perinatal update. it takes an island! public health prevention programs screening diagnosis contact...

Perinatal UpdatePerinatal Update

It Takes An Island!It Takes An Island!

April 2009 www.aidsetc.org 3

New Information New Information

Includes: Lessons Learned from Clinical Trials of ARV

Interventions to Reduce Perinatal HIV Transmission

Neonatal Postnatal Care

ARV Drug Use in Pregnant HIV-Infected Women (see Tables 1, 2, and 3 in the Perinatal Guidelines)

Safety and Toxicity of ARV Agents in Pregnancy Supplement (see Perinatal Guidelines)

New Ratings for Recommendations (see Perinatal Guidelines)

Preconception Counseling Preconception Counseling andandCare for HIV-Infected Care for HIV-Infected WomenWomenof Childbearing Ageof Childbearing Age

RecommendatiRecommendationsons

Contraception counseling to avoid unintended pregnancy is an essential part of care

Counsel on safe sexual practices, eliminating alcohol, illicit drug use, and smoking

Educate about risk factors for perinatal HIV transmission and strategies for reducing them

Encourage testing and counseling of partners

Counsel on reproductive options that prevent HIV exposure to uninfected partner


RecommendatioRecommendations ns (2)(2)

For women of childbearing potential, consider effectiveness of ARVs as well as teratogenic effects

◦ In women who intend to become pregnant, avoid EFV

Attain a stable, maximally suppressed VL prior to conception

Breast-feeding is not recommended in the United States (risk of HIV transmission via breast milk)


Management of the Pregnant Woman with an HIV-Infected Male Partner

Pregnant Woman with Pregnant Woman with an an HIV-Infected Male HIV-Infected Male PartnerPartnerTest for HIV (unless patient declines)

◦ 2nd HIV test in 3rd trimester, before 36 weeks if possible

If patient presents in labor: rapid HIV testIf seroconversion is suspected, do HIV

RNA and antibody test; repeat test in 4-6 weeks◦ If positive: initiate interventions to reduce

perinatal transmission risk

◦ If negative: counsel to reduce risk of transmission from partner


Antepartum Care Antepartum Care for HIV-Infected for HIV-Infected WomenWomen

Transmission and Maternal HIV Transmission and Maternal HIV RNARNA

Risk of perinatal transmission greater with higher maternal HIV RNA viral load (VL)

However, perinatal transmission can occur even at undetectable maternal VL

◦ Plasma VL may not accurately predict transmission risk

◦ VL level should not be a determining factor in deciding whether to start ART for perinatal prophylaxis

ARV prophylaxis to prevent perinatal transmission

is recommended for all HIV-infected women


Use of ARVs during Use of ARVs during Pregnancy: General Pregnancy: General PrinciplesPrinciples

Initial evaluation should include:◦Assessment of HIV disease status

◦Recommendations on ART or assessment of current ARV regimen

Recommend ARV therapy/prophylaxis to ALL pregnant HIV-infected women

Discuss known benefits and potential risks ofARVs during pregnancy


General PrinciplesGeneral Principles (2)(2)

If HIV RNA is detectable, do resistance testing before starting/modifying therapy

Individualize ART

Emphasize the importance of adherence to treatment and prophylaxis

Assure coordination of comprehensive services


HIV-Infected Pregnant HIV-Infected Pregnant Women Currently on Women Currently on ARTART

Continue ART, if possible; avoid treatment interruption

Avoid EFV in the 1st trimester: switch to an alternative ARV, if possible

Order ARV resistance tests if detectable viremia

If on NVP with suppressed VL and tolerating it, continue NVP

Include ZDV in regimen, unless contraindicated


ARV NaiveARV Naive If patient meets criteria for initiation of ART, start

standard potent combination therapy◦ For a patient who requires ART for her own health,

start as soon as possible, including in 1st trimester

◦ Consult data on specific ARVs in pregnancy

If patient does not require treatment for her own health: 3-drug combination ARV regimen for perinatal prophylaxis ◦ May delay until after 1st trimester

◦ ZDV monotherapy for prophylaxis not recommended, but may be considered if VL <1,000 copies/mL


ARV Naive ARV Naive (2)(2)

Perform resistance testing before selection of ARVs

Include ZDV in ARV regimen when feasible

NVP: can be initiated for pregnant women with CD4 counts of <250 cells/µL

◦ If CD4 cell count is >250 cells/µL, initiate NVP only if benefit outweighs risk (increased risk of hepatic toxicity)

Avoid EFV in 1st trimester


Women Not Currently on Women Not Currently on ARVs with History of ARVs with History of Prophylaxis or TreatmentProphylaxis or Treatment

Obtain history of prior ARV regimens and results of resistance testing

Perform drug resistance testing before starting ARVs ◦ Results may not be accurate; interpret with caution

Select ARVs based on ARV history and resistance testing; monitor virologic response closely◦ Avoid drugs that may harm the fetus or mother (eg,

EFV, d4T + ddI)If poor virologic response, repeat resistance

testing and consult experts


Special Considerations for Special Considerations for ARV UseARV Useby Pregnant Women and by Pregnant Women and InfantsInfantsPregnancy may alter ARV absorption,

distribution, and metabolism

◦ARV dosing and toxicity risk may be affected

Some PIs may require altered dosing

Limited data to guide treatment in pregnant women

Report all cases of ARV drug exposure to Antiretroviral Pregnancy Registry


Special Considerations for Special Considerations for ARV Use ARV Use (2)(2)

Potential adverse effects during pregnancy:◦EFV: Avoid during 1st trimester of

pregnancy; possible risk of neural tube defects

◦TDF: Concern for possible fetal bone effects; monitor for renal toxicity in pregnancy

◦Combination of d4T + ddI: increased risk of lactic acidosis and hepatic steatosis


Special ConsiderationsSpecial Considerations for for ARV Use ARV Use (3)(3)

◦Use with caution during pregnancy: NVP: Increased risk of hepatotoxicity; do not initiate in women with CD4 counts of >250 cells/µL unless benefits clearly outweigh risks

◦Screen for hyperglycemia: Standard glucose loading test at 24-28 weeks Consider earlier screening if on chronic PI-based therapy

◦Risk of lactic acidosis/hepatic steatosis owing to NRTIs: Monitor hepatic enzymes, electrolytes monthly in 3rdtrimester; assess often for new symptoms


Stopping ART during Stopping ART during PregnancyPregnancy

Avoid interruption of ART, if possibleIf discontinuation required, stop and reinitiate

all drugs at the same time, except:

◦ If on NNRTI, if possible stop NNRTI first, continue othersfor approximately 7 days NNRTIs have long half-life; optimal interval between stopping

NNRTI and other ARV drugs not known

If restarting NVP after interruption of >2 weeks,restart with standard 2-week dosage escalation


Failure of Viral Failure of Viral SuppressionSuppression

Assess resistance, adherence, dosing, and problems with absorption

Consider modification of ARV regimen

Consult with an expert

Scheduled cesarean delivery recommended if HIV RNA >1,000 copies/mL near time of delivery


Monitoring Woman and Monitoring Woman and FetusFetus

Monitor CD4 cell count at initial visit and every 3 months thereafter

Monitor plasma HIV RNA levels to assess rapid and sustained lowering

◦ At initial visit◦ 2-6 weeks after starting/changing ARV regimen◦ Monthly until RNA levels undetectable◦ Every 2 months during pregnancy◦ At 34-36 weeks for decision on mode of delivery


Monitoring Woman and Monitoring Woman and FetusFetus (2)(2)

◦Perform resistance testing for women with suboptimal VL suppression or rebound

◦Monitor for ARV drug complications

◦Ultrasound recommendations:

1st trimester – confirmation of gestational age and potential timing for cesarean delivery, if needed

2nd trimester – assess fetal anatomy for women oncombination ARVs (especially EFV) during 1st trimester


ARV Resistance in ARV Resistance in PregnancyPregnancy

Resistance to ARVs may:

◦Decrease efficacy of perinatal prophylaxis

◦Limit future maternal treatment options

◦Limit treatment options in infected infants


Incidence of Incidence of Resistance with Resistance with Prophylactic Prophylactic RegimensRegimensSingle-dose NVP added to an ongoing

ART regimen not recommended

◦ No additional efficacy

◦ May result in NVP drug resistance


Prevention of ARV Drug Prevention of ARV Drug ResistanceResistance

Select ARVs according to ART history and resistancetest results

Maximally suppress viral replication Counsel patient about adherenceIf stopping NVP / NNRTI-containing regimen,

consider continuing NRTIs for 7 days after stopping NNRTI ◦ NNRTIs have very long half-lives

◦ Need to “cover” period of persisting NNRTI exposure

◦ Optimal time to continue NRTIs is not known


Intrapartum Care Intrapartum Care for HIV-Infected for HIV-Infected WomenWomen

Intrapartum ARV Intrapartum ARV Therapy/ProphylaxisTherapy/Prophylaxis

IV ZDV recommended for all HIV-positive women during labor

◦ Continue other ARVs orally on schedule, as possible

◦ When administering ZDV, discontinue d4T

If suboptimal VL suppression on ARV, single-dose intrapartum maternal + infant NVP not recommended

◦ Cesarean delivery if VL >1,000 copies/mL


Intrapartum ARV Intrapartum ARV Therapy/Prophylaxis Therapy/Prophylaxis (2)(2)

If no antepartum ARV therapy to mother, administerIV ZDV during labor and continue 6 weeks of infant ZDV

Unknown whether additional ARVs during labor and to neonate further reduces perinatal transmission

◦Some would add single-dose intrapartum maternal + infant NVP, with oral 3TC to mother + 7 days of ZDV/3TC to mother


Intrapartum ARV Intrapartum ARV Therapy/Prophylaxis Therapy/Prophylaxis (3)(3)

If woman’s HIV status unknown, administer rapid HIV antibody test

If test result is positive, give IV ZDV and initiate infant ZDV

Confirmatory HIV test done postpartum

If positive, give infant 6 weeks of ZDV

If negative, stop infant ZDV


HIV Transmission and Cesarean HIV Transmission and Cesarean DeliveryDelivery

Schedule at 38 weeks to reduce risk of transmission:

◦ For women with HIV RNA levels >1,000 copies/mL(whether on ARVs or not) near time of delivery

◦ For women with unknown HIV RNA levels◦ Benefits of C/S not clear after rupture of

membranesor onset of labor: base decision on clinical factors

Benefits of C/S unclear for women with HIV RNA levels <1,000 copies/mL

◦ Scheduled C/S may not further reduce risk of transmission


Maternal Risks by Mode of Maternal Risks by Mode of DeliveryDelivery

Counsel women about potential risks and benefits of cesarean vs vaginal delivery

C/S associated with greater risk of complications ◦ Compared with vaginal delivery in HIV-infected women

◦ Compared with C/S in HIV-uninfected women

◦ Scheduled C/S less risky than emergent C/S

Complications do not outweigh benefits of reduced HIV transmission for those at increased risk

Prophylactic narrow spectrum antibiotic generally recommended at time of C/S


Other Intrapartum Other Intrapartum Management IssuesManagement Issues

Avoid artificial rupture of membranes or invasive monitoring unless obstetrically indicated and duration is expected to be short

Use forceps or vacuum extractor only in select circumstances

Avoid use of Methergine for postpartum hemorrhage in women receiving PIs, EFV, or DLV ◦ Risk of exaggerated vasoconstrictive response

◦ Use if no other alternative, at low dosage and for short duration


Postpartum Postpartum Management Management for HIV-Infected Womenfor HIV-Infected Women

Postpartum Postpartum Follow-UpFollow-Up Coordinate medical services between obstetric

and HIV specialists

ART:

◦ Continuing or stopping depends on CD4 nadir, clinical symptoms, disease stage, and other factors

◦ If nadir CD4 <350 cells/µL or symptomatic, encourage continuing the regimen

◦ If started ART with nadir of CD4 >350 cells/µL, consult the provider on whether to continue therapy

◦ If no indication for therapy, stop ARVs after delivery

Adherence may be challenging in postpartum period


Postpartum Follow-Postpartum Follow-Up Up (2)(2)

Women with positive rapid HIV test result in labor ◦ Confirmation of HIV infection

◦ Counseling and comprehensive medical assessment

◦ Assessment of need for ART

◦ Supportive services to be assured prior to discharge

Breast-feeding not recommended (risk of HIV transmission via breast milk)


Postpartum Follow-Postpartum Follow-UpUp (3)(3)

Contraceptive counseling is critical

◦ Condom use important for prevention of HIV and STD transmission

◦ Unintended pregnancy rate is high with condom use alone

◦ Drug interactions between oral contraceptives and many PIs and NNRTIs

◦ For women who are certain they do not wish future childbearing: thorough counseling and discussion about permanent contraceptive methods


Neonatal Postnatal Neonatal Postnatal CareCare

Infants Born to Mothers with Infants Born to Mothers with Unknown HIV Infection Unknown HIV Infection StatusStatus

Rapid HIV antibody testing of mother or infant recommended◦ If positive:

Initiate ARV prophylaxis for infant immediately Perform confirmatory test (eg, Western blot) Positive infant antibody test cannot distinguish

maternal from infant infection – requires HIV virologic test

If confirmatory test is negative (in mother or infant), discontinue ARV prophylaxis


Infant ARV Infant ARV ProphylaxisProphylaxis

6-week ZDV chemoprophylaxis advised for all HIV-exposed neonates

◦Should be initiated within 6-12 hours of delivery

◦ If concerns about adherence or toxicity, may consider reducing infant prophylaxis from 6 to 4 weeks

◦Dosage is different for premature infants; consultwith pediatric HIV specialist


Infant ARV Infant ARV ProphylaxisProphylaxis (2)(2)

Combination therapy: ZDV + additional ARVs

◦Additional efficacy in prevention of infant infection not proven

◦Consult with a pediatric HIV specialist if considering additional ARVs in situations of increased transmission risk


Infant ARV Infant ARV ProphylaxisProphylaxis (3)(3)

Use of additional drugs will depend on: ◦ Maternal HIV RNA level near delivery

◦ Mode of delivery

◦ Gestational age at delivery

◦ Availability of drug formulation

◦ Dosing information for neonates (known for few ARVs)

Risks of toxicity in neonates are unclear◦ Limited data on most ARVs


Initial Management Initial Management of the HIV-of the HIV-ExposedNeonateExposedNeonate

Monitoring ARV effects◦CBC and differential before starting ZDV

Follow-up of hematologic monitoring varies by baseline results, clinical factors

If hematologic abnormalities identified, consult pediatric HIV specialist

◦LFTs may be required for infants exposed tocombination ARV therapy in utero or after birth

◦Serum lactate: recommended if infant develops severe clinical symptoms of unknown etiology If severely abnormal (>5 mmol/L), discontinue ARV prophylaxis

and consult pediatric HIV specialist


Initial Management Initial Management of the of the HIV-Exposed HIV-Exposed Neonate Neonate (2)(2)

Begin PCP prophylaxis (TMP-SMX) at 6 weeks,after completion of ZDV regimen, unless HIVhas been ruled out

Diagnosis of HIV infection in neonates: virologictests (HIV DNA or RNA)◦ Age 14-21 days,◦ 1-2 months, and◦ 4-6 months◦ Some experts test at birth


Long-Term Long-Term Follow-Up of Follow-Up of ARV-Exposed ARV-Exposed InfantsInfantsChildren with significant organ system

abnormalities of unknown etiology: evaluate for mitochondrialdysfunction

Other possible early and late effects of in utero ARV exposure are not fully known

Follow-up should continue into adulthood

◦ Should include yearly physical examination

◦ For adolescent females, should include gynecologicevaluation with Pap tests


Infant FeedingInfant Feeding

It Takes An Island!It Takes An Island!

perinatal update. it takes an island! public health prevention programs screening diagnosis contact...

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