In addition to these evidence-based recommendations, the guideline development group also identifies points of best clinical practice in the original guideline document.
Classification of evidence levels (1++ to 4) and grades of recommendations (A-D) are defined at the end of the "Major Recommendations" field.
Antenatal HIV Screening
What Can Be Done to Ensure Continued High Uptake of Human Immunodeficiency Virus (HIV) Screening?
A - All pregnant women are recommended to have screening for HIV infection in every pregnancy at their booking antenatal visit. This enables those diagnosed with HIV to take up interventions that can prevent mother-to-child transmission and significantly improve their own health.
D - All pregnant women who are HIV positive should be referred promptly for assessment and for their pregnancies to be managed within a multidisciplinary team.
All women booking for antenatal care should have one blood sample tested for HIV, syphilis, rubella and hepatitis B. All doctors and midwives should be competent to obtain consent for these tests and should request the tests according to local protocols. [Evidence level 4]
What Type of HIV Test Should Be Used?
D - Fourth-generation laboratory assays are recommended as the first-line HIV test for antenatal screening.
D - Where a woman has her HIV screening test at 26 weeks of gestation or later, an urgent request should be made and the result issued by the laboratory with 24 hours.
D - Rapid HIV tests are recommended for women with unknown HIV status who present in labour and a reactive result should be acted on immediately.
The time between acquiring HIV infection and testing HIV antibody positive is known as the window period, which is usually up to 3 months in duration (rarely up to 6 months). During this period of seroconversion, an individual will test negative for HIV antibodies. The recommended first-line HIV tests for antenatal screening are fourth-generation assays that test for both HIV antibody and p24 antigen simultaneously. This type of assay reduces the diagnostic window to 1 month, as p24 antigen is detectable during seroconversion. Assays must have a high sensitivity (greater than 99.9%) and specificity (greater than 99.5%) and be able to detect all the major subtypes of HIV. A reactive result on initial testing is always confirmed as positive by testing the same sample with two further independent assays to confirm that the reactivity is specific for HIV. A confirmatory HIV test on a second sample is then made. [Evidence level 4]
For women having an HIV test at or beyond 26 weeks of gestation (in the event of late booking or delay in consenting to HIV screening), an urgent HIV test using a fourth-generation assay should be requested so that, in the event of a positive result, there is sufficient time for appropriate counselling, multidisciplinary team involvement and initiation of antiretroviral therapy. [Evidence level 4]
Rapid HIV tests deliver results within 20 minutes of the specimen (finger-prick or mouth swab) being taken. Most of the rapid-test devices currently in use test for antibody only (not p24 antigen), so these tests are likely to test negative during seroconversion. Outside seroconversion, they are of equivalent sensitivity but lower specificity compared with screening assays. They are recommended in clinical situations where a rapid HIV diagnosis will affect the immediate management of the patient, such as in labour. Rapid HIV tests are often performed by hospital laboratories. However, they can be undertaken by appropriately trained delivery suite staff (point-of-care testing), provided that they are overseen by the local laboratory and a robust quality assurance programme is in place. All reactive rapid tests must be confirmed as positive by the laboratory. [Evidence level 4]
How Can Seroconversions in Pregnancy Be Prevented and Identified?
D - All women testing HIV negative at booking should have access to information about safe sex and high risk scenarios for HIV transmission. Repeat testing should be available at any time during pregnancy. Women judged to be at continued high risk of HIV acquisition may also be offered a repeat HIV test.
How Should HIV Test Results Be Recorded and Communicated?
D - Midwives and doctors reviewing women during antenatal care should ensure that the HIV result is clearly documented.
Dates and details of test discussions, who was involved, decisions, samples taken and when results were available and were given should be recorded. Local protocols covering test turnaround times, receipt of results and referral of women with positive test results should be developed. These should be based on Department of Health Standards currently being developed as part of the IDiPS Programme (http://infectiousdiseases.screening.nhs.uk ). There should be a clear line of designated responsibility for communicating positive results and following up late results. Delivery suite staff must be aware of a woman's HIV status. Test results should be available on delivery suites to all clinical staff. [Evidence level 4]
Professional Approach to the Antenatal Care of Women Who Are HIV Positive
What Is the Role of the Multidisciplinary Team and Who Should It Include?
D - All antenatal care for women who are HIV positive should be managed by a multidisciplinary team, including (as a minimum) an HIV physician, obstetrician, specialist midwife, health advisor and paediatrician.
D - All women who are newly diagnosed as HIV positive should have an early assessment of their social circumstances.
What Are the Psychosocial and Ethical Issues?
D - Pregnant women should be reassured that their confidentiality will be maintained.
B - Women who are HIV positive should be advised about safer-sex practices and the use of condoms, to prevent transmission of HIV and other sexually transmitted infections to an uninfected partner.
Individual counselling should be available for any individual who is HIV positive who wishes to consider unprotected sexual intercourse with a partner who is HIV negative or whose HIV infection status is not yet known. The availability of post-exposure prophylaxis should be discussed. A woman who is HIV positive whose partner is also HIV positive should be counselled about the low but possible risk of superinfection associated with unprotected sex. [Evidence level 4]
D - Women should be encouraged to disclose their HIV status to their partner and should be given appropriate support. It is also recommended that women with existing children of unknown HIV status should have them tested for HIV.
D - In rare cases where women refuse interventions to prevent mother-to-child transmission of HIV, despite supportive guidance from the multidisciplinary team, a pre-birth planning meeting should be held with social services to discuss issues of safeguarding.
The input of the multidisciplinary team is crucial to support women who are reluctant to accept these interventions, as they are often the most isolated and unsupported. Despite all efforts, where the multidisciplinary team is unable to influence a mother's views antenatally, a pre-birth planning meeting with social services should be held. The mother should be informed that it is the paediatrician's role to advocate on behalf of the child's wellbeing and therefore to prevent, where possible, HIV infection. If the mother continues to refuse any intervention package, then legal permission should be sought at birth to treat the infant for 4 weeks with antiretroviral therapy and to prevent breastfeeding. [Evidence level 4]
Interventions to Prevent Disease Progression in the Mother and Prevent Mother-to-Child Transmission of HIV
A detailed description of interventions recommended in pregnancy is published by the British HIV Association (BHIVA) guidelines and can be accessed at www.bhiva.org/PregnantWomen2008.aspx .
What Interventions Prevent Disease Progression in the Mother?
A - Women who require HIV treatment for their own health should take highly active antiretoviral therapy (HAART) and should continue treatment following delivery.
HAART regimens have become the standard of care for all individuals who are HIV positive who require antiretroviral therapy for their own health. The timing of initiation of HAART is important; delaying treatment until the CD4 lymphocyte count has fallen below 200 × 106/l is associated with a substantially greater risk of disease progression and death. [Evidence level 2++]
Current BHIVA guidelines for the general HIV population recommend initiation of HAART for those with symptomatic HIV infection and/or a falling or low CD4 lymphocyte count (less than 350 × 106/l). In addition, those with CD4 lymphocyte counts less than 200 × 106/l are at risk of opportunistic infections; they should be given prophylaxis against Pneumocystis carinii pneumonia (PCP) and cotrimoxazole is usually the first-line agent. [Evidence level 4]
In pregnancy, the criteria for initiating HAART for maternal health reasons and for PCP prophylaxis are the same as for the general population with HIV. However, it may be possible to delay treatment until after the first trimester. [Evidence level 4]
What Interventions Prevent Mother-to-Child Transmission of HIV?
B - Women should be advised that, in the UK and other resource-rich settings, in the absence of breastfeeding, the risk of mother-to-child transmission of HIV in women taking HAART during pregnancy is less than 1%.
Avoidance of Breastfeeding
B - All women in resource-rich settings who are HIV positive should be advised to avoid breastfeeding.
All pregnant HIV positive women should be advised to take antiretroviral therapy:
- A - For women who require HIV treatment for their own health, their prescribed HAART regimen should be continued throughout pregnancy and postpartum.
- B - For women who do not require HIV treatment for their own health, HAART should be initiated between 20 and 28 weeks and discontinued at delivery.
- A - For women who do not require HIV treatment for their own health, have a viral load less than 10,000 copies/ml and are prepared to be delivered by elective caesarean section, an acceptable alternative to HAART is zidovudine (ZDV) monotherapy initiated between 20 and 28 weeks, given orally twice daily, intravenously at delivery and discontinued immediately thereafter.
Mode of Delivery
Delivery by elective caesarean section at 38 weeks to prevent labour and/or ruptured membranes is recommended for:
- A - Women taking HAART who have a plasma viral load greater than 50 copies/ml.
- A - Women taking ZDV monotherapy as an alternative to HAART.
- D - Women with HIV and hepatitis C virus co-infection.
B - A planned vaginal delivery can be offered to women taking HAART with plasma viral loads of less than 50 copies/ml.
D - Delivery by elective caesarean section for obstetric indications or maternal request should be delayed until after 39 completed weeks of gestation in women with plasma viral loads of less than 50 copies/ml, to reduce the risk of transient tachypnoea of the newborn.
Antenatal Care for Pregnant Women Who Are HIV Positive
What Antenatal Blood Tests for Infections Are Recommended for Women Who Are HIV Positive?
D - Women who are HIV positive are recommended to have a screening blood test for syphilis, hepatitis B and rubella in every pregnancy at their booking antenatal visit, in keeping with recommendations for the general population.
D - Additional recommended blood tests for women who are HIV positive include hepatitis C, varicella zoster, measles and toxoplasma.
D - Women who are HIV positive taking HAART at the time of booking should be screened for gestational diabetes.
What Immunisations Should Be Undertaken?
D - Hepatitis B, pneumococcus and influenza immunisation are recommended for all individuals who are HIV positive; these immunisations can be safely administered in pregnancy.
C - Varicella zoster and measles, mumps and rubella (MMR) vaccines are contraindicated in pregnancy. Women testing immunoglobulin G negative for these infections should be considered for immunisation postpartum, depending on their CD4 count.
When Should Screening for Genital Infections Be Undertaken?
D - Women who are HIV positive should be screened for genital infections at booking (or after multidisciplinary team referral if diagnosed HIV positive in pregnancy) and again at 28 weeks. Any infection detected should be treated according to UK national guidelines.
How Should Screening for Aneuploidy Be Undertaken?
D - Screening for aneuploidy should be offered to all pregnant women who are HIV positive in accordance with national guideline.
First-trimester screening for Down syndrome should be offered in accordance with national guidelines. [Evidence level 4]
How Safe Is invasive Diagnostic Testing?
D - Women who are HIV positive considering invasive diagnostic testing should be counselled in a fetal medicine unit and the advice of the HIV physicians sought concerning reducing the risk of HIV transmission.
When any woman undergoes invasive diagnostic testing, the obstetrician carrying out the procedure should be aware of the woman's HIV antibody test result. For women known to be HIV positive who have started HAART but whose viral load is greater than 50 copies/ml, it may be advisable to delay the amniocentesis until the maternal viral load is less than 50 copies/ml. For women not already taking HAART, administration of antiretrovirals to cover the procedure is advised. When performing amniocentesis, the placental route is absolutely contraindicated. [Evidence level 4]
When Should Ultrasound Scanning Be Undertaken?
D - Many women who are HIV positive will have been exposed to potentially teratogenic drugs during the first trimester. Dating and anomaly scans should be offered according to national guidelines.
What Additional Monitoring Is Necessary?
D - Monitoring of plasma viral load and drug toxicities should be undertaken as directed by the HIV physicians.
Comprehensive guidance is given in the BHIVA guideline. Resistance testing is performed at diagnosis. Maternal plasma viral load is the most important predictor of transmission. As a minimum, it is measured every trimester, at 36 weeks gestation and at delivery. Assessment of full blood count, urea and electrolytes and liver function is undertaken regularly to monitor for drug toxicities. [Evidence level 4]
When Should a Decision Regarding Mode of Delivery Be Taken?
D - A plan regarding mode of delivery should be made at around 36 weeks following detailed discussion with the mother.
Women taking HAART who have a viral load of less than 50 copies/ml at 36 weeks may be offered a planned vaginal delivery. A plan for intrapartum care should be clearly documented. The decision for vaginal delivery should be reviewed when the woman presents in labour: the result of any plasma viral load sample taken after the documented plan should be checked and confirmed as less than 50 copies/ml. [Evidence level 4]
For women taking HAART with a viral load of less than 50 copies/ml who do not wish to deliver vaginally, caesarean section should be scheduled for 39+ weeks, to minimise the risk of transient tachypnoea of the newborn. For women with a viral load greater than 50 copies/ml and those taking ZDV monotherapy as an alternative to HAART, caesarean section should be scheduled for 38 weeks; for these women, earlier delivery is justified because the risk of perinatal HIV transmission associated with labour and/or ruptured membranes is considered to outweigh the risk of transient tachypnoea. [Evidence level 4]
Management of Antenatal Complications
What Are the Complications of HIV and Adverse Effects of HAART?
D - For any woman who is HIV positive who becomes acutely unwell in pregnancy, close liaison between the obstetricians and HIV physicians is mandatory to avoid diagnostic error.
D - HIV-related complications should also be considered as a cause of acute illness in pregnant women whose HIV status is unknown, particularly those who are not booked for antenatal care. In these circumstances, rapid HIV testing should be considered.
What Is the Risk of Preterm Delivery?
B - Women who are HIV positive should be counselled about the increased risk of preterm delivery associated with HAART.
How Should Preterm Labour Be Managed?
D - For women presenting with threatened preterm labour, initial assessment is in accordance with guidelines for the general population. The multidisciplinary team should be involved so that a clear plan of care is in place should preterm labour supervene.
The usual indications for steroids apply. A genital infection screen should be undertaken. Tocolysis may be initiated as appropriate. Close liaison with the HIV physicians and paediatricians will ensure that a clear plan of care is put into place. [Evidence level 4]
C - For women in preterm labour, urgent advice should be sought from the HIV physicians and paediatricians about the choice of antiretroviral therapy. Infants born below 32 weeks of gestation are at increased risk of HIV but may be unable to tolerate oral medication. Antiretroviral therapy administered to the mother just before and during delivery will provide prophylaxis for the neonate.
How Should Preterm Prelabour Rupture of the Membranes Be Managed?
D - Where preterm prelabour rupture of the membranes occurs after 34 weeks of gestation, delivery should be expedited.
A genital infection screen should be undertaken and consideration should be given to starting intravenous broad-spectrum antibiotics. At this gestation, the small risk of neonatal morbidity and mortality associated with prematurity is outweighed by the risk to both mother and neonate of chorioamnionitis and the risk of perinatal HIV transmission. If plasma viral load is less than 50 copies/ml and there are no obstetric contraindications, augmentation of labour may be considered. [Evidence level 4]
D - Where preterm prelabour rupture of the membranes occurs before 34 weeks of gestation, the decision as to whether to expedite delivery should be made after multidisciplinary team consultation, involving the HIV physicians and paediatricians.
Steroids should be administered in the usual way. A genital infection screen should be undertaken. Oral erythromycin should be started in accordance with national guidelines and consideration should be given to starting intravenous broad-spectrum antibiotics. Evidence of chorioamnionitis and fetal distress are indications for prompt delivery. In other cases, the multidisciplinary team discussion will consider the adequacy of maternal HAART, plasma viraemia and the presence of any other pregnancy or HIV-related comorbidities. The timing of delivery will take into consideration the risk of complications associated with prematurity, the availability of neonatal facilities and the risk of perinatal HIV transmission. Such complex decisions should involve the paediatricians and HIV physicians. Expert advice from outside the host institution may be helpful. [Evidence level 4]
How Should Prelabour Rupture of the Membranes at Term Be Managed?
D - In the case of prelabour rupture of the membranes at term, delivery should be expedited.
D - Broad-spectrum intravenous antibiotics should be administered if there is evidence of genital infection or chorioamnionitis.
How Should Prolonged Pregnancy Be Managed?
D - For women on HAART with a plasma viral load of less than 50 copies/ml, the decision regarding induction of labour should be individualised. There is no contraindication to membrane sweep or to the use of prostaglandins.
If a woman remains undelivered beyond 41 weeks of gestation, is keen to achieve a vaginal delivery, is taking HAART and has a plasma viral load of less than 50 copies/ml, induction of labour may be considered, particularly if the cervix is favourable. Otherwise, an elective caesarean section should be performed. [Evidence level 4]
What Is the Role of Vaginal Birth after Caesarean Section?
D - A trial of scar may be considered for women taking HAART whose plasma viral load is less than 50 copies/ml.
How Should Women Diagnosed in Late Pregnancy but before the Onset of Labour Be Managed?
D - Women diagnosed with HIV late in pregnancy should have a rapid multidisciplinary team assessment and HAART should be commenced as soon as possible.
With improved turnaround times for viral load testing, a woman diagnosed HIV positive beyond 32 weeks may still have her pregnancy managed with a view to planned vaginal delivery if she commences HAART and achieves a viral load of less than 50 copies/ml by 36 weeks. If the viral load is greater than 50 copies/ml at 36 weeks, she should be scheduled for an elective caesarean section at 38 weeks, should continue her HAART regimen and be given intravenous ZDV at delivery. [Evidence level 4]
How Should Women Diagnosed with HIV during Labour Be Managed?
D - For women who are HIV positive who are diagnosed during labour, urgent advice should be sought from the HIV physicians regarding optimum HAART; delivery should be by caesarean section and, where possible, should be timed with respect to antiretroviral administration.
If the woman's HIV status is unknown, a rapid test for HIV is recommended and a reactive result should be acted on immediately. Urgent advice should be sought from the HIV physicians about the choice of antiretroviral therapy. In these circumstances, the HAART regimen is likely to include intravenous ZDV (the only licensed antiretroviral available for parenteral use) and oral nevirapine (an antiretroviral with rapid placental transfer and of proven benefit in reducing transmission). If delivery is not imminent, a caesarean section should be performed. Where possible, delivery should be timed to be at least 2 hours after administration of nevirapine. A confirmatory test should be taken, together with samples for CD4 count, viral load and resistance testing. The paediatricians should be informed so that neonatal care can be planned. [Evidence level 4]
Management of Delivery
How Should Caesarean Section Be Managed?
D - If intravenous ZDV is indicated, the infusion should be started 4 hours before beginning the caesarean section and should continue until the umbilical cord has been clamped.
D - The surgical field should be kept as haemostatic as possible and care should be taken to try to avoid rupturing the membranes until the head is delivered through the surgical incision. The cord should be clamped as early as possible after delivery.
D - A maternal sample for plasma viral load and CD4 lymphocyte count should be taken at delivery.
The decision for elective caesarean section will usually be made at or before around 36 weeks gestation. Details of which antiretrovirals should be taken and whether they should be continued postpartum should be documented in that plan. For those women requiring intravenous ZDV, the infusion should be started 4 hours before beginning the caesarean section and continued until the umbilical cord has been clamped. [Evidence level 4]
For all caesarean sections, whether elective or emergency, care should be taken to ensure that the surgical field is as haemostatic as possible and, where possible, that the membranes are left intact until the head is delivered through the surgical incision. The cord should be clamped as early as possible after delivery. Peripartum antibiotics should be administered in accordance with national guidelines for the general population. [Evidence level 4]
How Should Planned Vaginal Delivery Be Managed?
D - Only women with a plasma viral load of less than 50 copies/ml should be offered a planned vaginal delivery.
D - Invasive procedures such as fetal blood sampling and fetal scalp electrodes are contraindicated.
D - If labour progress is normal, amniotomy should be avoided unless delivery is imminent.
D - Amniotomy and possible use of oxytocin may be considered for augmentation of labour.
D - If instrumental delivery is indicated, the use of forceps is preferable to ventouse.
What Support Should Be Given to Women with Respect to Avoidance of Breastfeeding?
B - Women in resource-rich countries who are HIV positive should be advised not to breastfeed.
Women should be given appropriate support with regard to artificial (infant formula) feeding. This is particularly important for women whose families are unaware of their HIV status and where the cultural norm is to breastfeed.
Cabergoline 1 mg orally given within 24 hours of birth is recommended for all mothers in the UK who are HIV positive.
What Contraceptive Advice Should Be Given?
D - All women who are HIV positive should receive guidance about contraception in the immediate postpartum period.
What Immunisations Should Be Offered to the Mother?
D - MMR and varicella zoster immunisation may be indicated. Advice of HIV physicians should be sought.
Hepatitis B, pneumococcal, and influenza vaccines are recommended for all people who are HIV positive (between October and March). These vaccines can be safely administered in pregnancy or postpartum. [Evidence level 4]
Care of the Neonate
What Antiretroviral Therapy Should Be Administered to the Neonate?
A - All neonates born to women who are HIV positive should be treated with antiretroviral therapy within 4 hours of birth.
Should Prophylaxis against PCP Be Administered to the Neonate?
C - Prophylaxis against PCP is recommended only for infants born to mothers at high risk of transmission.
How and When Should the Infant Be Tested for HIV?
D - Infants should be tested at 1 day, 6 weeks and 12 weeks of age. If all these tests are negative and the baby is not being breastfed, the parents can be informed that the child is not HIV-infected. A confirmatory HIV antibody test is performed at around 18 months of age.
What Interventions Are There to Minimise the Risk of Transmission between Discordant Couples at Conception?
B - Couples who are serodiscordant for HIV infection and who choose to have sexual intercourse should be advised to use condoms.
B - Serodiscordant couples where the female partner is HIV negative should be advised that assisted conception with either donor insemination or sperm washing is significantly safer than timed unprotected intercourse.
How Should the Health of the Mother Who Is HIV Positive and Her Fetus Be Optimised Periconceptually?
D - Couples are recommended to delay conception until plasma viraemia is suppressed, prophylaxis against PCP is no longer required and any opportunistic infections have been treated.
D - Folate supplementation should be administered in accordance with national guidelines. For women taking cotrimoxazole, higher dose folate (5 mg) should be administered.
B - All women who are HIV positive are recommended to have yearly cervical cytology.
Classification of Evidence Levels
1++ High-quality meta-analyses, systematic reviews of randomised controlled trials or randomised controlled trials with a very low risk of bias
1+ Well-conducted meta-analyses, systematic reviews of randomised controlled trials or randomised controlled trials with a low risk of bias
1- Meta-analyses, systematic reviews of randomised controlled trials or randomised controlled trials with a high risk of bias
2++ High-quality systematic reviews of case–control or cohort studies or high-quality case–control or cohort studies with a very low risk of confounding, bias or chance and a high probability that the relationship is causal
2+ Well-conducted case–control or cohort studies with a low risk of confounding, bias or chance and a moderate probability that the relationship is causal
2- Case–control or cohort studies with a high risk of confounding, bias or chance and a significant risk that the relationship is not causal
3 Non-analytical studies; e.g., case reports, case series
4 Expert opinion
Grades of Recommendations
A - At least one meta-analysis, systematic review or randomised controlled trial rated as 1++, and directly applicable to the target population; or
A systematic review of randomised controlled trials or a body of evidence consisting principally of studies rated as 1+, directly applicable to the target population and demonstrating overall consistency of results.
B - A body of evidence including studies rated as 2++ directly applicable to the target population, and demonstrating overall consistency of results; or
Extrapolated evidence from studies rated as 1++ or 1+
C - A body of evidence including studies rated as 2+ directly applicable to the target population and demonstrating overall consistency of results; or
Extrapolated evidence from studies rated as 2++
D - Evidence level 3 or 4; or
Extrapolated evidence from studies rated as 2+
Good Practice Point - Recommended best practice based on the clinical experience of the guideline development group