Case 26 A 26-year-old woman diagnosed HIV positive on routine antenatal screening

 Case 26 A 26-year-old woman diagnosed HIV

positive on routine antenatal

screening

Mrs Oktie-ebuh, a 26-year-old, attends her local surgery

requesting antenatal care. She has recently moved to the UK

from Nigeria to join her husband who is a student at the

local university. She is 16 weeks’ pregnant and had her

initial care in Nigeria, including a dating scan. Her

community midwife carries out the antenatal check up and

provides her with information about the care in her

pregnancy. She also obtains blood for routine antenatal

screening including an infection screen after consent.

Ten days later, Mrs Oktie-ebuh receives a letter from the

obstetric consultant with a clinic appointment to discuss the

results of her recent blood tests. Her blood results are as

below:

How will you interpret these

blood results?

Her results indicate that she is rhesus positive and not

anaemic. She is at low risk for having a baby with Down ’ s

syndrome and spina bifida. She has tested positive for

HIV infection and has chronic hepatitis B infection.

Obstetrics and Gynaecology: Clinical Cases Uncovered.

By M. Cruickshank and A. Shetty. Published 2009 by Blackwell

Publishing. ISBN 978-1-4051-8671-1.

Hb 135g/L

Blood group O rhesus positive

Down’s syndrome

screening risk

1:1856

Serum alphafetaprotein

<2Mean of median

Rubella screen Immune

Treponema pallidum Negative

HIV screen Positive

Hepatitis B screen Hepatitis B surface Antigen: positive

Hepatitis B core Antigen: negative

Hepatitis B core Antibody: positive

Hepatitis e Antigen: negative

Mrs Oktie-ebuh wonders what could be the problem with

the blood tests, as she feels well and, so far, has had an

uneventful pregnancy.

KEY POINT

Pregnant women should be offered screening for HIV early

in pregnancy as appropriate interventions can reduce

maternal–child transmission.

What important issues will you consider

when counselling this woman who has

tested positive for HIV infection?

This diagnosis may be profoundly shocking and a life -

changing experience for the woman and therefore needs

sensitive handling. As a clinician some important issues

to consider are:

• Confidentiality

• Empathy while communicating the results

• HIV status of partner

• HIV status of existing children

What specific information do you

need from Mrs Oktie-ebuh’s history

and examination?

• Details of any medical problems including medications and the pregnancy so far

• Past obstetric history:

 previous pregnancies166 Part 2: Cases

PART 2: CASES

 gestation at delivery

 mode of delivery

• Past history of blood transfusion and sexually transmitted infections

• Patient ’ s awareness of her HIV and hepatitis status

• HIV status of her existing children and partner

• Assessment of her social circumstances (Box 26.2 )

• Detailed general and systemic examination

Mrs Oktie-ebuh is a primigravida who has had an uneventful

pregnancy so far. She is fit and well and denies any major

medical problems, including any allergies. There are no

abnormalities noted on examination.

She was unaware of her HIV and hepatitis status and is

upset and shocked at disclosure of the test results. During

the long consultation, her consultant explained in detail the

implications of her HIV and hepatitis status, including the

effect of the diagnosis on her pregnancy. She also discussed

the measures for combating the risk of transmission to her

baby and the need for compliance with clinic appointments

and the recommended treatment, which would be overseen

by a specialist team of medical personnel experienced in

dealing with HIV infections (Boxes 26.3 & 26.4).

Box 26.1 HIV: burden of infection

Approximately 3 million HIV positive pregnant women give

birth each year, of whom 75% reside in sub-Saharan

Africa, which also accounts for most of the 700,000 new

HIV infections among children annually

Prevalence of HIV among pregnant women is on the rise

in the UK, especially in the inner city areas of London, and

most of these women are of black African ethnicity.

In 2005, 1100 children were born to HIV positive

women in the UK.

Box 26.2 Psychosocial issues

• HIV positive pregnant women should be encouraged to

disclose their HIV status to their partner

• Testing of any existing children for HIV is recommended

• A thorough early assessment of social circumstances of

a newly diagnosed HIV positive pregnant woman is

essential

Box 26.3 HIV in pregnancy

• Mother–child transmission of HIV varies between 15%

and 30% in untreated or undiagnosed mothers

• In absence of intervention, >80% of perinatal

transmissions occur late in the third trimester,

intrapartum (majority) and postnatally through

breastfeeding

• Vertical transmission can be reduced to <1% with

appropriate measures

• Interventions include:

• antiretroviral therapy (ART) to mother and neonate

• prelabour caesarean section (PLCS)

• avoidance of breastfeeding

• Advanced maternal disease, low CD4 lymphocyte counts

and high plasma viral load are associated with an

increased risk of transmission

• Principal obstetric risk factors for transmission are

vaginal delivery in the presence of a significant viral

load, duration of membrane rupture and delivery prior

to 32 completed weeks’ gestation

• Pregnancy does not adversely affect HIV progression or

survival

• Earlier studies had suggested an association between

HIV and an increased risk of miscarriage, preterm

delivery and intrauterine growth restriction but more

recent studies have not confirmed this

• With advances in ART, HIV infection in the industrialized

world is regarded as a carrier state or chronic infection

• Symptomatic disease is rare and can be associated with

opportunistic infections (e.g. Pneumocystis,

cytomegalovirus, Toxoplasma)

Box 26.4 HIV and hepatitis B virus co-infection

• Materno-fetal transmission of hepatitis B virus (HBV)

infection is related to the level of viraemia

• Transmission is >90% in women positive for HbeAg

compared to 40% transmission in women negative for

HbeAg

• Active measures can effectively prevent transmission to

fetus. These measures include hepatitis B vaccination of

the infants born to HBsAg positive mothers at birth, 1

month, 2 months and 12 months of age. In infants born

to mothers with high risk of infectivity (HBeAg positive),

HBV immunoglobulin at birth is also indicated

• Pregnant women with HIV–HBV co-infection should be

treated with a regimen that includes agents active

against HIV and HBV as requiredCase 26 167

PART 2: CASES

What other investigations would you

like to carry out at this stage?

Obtain blood for:

• Plasma viral load

• CD4 lymphocyte count

• HIV genotype

• Hepatitis C screen

• Full blood count, baseline liver function and renal

function tests

• Haemoglobinopathy screen in view of her ethnicity

How will you manage this woman who

has been diagnosed with HIV infection

at 18 weeks’ gestation?

The aim of management is to minimize the risk of

materno - fetal transmission while not increasing maternal or neonatal morbidity.

Specific management

• Antiretroviral therapy

• Obstetric management

Mr and Mrs Oktie-ebuh attended the combined

multidisciplinary clinic as arranged. Mr Oktie-ebuh had his

blood taken for HIV screening.

The HIV physician discussed the treatment options and

explained that in view of the high viral load she would

require a combination of three antiretroviral drugs to

minimize the risk of materno-fetal transmission. The

effect of therapy would be monitored regularly with viral

load estimation by means of blood tests.

The couple’s main concern was the effect of the antiviral

therapy on the pregnancy and their baby.

What are the side-effects of

antiretroviral therapy?

Antiretroviral therapy

Of more than 20 compounds currently licensed for treatment of HIV 1 infections in the UK, only ziduvidine

(ZDV) is specifically indicated for use in pregnancy.

Information about safety of antiretroviral therapy (ART)

in pregnancy is limited. The risk of transmission should

KEY POINT

Maternal plasma viral load is the strongest predictor of

vertical transmission. Low or undetectable plasma viral

load is associated with very low risk of transmission.

Screening for genital infections

Infections to be screened for include: Chlamydia trachomatis, Nisseria gonorrhoea, Bacterial vaginosis and Treponema pallidum serology. Screening should be carried out

at presentation and repeated in the third trimester. Any

infection should be treated as per national guidelines

including a test for cure and partner notification as indicated to prevent reinfection.

KEY POINT

There is a higher prevalence of sexually transmitted infection

amongst HIV positive women. Evidence suggests that the

risk of chorioamnionitis, premature rupture of membranes

(PROM) and preterm labour increased in presence of genital

infections. Antenatal HIV care should be delivered by a

multidisciplinary team consisting of HIV physician,

obstetrician, paediatrician and specialist midwife along with

involvement of the woman’s GP, community midwife, social

workers and voluntary support groups as required.

The results of Mrs Oktie-ebuh’s investigations are as follows:

Hb 133g/L

Haemoglobinopathy

screen

No haemoglobinpathy detected

Renal and liver function

tests

Within normal limits

Hepatitis C screen Negative

Plasma viral load for HIV 14,000 copies/mL

CD4 lymphocyte count 340 × 106/L

HIV genotype HIV 1, non-B subtype (subtype

A) (Box 26.5)

Genital infection screen Negative

Box 26.5 HIV types: HIV 1 and HIV 2

• Most HIV infections in Europe are with HIV type 1

• Infection with HIV type 2 is usually limited to West

Africa; however, with global migration the population

dynamics are changing

• Although the two are related, there are important

differences between HIV 1 and HIV 2 that influence

natural history, pathogenicity and response to therapy

• Making the correct diagnosis is important as therapy

differs significantly if HIV 2 is detected

• NNRTIs of ART have no activity against HIV 2

Not all laboratories differentiate between the two virus

types, so it is important that patients at risk of HIV 2 have

appropriate investigations performed168 Part 2: Cases

PART 2: CASES

be balanced against the toxicities of ART. Apart from

didanosine and efavirenz, embryonal toxicity has not

been reported with other drugs (Table 26.1 ).

Treatment regimens

Efficacy relates to reducing infection in the neonate,

maintaining or improving maternal health and preserving maternal therapeutic options.

Ziduvidine monotherapy

ZDV monotherapy is a valid option for women:

• With a viral load <6 – 10,000 HIV RNA copies/mL

• Not requiring combination therapy for their own

health

• Not wishing to take combination therapy

• Willing to deliver by prelabour caaesarean section

(PLCS)

• To commence prior to 30 weeks

ZDV in combination with PLCS is said to reduce the

risk of transmission to <1%.

Highly active antiretroviral therapy

Highly active antiretroviral therapy (HAART) is a combination therapy containing three or more drugs and

usually includes two nucleoside reverse transcriptase

inhibitors (NRTIs) plus non - nucleoside reverse transcriptase inhibitor (NNRTI)/boosted protease inhibitor

(PI). The indications for the use of HAART in pregnancy

are:

• For maternal health

• If baseline viral load >10,000 HIV RNA copies/mL and

no maternal indication for HAART, commencing at

22 – 24 weeks

• As an alternative to ZDV monotherapy and PLCS

• Drug resistance detected on genotype or phenotype

• Therapy commenced prior to pregnancy should be

continued throughout pregnancy

Evidence suggests that use of HAART is associated

with preterm delivery, especially before 34 weeks.

Short-term antiretroviral therapy

Short - term antiretroviral therapy (START) is HAART

used for prevention of mother – child transmission during

pregnancy. It should be discontinued after delivery when

viral load <50 copies/mL.

It was discussed with the couple that although there were

limited safety data on the effects of ART in pregnancy,

evidence suggests that in general it is well tolerated and

appears reasonably safe for the mother and the baby

(Box 26.6).

Obstetric management of pregnancy

and delivery

Antenatal c are

The important aspects of antenatal care are confidentiality, multidisciplinary approach and instituting an agreed

care plan. Periconceptual folic acid (5 mg/day) is recommended, especially if the woman is on co - trimoxazole for

Pneumocystis prophylaxis. Dating scan, serum screening

and mid - trimester anomaly scan should be offered

routinely.

Table 26.1 Classes of drugs used for antiretroviral therapy in

pregnancy along with their side-effects.

Classification Examples Problems

Nucleoside

reverse

transcriptase

inhibitor (NRTI)

Ziduvidine (ZDV) Well tolerated

Lamivudine Lactic acidosis (rare)

Stavudine Hepatic dysfunction

Protease

inhibitor (PI)

Indinavir Gastrointestinal

side-effects (common)

Saquinavir Anaemia

Hepatic dysfunction

Non-nucleoside

reverse

transcriptase

inhibitor (NNRTI)

Nevirapine Hepatic toxicity

Rash, Stevens–Johnson

syndrome

Box 26.6 Monitoring antiretroviral therapy

ART is monitored using HIV plasma viral load, CD4

lymphocyte count and clinical status. Plasma viral load is

the most important determinant of mother–child

transmission

Viral load should be quantified:

• At presentation

• At least every 3 months and at 36 weeks in women on

established therapy

• Two weeks after starting or changing therapy

• At delivery

A second assay should be used where there are

discrepancies between the viral load, CD4 cell count and

the clinical statusCase 26 169

PART 2: CASES

During her pregnancy Mrs Oktie-ebuh is reviewed regularly

at the multidisciplinary clinic. She has tolerated the three

drug HAART regimen very well with no evidence of any

side-effects. The plasma HIV RNA viral load showed a

dramatic response to the ART and was <50 copies/mL

(undetectable) at 30 weeks’ gestation.

Her pregnancy is progressing well. Infection screen for

genital infections is repeated at 28 weeks and reported as

negative. She is now 34 weeks’ pregnant and is due to

attend the clinic to discuss a plan for her delivery.

What are the important factors to

consider when deciding the mode of

delivery for a HIV positive pregnant

woman? How will you help this woman

to make an informed choice?

Vaginal delivery would be an option for Mrs Oktie - ebuh

as her viral load was <50 copies/mL. Precautions to minimize the risk of transmission – including avoiding an

early artificial rupture of membranes (ARM), fetal blood

sampling (if there were concerns about fetal well - being)

and a fetal scalp electrode in labour – would be advised

(Box 26.7 ).

Mrs Oktie-ebuh opted for a PLCS, which was arranged for

39 weeks. She was advised to seek help if she laboured

prior to the arranged procedure.

Postnatal care

Breastfeeding constitutes a transmission risk despite ART

and is therefore not recommended. Consider cabergoline

for lactation suppression if indicated. Watch for postnatal

depression as women of this group are at increased risk

of depression post delivery.

Care of the neonate

All babies born to HIV positive mothers should be followed up by a paediatrician. Infants should be given ZDV

or alternative suitable monotherapy for 4 weeks. Triple

therapy should be given to neonates born to untreated

mothers or women with detectable viraemia despite

combination therapy.

Mrs Oktie-ebuh underwent an uneventful caesarean section

as scheduled. She delivered a baby boy weighing 3.78kg in

good condition with normal Apgar scores. The baby was

exclusively formula fed as per plan. All relevant investigations

were carried out for screening and the baby was

commenced on oral AZT. He also received a vaccination

against hepatitis B.

The mother and baby made an uneventful recovery and

were discharged home 7 days after the procedure.

Arrangements were made to follow the baby at the

paediatric clinic, while Mrs Oktie-ebuh was to be reviewed

at the clinic by her HIV physician.

Contraceptive advice was given supplemented by leaflets

prior to her discharge from the hospital.

KEY POINT

Prelabour caesarean section has been shown to reduce the

risk of perinatal HIV transmission and is of most benefit in

women with a high viral load.

Box 26.7 Mode and timing of delivery

A blanket policy of caesarean section for all HIV positive

women is not appropriate, but HIV should be taken into

equation when considering mode of delivery for obstetric,

medical and patient preference indications.

In addition to obstetric indications, PLCS is indicated for:

• Women on ZDV monotherapy

• Women on combination therapy with detectable

viraemia

PLCS should be considered for women with HIV–HCV

co-infection. PLCS should be planned for:

• 38 weeks if on ZDV monotherapy or with detectable

viraemia

• 39 weeks if on HAART and undetectable viraemia

Vaginal delivery is an option for women with

undetectable viraemia on HAART. If anticipating a vaginal

delivery avoid induction of labour, leave the membranes

intact for as long as possible and avoid invasive fetal

monitoring and traumatic instrumental delivery.

Intravenous ZDV is indicated predelivery for mothers on

ZDV monotherapy or >50HIV RNA copies/mL on HAART.170 Part 2: Cases

PART 2: CASES

CASE REVIEW

This 26 - year - old well Nigerian woman booked at 16 weeks ’

gestation at her local GP surgery for antenatal care in her

first pregnancy. The results of the routine screening blood

tests indicated that she was HIV positive and was a carrier

for hepatitis B virus infection. The importance of offering

antenatal screening for infections should not be underestimated as appropriate diagnosis and timely interventions

can minimize the risk of vertical transmission of infections. This woman was a recent migrant from a high - risk

area and was therefore at increased risk of such an infection. There is a higher prevalence of other sexually transmitted infections amongst this group of women, as was the

case with this woman, who was found to be a carrier for

hepatitis B virus infection. The sexually transmitted infection screen is an important aspect of management as these

infections can lead to an increased incidence of PROM and

preterm labour, possibly as a result of chorioamnionitis.

This woman was appropriately managed in a multidisciplinary setting and was commenced on a three drug ART

(HAART) regimen for prevention of vertical transmission

at 18 weeks. Combination therapy is indicated in women

with HIV viral load >10,000 HIV RNA copies/mL even if

the ART is not for maternal health reasons. If the viral load

is <6 – 10,000 copies/mL and the patient is willing to deliver

by a PLCS, then ZDV monotherapy is an option. If ART is

not indicated for maternal health, it is commenced late in

second trimester to minimize the adverse effects.

Maternal viral load is the most important determinant

of the risk of vertical transmission. Although the safety

data for ART use in pregnancy are not extensive, apart

from didanosine and efavirenz there have been no concerns raised about embryo toxicity. This patient tolerated

the ART well and her plasma viral load showed a dramatic

decline to <50 copies/mL over few weeks, indicating a good

response.

The mode of delivery was discussed at 34 weeks ’ gestation and the advantages and disadvantages of a caesarean

delivery and vaginal birth were also discussed along with

supporting evidence. Until recently, a PLCS was thought to

be the optimum mode of delivery for pregnant women

with HIV infection. However, more recent evidence suggests that in women with undetectable viral load on

HAART, there is an option of a vaginal delivery as the risk

of vertical transmission is minimal.

This woman opted for a PLCS, which was performed at

39 weeks. Her baby was tested for HIV infection and commenced on ZDV monotherapy prophylaxis to further

prevent the risk of infection. He also received vaccination

against hepatitis B virus infection to prevent transmission

of infection.

Breastfeeding is an important means of HIV transmission and is contraindicated to help minimize the risk.

Adequate follow - up was arranged for both the mother

and her baby with the HIV physicians and paediatricians,

respectively. She was also given contraceptive advice prior

to her discharge from the hospital.

KEY POINTS

• Prevalence of HIV infection among pregnant women is on

the rise in the UK

• Antenatal screening for HIV should be offered to all

pregnant women early in pregnancy

• HIV positive pregnant women should be screened for

genital infections at pregnancy and at 28 weeks

• Interventions such as ART, delivery by PLCS and avoidance

of breastfeeding reduces the transmission risk from

15–20% to <1%

• Pregnant women with HIV infection are best managed by

a multidisciplinary team

• Safety data on the use of ART in pregnancy are limited

• Maternal plasma viral load is the most important

determinant of mother–child transmission

• Mode of delivery should be discussed around 34–36

weeks and should involve the women, her obstetrician

and the HIV physician

• Vaginal delivery is an option for women with

undetectable viraemia on HAART

• All babies born to HIV positive mothers should be

followed up by a paediatrician and receive appropriate

ART