2006/3 nadine johnson pmtct new approaches nadine johnson consultant and lecturer department of...

2006/3 Nadine Johnson

PMTCT PMTCT New ApproachesNew Approaches

Nadine JohnsonNadine JohnsonConsultant and LecturerConsultant and Lecturer

Department of Obstetrics and Department of Obstetrics and GynaecologyGynaecology

University Hospital of the West University Hospital of the West IndiesIndies


ObjectivesObjectives

Review the risk factors associated with transmission of HIV from a woman to her baby.

Discuss interventions currently being used to prevent HIV mother-to-child transmission.

Discuss the new recommended MOH regimes for prevention of mother-to-child transmission.


Kingston Kingston Paediatric and Paediatric and Perinatal HIV Perinatal HIV

/AIDS Programme/AIDS Programme(KPAIDS)(KPAIDS)

September 2002-September 2002-August 2005August 2005


Results-KPAIDS Results-KPAIDS Treatment Site N =369Treatment Site N =369


Socio-Demographic Factors

Age ( Range ) 15 – 42

Mean Age 27

Parity (Range) 0 – 9

Median Parity 2

Employed 112 (30%)

Results - KPAIDSResults - KPAIDS


Prevention of Prevention of Mother to Child Mother to Child Transmission.Transmission.

How?How?


GOALS OF ANTENATAL CAREGOALS OF ANTENATAL CARE

Standard clinical evaluation HIV disease stage

Evaluate degree of immunodeficiency CD4+ count,

Assess risk of disease progression as determined by level of plasma HIV-RNA (viral load)

Document history of prior or current ARV use Discuss known or unknown risks/benefits of therapy

during pregnancy Develop strategy for long term evaluation and

management of mother and infant


Timing of Perinatal HIV Timing of Perinatal HIV TransmissionTransmission

In utero 25%–40% In utero 25%–40% Intrapartum 60%–75% Intrapartum 60%–75% Addition risk with breastfeedingAddition risk with breastfeeding

14% 14% risk with established infection risk with established infection 29% 29% risk with primary infection risk with primary infection

Current evidence suggests most Current evidence suggests most transmission occurs during the transmission occurs during the intrapartum periodintrapartum period


Factors Influencing Perinatal Factors Influencing Perinatal TransmissionTransmission

Maternal FactorsMaternal Factors HIV-1 RNA levels (viral load [VL])HIV-1 RNA levels (viral load [VL]) Low CD4 lymphocyte countLow CD4 lymphocyte count Other infections, Hepatitis C, CMV, bacterial vaginosisOther infections, Hepatitis C, CMV, bacterial vaginosis BreastfeedingBreastfeeding

Obstetrical FactorsObstetrical Factors Length of ruptured membranes/chorioamnionitisLength of ruptured membranes/chorioamnionitis Vaginal delivery Vaginal delivery Invasive proceduresInvasive procedures

Infant FactorsInfant Factors PrematurityPrematurity


Measures to Reduce Measures to Reduce MTCTMTCT

During pregnancy: During pregnancy: Provide voluntary counseling and HIV testing Provide voluntary counseling and HIV testing

plus psychosocial supportplus psychosocial support Diagnose and provide aggressive treatment of Diagnose and provide aggressive treatment of

STDs and other infections as early as possibleSTDs and other infections as early as possible Provide basic antenatal care including:Provide basic antenatal care including:

Iron SupplementationIron Supplementation Education about MTCT and infant feeding optionsEducation about MTCT and infant feeding options ART for MTCTART for MTCT Risk reduction/safer sex measuresRisk reduction/safer sex measures



During Labor and Delivery:During Labor and Delivery: Delay rupturing of membranes (ROM)Delay rupturing of membranes (ROM) Do only minimal digital examinations Do only minimal digital examinations

after ROMafter ROM Reduce use of assisted delivery with Reduce use of assisted delivery with

forceps/ vacuumforceps/ vacuum Reduce use of episiotomy Reduce use of episiotomy Elective caesarean section has a more Elective caesarean section has a more

protective effect against MTCT than protective effect against MTCT than vaginal deliveryvaginal delivery



After Delivery:After Delivery: Avoid mechanical nasal suctionAvoid mechanical nasal suction Clean the newborn immediately of all Clean the newborn immediately of all

maternal secretions and bloodmaternal secretions and blood Advise against breast feeding Advise against breast feeding If breastfeeding is chosen as an option: If breastfeeding is chosen as an option:

encourage exclusive breastfeeding and encourage exclusive breastfeeding and advise early cessation (up to 6 months)advise early cessation (up to 6 months)


Measures to Reduce MTCTMeasures to Reduce MTCT

Today, risk of perinatal transmission Today, risk of perinatal transmission can be <2% withcan be <2% with Effective antiretroviral therapy (ART)Effective antiretroviral therapy (ART) Elective cesarean section (C/S) as Elective cesarean section (C/S) as

appropriateappropriate No breastfeedingNo breastfeeding


ARV Therapy and MTCT

Without antiretroviral (ARV) drugs during Without antiretroviral (ARV) drugs during pregnancy, mother-to-child transmission (MTCT) pregnancy, mother-to-child transmission (MTCT) has ranged from 16%–25% in North America and has ranged from 16%–25% in North America and Europe Europe

ARV therapy can produce a significant reduction ARV therapy can produce a significant reduction in mother to child transmission of HIV in mother to child transmission of HIV PACTG 076 (1994)PACTG 076 (1994) showed that administration of AZT to showed that administration of AZT to

womenwomen from 14from 14thth week of pregnancy week of pregnancy during labourduring labour to the newborn to the newborn

Decreased the risk of MTCT by nearly 70% in the Decreased the risk of MTCT by nearly 70% in the absence of breastfeeding absence of breastfeeding


ZDV Perinatal Transmission ZDV Perinatal Transmission Prophylaxis Regimen: ACTG 076 Prophylaxis Regimen: ACTG 076

TrialTrial

Decreased Transmission From 25% to 8%Decreased Transmission From 25% to 8%

AntepartAntepartumum

Initiation at 14–34 weeks gestation and Initiation at 14–34 weeks gestation and continued throughout pregnancycontinued throughout pregnancy

PACTG 076 regimen: ZDV 5 times dailyPACTG 076 regimen: ZDV 5 times dailyAcceptable alternative regimen: ZDV 2 Acceptable alternative regimen: ZDV 2 or 3 times daily (depending on dose)or 3 times daily (depending on dose)

IntrapartIntrapartumum

During labor, ZDV IV over 1 hour, During labor, ZDV IV over 1 hour, followed by a continuous infusion of IV followed by a continuous infusion of IV until deliveryuntil delivery

PostpartPostpartumum

Oral administration of ZDV to newborn Oral administration of ZDV to newborn for first 6 weeks of life, beginning at 8–for first 6 weeks of life, beginning at 8–12 hours after birth12 hours after birth


Mechanism of Action - Mechanism of Action -

ZidovudineZidovudine Slight reduction in viral load

accounts for only 17 % of reduction in HIV transmission.

Reduces the concentration of HIV within cervico-vaginal secretions.

Unlike other HIV medications, ZDV becomes fully active within the placenta.


SHORT COURSE ZDV SHORT COURSE ZDV PROPHYLAXIS REGIMENS PROPHYLAXIS REGIMENS

Regimens were designed and Regimens were designed and evaluated in clinical trials in evaluated in clinical trials in resource-limited countries.resource-limited countries.

Following Following Results of PACTG 076 Results of PACTG 076 Data suggesting Data suggesting

most transmission occurs during delivery most transmission occurs during delivery in utero transmission predominantly occurs in utero transmission predominantly occurs

during the last two months of pregnancy during the last two months of pregnancy


HIVNET 012HIVNET 012 Single dose Single dose intrapartum/newborn intrapartum/newborn

NevirapineNevirapine Non-nucleoside reverse transcriptase

inhibitor Reduce risk of transmission by 47%Reduce risk of transmission by 47% Protocol is the most commonly used in Protocol is the most commonly used in

low –resource settings because of itslow –resource settings because of its demonstrated efficacy in clinical trials in reducing demonstrated efficacy in clinical trials in reducing

MTCTMTCT low costlow cost ease of use in MTCT programs ease of use in MTCT programs


HIVNET 012HIVNET 012

Short-course ARV regimens, that do not Short-course ARV regimens, that do not fully suppress viral replication, may be fully suppress viral replication, may be associated with the development of associated with the development of ARV drug resistanceARV drug resistance 19% of the women developed resistance 19% of the women developed resistance

postpartum. postpartum. Associated with HIV viral load and CD4 cell Associated with HIV viral load and CD4 cell

countcount at delivery at delivery Detectable transient nevirapine resistance Detectable transient nevirapine resistance

mutations were also observed at 6 - 8 mutations were also observed at 6 - 8 weeks of age in 46% of infants who became weeks of age in 46% of infants who became infected despite NVP prophylaxis infected despite NVP prophylaxis


Intrapartum exposure to Intrapartum exposure to nevirapine and subsequent nevirapine and subsequent

maternal responses to maternal responses to nevirapine-based antiretroviral nevirapine-based antiretroviral

therapy.therapy. Jourdain GJourdain G, , et alet al Perinatal HIV Prevention Perinatal HIV Prevention

Trial GroupTrial Group. . Department of Immunology and Infectious Department of Immunology and Infectious

Diseases, Harvard School of Public Health, Diseases, Harvard School of Public Health, Boston, Boston,

CONCLUSIONCONCLUSION Women who received intrapartum nevirapine Women who received intrapartum nevirapine

were less likely to have virologic suppression were less likely to have virologic suppression after 6 months of postpartum treatment with after 6 months of postpartum treatment with a nevirapine-containing regimena nevirapine-containing regimen..


? Zidovudine Resistance? Zidovudine Resistance

Data from PACTG 076 indicate that Data from PACTG 076 indicate that a transient course of ZDV a transient course of ZDV monotherapy during pregnancy monotherapy during pregnancy appears safe and unlikely to induce appears safe and unlikely to induce resistance in a relatively healthy resistance in a relatively healthy population of infected women. population of infected women.

Time-limited use of ZDV prophylaxis Time-limited use of ZDV prophylaxis alone during pregnancy would be alone during pregnancy would be appropriateappropriate


? Role of Highly ? Role of Highly Active Antiretroviral Active Antiretroviral

Therapy (HAART) Therapy (HAART) /Triple Therapy/Triple Therapy

2NRTI + NNRTI2NRTI + NNRTIoror

2 NRTI + PI 2 NRTI + PI


The Role of HAART Women and Infants Transmission Study (WITS)

1990 Collaborative, multi-site, longitudinal, natural history

study of U.S. women with human immunodeficiency virus (HIV) infection and their offspring.

Confirmed rate of MTCT of HIV correlates with the maternal-serum HIV viral load at delivery:

Higher maternal viral load, greater chance of HIV transmission. HAART effectively lower patients viral load and

thus further reduce mother-to-child transmission 1.2 % transmission rate Very low transmission if viral load is <1000 Very low transmission if viral load is <1000

copies/ml copies/ml However, no definite viral-load threshold below

which mother-to-child transmission of HIV will not occur.


STARTSTART Short-term antiretroviral therapyShort-term antiretroviral therapy Standard HAART regimens commencing in the 2nd Standard HAART regimens commencing in the 2nd

trimester with the intention to achieve undetectable trimester with the intention to achieve undetectable viral loads of <50 copies per ml prior to deliveryviral loads of <50 copies per ml prior to delivery. .

Protease-inhibitor based combination is recommended. Protease-inhibitor based combination is recommended. PIs have a greater barrier to resistance development than PIs have a greater barrier to resistance development than

NNRTIs and can be stopped concurrently with the nucleoside NNRTIs and can be stopped concurrently with the nucleoside backbone. backbone.

PI pill burden and tolerance is improving with newer PI pill burden and tolerance is improving with newer formulationsformulations

Low incidence of severe short-term side-effects. Low incidence of severe short-term side-effects. If non-nucleosides are used, these must be discontinued If non-nucleosides are used, these must be discontinued

1-2 weeks prior to the nucleoside backbone to reduce 1-2 weeks prior to the nucleoside backbone to reduce the likelihood of the emergence of resistance the likelihood of the emergence of resistance


Thai Perinatal HIV Thai Perinatal HIV Prevention Trial (PHPT-Prevention Trial (PHPT-

2),Thailand 2),Thailand Antenatal: ZDV from 28 weeks. Antenatal: ZDV from 28 weeks.

Intrapartum: ZDV alone or ZDV plus Intrapartum: ZDV alone or ZDV plus single-dose NVP at onset of laboursingle-dose NVP at onset of labour

Postpartum ZDV for one week with or Postpartum ZDV for one week with or without single-dose NVP (infant)without single-dose NVP (infant)

Vertical transmission rate of 1.9%Vertical transmission rate of 1.9% with addition of single dose Nevirapine with addition of single dose Nevirapine to mother and infant.to mother and infant.

Currently WHO recommended Currently WHO recommended regime for low –resource settingsregime for low –resource settings


Persistence of nevirapine Persistence of nevirapine exposure during the postpartum exposure during the postpartum period after intrapartum single-period after intrapartum single-dose nevirapine in addition to dose nevirapine in addition to zidovudine prophylaxis for the zidovudine prophylaxis for the prevention of mother-to-child prevention of mother-to-child

transmission of HIV-1.transmission of HIV-1. Cressey TR et al. Cressey TR et al. J Acquir Immune Defic SyndrJ Acquir Immune Defic Syndr

20052005 CONCLUSIONS: Significant NVP concentrations CONCLUSIONS: Significant NVP concentrations

remained for up to 20 days in these Thai women. remained for up to 20 days in these Thai women. To ensure that coverage is maintained until NVP To ensure that coverage is maintained until NVP

concentrations fall to non-suppressive levels, 1 concentrations fall to non-suppressive levels, 1 month of additional antiretroviral treatment month of additional antiretroviral treatment after delivery should be considered to prevent after delivery should be considered to prevent the emergence of resistant viruses. the emergence of resistant viruses.


Not Just PMTCT

Many pregnant women infected with HIV will also be candidates for treatment of their own HIV infection.

Appropriate antiretroviral treatment of HIV must be provided to women who require it, irrespective of the decision to provide antiretroviral agents for prophylaxis.


Jamaican Jamaican GuidelinesGuidelines

Ministry of HealthMinistry of Health

AdaptationAdaptation


Criteria for Triple ARV Criteria for Triple ARV TherapyTherapy

All women with clinical AIDS All women with clinical AIDS

Women with a CD4 count of Women with a CD4 count of ≤ ≤ 200/mm200/mm33

Women with CD4 levels 200 - Women with CD4 levels 200 - 350/mm350/mm33, , Doctor should assess when to start Doctor should assess when to start

therapy, by looking at the presence of therapy, by looking at the presence of clinical featuresclinical features


Women diagnosed in Women diagnosed in pregnancypregnancy

CD 4 count < 200/mmCD 4 count < 200/mm33

Require antiretrovirals for own health Require antiretrovirals for own health Should begin regime compatible with the PMTCT Should begin regime compatible with the PMTCT

regime.regime. Women in the first trimester may consider delaying Women in the first trimester may consider delaying

initiation of ARTinitiation of ART Consider severity of maternal HIV disease and potential benefits

and risks of delaying ART until after first trimester For women who are severely ill, the benefit of early For women who are severely ill, the benefit of early

initiation may outweigh theoretical risk to fetusinitiation may outweigh theoretical risk to fetus

If If do notdo not require ARV’s for own health then offer require ARV’s for own health then offer PMTCT prophylaxisPMTCT prophylaxis


Option A - Option A - CD4 Counts CD4 Counts ≥≥ 350 350

Offer PMTCT prophylaxisOffer PMTCT prophylaxis MotherMother StartStart

ZDV 300 mg bid at 28 weeks gestation (or as ZDV 300 mg bid at 28 weeks gestation (or as soon as possible thereafter)soon as possible thereafter)

From onset of labour until delivery;-From onset of labour until delivery;- ZDV 300 mg PO every 3 hours ZDV 300 mg PO every 3 hours PLUSPLUS Single dose Nevirapine at onset of labour.Single dose Nevirapine at onset of labour.

Do not continue 3-hourly AZT dosing for Do not continue 3-hourly AZT dosing for longer than 24 hours.longer than 24 hours.

Continue AZT for one week after delivery.Continue AZT for one week after delivery.


Option A - Option A - CD4 Counts CD4 Counts ≥≥ 350 350

To Infants AZTTo Infants AZT ZDV 4 mg/kg (0.4 ml/kg) p.o every 12 ZDV 4 mg/kg (0.4 ml/kg) p.o every 12

hours for one weekhours for one week And a single dose of 2mg/kg of And a single dose of 2mg/kg of

NevirapineNevirapine suspension at birth suspension at birth Premature (<34 wk EGA) infant dosage: Premature (<34 wk EGA) infant dosage:

2 mg/kg Po q 12 hr for 2 weeks then 3 2 mg/kg Po q 12 hr for 2 weeks then 3 mg/kg Po q 12 hr for four weeksmg/kg Po q 12 hr for four weeks


Option B - Option B - CD4 levels 200 - CD4 levels 200 - 350/mm3350/mm3

Remember this is a special category Remember this is a special category of patient.of patient.

Asymptomatic - give PMTCT Asymptomatic - give PMTCT prophylaxisprophylaxis

Symptomatic, then patient requires Symptomatic, then patient requires HAART therapy.HAART therapy.

NOTE WELL - NEVIRAPINE must NOTE WELL - NEVIRAPINE must not be used for HAART in women not be used for HAART in women with CD4 count >/250with CD4 count >/250mm3mm3


Option C - Late PresentationOption C - Late Presentation

After 38 weeks or during labourAfter 38 weeks or during labour has not received AZThas not received AZT

Mother Mother Single dose 200 mg of Single dose 200 mg of NevirapineNevirapine

tablet at onset of labour. tablet at onset of labour.


Option COption C

Newborn infant Newborn infant 1.1. AZT for 1 weekAZT for 1 week2.2. NevirapineNevirapine suspension 2mg/kg suspension 2mg/kg

• within 72 hours after birth but within 72 hours after birth but preferably within 24 hours preferably within 24 hours

If AZT unavailable and Mother received If AZT unavailable and Mother received Nevirapine Nevirapine << 2 hours before delivery 2 hours before delivery

2 doses of Nevirapine 24 hours apart within 2 doses of Nevirapine 24 hours apart within 72 hours after birth . 72 hours after birth .


Option D - CD4 count < 200 Option D - CD4 count < 200

Commence ARV triple therapy at end of Commence ARV triple therapy at end of first trimesterfirst trimester

Zidovudine/Lamivudine Zidovudine/Lamivudine plus (plus (Nelfinavir/ Nelfinavir/ Kaletra or Nevirapine ) Kaletra or Nevirapine )

Continues meds intra-partumContinues meds intra-partum To InfantsTo Infants

ZDV 4 mg/kg (0.4 ml/kg) Po every 12 hours for ZDV 4 mg/kg (0.4 ml/kg) Po every 12 hours for one weekone week

And a single dose of 2mg/kg of And a single dose of 2mg/kg of NevirapineNevirapine suspension at birth. suspension at birth.


UNKNOWN HIV STATUS AT UNKNOWN HIV STATUS AT TIME OF LABOURTIME OF LABOUR

All opportunity for intervention is All opportunity for intervention is not lostnot lost

Diagnosis at the time of labour and Diagnosis at the time of labour and delivery is still important point of delivery is still important point of entry for both preventive and entry for both preventive and treatment servicestreatment services


UNKNOWN HIV STATUS AT TIME UNKNOWN HIV STATUS AT TIME OF LABOUROF LABOUR

Counselling and rapid testing during Counselling and rapid testing during labourlabour

Women testing positive Women testing positive Offer maternal single dose nevirapine Offer maternal single dose nevirapine

prophylaxisprophylaxis AZT to infant x 6 weeks. AZT to infant x 6 weeks.

Imminent deliveryImminent delivery Omit maternal dose Omit maternal dose AZT to infant for 6 weeks ( ideally)AZT to infant for 6 weeks ( ideally) or or Administer infant nevirapine dose as soon as Administer infant nevirapine dose as soon as

possible after birth. possible after birth. Already DeliveredAlready Delivered

Offer counselling and rapid testing shortly Offer counselling and rapid testing shortly after delivery after delivery

Mother positiveMother positive Postpartum AZT x 6 weeks to the infantPostpartum AZT x 6 weeks to the infant


As access to ARV treatment As access to ARV treatment becomes more widely becomes more widely

available available

women not only live longer, women not only live longer, but take advantage of their but take advantage of their

reproductive potential.reproductive potential.

Two further Clinical Two further Clinical ScenariosScenarios


HIV-INFECTED WOMEN on HIV-INFECTED WOMEN on ARV’s WHO BECOME ARV’s WHO BECOME

PREGNANTPREGNANT

Existing concerns relating to potential Existing concerns relating to potential effects of ARV drugs on the developing effects of ARV drugs on the developing fetusfetus

Suspending treatment during the first Suspending treatment during the first trimester not recommendedtrimester not recommended

Avoid EFV in first trimesterAvoid EFV in first trimester Replace with NFV or Lopinovir/r, NVP, Replace with NFV or Lopinovir/r, NVP,

because of a possible risk of CNS birth because of a possible risk of CNS birth defects.defects.


HIV-INFECTED WOMEN on HIV-INFECTED WOMEN on ARV’s WHO BECOME ARV’s WHO BECOME

PREGNANTPREGNANT Nausea and vomiting cNausea and vomiting common in early pregnancyommon in early pregnancy Weeks 6 and 16 Weeks 6 and 16 Continue 2nd and 3rd trimester in ~ 20 %Continue 2nd and 3rd trimester in ~ 20 % Incidence may be increased in women taking ART Incidence may be increased in women taking ART May affect adherence and occasionally require May affect adherence and occasionally require

temporary discontinuation.temporary discontinuation. If treatment discontinued, stop all ARV drugs If treatment discontinued, stop all ARV drugs

simultaneously and restart together to decrease simultaneously and restart together to decrease risk of developing drug resistancerisk of developing drug resistance..

Continue ARV treatment with the full regimen Continue ARV treatment with the full regimen during labour.during labour.

Infant AZT for 1 week Infant AZT for 1 week


HIV-INFECTED WOMEN WITHHIV-INFECTED WOMEN WITHINDICATIONS FOR INITIATING ARV’SINDICATIONS FOR INITIATING ARV’S

WHO MAY BECOME PREGNANTWHO MAY BECOME PREGNANT

Choice of ARV regimen for women with Choice of ARV regimen for women with potential to become pregnant must potential to become pregnant must consider consider Possibility that drugs may be received during Possibility that drugs may be received during

the first trimester:the first trimester: During the period of organogenesisDuring the period of organogenesis Before pregnancy recognized Before pregnancy recognized

EfavirenzEfavirenz Potentially teratogenic Potentially teratogenic Avoid if effective contraception cannot be ensuredAvoid if effective contraception cannot be ensured


HIV-INFECTED WOMEN WITHHIV-INFECTED WOMEN WITHINDICATIONS FOR INITIATING ARV’SINDICATIONS FOR INITIATING ARV’S

WHO MAY BECOME PREGNANTWHO MAY BECOME PREGNANT

Recommended first - line ARV Recommended first - line ARV regimens regimens

1.1. ZDV +3TC ZDV +3TC +(NVP/Nelfinavir/Kaletra)+(NVP/Nelfinavir/Kaletra)

2.2. d4T +3TC d4T +3TC +(NVP/Nelfinavir/Kaletra)+(NVP/Nelfinavir/Kaletra)


Nucleoside/Nucleotide Reverse Nucleoside/Nucleotide Reverse Transcriptase Inhibitors Transcriptase Inhibitors

(NRTIs(NRTIs)) NRTIs associated NRTIs associated

withwith lactic acidosis lactic acidosis hepatic steatosis hepatic steatosis body fat body fat

redistribution redistribution (lipodystrophy(lipodystrophy


Agent Adverse Events CommentsZidovudine Anemia,

neutropenia Fatigue, malaise,

headache Nausea, vomiting Myalgia, myopathy Hyperpigmentation

of skin and nails

Twice-daily dosing preferred over thrice-daily dosing.

Fatigue, nausea, headache, and myalgia usually resolve 2-4 weeks after initiation.

Adjust dosage for renal insufficiency or failure.

Lamivudune Headache, dry mouth

Adverse effects occur infrequently.

Adjust dosage for renal insufficiency or failure.

Active against hepatitis B virus. In patients with HIV and hepatitis B coinfection, hepatitis may flare upon discontinuation of lamivudine.

Stavudine Peripheral neuropathy

Pancreatitis

Diarrhea

Of the NRTIs, stavudine has greatest risk of lipodystrophy and other mitochondrial toxicity.

Increased risk of lactic acidosis and hepatic steatosis when combined with didanosine;

Avoid combination in pregnant women.


Nonnucleoside Reverse Nonnucleoside Reverse Transcriptase Inhibitors Transcriptase Inhibitors

(NNRTIs)(NNRTIs)

All NNRTIs may have significant All NNRTIs may have significant interactions with other drugs; interactions with other drugs; dosage adjustment of interacting dosage adjustment of interacting agents may be requiredagents may be required


Agent Adverse events Comments

Nevirapine Rash, Stevens-Johnson

syndrome, Toxic epidermal

necrolysis

Elevations in liver function tests, hepatitis, liver failure

• Initial dose of 200 mg per day for first 14 days, then 200 mg twice daily, decreases frequency of rash.

Most rash develops within first 6 weeks of therapy

Hepatotoxicity may be life threatening.

More common at higher CD4 cell counts

Patients with hepatitis B or C.

Nevirapine should not be initiated in women with CD4 >250 cells/µL

Monitor liver tests closely for the first 16 weeks of treatment.


Protease InhibitorsProtease Inhibitors All PIs are associated with metabolic All PIs are associated with metabolic

abnormalitiesabnormalities dyslipidemia, dyslipidemia, hyperglycemia, hyperglycemia, insulin resistance, insulin resistance, and lipodystrophy. and lipodystrophy.

Need to screen for Gestational Need to screen for Gestational Diabetes Diabetes

May increase the risk of bleeding in May increase the risk of bleeding in hemophiliacs and hemophiliacs and

May have significant interactions with May have significant interactions with other drugs other drugs dosage adjustments may be required.dosage adjustments may be required.


Agent Adverse Events Comments

Lopinavir/ritonavir

Diarrhea, nausea, vomiting

Dyslipidemia Elevations in liver

function tests Taste perversion

• Avoid combining oral solution with metronidazole or disulfiram.

• Alcohol in the oral solution may cause disulfiram-like reaction.

Nelfinavir Diarrhea Nausea, vomiting Elevations in liver

function tests

Avoid combining oral solution with metronidazole or disulfiram.

Alcohol in the oral solution may cause disulfiram-like reaction.


Monitoring during Monitoring during Pregnancy Pregnancy

Similar to non-pregnant individuals Similar to non-pregnant individuals Closer monitoring may be warranted Closer monitoring may be warranted

in women receiving combination in women receiving combination antiretroviral therapy. antiretroviral therapy.

Measurement of CD4 cell count and HIV Measurement of CD4 cell count and HIV RNA levels approximately 3-4 monthsRNA levels approximately 3-4 months

Potential side effects of antiretroviral Potential side effects of antiretroviral administration.administration.


Laboratory Evaluation Laboratory Evaluation

Routine pregnancy screen including:Routine pregnancy screen including: CBC (Hb, WBC, diff, plat.);CBC (Hb, WBC, diff, plat.); VDRL, RPRVDRL, RPR UrinalysisUrinalysis CD4 CountCD4 Count HBsAg HBsAg Renal Function tests (urea, Renal Function tests (urea,

creatinine, electrolytes and creatinine, electrolytes and urinalysis)urinalysis)


Laboratory EvaluationLaboratory Evaluation LFTs, serum proteins, Alb, Glob. on LFTs, serum proteins, Alb, Glob. on

initiating treatmentinitiating treatment Serum lipidsSerum lipids Glucose, OSTGlucose, OST CXRCXR Pap smearPap smear Viral LoadViral Load


Monitoring during Monitoring during PregnancyPregnancy

FetusFetus Assessment of fetal anatomy with a Assessment of fetal anatomy with a

level II ultrasound in the second level II ultrasound in the second trimestertrimester

Assessment of fetal growth and well-Assessment of fetal growth and well-being during the third trimester. being during the third trimester.


Opportunistic Infection Opportunistic Infection ProphylaxisProphylaxis

Routine HIV-1 care should include institution of Routine HIV-1 care should include institution of OI prophylaxis when indicatedOI prophylaxis when indicated Pneumocystis carinii Pneumocystis carinii pneumonia pneumonia CD4 < 200.CD4 < 200.

1 Double strength Bactrim o.d1 Double strength Bactrim o.d Folate antagonist Folate antagonist First trimester exposure associated with an increased First trimester exposure associated with an increased

frequency of cardiac, neural tube and renal tract frequency of cardiac, neural tube and renal tract malformations. malformations.

Supplementation negates riskSupplementation negates risk Mycobacterium avium intracellulareMycobacterium avium intracellulare CD 4 < 50CD 4 < 50

Azithromycin 1200mg weeklyAzithromycin 1200mg weekly Herpes simplex virusHerpes simplex virus Mycobacterium tuberculosisMycobacterium tuberculosis Toxoplasma if IgG positive and Toxoplasma if IgG positive and CD4 <100CD4 <100

1 Double strength Bactrim o.d1 Double strength Bactrim o.d


Women who become Women who become unwell during pregnancyunwell during pregnancy

Signs and symptoms of pre-eclampsia, Signs and symptoms of pre-eclampsia, obstetric cholestasis or other liver obstetric cholestasis or other liver dysfunction may have a pregnancy related dysfunction may have a pregnancy related problemproblem

Consideration should be given to the Consideration should be given to the adverse effects of the ART. adverse effects of the ART.

Vomiting and malaise should be Vomiting and malaise should be investigated for acidosis, hepatitis and investigated for acidosis, hepatitis and pancreatitis. pancreatitis.

If there is a lactic acidosis consideration If there is a lactic acidosis consideration should be given to discontinuing the ARTshould be given to discontinuing the ART


RememberRemember

Many HIV-1-infected pregnant women Many HIV-1-infected pregnant women are diagnosed during the pregnancy.are diagnosed during the pregnancy.

Adherence to therapy can be difficult Adherence to therapy can be difficult due to due to multiple physical and emotional stresses multiple physical and emotional stresses compounded by the diagnosis of HIV-1 compounded by the diagnosis of HIV-1

infection. infection.


Adherence to ARTAdherence to ART

Vital importance for the success of Vital importance for the success of therapytherapy

Pregnant women may need extra support Pregnant women may need extra support and planning in this area, especially if and planning in this area, especially if there are practical or psychosocial issues there are practical or psychosocial issues that may impact adversely on adherence. that may impact adversely on adherence.

Referral to peer support workers, Referral to peer support workers, psychology support and telephone psychology support and telephone contact may all be considered.contact may all be considered.


Maternal toxicity and pregnancy Maternal toxicity and pregnancy complications in human complications in human

immunodeficiency virus-infected women immunodeficiency virus-infected women receiving antiretroviral therapy: PACTG receiving antiretroviral therapy: PACTG

316316 Am J Obstet Gynecol. 2004 Feb;190(2):506-16 Am J Obstet Gynecol. 2004 Feb;190(2):506-16 Watts et alWatts et al OBJECTIVE: evaluate rates of maternal toxicity, pregnancy OBJECTIVE: evaluate rates of maternal toxicity, pregnancy

complications, and peripartum morbidity by type and complications, and peripartum morbidity by type and duration of antiretroviral therapy (ART) during pregnancy. duration of antiretroviral therapy (ART) during pregnancy.

RESULTS:RESULTS: 1,407 were included: 288 mono Rx late, 34 mono Rx early, 327 1,407 were included: 288 mono Rx late, 34 mono Rx early, 327

combo, no PI late, 175 combo, no PI early, 320 combo, PI late, combo, no PI late, 175 combo, no PI early, 320 combo, PI late, and 263 combo, PI early. and 263 combo, PI early.

Symptoms and laboratory abnormalities of moderate grade or Symptoms and laboratory abnormalities of moderate grade or more occurred in less than 5% of women. more occurred in less than 5% of women.

Only gestational diabetes (highest in combo PI early) varied Only gestational diabetes (highest in combo PI early) varied significantly by therapy group.significantly by therapy group.

CONCLUSION: In HIV-infected women receiving prenatal CONCLUSION: In HIV-infected women receiving prenatal care and ART, adverse events were uncommon.care and ART, adverse events were uncommon.


ResultsResultsAntiretroviral TherapyAntiretroviral Therapy


PMTCT Plus - Beyond PMTCT Plus - Beyond PMTCTPMTCT

It is now well recognized that HIV affects It is now well recognized that HIV affects the whole family.the whole family.

Our ultimate and ideal goal should thus Our ultimate and ideal goal should thus be adaptation of a family centred model of be adaptation of a family centred model of care. care.

Beyond prevention of mother to child Beyond prevention of mother to child transmission transmission

Emphasis on continued multidisciplinary Emphasis on continued multidisciplinary care of women, children and partners care of women, children and partners after pregnancyafter pregnancy


Thank You !Thank You !

2006/3 nadine johnson pmtct new approaches nadine johnson consultant and lecturer department of...

Documents

nadine johnson factors

risk factors

nadine johnson measures

transmission of hiv

nadine johnson objectives

infant slide

hiv mother

intrapartum period slide