HIV IN PREGNANCYDR AHMAD ZHARIF BIN HUSSEIN

HIV

(HIV) Human immunodeficiency virus is a lentivirus (a member of the retrovirus family) that causes Acquired Immunodeficiency Syndrome (AIDS)

Discovered in 1983

HIV has been divided into two primary strains

HIV-1 and HIV-2

HIV is a retrovirus that is believed to have evolved from a simian immunodeficiency virus.

Group - Group VI (-ssRNA)

Family - Retroviridae

Genus - Lentivirus

It is composed of two copies of positive single-stranded RNA.

STRUCTURE HIV

HIV is different in structure from other retroviruses.

ETIOLOGY

The 3 main route of transmission is via;

o blood, blood products

o sexual contact

o mother to child in intrauterine infection, perinatal transmission, or the mother’s milk.

GUIDELINES FOR HIV IN PREGNANCY

RCOG –GREEN TOP NO 39 MANAGEMENT OF HIV IN PREGNANCY 2010

British HIV Association guidelines for the management of

HIV infection in pregnant women 2012(NICE)

Guidelines

Objectives to increase in the proportion of vaginal deliveries and a reduction in

the number of emergency CS.

To reduce the risk of MTCT

Contents Antenatal HIV management

Intrapartum HIV management

Postpartum HIV management

Neonatal HIV management

Antenatal management

Recommended to have screening for HIV infection in every pregnancy at their booking antenatal visit. - can prevent mother-to-child transmission and significantly improve their own health.

women who are HIV positive should be referred promptly for assessment and for their pregnancies to be management within a multidisciplinary team.

If a woman declines screening, her reasons should be explored sensitively to ensure that she has received accurate information on which to base her decision.

Involvement of a senior health professional should be considered. The decision to decline screening should be documented in the maternity notes and screening offered again at around 28 weeks

Multidisciplinary team

HIV positive patients should be managed by a multidisciplinary team.

HIV physician

an Obstetrician

a Midwife

a Paediatrician

a Psychiatric team

support groups

“Confidentiality is important.& an early assessment of their social circumstances.”

HIV test

Rapid HIV tests are recommended for women with unknown HIV status who present in labour and a reactive result should be acted on immediately

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.

ADVICE

Safer sex practice-use condom

Appropriate support

To screen others children and partners who unknown HIV status

Antenatal care

Screening for Down syndrome and fetal anomalies should be offered.

A detailed ultrasound scan for fetal anomalies is important after first-trimester exposure to HAART(exposed to potentially teratogenic drugs)- between 18 + 0 and 20 + 6 weeks’ gestation ,In past theoretical increased risk of anomaly due to first trimester ART exposure.

The combined screening (the ‘triple test’+ NT scan)for trisomy 21 is recommended as this has the best sensitivity and specificity and will minimize the number of women who may need invasive testing

Invasive prenatal diagnosis

The risk of mother-to-child transmission with chorionic villus sampling or second-trimester amniocentesis hasn’t been estabilished.

If invasive prenatal diagnosis is contemplated, the advice of the fetal medicine specialist and HIV physician should be seeked and prophylaxis with HAART considered.

Invasive prenatal diagnostic testing should not be performed until after HIV status of the mother is known and should be ideally deferred until HIV VL has been adequately suppressed Where possible, amniocentesis should be deferred until VL is <50 HIV

RNA copies/mL

Recommended

• All pregnant women who are HIV positive should be screened for syphilis, hepatitis B,C & other genital infection

• When to do ?• This should be done as early as possible in

pregnancy • repeated at around 28 weeks.

• Bacterial vaginosis is associated with around a two-fold increased risk of preterm delivery & have been shown to stimulate HIV in vitro.

• HIV positive taking HAART at the time of booking should be screened for gestational diabetes.

Antiretroviral therapy

Aims: prevention of mother-to-child transmission

treatment of the mother to prevent maternal disease progression

The decision to start,modify or stop anti-retroviral therapy should be undertaken by an HIV physician

in close liaison with other health professionals

obstetrician

paediatrician.

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.

c) 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 monotherapy initiated between 20 and 28 weeks, given orally twice daily, intravenously at delivery and discontinued immediately thereafter

Timing Antenatally

Intrapartum

Neonatal period(4-6 weeks)

Choice of antiretroviral therapy & Timing is decided by HIV physician.

Plasma viral load & CD4 counts regularly monitored.

Patients on antiretroviral therapy should be monitored for toxicity full blood count

urea and electrolytes

liver function tests- Hepatoxicity

Lactate –(Lactic acidosis)

blood glucose-GDM

In women who commence HAART in pregnancy a VL should be performed 2–4 weeks after commencing HAART, at least once every trimester, at 36 weeks and at delivery

presented with an opportunistic infection, initiation of HAART should not be delayed.

Treatment is indicated based on CD4 cell count only,

Treatment to the start of the second trimester is reasonable, particularly if the patient is experiencing nausea and/or vomiting of pregnancy

Type of ARV drug

Nucleoside reverse transcriptase inhibitors (NRTI) and nucleotide reverse transcriptase inhibitors (NtRTI)  deoxythymidine, zidovudine, stavudine, didanosine, zalcitabine,

abacavir, lamivudine, emtricitabine, and tenofovir.[6]

Non-Nucleoside reverse transcriptase inhibitors (NNRTI)  nevirapine, delavirdine, efavirenz, and rilpivirine.[6]

Integrase inhibitors  Raltegravir &Elvitegravir.[3]

Protease inhibitors  Lopinavir, Indinavir,Nelfinavir, Amprenavir and Ritonavir. Maturation

inhibitors

Nucleoside reverse transcriptase inhibitors (NRTI) and nucleotide reverse transcriptase inhibitors (NtRTI)

nucleoside and nucleotide analogues which inhibit reverse transcription. NRTIs are chain terminators such that once incorporated, work by preventing other nucleosides from also being incorporated because of the absence of a 3’ OH group. ; they both act as competitive substrate inhibitors

Zidovudine monotherapy can be used in women planning a CS who have a baseline VL <10 000 HIV RNAcopies/mL and CD4 cell count >350 cells/mL.

Emtricitabine is structurally similar to lamivudine but has a longer half-life

Non-Nucleoside reverse transcriptase inhibitors (NNRTI) 

inhibit reverse transcriptase by binding to an allosteric site of the enzyme; NNRTIs act as non-competitive inhibitors of reverse transcriptase. NNRTIs affect the handling of substrate (nucleotides) by reverse transcriptase by binding near the active site and causing “molecular arthritis”

Efavirenz-earlier it contraindication in pregnancy

Report:{3 offspring of 20 the first trimester had significant

abnormalities at birth: one had anencephaly and unilateral

anophthalmia; the second microphthalmia; and the third a cleft palate}

On current evidence, that efavirenz can be used in pregnancy.

Integrase inhibitors

Inhibit the enzyme integrase, which is responsible for integration of viral DNA into the DNA of the infected cel

Protease inhibitors 

block the viral protease enzyme necessary to produce mature virions upon budding from the host membrane. Particularly, these drugs prevent the cleavage of gag and gag/pol precursor proteins

Is are highly protein-bound and placental transfer in humans appears to be limited

HAART

 regimens consist of three(3) drugs: 2 NRTIs + 1 PI/NNRTI/II

UK are now rarely prescribed zidovudine as part of HAART

zidovudine plus lamivudine, tenofovirplus emtricitabine or abacavir plus lamivudine are acceptable nucleoside backbones

the efficacy of HAART in pregnancy are based on a three/four-drug combination, including a zidovudine/lamivudine backbone

In the absence of specific contraindications, it is recommended that the third agent in HAART should be efavirenz or nevirapine (if the CD4 cell count is <250 cells/mL) or a boosted PI

Zidovudine Vs START

Zidovudine START

may allow the emergence of resistant virus

maternal plasma viraemia is more likely to be suppressed to undetectable levels

exposure of the mother and fetus to larger numbers of potentially toxic drugs

No routine dose alterations are recommended for ARVs during pregnancy if used at adult licensed doses

third-trimester TDM if combining tenofovir and atazanavir

should have commenced ART by week 24 of pregnancy

combination of zidovudine, lamivudine and abacavir can be used if the baseline VL is <100 000 HIV RNA copies/mL plasma

If the VL is unknown or >100 000 copies/mL a three- or four-drug regimen that includes raltegravir is suggested

HBV infection

All HBV/HIV coinfected women should receive HAART

containing tenofovir with emtricitabine or lamivudine unless contraindicated

Combining lamivudine/emtricitabine with tenofovir may also reduce the risk of breakthrough HBV viraemia

CD4 cell count is <500 cells/mL, HAART should be continued postpartum

CD4 cell count is >500 cells/mL and there is no other indication to treat HBV, consideration should be given to continuing anti-HBV treatment postpartum with HAART incorporating tenofovir and emtricitabine

If a decision is taken to discontinue therapy,careful monitoring of liver function is imperative, there is HBV viraemia and evidence of liver inflammationor fibrosis, HAART containing tenofovir and emtricitabine should be continued

In the absence of obstetric complications, normal vaginal delivery can be recommended if the mother has fully suppressed HIV VL on HAART

Neonatal immunization with or without HBIG should commence within 24 h of delivery

HCV

On diagnosis of new HCV infection, confirmation of HCV viraemia with quantitative VL and genotype,assessment of hepatic inflammation and function and concomitant liver disease should be performed.

LFTs should be repeated at 2 weeks after commencingHAART to detect evidence of hepatotoxicity

Coinfected mothers with HCV should not be treated for HCV with pegylated interferon with or without ribavirin and all women who discover they are pregnant while receiving treatment should discontinue both pegylated interferon and ribavirin immediately. HCV antiviral therapy is contraindicated in pregnant women due to possible

teratogenicity

In all non-immune HCV coinfected women after the first trimester, vaccination against HBV is recommended

Failure to suppress

Treatment of HAART during pregnancy has not achieved a plasma VL of <50 copies/mL at 36 weeks the following interventions

are recommended:

• Review adherence and concomitant medication.

• Perform resistance test if appropriate.

• Consider TDM.

• Optimize to best regimen.

• Consider intensification.

these interventions should be undertaken as soon as possible

Intrapartum management

Mode of delivery Elective caesarean section at 38 weeks to prevent labour and/or ruptured

membranes is recommended for:

women taking HAART who have a plasma viral load greater than 50 copies/ml.

women taking ZDV monotherapy as an alternative to HAART.

women with VL >400 HIV RNA copies/mL regardless of ART

Vaginal delivery

can be offered to women taking HAART with plasma viral loads of less than 50 copies/ml.

Elective caesarean section for obstetric indications or maternal request should be delayed till 39-40 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.

“A plan regarding mode of delivery should be made at around 36 weeks following detailed discussion with the mother”

LSCS

A zidovudine infusion should be started four hours before beginning the caesarean

section

Should continue until the umbilical cord has been clamped.

A maternal sample for plasma viral load and CD 4 should be taken at delivery.

The cord should be clamped as early as possible after delivery and the baby should be bathed immediately after the birth.

a technique of ‘bloodless’ caesarean section may further reduce the risk of mother-tochild transmission. opening the uterus with a staple gun,which simultaneously cuts and

giveshaemostasis.

This should be sheduled at 38 weeks to reduce the risk of spontaneus labour or membrane rupture.

Contamination of the baby with maternal blood should be avoided Secure the bleeding points

Cord clamped as soon as possible

Not to rupture membrane till fetal head out

Drainage should be used and they should be used to closed suction system

Universal precautions :gloves, aprons & face protection should be employed.

VBAC

VBAC should be offered to women with a VL <50 HIV RNA copies/Ml

In Labour

planned vaginal delivery should have their membranes left intact for as long as possible (ARM if have indication)

Use of fetal scalp electrodes and fetal blood sampling should be avoided.

Women should continue their HAART regimen throughout labour .

If an intravenous infusion of zidovudine is required it should be commenced at the onset of labour and continued until the umbilical cord has been clamped.

A maternal sample for plasma viral load should be taken at delivery.

The cord should be clamped as early as possible after delivery and the baby should be bathed immediately after the birth.

Vaginal delivery

Forceps preferred to Vacuum

Remove maternal blood stain with alcohol wipe prior to Vitamin K injection

Universal precautions :gloves, aprons & face protection should be employed.

Amniotomy and possible use of oxytocin may be considered for augmentation of labour.

Preterm delivery

Initial assessment

The multidisciplinary team should be involved so that a clear plan of care

indications for steroids apply.

A genital infection screen should be undertaken.

Tocolysis may be initiated as appropriate.

Urgent advice-from the HIV physicians and paediatricians about the choice of anti-retroviral therapy. Infants born below 32 weeks of gestation are at increased risk of HIV but may be unable to tolerate oral medication.

Anti-retroviral therapy administered to the mother just before and during delivery will provide prophylaxis for the neonate

a single dose of oral nevirapine (200 mg) given at least 2 hours before delivery,

a double dose of oral tenofovir (600 mg) and intravenous ZDV.

SROM in HIV

SROM-spontaneus rupture of Membranes ruptured membranes for more than four hours , associated with

double the risk of HIV transmission.

These studies also demonstrated a 2% incremental increase in transmission risk for every hour of rupturedmembranes up to 24 hours.

The relevance of these studies for women taking HAART who have undetectable viral loads is uncertain.

delivery should be expedited.

should be given to startingintravenous broad-spectrum antibiotics.

PPROM in HIV

PPROM-preterm prelabour rupture of membranes If there is preterm rupture of membranes, with or without labour, the risk

of HIV transmission should be set against the risk of preterm delivery.

Preterm infants are more likely to be infected with HIV.

To the use of short-term steroids to promote fetal lung maturation.

Oral erythromycin -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.

Less 34/52 – multidiscipline team involvement and obstetric indication for decision time of delivery

After 34/52- delivery expedited

ECV

ECV can be performed in women with HIV

ECV should be offered to women with a VL <50 copies/mL and breech presentation at >36 + 0 weeks in the absence of obstetric contraindications

Induction

previously been avoided as there were concerns about the duration of ruptured membranes and risk of MTCT but recent evidence would appear to be reassuring on this point

Late diagnose & unknown HIV status

Rapid multidisciplinary team assessment and HAART should be commenced ASAP vaginal delivery if she commences HAART and achieves a viral load of less

than 50 copies/ml by 36 weeks.

elective caesarean section at 38/52 -If the viral load is greater than 50 copies/ml at 36 weeks

Diagnosed during labour, urgent advice should be sought from the HIV physicians regarding optimum HAART; delivery should be by caesarean section and, wherepossible, should be timed with respect to anti-retroviral administration. HAART regimen(intravenous ZDV and oral nevirapine (an anti-retroviral with

rapid placental transfer and of proven benefit in reducing transmission)

delivery should be timed to be at least 2 hours after administration of nevirapine

An untreated woman presenting in labour at term should be given a stat dose of nevirapine 200 mg and commence fixed-dose zidovudine with lamivudine and raltegravir.

It is suggested that intravenous zidovudine be infused for the duration of labour and delivery.

Postpartum management

women with HIV advised not to breast feed

Neonate infections. PCR is done as maternal antibodies cross the placenta

Typically, tests are carried out at birth, then at three weeks, six weeks and six months.

definitive test is the HIV antibody test: a negative result at 18 months of age confirms that the child is uninfected.

should receive guidance about contraception in the immediate postpartum period.

Management of the neonate

All infants born to women who are HIV positive should be treated with anti-retroviral therapy from birth.

Usually treatment is discontinued after four to six weeks

Zidovudine monotherapy is recommended if maternal VL is <50 HIV RNA copies/mL at 36 weeks’ gestation or thereafter before delivery (or mother delivered by CS while on zidovudine monotherapy).

There are two situations where triple combination ART for neonates is advised:

(i) Post-delivery infant-only prophylaxis: mother found to be HIV positive after delivery, which is only effective if given within 48–72 h of birth

(ii) Detectable maternal viraemia (>50 HIV RNA copies/mL) at delivery, mother may be on HAART or not:

• delivery before complete viral suppression is achieved (e.g. starting HAART late or delivery premature);

• viral rebound with or without resistance, with or without poor adherence;

• unplanned delivery ( e.g. premature delivery before starting ART or late presentation when maternal HIV parameters may be unknown).

Infants <72 h old, born to untreated HIV-positive mothers

Recommendation for for HIV-infected mother in labor who had no prior therapy

1. Single dose Nevirapine during labor and a single dose to the neonate at age 48h.

2. Intrapartum AZT, the 6 weeks of AZT to the neonate.(2mg/kg 4 times daily)

3. The two dose Nevirapine combined with the intrapartum and 6 weeks AZT regimen.

IN case of maternal HIV antiretroviral resistance:

AZT is still recommended to the infant, plus other medications based on maternal HIV resistance pattern.

Neonatal care

HIV DNA PCR (or HIV RNA testing) should be performed on the following occasions: _ During the first 48 h and before hospital discharge.

_ 2 weeks post infant prophylaxis (6 weeks of age).

_ 2 months post infant prophylaxis (12 weeks of age).

_ On other occasions if additional risk (e.g.breastfeeding).

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

PCP

PCP prophylaxis, with co-trimoxazole, should be initiated from age 4 weeks in:

• All HIV-positive infants

• In infants with an initial positive HIV DNA/RNA test result (and continued until HIV infection has been excluded).

• Infants whose mother’s VL at 36 weeks’ gestational

age or at delivery is >1000 HIV RNA copies/mL despite

HAART or unknown (and continued until HIV infection

has been excluded).

Immunization

Hepatitis B, pneumococcus and influenza immunisation are recommended for all individuals who are HIV positive; these immunisations can be safely administered in pregnancy.

Varicella zoster and measles, mumps and rubella vaccines are contraindicated in pregnancy. Women testing immunoglobulin G negative for these infections should be considered for immunisation postpartum, depending on their CD4 count

Continuation of ARV

ARV therapy should be continued in all pregnant

women who commenced HAART with a history of an AIDS-defining illness or with a CD4 cell count <350 cells/mL

ART should be continued in all women who commenced HAART for PMTCT with a CD4 cell count of between 350 and 500 cells/mL during pregnancy who are coinfected with HBV or HCV

  ART should be discontinued in all women who commenced HAART for PMTCT with a CD4 cell count >500 cells/mL unless there is discordance with her partner or co-morbidity

Prepregnancy management

Couples who are serodiscordant for HIV infection and who choose to have sexual intercourse should be advised to use condoms.

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.

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.

Folate supplementation should be administered in accordance with national guidelines. For women taking cotrimoxazole, higher dose folate (5 mg) should be administered.

All women who are HIV positive are recommended to have yearly cervical cytology.

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