Abacavir oral solution (BABY)

3.7 Tenofovir granules (BABY)

List of abbreviations

ART Antiretroviral therapy

BHIVA British HIV Association

CS Caesarean section

cART Combination antiretroviral therapy

GUM Genitourinary medicine

HIV Human immunodeficiency virus

IV Intravenous

MDT Multidisciplinary team

MTCT Mother-to-child transmission

PLCS Pre-Labour Caesarean Section

PEP Post-exposure prophylaxis

PPE Personal protective equipment

ROM Rupture of membranes

SROM Spontaneous rupture of membranes

VBAC Vaginal birth after caesarean section

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1. Introduction

1.1. Background

Untreated HIV infection in pregnant women results in mother-to-child transmission (MTCT; also called vertical transmission) to approximately 15-26% of infants, but with a combination of interventions this can be reduced to <1%. All UK hospitals have a policy to offer antenatal HIV screening to pregnant women. Approximately 1000 women living with HIV become pregnant each year, of whom about three-quarters are from sub-Saharan Africa, but many infections have been found in women without obvious risk factors.

The core aspects of perinatal management of HIV infection needed to minimise vertical transmission are:

Antenatal diagnosis of HIV

Effective maternal combination antiretroviral therapy (cART) to suppress HIV viral load during pregnancy

Pre-labour caesarean section (PLCS) at 38-39 weeks’ gestation or safe vaginal delivery

Intravenous (IV) ZIDUVIDINE to mother during delivery if HIV viral load is not adequately suppressed

Oral or IV ART post-exposure prophylaxis (PEP) to the baby for 2-4 weeks depending on risk assessment

Complete avoidance of breastfeeding

With effective implementation of these interventions, current vertical transmission rates are estimated at 0.27%. When perinatal transmission has occurred, it has often been to women who did not know their HIV status prior to delivery, many of whom declined antenatal testing.

A coordinated multi-disciplinary team (MDT) approach is needed for optimal perinatal care and facilitated by a comprehensive Perinatal Care Plan (Section 2). Within the Mersey, Cheshire and North Wales region, support is provided by the HIV care network (www.liv.ac.uk/hiv) and best accessed via the HIV MDT meetings (2:30pm, second Friday of month, Royal Liverpool University Hospital; videoconferencing available) or directly from group members. Advice is also available from the paediatric HIV team at St Mary’s Hospital, London. Please see APPENDIX 2 of accompanying perinatal care plan document for all relevant contact details.

1.2. Purpose

The overall purpose of these guidelines is to provide guidance on best practice in the treatment and management of women living with HIV during pregnancy and postpartum, and their infants. They are aimed at clinical professionals involved with, and responsible for, the care of pregnant women living with HIV.

1.3. Sources of recommendations

The recommendations within this document are largely based on British HIV Association guidelines for management of HIV in pregnancy and postpartum 2018 (see references). These guidelines provide additional detail and should be referred to for cases which are not straightforward (e.g. possible viral resistance, unsuppressed viral load, late presentation, or diagnosis at or after delivery). Each HIV unit or centre should be able to respond appropriately to every possible scenario described in the BHIVA guidelines.

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1.4. Major changes from previous version

These guidelines supersede the regional guidelines Management of HIV Infection in Pregnant Women 2014. In line with updates to BHIVA guidelines, the following changes have been made:

Preferred and alternative ART agents for use in pregnancy have been specified; NEVIRAPINE has been removed as a suggested component of cART; recommendations on the use of RALTEGRAVIR,

RILPIVIRINE, DOLUTEGRAVIR, ELVITEGRAVIR and COBICISTAT have been updated.

All women (including elite controllers) are recommended to start on cART and remain on it lifelong.

The length of infant post-exposure prophylaxis has been shortened to 2 weeks where the risk of

vertical transmission is VERY LOW.

The use of CABERGOLINE in non-breastfeeding women is also discussed.

2. The perinatal care plan

An individual perinatal care plan should be available for all HIV-infected mothers. The model perinatal care plan (APPENDICES 1-3) is standardised throughout Mersey, Cheshire and North Wales (available at www.liv.ac.uk/hiv). The plan contains the names and contacts of key health care providers involved in the care of the mother and her hospital record numbers at each unit (e.g. Genitourinary Medicine (GUM), Obstetrics), as well as details of disclosure of HIV status to the patient’s family and GP. Relevant baseline investigation results, details of ART and other medications, and information discussed with the mother are listed. The planned mode of delivery with the date for any PLCS will be documented.

The care plan should be completed by the physician overseeing the management of HIV. It should be completed soon after cART has been started, and no later than 28 weeks. Do not wait for the viral load to become undetectable prior to completion.

Copies of this care plan should be lodged in the following places:

HIV clinic records

Obstetric notes

Patient hand carried notes (if the patient is agreeable)

Labour ward

Midwife

Paediatrician

Neonatologist

GP (unless consent withheld)

Infectious Diseases Unit Ward 3Y - Royal Liverpool University Hospital

2.1. Electronic database at Royal Liverpool University Hospital

A register of current pregnancies and electronic storage of perinatal care plans is maintained by the HIV Specialist Nursing team at the Royal Liverpool University Hospital on behalf of the network. The HIV physician in charge of a woman’s care should send a completed perinatal care plans and any updates via secure email to the HIV Specialist Nursing team: rlb-tr.HIV-Pregnancy-Network@nhs.net who are then responsible to forward securely to the teams at Alder Hey and Liverpool Women’s Hospital for all HIV pregnancies in network.

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The perinatal care plan does not operate in lieu of clinic letters which should be copied to all relevant teams involved in the management of the mother. Dissemination of the latest maternal HIV viral load results in particular is vital as this will materially affect management during delivery and afterwards.

2.2. Pharmacy aspects in the Obstetric Unit

Upon receipt of the Care Plan, the Obstetrician should notify pharmacy of the anticipated drug requirement.

ZIDOVUDINE (RETROVIR) infusion (for the mother) should be available on the labour ward if required, together with ZIDOVUDINE oral suspension for the baby. Reserve stocks of ZIDOVUDINE infusion and ZIDOVUDINE oral suspension are kept in the pharmacy emergency drug store cupboard at the Liverpool Women’s Hospital (please check your own local availability if outside of Liverpool). It is the responsibility of the Obstetrician to liaise with the Lead Pharmacist in their organisation to ensure that the required medication for each individual woman is in stock and readily available.

Three drug infant PEP for the baby should be available if required (see section 7), and is also stocked at the Liverpool Women’s Hospital and Alder Hey Hospital (contact details in APPENDIX 2 of perinatal care plan). All of the oral medications will require the completion of label details prior to use and should be transferred with the baby at all times until the course of treatment has been completed. Please see APPENDIX 3 regarding dilution of IV ZIDOVUDINE and administration of all medications to infants.

2.3. Infection Control

Refer to the section on Management of Blood-borne Viral Pathogens Policy in the current edition of your hospital Infection Control Manual.

There are no additional items of personal protective equipment (PPE) required because the mother is carrying a blood-borne virus. Recommended PPE is in accordance with the nature of the procedure and should be described in detail in the hospital policy.

In the event of an inoculation injury refer to your Trust’s Needlestick and Inoculation Injuries Policy; immediately seek specialist advice and contact occupational health as per Trust policy. A risk assessment of the incident will be carried out to ascertain whether HIV PEP is required. Note that current guidance suggests that PEP is not routinely recommended after occupational exposure from a patient with an undetectable HIV viral load.

3. Maternal antenatal HIV care

3.1. Antenatal screening

Screening for HIV infection should proceed according to local policy. Additional input from the GUM team may be required for women whose initial screen is negative but remain at continuing risk of acquiring HIV infection in pregnancy. This risk assessment needs to be recorded and repeat HIV testing offered throughout the pregnancy. Rapid near patient testing should be considered for women who arrive in labour unbooked and a reactive result acted upon.

3.2. General principles of HIV management

Patients will usually present with HIV in pregnancy either as a new diagnosis during antenatal screening, or as a pregnancy in a woman with known HIV infection. In either case, prompt referral should be made

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between the obstetrician, specialist midwife, HIV physician and clinical nurse specialist, and the lead paediatrician notified. The management of HIV pregnant women requires an MDT approach with seamless communication between all parties. Central to this are the perinatal care plan (see above and attached) and clinic letters that crucially include HIV viral load results (particularly during the third trimester).

3.3. Baseline assessment

For both women newly diagnosed with HIV during pregnancy and those already engaged in HIV care, a comprehensive baseline assessment is required and should include the following if not already complete, along with additional investigations as per individual circumstances:

Confirmatory HIV serology and discussion of diagnosis

Confidentiality and awareness among family and friends discussed and documented

HIV and AIDS Reporting System (HARS) and Sexual Health and HIV Activity Property Type (SHHAPT) coding, if required

Arrangements for testing partner(s) and any previous children and safer sex advice

Relevant printed information (e.g. HIV i-Base “Guide to HIV, Pregnancy and Women’s Health”) given following appropriate discussion

Initial physical examination in relation to HIV disease and investigations pertinent to findings

Haematology and biochemistry: FBC, U&E, LFTs, glucose

Serology: Hepatitis A, B & C, CMV, toxoplasma, syphilis, rubella, measles, VZV

Risk assessment for latent TB infection and interferon-gamma releasing assay, if indicated

Sexual health screen in GUM (including for bacterial vaginosis) with any genital tract infections identified treated in accordance with BASHH guidelines.

CD4 cell count

HIV viral load

HIV resistance genotype with results available prior to initiation of treatment, except for late-presenting women (i.e. after 28 weeks)

Psycho-social support, including HIV social worker assessment, voluntary sector support and domestic violence assessment

ART planned (with regional network input as needed), discussed and documented with adherence reinforced.

Discuss postpartum contraception, taking drug-drug interactions between ART and hormonal contraception into consideration

The perinatal care plan must be completed by the HIV physician by 28 weeks with letter to neonatologist to be completed by HIV physician with 36 week viral load result, with copies lodged appropriately.

3.4. Monitoring during pregnancy

Ongoing management should ensure adequate virological control and identify adverse drug effects.

HIV viral load should be undetectable (i.e. <50 copies/ml) at delivery, ideally by 36 weeks’ gestation

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In women who commence cART in pregnancy, an HIV viral load should be performed 2–4 weeks after commencing cART, at least once every trimester, at 36 weeks and at delivery.

The results of the week 36 HIV viral load must be circulated via letter to the obstetric and paediatric teams, highlighting any revisions to the perinatal management.

Repeat sexual health screen should be performed at 28/40 gestation with genital tract infections treated as appropriate. Women with herpes simplex infection should be reviewed by GUM to discuss risks and benefits of suppressive treatment.

LFTs should be performed as per routine on initiation of cART and then with each routine blood test to identify hepatotoxicity related to ART and/or the development of obstetric complications (e.g. obstetric cholestasis, pre-eclampsia, HELLP syndrome).

3.5. When to start cART during pregnancy

All pregnant women, including elite controllers, should start cART during pregnancy and be advised to continue lifelong treatment. In determining the optimal time to start on cART, the potential risks of congenital abnormality following exposure to cART, in particular the first trimester, maternal health and the risk of vertical transmission to the infant should be considered. All women should have commenced cART by week 24 of pregnancy (see BHIVA guidance for further detail).

3.6. What cART to start during pregnancy

The preferred and alternative cART regimens for use in pregnancy are shown in Table 1. The choice of therapy should be individualised for each woman and modified depending on tolerability, resistance and prior ART history whilst including one or more agents that cross the placenta, noting that:

Concerns about long-term toxicity of cART may be less relevant during pregnancy as after delivery cART may be switched to a regimen preferable for long-term use.

Non-standard regimens including protease inhibitor monotherapy and triple nucleoside regimens are not recommended.

No routine dose alterations are recommended for ART agents during pregnancy if used at standard adult licensed doses, apart from RALTEGRAVIR (see below).

COBICISTAT-boosted agents (i.e. ELVITEGRAVIR/COBICISTAT; DARUNAVIR/COBICISTAT; ATAZANAVIR/COBICISTAT) are not recommended.

ZIDOVUDINE monotherapy is not recommended and should only be used in women declining cART with a viral load <10,000 copies/mL and willing to have a caesarean section.

Please especially consider prompt network advice for women not on treatment with a high HIV viral load (i.e. >30,000 copies/ml) or who present late in pregnancy (i.e. >28/40 gestation) or who fail to achieve virological suppression (see section 8).

Hepatitis B co-infection may require cART containing TENOFOVIR. Please discuss all HIV/Hepatitis B or C co-infected pregnant women with the Infectious Diseases Unit, Royal Liverpool University Hospital.

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Table 1. Preferred and alternative ART agents in pregnancy

Preferred Alternative

NRTI backbone Abacavir/Lamivudine Tenofovir DF/Emtricitabine

Zidovudine/lamivudine

Third agent Efavirenz Atazanavir/r

Rilpvirine Darunavir/r Raltegravir Dolutegravir

Notes: /r denotes ritonavir booster

Nucleoside reverse transcriptase inhibitors

With increased experience TENOFOVIR DF/EMTRICITABINE and ABACAVIR/LAMIVUDINE are now considered the preferred nucleoside backbones.

TENOFOVIR ALAFENAMIDE is not recommended in pregnancy.

Non-nucleoside reverse transcriptase inhibitors

There is insufficient registry data on first trimester exposure to comment on teratogenicity risk for ETRAVIRINE and MARAVIROC.

NEVIRAPINE is no longer recommended as a component of cART for pregnant women. A single dose may however be given (regardless of CD4 count) during labour or to cover any invasive intrauterine procedure (see section 4.3).

Integrase inhibitors

RALTEGRAVIR must be dosed at 400 mg BD as there are no data to support the use of 1200 mg od in pregnancy.

DOLUTEGRAVIR is not recommended until after 8 weeks’ gestation (confirmed by scan) due to a report of increased risk of neural tube defects among infants of women who become pregnant while taking DOLUTEGRAVIR-based regimens.

Integrase inhibitor-based regimen may be considered as the third agent of choice (or an additional fourth drug) in patients commencing cART after 28 weeks’ gestations or with a high (i.e. >30,000 copies/mL) or unknown baseline viral load.

Protease inhibitors

All protease inhibitors should be boosted using RITONAVIR.

Pharmokinetic data suggest lower plasma levels of all boosted protease inhibitors in the third trimester of pregnancy (weeks 29-40). However, available evidence suggests that routine dose alterations are not recommended.

ATAZANAVIR/r is recommended over DARUNAVIR/r and LOPINAVIR/r which have an increased risk of pre-term delivery. Bilirubin should be carefully monitored with ATAZANAVIR use due to the risk of maternal hyperbilirubinaemia, although there is no evidence of neonatal harm (e.g. kernicterus). It should not be used unboosted and therapeutic drug monitoring (TDM) should be considered in

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the third trimester, especially if dosing off-licence or combining TENOFOVIR with ATAZANAVIR (reduced levels when co-prescribed).

DARUNAVIR/r should be prescribed at the twice daily dose (600/100 mg bd) if known resistance, and possibly when initiated in pregnancy.

3.7. Managing the risks and complications of treatment

Nausea and vomiting after initiation of antiretroviral therapy may be managed conservatively or with use of CYCLIZINE or PROMETHAZINE.

Consider lactic acidosis if any woman presents with vomiting, malaise, oedema, abdominal pain and raised transaminases.

Abnormalities in liver function tests can be due to cART, obstetric cholestasis, pre-eclampsia, HELLP syndrome and fatty liver. Serum bile acids and other investigations for liver disease may be required.

Where there is risk of treatment failure due to reduced or intermittent drug exposure with hyperemesis gravidarum, discuss at HIV MDT.

Proteinuria: consider TENOFOVIR renal toxicity (e.g. Fanconi syndrome, if accompanied by glycosuria); pre-eclampsia (check blood pressure); or urinary tract infection.

Glycosuria: consider Fanconi syndrome (if on TENOFOVIR) or gestational diabetes.

There is a possible association of preterm delivery with cART

4. Antenatal obstetric management

4.1. Overview of assessment and monitoring

Early referral to obstetrician with special interest in HIV

Review obstetric history (e.g. pre-eclampsia, pre-term delivery)

Refer to National UK NSC Infectious Diseases Antenatal Screening guidance for all pregnant population screening standards and service specifications

Foetal ultrasound imaging should be performed as per national guidelines regardless of maternal HIV status.

Report pregnancy to National Study of HIV in Pregnancy and Childhood (www.nshpc.ucl.ac.uk) (to be done by obstetric team) and Antiretroviral Pregnancy Registry (www.apregistry.com) in woman on newer ARVs ie Dolutegravir, Elvitegravir, Cobicistat, Raltegravir once daily ( to be done by HIV physician)

1st trimester screening for trisomies 21, 18 & 13 is recommended as we offer NIPT (reflex DNA) with the high chance Combined screens – this has the best sensitivity and specificity and will minimize the number of women who may need invasive testing

If invasive testing is required, then ideally this should deferred until HIV viral load is adequately suppressed to <50 copies/mL or at least until cART has been initiated (cART to include raltegravir and given a single dose of nevirapine 2–4 hours prior to the procedure).

External cephalic version (ECV) can be offered to women with plasma viral load <50 HIV RNA copies/mL.

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Mode of delivery discussed and documented in perinatal care plan

Early correspondence to HIV physician and paediatrician indicating the management plan for the baby at delivery

4.2. Preparations for delivery

Advise women on the importance of attending delivery suite early if possible rupture of membranes or preterm labour

Mother should be advised to bring her HIV medications into hospital with her; care should be taken not to miss doses of ART around and following delivery.

Inform pharmacy of the need for medication to be in stock to cover the delivery in the event of an unexpected early delivery

Advise complete avoidance of breast feeding and referral to infant feeding team if available. Women should be offered CABERGOLINE to suppress lactation.

4.3. Mode of delivery

The benefit of PLCS in reducing HIV transmission has been shown in studies that predate the availability of cART. When maternal HIV viral load is undetectable on cART the rate of MTCT is the same for PLCS and vaginal delivery. Caesarean section performed in labour has no added benefit in terms of reduction to MTCT. There should be MDT discussion about the timing and mode of delivery but general recommendations are:

For women with a viral load of <50 copies/mL at 36 weeks, and in the absence of obstetric contraindications, planned vaginal delivery should be supported.

For women with a viral load of 50–399 copies/mL at 36 weeks, PLCS should be considered, taking into account actual value and trajectory of viral load, treatment duration and adherence, obstetric factors and the woman’s views.

If the viral load is ≥400 copies/mL at 36 weeks, PLCS is recommended

Vaginal birth after caesarean section (VBAC) should be offered to women with a viral load <50 copies/ml.

If PLCS is being performed primarily to decrease risk of MTCT, delivery should be between 38-39 weeks’ gestation. A course of steroids should be considered to decrease the risk of transient tachypnoea of the newborn if PLCS occurs before 38 weeks. Where PLCS is undertaken only for obstetric indications and viral load is <50 copies/mL, the usual obstetric considerations apply and the CS will usually be performed after 39 weeks’ gestation.

If a single dose of NEVIRAPINE is to be used during labour or to cover any intrauterine invasive procedure, the risk of resistance should be minimised by appropriate cover with other ART for a minimum of 21 days.

4. Care during labour and delivery

5.1. Planned vaginal delivery

In women for whom a vaginal delivery has been recommended and labour has commenced, obstetric management should follow the same principles as for the HIV-uninfected population, apart from duration of rupture of membranes (ROM).

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The MTCT data originate from the pre-ART era. There is a lack of data regarding fetal blood sampling and the use of scalp electrodes from the cART era. Whilst it is felt that it is unlikely that their use confers an increased risk of transmission in a woman with an undetectable HIV viral load, this cannot be proven from the current evidence. Regional advice is to avoid if HIV viral is detectable and discuss with on-call Consultant Obstetrician prior to use in patients with undetectable viral load.

5.2. Coordination of care

Inform Consultant Obstetrician or his/her team (or duty team if out of hours) when the mother presents in labour. Also notify Paediatric/Neonatal on-call team.

In the event of threatened pre-term delivery, ROM, vaginal bleeding, or regular painful contractions, similarly discuss with on call Obstetric Registrar or Consultant and arrange admission.

5.3. Management of pre-labour spontaneous rupture of membranes (SROM)

In all cases of term pre-labour SROM, delivery should be expedited.

If maternal HIV viral load is <50 copies/ml immediate induction or augmentation of labour is recommended, aiming for delivery within 24 hours. Have a low threshold for treatment of intrapartum pyrexia.

For women with SROM and a last measured viral load 50–399 copies/mL, immediate CS is recommended, but should take into account the actual value and trajectory of viral load, treatment duration and adherence, obstetric factors and the woman’s views.

For women with SROM and maternal HIV VL ≥400 copies/mL, immediate CS is recommended.

Preterm SROM at ≥34 weeks is managed as that of term SROM, except that women will require group B streptococcus prophylaxis in line with national guidelines.

When preterm SROM occurs at <34 weeks intramuscular steroids should be administered in

accordance with national guidelines.

5.4. Intrapartum zidovudine

Intrapartum IV ZIDOVUDINE is required if the most recent maternal HIV viral load is >1,000 copies/ml or unknown. Commence at onset of labour or 4 hours before PLCS and continue until umbilical cord clamped (see APPENDIX 3.1 of care plan for administration and dosing). Do not delay caesarean section to complete IV ZIDOVUDINE if in labour or if amniotic membranes have ruptured.

Intrapartum IV ZIDOVUDINE is not recommended if the most recent maternal HIV viral load is <1,000 copies/ml but might be considered if mother is prescribed ZIDOVUDINE MONOTHERAPY or if HIV viral load is between 50-1,000 copies/ml, although continued oral dosing of their current regimen is a reasonable alternative.

Contact pharmacy urgently (or on-call pharmacist if out of hours) in the case of drug supply problems.

5.5. New HIV diagnosis presenting in labour

Women presenting in labour, SROM or otherwise requiring delivery with unknown HIV status must be advised to have an urgent point-of-care HIV test. If the test is positive (reactive), a confirmatory test should

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be performed, but all women should be commenced on the following to prevent vertical transmission pending formal serological confirmation:

Stat dose of NEVIRAPINE 200 mg

If preterm, consider stat oral double dose TENOFOVIR DF

Commence oral ZIDOVUDINE 300 mg bd, LAMIVUDINE 150 mg bd and RALTEGRAVIR 400 mg bd

Administer intravenous zidovudine for the duration of labour

Infant to receive combination post-exposure prophylaxis (see section 7).

5.6. Maternal care

cART continues throughout delivery period as per antenatal period. Do not discontinue any ART medication. Ensure that doses are not missed during or after delivery. It is better to give a dose late (even if the next dose is due shortly) and delay the next dose slightly, than to miss a dose entirely.

Discuss with the mother the use of a stat dose of CABERGOLINE to suppress lactation.

6. Post-natal care

6.1. Neonatal care

Place pages 6-8 of perinatal care plan into baby’s notes as a Neonatal Care Plan.

There is no need for routine paediatric attendance at birth.

Routine admission to the Neonatal Unit is unnecessary; babies should only be admitted if there is a specific medical indication for special or intensive neonatal care.

Staff should use universal precautions as per local policy when attending to the cord or taking blood samples, and when handling the baby until he/she is bathed.

Clean the baby’s skin in accordance with local guidelines before giving vitamin K (intramuscular or oral according to unit policy).

Administer ART prophylaxis as specified in the perinatal care plan as soon as possible and certainly within 4 hours. Do not delay for blood sampling (see section 7).

The baby does not require CO-TRIMOXAZOLE prophylaxis for Pneumocystis jiroveci pneumonia (PCP) unless HIGH RISK (see section 7.5).

Inform the Paediatric Infectious Diseases Specialist Nurse at Alder Hey Hospital (Liverpool deliveries only) and mother’s HIV team in office hours that the baby has been born

6.2. Infant feeding

In the UK and other high-income settings, the safest way to feed infants born to women with HIV is with formula milk, as there is on-going risk of HIV exposure after birth.

Women should be advised not to breast feed, provided with free formula feed and offered CABERGOLINE to suppress lactation.

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6.3. Diagnosis of HIV transmission to the baby

Specimens should be labelled “Biohazard” and handled according to Trust policy until the baby’s HIV status is determined.

Within 48hrs of birth send ‘Day 1’ specimens from neonate: 1 ml EDTA sample for “HIV proviral DNA PCR” (NB. not HIV viral load) plus FBC and LFT. Send with a 5ml EDTA sample from mother to ensure “HIV proviral DNA PCR” amplifies to mother’s HIV type.

Microbiology Laboratory should send specimens to Virus Reference Department at Public Health England, Colindale, London and ensure results are sent to the paediatrician who is following infant.

Infant testing is repeated at intervals as indicated in Table 2. If any infant has a positive HIV proviral DNA PCR result, please contact the on-call Paediatric Infectious Disease Consultant (Dr Andrew Riordan, Dr David Porter, Dr Beatriz Larru) or Paediatric Infectious Diseases Specialist Nurse (Cathryn Benson) at Alder Hey Hospital as soon as possible (0151 228 4811). In their absence contact the Paediatric Infectious Diseases Consultant (via switchboard 0207 886 6666) or HIV coordinator (0207 886 6349) at St Mary’s Hospital, London,

HIV RNA viral testing is an acceptable alternative for laboratories able to use low volume neonatal samples. This is not currently the case in Liverpool, please discuss with your local virology service.

Table 2. Laboratory testing for diagnosis of infant HIV status

Non-breastfed infants Breastfed infants

During first 48 hours and prior to hospital discharge

During first 48 hours and prior to hospital discharge

If HIGH RISK, at 2 weeks of age At 2 weeks of age

At 6 weeks (or at least 2 weeks after cessation of infant prophylaxis)

Monthly for duration of breast feeding

At 12 weeks (or at least 8 weeks after

cessation of infant prophylaxis)

At 4 and 8 weeks after cessation of breast feeding

On other occasions if additional risk

HIV antibody testing for seroreversion should be checked at age 18–24 months.

HIV antibody testing for seroreversion should be checked at age 18–24 months.

6.4. Discharge from hospital

Prescribe the full course of ART prophylaxis for the baby upon discharge as per risk assessment (see below). Ensure ART is prescribed at convenient times and the parent(s)/carer know when to give it.

The baby can be discharged when well and tolerating oral medication as per consultant decision.

Remember to report births to the British Paediatric Surveillance Unit.

Write a discharge letter to the paediatrician requesting a follow-up appointment at 6 weeks post-partum.

Do not copy letter to GP unless mother agrees (refer to perinatal care plan). Do not fax to open lines.

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6.5. Immunisations

If there is VERY LOW or LOW RISK of HIV transmission (see section 7.1) and BCG at birth is indicated, it should not be delayed.

Otherwise immunisations should be given as per the national schedule outlined in the Green Book

Rotavirus vaccine is not contraindicated (unless HIV diagnosis has been confirmed and infant is severely immunosuppressed).

6.6. Maternal post-natal management

Only those health professionals directly involved with care of the baby should know that mother is HIV positive.

Maternal blood sample for “HIV proviral DNA PCR” at same time as neonatal test, as per above.

Ensure that doses of ART are not missed and if any have been omitted, it is better to give treatment straight away followed by ALL other scheduled doses, than to wait until the next prescribed dose.

Continued cART is recommended. If cART is to be stopped, take particular care with regard to half-lives of individual drugs; if stopping a NNRTI containing regimen a staggered withdrawal is recommended (seek advice if in doubt). A further resistance test is recommended to ensure that mutations are not missed with reversion during the off- treatment period.

Breast feeding is not recommended, and this will have been discussed with mother.

Contraceptive options discussed (and effect of antiretroviral therapy on contraceptive options).

Check that HIV Follow up organised (under no circumstances should the patient ever be at risk of running out of medication).

7. Infant post-exposure prophylaxis (PEP)

7.1. Risk assessment

Infant post-exposure prophylaxis (PEP) is used to further reduce the risk of MTCT. The recommended type (i.e. single or combination therapy) and duration of PEP depends upon a risk assessment based on the mother’s duration of cART use and her HIV viral load during late pregnancy. BHIVA 2018 guidelines recommend a shortened 2-week course of PEP for VERY LOW RISK infants (as defined below) based on the absence of any reported transmissions in ‘real world’ settings to infants who have fulfilled these criteria and completed 2 weeks of PEP.

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Table 3. Risk assessment for selecting infant post-exposure prophylaxis

Very low risk Low risk High risk

Risk assessment criteria

Mother has been on cART >10 weeks

AND

2 documented maternal HIV viral load <50 copies/mL during pregnancy ≥4 weeks apart

AND

Maternal HIV viral load <50 copies/mL at or after 36 weeks

Maternal HIV viral load <50 copies/mL at or after 36 weeks but other very low risk criteria not fulfilled

OR

Infant born prematurely (<34 weeks) but most recent maternal HIV viral load <50 copies/mL

Maternal birth HIV viral load known to be or likely to >50 copies/mL on day of birth

OR

Uncertainty about recent maternal adherence to cART

OR

HIV viral is not known

OR

Maternal HIV is discovered after delivery and baby is less than 72 hours old.

Recommended PEP 2 weeks of zidovudine monotherapy

4 weeks of zidovudine monotherapy

Combination PEP

7.2. Zidovudine monotherapy

Oral ZIDOVUDINE (RETROVIR, AZT; 4mg/kg BD) should be commenced as soon as possible after birth, and at least within 4 hours

If unable to feed, give ZIDOVUDINE IV infusion - See APPENDIX 3 care plan. This should be changed to the oral preparation once enteral feeds tolerated and continued to complete 2 or 4 weeks as per risk assessment.

In the context of known maternal resistance to ZIDOVUDINE with VERY LOW or LOW RISK, ZIDOVUDINE monotherapy is still recommended for infant PEP.

7.3. Combination post-exposure prophylaxis

If combination PEP is being considered, regional and/or national advice should be sought to devise a suitable regimen.

Use of combination PEP should be commenced as soon as possible after birth, and at least within 4 hours

For infants born to ART-naïve women, or where drug resistance is unlikely, ZIDOVUDINE (AZT), LAMIVUDINE (3TC) and NEVIRAPINE is a well-tolerated combination regimen with the most clinical experience.

If mother is taking regular NEVIRAPINE (i.e. not single dose) for >3 days during pregnancy, give NEVIRAPINE to the baby at 4mg/kg OD for 2 weeks only. If mother has had <3 days of NEVIRAPINE, give 2mg/kg OD for one week, then 4mg/kg OD for the second week.

In special circumstances in which there is maternal drug resistance, alternative treatment for the baby may be needed. All these cases should be discussed with a paediatric HIV consultant. If advice is not immediately available, commence standard three-drug PEP (ZIDOVUDINE, LAMIVUDINE and NEVIRAPINE) until guidance is provided.

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ZIDOVUDINE is the only IV therapy available for neonates unable to tolerate enteral feeds; discuss its use with a Paediatric HIV consultant. Once the baby can tolerate oral medication, triple therapy should be commenced to complete 4 weeks total therapy.

Infant PEP should not be given beyond 4 weeks.

There is probably no benefit from commencing HIV treatment after 72 hours.

Contact the Paediatric Infectious Disease consultants at Alder Hey Hospital (Dr Andrew Riordan, Dr David Porter, Dr Beatriz Larru; 0151 228 4811) or the Paediatric HIV Clinic team at St Mary’s, London (via switchboard 0207 886 6666) for advice. Prof Saye Khoo, Dr Mas Chaponda, Dr Emily Clarke, Dr Rebecca Thomson-Gloverand the other members of the Mersey, Cheshire and North Wales HIV network listed in the care plan are also available for advice.

7.4. ART prescribing and administration advice

The paediatrician will be required to prescribe the medication. Doses should be prescribed in milligrams (mg) and in millilitres (mL). ZIDOVUDINE, LAMIVUDINE & NEVIRAPINE oral liquids are all 50 mg in 5 ml strength.

Consider letting the mother have responsibility for giving treatment to her baby when on the postnatal ward. She should be confident in administration of the medication prior to discharge.

Ensure that the ART drugs are transferred with the baby from the labour ward.

7.5. Co-trimoxazole prophylaxis

Prophylaxis against Pneumocystis jirovecci pneumonia (PCP) is not routinely required even for infants of mothers with detectable viral load at delivery.

CO-TRIMOXAZOLE prophylaxis is only to be used from 4 weeks of age if HIV PCR screening is positive at any stage or if the infant is confirmed to be diagnosed with HIV. This should only be stopped if HIV infection is subsequently excluded.

Paediatric CO-TRIMOXAZOLE suspension contains 240 mg of combined product per 5 mL

For infants ≥2kg, the dose is 120 mg once daily 3 times a week

For infants <2kg, the dose is 60 mg once daily 3 times a week

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9. Antiretroviral therapy management plan under various scenarios

The choice of HIV drugs for the mother is outlined in section 3.6. Possible scenarios are outlined in more detail below and also in British HIV Association guidelines for management of HIV in pregnancy and postpartum 2018.

Scenario Interventions for Mother Interventions for Baby

Women who conceive on cART Maintain or optimise cART. Some regimens may need to be modified depending on tolerability, resistance and prior ART history (e.g. COBICISTAT-boosted agents, once daily dosed RALTEGRAVIR; see section 3.6).

ZIDOVUDINE monotherapy for 2-4 weeks or combination infant PEP according to risk assessment (see section 7).

Women not on cART prior to pregnancy or diagnosed in early pregnancy

All pregnant women, including elite controllers, should start ART during pregnancy as soon as they are able to do so and before 24 weeks of pregnancy and be advised to continue lifelong treatment.

ZIDOVUDINE monotherapy for 2-4 weeks or combination infant PEP according to risk assessment (see section 7).

Women who present late in pregnancy (after 28 weeks’ gestation)

Immediate 3 or 4 drug cART including RALTEGRAVIR if HIV unknown or VL >100,000 copies/mL. Revise when clinical, virological and immunological status determined.

ZIDOVUDINE monotherapy for 4 weeks if confirmed LOW RISK; combination infant PEP if HIGH RISK (see section 7).

Women who initiate cART in pregnancy and have not achieved a plasma VL of <50 by 36 weeks’ gestation

Review adherence and concomitant medication for drug interactions; consider therapeutic drug monitoring (TDM) and resistance genotype; optimise cART and consider intensification.

Combination infant PEP

Women who present in labour: point of care HIV test reactive (i.e. unconfirmed HIV positive) and treatment naïve

Baseline bloods to include CD4, viral load and genotype

Give stat dose NEVIRAPINE 200mg orally and if preterm, consider stat oral double dose TENOFOVIR DF

Start cART with ZIDOVUDINE, LAMIVUDINE and RALTEGRAVIR

Commence IV ZIDOVUDINE for duration of labour (see section 5.5)

Emergency caesarean section 2 hours post single dose NEVIRAPINE if not about to deliver

Combination infant PEP

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Scenario Interventions for Mother Interventions for Baby

Threatened pre-term delivery +/- rupture of membranes

High vaginal swab for bacteriology; Group B strep treatment as per national guidelines

If <34 weeks’ gestation, give intramuscular steroids as per national guidelines.

Give IV ZIDOVUDINE if HIV viral load >1,000 copies/mL or unknown.

If mother not on ART, follow above guidance for new diagnosis of HIV in labour.

Expedite vaginal delivery or CS based at maternal viral load (see section 5.3)

ZIDOVUDINE monotherapy for 4 weeks if confirmed LOW RISK; combination infant PEP if HIGH RISK (see section 7)

Infant presents after delivery Determined by her clinical, virological and immunological status and previous treatments, if any

Combination infant PEP for 4 weeks if <72 hours since delivery

Pregnancy in women with HIV-2 Infection Managed in similar way to HIV-1, but refer to BHIVA guidelines on Management of HIV-2. Note: NNRTI are ineffective.

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References and other sources of information

Merseyside, Cheshire and North Wales HIV Managed Clinical Network. Standard Operating Procedure (SOP) for Electronic Transfer and Storage of Perinatal Care Plans; 1 September 2014 - 1 September 2016.

Mersey, Cheshire, and North Wales HIV Managed Care Network. Guidelines for Post Exposure Prophylaxis (PEP) for HIV: Occupational and Sexual Exposure, July 2016. https://www.liverpool.ac.uk/translational-medicine/research/infection-pharmacology/guidelines/

British HIV Association guidelines for management of HIV in pregnancy and postpartum 2018. www.bhiva.org/Guidelines.aspx

British HIV Association Standards of care for people living with HIV 2018 www.bhiva.org/standards-of-care-2018

Guide to HIV, pregnancy and women’s health. HIV i-Base March, December 2015 www.i-Base.info

CHIVA Standards of Care for Infants, Children and Young People with HIV 2017 (Including infants born to mothers with HIV). www.chiva.org.uk/files/5215/3987/5455/CHIVA_STANDARDS_2017.pdf

Peters H, Thorne C, Tookey PA, Byrne L. National audit of perinatal HIV infections in the UK, 2006–2013: what lessons can be learnt? HIV Medicine 2018; 19(4): 280-289.

National UK NSC Infectious Diseases Antenatal Screening guidance https://www.england.nhs.uk/wp-content/uploads/2017/04/Gateway-ref-07836-180913-Service-specification-No.-15-NHS-IDPS.pdf

Public Health England https://www.gov.uk/government/publications/hiv-explaining-the-screening-result