hiv infection and pregnancy

8/8/2019 Hiv Infection and Pregnancy

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HIV INFECTION AND PREGNANCYHIV INFECTION AND PREGNANCY

Dr Kilewo C. D.S

Muhimbili University College of

Health Sciences


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DISPOSITIONDISPOSITION Epidemiology of MTCT

HIV/AIDS and Pregnancy

MTCT

PMTCT

Use of ARVs in Pregnancy


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Concerns of infected mothersConcerns of infected mothers Is it Safe to be HIV+ and Pregnant?

What Are the Risk of Transmitting HIV?

Does all babies born to HIV infected mothers Test Positive for the virus?

Why is prenatal Care So important ? How can you reduce the risk of transmission?

What about anti-HIV Drug Therapy?

What about combination Anti-HIV Therapy?

What about potential side effect of combination Therapy?

Which Anti-HIV Drugs are Recommended forpregnant Women

What if I Become Pregnant while I`m on Therapy?

Should HIV + pregnant women Have Drug Resistance Test?

What about Cesarean Sections ?

What About Breast Feeding? What Else can I Do?


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ObjectivesObjectivesBy the end of this session participants will be able

to:

Describe MTCT and Timing & influencing factors Discuss PMTCT and Interventions

Discuss reasons forprovision of ARVs topregnant women

Describe different regimens used for PMTCT inTanzania

Describe contraindications and side effects forARVs


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INTRODUCTIONINTRODUCTION--11 By the end of 2003, 26.1 millionpeople were

estimated to be living with HIV/AIDS in Africa ,

including 3 million children. In Africa, 60% of HIV-1 positive adults are

women 80% all of child bearing age

Data from antenatal clinics show that in several

parts of central and southern Africa between 30

50 % of antenatal women are infected by HIV-1

(UNAIDS/WHO,2001)


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INTRODUCTIONINTRODUCTION--22 The distribution of HIV/AIDS according to age

sex show that the most effected age group is 15-49

years. Youth between the age 15-24 yearscontribute 60% of the new infections. Youngwomen are more infected in the younger age thanmen but in the older age men take over.

At present the Industrialized world has been ableto reduce MTCT from 25% to < 1%. De

In poor resource countries prophylactic use ofshort courses of ARV will reduce the risk ofMTCT by between 40-60%


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INTRODUCTIONINTRODUCTION--33More women who know they are infected choose to becomepregnant because of therapeutic advances in care and

prevention of MTCT. HIV-1/AIDS remains strongly stigmatizing, such that

HIV+ African women still choose to breastfeed despite ofknowing that there is risk of transmitting the virus through

breast milk About 2.6 mil HIV positive women becomepregnant

every year worldwide giving birth to 800,000 infectednewborns (1900 babies/day). .At least 90% of childreninfected and affected by HIV-1 live in sub- SaharaAfrica(Dabis F,2000;Dray-Spira , 2000).


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INTRODUCTIONINTRODUCTION--44 High fertility rates found in many

developing countries is an additional risk

for MTCT HIV/AIDS is now a major common

medical problem encountered in

reproductive health in many developingcountries and this is a challenge in the

management ofpregnancy and delivery


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INTRODUCTIONINTRODUCTION--55

The prevalence of HIV infection among antenatalmothers varies from country to country but is highestin sub=Saharan Africa particularly in East, Central,and Southern Africa where the rates are 10 - 30%

In Tanzania HIV prevalence among pregnant womenis 5.6 - 16% and that 72000 [25000 through BF]children are estimated to be infected in this wayannually

Without any intervention the cumulative risk inMTCT is close to 40% in which 1/3 is attributed tobreastfeeding


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INTRODUCTIONINTRODUCTION--66 Due to therapeutic advances in care especially

the use of HAART has enabled Industrialized

countries to reduced the risk of MTCT to aslow as 1%.

In poor resource countries prophylactic use of

short courses of ARV will reduce the risk of

MTCT by between 40-60%


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EFFECT OF PREGNANCY ON DISEASEEFFECT OF PREGNANCY ON DISEASE

PROGRESSIONPROGRESSION

The CD4 percentage rather than absolute countwould be a more accurate measure of immune

function for HIV infected women.(Miotti,1992;Brettle,1995)

Most studies up to now have not demonstratedpregnancy accelerating the HIV disease

progression. This suggests that pregnancy does not accelerate

the decline in CD4 cells.

Pregnancy does not affect the course of HIV

Infection


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Effect of HIV on pregnancy course andEffect of HIV on pregnancy course and

outcomeoutcome

Spontaneous abortion:

Limited data but evidence of increased risk

Stillbirth: No association noted in developed

countries; evidence of increased risk in

developing countries

Intrauterine growth retardation:Evidence ofincreased risk


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Pregnancy course and outcome contdPregnancy course and outcome contd

Low birth weight(


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Threat to Child survivalThreat to Child survival

Infant mortality: limited data from developed

countries; evidence of increased risk in developingcountries.

More than 90% of HIV-1 infected children acquire

their infection from their mothers. This threatens

their survival. Mortality is estimated at26-45% by

the 1stbirthday and 35-59% at 2 years(Spira R,

1999)


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MOBIDITYMOBIDITY

Exposure to maternal HIV-1 infection does notaffect the risk of survival of children who are not

infected themselves since their mortality rate is notsignificant different to the background mortality ofuninfected children born to uninfected mothers

There is an increased risk of morbidity of HIV-1infected and exposed children. Infectiouscomplications are prevented by prophylaxis withcotrimoxazole to all exposed new borns until thediagnosis of HIV-1 is made

Modification in infant feeding guidelines toaddress infant feeding in HIV + mothers


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MOTHER TO CHILD TRANSMISSIONMOTHER TO CHILD TRANSMISSION

OF HIVOF HIV--1 (MTCT)1 (MTCT)

90% of HIV/AIDS in children


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FACTORS INFLUENCING MTCTFACTORS INFLUENCING MTCT

Viral

Viral load high viral load new infection- advanced disease

stage

Viral resistance

Viral genotype, phynotype

Genital tract viral load


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Factors MTCT cont d 2Factors MTCT cont d 2

Maternal factors

Immunity - Low CD4 count

- Antibodies -Ant gp 120, Ant gp 41, Ant p24

antigen ,

Autologous neutralizing antibodies- Beta chemokine

All above may influence MTCT

Clinical stage of disease

Maternal nutrition

Behavioural factors


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Factors for MTCT cont d 3Factors for MTCT cont d 3

ObstetricsMode of delivery SVD

- Cesarean section is protective(50%)

- C/s +HAART can lower the transmission risk

during bath as low as 1%

Duration of Fetal membranes rupture

Invasive fetal monitoring and delivery procedures

Episiotomy

Disruption of fetal placenta barier (choroamnionitis, abruption

placenta and malaria infection)

ARV


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Factors for MTCT cont d 5Factors for MTCT cont d 5

Infant

Pattern of Infant feeding Prolonged breastfeeding

- Mixed breastfeeding

Condition of the breast Mastitis

- breast abscess

- Nipple cracks

GIT infection


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Factors MTCT cont 4Factors MTCT cont 4

Fetal

Prematurity immature immune system

Genotype - genetic susceptibility as expressed by

HLA genotype .

Multiple gestation


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PREVENTION OF MOTHER TO CHILDPREVENTION OF MOTHER TO CHILD

TRANSMISSION OF HIV(PMTCT)TRANSMISSION OF HIV(PMTCT)

Based on potential factors impacting perinatal HIV transmission

Several basic approaches to prevent this should be employed.

They include decreasing viral load, Decreasing viral exposure.

Identifying and treating modifiable factors.

Strategies for PMTCT

Primary prevention of HIV-1

Voluntary confidential counseling testing for HIV(VCCT)

Obstetric care

ART prophylaxis to reduce viral load

Infant feeding options

Care for the HIV infected mothers


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VCTVCT

Counseling for HIV testing

Counseling for Infant feeding option

Counseling on ARV compliance

Counseling on family planning


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Obstetric careObstetric care

Comprehensive antenatal care

- Screen for STDs and treatment including partner

- Micronutrient supplementation Iron, folate,multivit

- Prophylaxis for malaria (SP)

- Deworming (albendazole )

- Avoid invasive fetal monitoring procedures Modified intarapartum care

- Delay artificial rupture membrane until 7-8 cm dilatation

of the cervix

- Avoid traumatic instrument delivery

- vaginal cleansing with chlohexidine 0.25%- avoid unnecessary episiotomies


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Postnatal carePostnatal care

Protect against bacterial infection

Support counseling

Nutritional support

Contraception

Medical care for the mother and her Infant. Prophylaxis with

infant cotrimoxazole


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USE OF ARVsUSE OF ARVs

ARV Prophylaxis

ARV Treatment


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Infant feeding optionInfant feeding option

It is worth to note that it is insufficient to prevent transmission only

during pregnancy and birth as most of the protection achieved

is lost if the infant breast feed for a long period and this is

mainly due to BF

.When safe alternative are available BF is to be discouraged

1. Breastfeeding Exclusive BF but for a short period(4-6 month)

Exclusive replacement feeding

Wet nursing from an HIV negative mother

2. Other optionsPasteurized breast milk

Heat treated breast milk

Infant formula

Modified animal milk


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Maternal careMaternal care

Medical

screen and treat opportunistic infections both viral and

bacterial

Prophylaxis cotrimoxazole for symptomatic individuals or

those with CD4 counts less than 200cells/mm3.Adults dose is a

double strength tablets{160mgTMP +800mgSMX} once daily or twostrength tablets{80mgTMP+400mgsmx} taken twice daily.Avoid

treatment in the first and the last trimestres

- INH prophylaxis in consultation with TB

expert after excluding active disease

Nutritional Support

psychosocial support

Networking with other organizations eg legal aid and access to treatment

programs


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Maternal care cont dMaternal care cont d

Where feasible consider treatment with HAART according to

National guidelines for initiating potent ARVs which are not different for non

pregnant women

If a mother is to start triple therapy it should be differed until the second

trimester [12WKS].

If the mother is already on triple therapy and she wants to conceive she should

discussion with a physician and obstetrician on the advantages and

disadvantages on interrupting

Linking HIV infected women to treatment units.


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Use of Antiretrovirals (ARVs)Use of Antiretrovirals (ARVs)for PMTCTfor PMTCT


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Three Major Interventions thatThree Major Interventions that

are most effective in pmtctare most effective in pmtct Use of ARVS- prophylactic

- Treatment

C/S delivery

Exclusive Replacement infant feeding


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Classification of DrugsClassification of Drugs

available for HIV therapyavailable for HIV therapyNRTI NNRTI PI FI

Zidovudine (AZT) Efavirenz (EFV) Indinavir (IDV) Enfuvirtide (EStavudine (D4T) Delavirdine (DLV)Nelfinavir (NFV)

Lamivudine (3TC) Nevirapine (NVP) Saquinavir (SQV)Didanosine (ddl) Amprenavir (APV)Abacavir (ABC) Ritonavir (RTV)Zalcitabine (ddC) Lopinavir (LPV/

Emtricitabine (FTC) Atazanavir (A

NtRTI

Tenofovir (TFV)


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HIV - Life Cycle

CD4


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HIV - Life Cycle

CD4

Co-receptor(CCR5 or CXCR4)

CD4 Binding


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ARV Mechanisms Which InterruptARV Mechanisms Which Interrupt

HIV Viral ReplicationHIV Viral Replication

HIV virion

NRTIS& NNRTIS PROTEASEWORK HERE INHIBITORS

WORK HERE

VIRAL

DNA

Host DNA

PROTEAS

EHOST DNA

Reverse

Transcriptase

HIVENTERS

CD4 CELL

ACTIVE HIV

HIV

VIRION

BUDS

INACTIVEHIV

VIRAL RNA

CD4 CELL


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Potential Indications for ARVPotential Indications for ARV

in HIVin HIV Acute HIV infection

Early HIV infection

Long standing infection

AIDS

Post-Exposure Prophylaxis (PEP)

Prevention of Mother-to-child HIV transmission


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Goals of ARV therapyGoals of ARV therapy

Impossible to eradicate HIV

Primary

Significantly interrupt viral replication

Maximal & durable suppression of viral load (to


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Tools to achieve GoalsTools to achieve Goals

of ARVof ARVMaximize adherence

Rational sequencing of drugsPreserve future options

Use of resistance testing


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Selecting ARV regimen forSelecting ARV regimen for

pmtctpmtct For HIV positive pregnant women who do

not yet need treatment for their own disease

the use ofARV prophylaxis forpreventingMTCT is recommended

For HIV positive pregnant women who

need ARVs for their own disease long termARV treament should be provided


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Factors influencing choice of ARVFactors influencing choice of ARV

regimen for PMTCT programregimen for PMTCT program Cost benefits

Feasibility of existing health system to deliver the program -simple/complex regimen which might be more efficient

When VCT can be done before pregnancy/duringpregnancy /labour/postpartum

Social cultural context

Proportion of mothers attending ANC and delivering at healthyfacility

Acceptability and easy of dosage schedule

The efficacy and safety of different ARV regimens including potentialto compromise future treatment options


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ARV ProphylaxisARV Prophylaxis

Current prophylactic antiretroviral regimens for useCurrent prophylactic antiretroviral regimens for use

in pregnancy to prevent mother to childin pregnancy to prevent mother to child

transmission of HIVtransmission of HIV--11Protocol regimen Duringpregnancy

Intrapartum Postnatal

mother

Infant Breastfeed %

reduction

ACTG 076 ZDV 100mgx5

Per day

from 14

2mg/kgIV

then 1mg /kg

NIL 2mg/kgx

4 per

day for6 weeks

No 68% at 18

months

Thailand ZDV 300mgx2

Per day

from week

36

300mg every 3

hrs

NIL NO No 51% at 6

months

Ivory coast ZDV 300mgx2

per day

from 36

300mg every 3

hrs

NIL NO Yes 37% at 3

months

Long short course

(LS)ZDV

300mgBID

Starting at

week 28

300mg every 3

hrs

NIL ZDV for

3 days

No 4.7% at 18

months

Long Long

course(LL)ZDV

300mg bid

starting atweek 28

300mg every 3

hrs

NIL yes No 6.5% at 18

months


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ARV prophylaxis cont dARV prophylaxis cont d

HIV Net 012

Nevirapine

No 1DOSE No 1dose Yes 50% at 4

month

Petra A

AZT +3TC

AZT 300 mg

bd+3TC150

mg bd a day

from week 36

AZT300m

g every 3

hours

+3TC 150

mg every

12 hrs

AZT+3T

C 7days

AZT+

3TC 7

days

Yes 61%at 6 weeks(p=0.001)21%

at month

18(p=0.11)

Petra BZDV+3TC

NO AZT=3TC AZT+3TC 7

days

yes 42% at 6weeks(p=0.015)

7% at month

18(p=0.60)


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ARV prophylaxis cont dARV prophylaxis cont d

Currently in Tanzania the following ARV are used for

Prophylaxis for PMTCT on

1. AZT short course starting from 36 weeks of gestation to labor and

delivery no postnatal prophylaxis.It is used

PMTCT pilot sites.

2. Nevirapine {NVP} is now used in selected sites where some NGOs

have shown interest to implement PMTCT .

3. The government has decided to use NVP for scaling up PMTCT

activities countywide.


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ARV regimens for PMTCT used inARV regimens for PMTCT used in

TanzaniaTanzania

Different regimens for PMTCT used in

Tanzania

Single drug regimen

Multiple (combination) drug regimen


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Single drug regimenSingle drug regimen

NevirapineNevirapine This is currently the drug of choice in

Tanzania. HIV positive pregnant women

who are >28 weeks of gestation should besupplied with a nevirapine tablet and

counselled to take it at the onset of labour.

Emphasize the importance of giving thedrug to the newborn as well.


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Dosage of NevirapineDosage of Nevirapine Mother: Nevirapine tablet 200mg at the

onset of labour

Newborn: Nevirapine syrup 2mg/kgwithin 72 hour of delivery

If vomiting occurs within 30 minutes after takingthe drug, the dose should be repeated. If vomiting

occurs after more than 30 minutes, no additionaldose is required.

If the mother delivers within an hour after takingthe Nevirapine delay the infant dose for 12hours


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Dosage of NevirapineDosage of Nevirapine If the woman took the NVP and is false labour for

48 hours, supply her with another NVP tablet to be

taken on the onset of true labour When delivery occurs within 2 hrs of the mother

taking NVP the infant should receive NVP syrup

as soon as possible and another dose at 72hrs

If the mother did not receive ARV then the infant

should receive NVP immediately followed by

AZT syrup for one week or NVP at 72 hrs


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Antiretroviral therapy forAntiretroviral therapy for

Infants postparturmInfants postparturm

When counselling and testing is possible during

labour, babies born to HIV positive mothersshould be given a prophylactic dose of Nevirapine(2mg/Kg) within 72 hours of birth.or

Syrup NVP immediately followed by AZT syrup

for one week Alternatively, they can be given prophylaxis with

AZT for 6 weeks at 2mg/kg/day.


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Combined Antiretroviral DrugsCombined Antiretroviral Drugs

Dual combination :Combivir( AZT +3TC);D4T+3TC;ddI+ AZT

Triple antiretroviral Drugs (HAART) inPregnancy:

This is a more effective regimen and is the standard

of care for HIV positive pregnant women in thedeveloped world. As the price of these drugs isgoing down more women from developingcountries will access them. HAART in pregnancyis able to reduce MTCT up to 1% in non-

breastfeeding populations.


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The recommended first lineThe recommended first line

combination regimen in Tanzaniacombination regimen in Tanzania

Zidovudine, lamivudine and Nevirapine.

This regimen is simple in terms of the number ofpills and the frequency of therapy. It includes -

Zidovudine (ZDV) 300mg twice daily (NRTI)-

Lamivudine (3TC) 150mg twice daily (NRTI)-

Nevirapine 200mg twice daily NNRTI) after leading dose of 200mg/day for 2 weeks.


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Recommended 2Recommended 2ndnd

linelinecombination in Tanzania:combination in Tanzania: This include Didanosine + Stavudine (Two

NRTIs) plus:

y PI Netfinavir or y PI with low dose Ritonavir (RTV) boosting:

o Saquinavir (SQV) RTV 1000/100mg bid or

o

Lopinavir (LPV) RTV 400/100mg bid oro Indinavir (IDV) RTV 800/100mg bid.


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Changing antiretroviralChanging antiretroviral

drugs:drugs:

Antiretroviral therapy should be stopped or

changed when there is evidence of: - Toxicity or intolerance to one or all drugs

- Failure as evidenced by patient becoming

symptomatic and progressive decline ofCD4 count and/or rise of viral load despiteof antiretroviral treatment.


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When changing treatment theWhen changing treatment the

following should be observed:following should be observed:

Never change a single drug in the combination if

the cause of changing is treatment failure, but

rather change at least two of the drugs. Never change to a single drug therapy

In selecting drugs choose drugs that have not

been used before, drugs that do not have cross-

resistance, and have no overlappingtoxicities or drug-drug interaction.


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Contra IndicationsContra Indications

Antiretroviral drugs should be avoided in the followingconditions:

Terminal stage of HIV illness. Poor compliance

In the first trimester ofpregnancy, if the patient was noton ARV before.

Protease inhibitors should not be used concurrently withTB treatment when Rifampicin/Rifabutin are being used.


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Tolerability of antiretroviralTolerability of antiretroviral

drugs:drugs:

Pregnant women may experience unusual

difficulty in tolerating ARVs due to nausea andvomiting, especially during the first trimester. AllARVs should be discontinued during periods ofintolerance, and an attempt should be made toidentify the best-tolerated regimen according to

national guideline of care. Glucose intolerance iscommon during pregnancy and is also acomplication of PI-based HAART; this indicatesthe need for careful glucose monitoring.


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Potential Side effectsPotential Side effects

Zidovudne(AZT) Anemia - HB never < 7

Stavudine(d4T) Lactic acidosis

Lamivudine(3TC) Mitocondrial toxicity Abacavir(ziagen) Hypersesitivity reaction

Nevirapine (Viramune)- Skin rush

Didanosine(ddI) lactic acidosis,

neuropathy Indinavir Jaundice,Diabetes,Renal stones

lipodystrophy


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Monitoring of pregnant women onMonitoring of pregnant women on

HAART:HAART:

Monitoring of FBP, LFTs, RBG, CD4 T

lymphocyte counts should be performed as

in non-pregnant patient according tonational guidelines for clinical management

of HIV/AIDS

Iss es in PMTCTIss es in PMTCT


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Issues in PMTCTIssues in PMTCT

1.VCT counselling and Testing Personnel- Infrastructure

- funding

- beyond health facility

VCT outside health Facility

Lay counselors

Opt out vctMandatory testing of infant

2. Stigma

3. Partner involvement

4. Cultural believes and practice

5. Beyond the infant (MTCT plus= access to HAART)

=prophylaxis for OI

=Nutritional support

= treat partner and any other

member of the family

6. Development of viral resistant strains

7. Future fertility


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Case study No 1Case study No 1

Ms A.J G6 P4+1 ALL C/S L4 from

Different fathers. She is PMTCT 1 admitted

in LW as emergency due to labourpains.She is in a state of denial, is sent for

c/s. How would you handle the case


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An HIV positive pregnant woman on

HAART(ZDV+3TC+NVP) arrives at your

locality because she wants to deliver nearhome as she believes she can get assistance

from her mother. You discover her HB to be

6gm/dl. Describe steps you will take


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A pmtct1 mother is well counseled and

motivated. Labourpains start at home and

she takes the NVP tablet. On arrival in theLW she is diagnosed as false labour.

Discuss further management.


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summarysummary

Importance of ARVs forpmtct

Classification

How they work to suppress viral replication andmultiplication

Regimens-used in Tanzania

NVP details

Indications Side efects

Monitoring


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ENDEND

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hiv infection and pregnancy

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