Perinatal Update

It Takes An Island! Public Health Prevention programs Screening Diagnosis Contact tracing Linkage to care Case management Psychosocial services STD screening/treatment Clinical Care Medical evaluation OB evaluation HIV OI prevention/treatment ARV treatment Nutrition Counseling Education (pt and family) Psychosocial support Adherence/retention Palliative care Policy Makers Leadership Resource appropriation Coordination/administration Communication Stigma reduction Community Psychosocial support Family support and respite Funding Community education Stigma reduction Spiritual care Best Outcome

April 2009www.aidsetc.org3 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 and Care for HIV-Infected Women of Childbearing Age

Recommendations 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 April 2009www.aidsetc.org5

Recommendations (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) April 2009www.aidsetc.org6

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

Pregnant Woman with an HIV-Infected Male Partner Test for HIV (unless patient declines) ◦ 2nd HIV test in 3rd trimester, before 36 weeks if possible If patient presents in labor: rapid HIV test If 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 April 2009www.aidsetc.org8

Antepartum Care for HIV-Infected Women

Transmission and Maternal HIV RNA 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 April 2009www.aidsetc.org10

Use of ARVs during Pregnancy: General Principles 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 of ARVs during pregnancy April 2009www.aidsetc.org11

General Principles (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 April 2009www.aidsetc.org12

HIV-Infected Pregnant Women Currently on ART 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 April 2009www.aidsetc.org13

ARV 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 April 2009www.aidsetc.org14

ARV Naive (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 April 2009www.aidsetc.org15

Women Not Currently on ARVs with History of Prophylaxis 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 April 2009www.aidsetc.org16

Special Considerations for ARV Use by Pregnant Women and Infants Pregnancy 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 April 2009www.aidsetc.org17

Special Considerations for ARV Use (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 April 2009www.aidsetc.org18

Special Considerations for ARV Use (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 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 3rd trimester; assess often for new symptoms April 2009www.aidsetc.org19

Stopping ART during Pregnancy Avoid interruption of ART, if possible If discontinuation required, stop and reinitiate all drugs at the same time, except: ◦ If on NNRTI, if possible stop NNRTI first, continue others for 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 April 2009www.aidsetc.org20

Failure of Viral Suppression 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 April 2009www.aidsetc.org21

Monitoring Woman and Fetus 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 weeks for decision on mode of delivery April 2009www.aidsetc.org22

Monitoring Woman and Fetus (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 on combination ARVs (especially EFV) during 1st trimester April 2009www.aidsetc.org23

ARV Resistance in Pregnancy Resistance to ARVs may: ◦ Decrease efficacy of perinatal prophylaxis ◦ Limit future maternal treatment options ◦ Limit treatment options in infected infants April 2009www.aidsetc.org24

Incidence of Resistance with Prophylactic Regimens Single-dose NVP added to an ongoing ART regimen not recommended ◦ No additional efficacy ◦ May result in NVP drug resistance April 2009www.aidsetc.org25

Prevention of ARV Drug Resistance Select ARVs according to ART history and resistance test results Maximally suppress viral replication Counsel patient about adherence If 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 April 2009www.aidsetc.org26

Intrapartum Care for HIV-Infected Women

Intrapartum ARV Therapy/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 April 2009www.aidsetc.org28

Intrapartum ARV Therapy/Prophylaxis (2) If no antepartum ARV therapy to mother, administer IV 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 April 2009www.aidsetc.org29

Intrapartum ARV Therapy/Prophylaxis (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 April 2009www.aidsetc.org30

HIV Transmission and Cesarean Delivery 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 membranes or 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 April 2009www.aidsetc.org31

Maternal Risks by Mode of Delivery 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 April 2009www.aidsetc.org32

Other Intrapartum Management 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 April 2009www.aidsetc.org33

Postpartum Management for HIV-Infected Women

Postpartum Follow- 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 April 2009www.aidsetc.org35

Postpartum Follow-Up (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) April 2009www.aidsetc.org36

Postpartum Follow-Up (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 April 2009www.aidsetc.org37

Neonatal Postnatal Care

Infants Born to Mothers with Unknown HIV Infection Status 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 April 2009www.aidsetc.org39

Infant ARV Prophylaxis 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; consult with pediatric HIV specialist April 2009www.aidsetc.org40

Infant ARV Prophylaxis (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 April 2009www.aidsetc.org41

Infant ARV Prophylaxis (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 April 2009www.aidsetc.org42

Initial Management of the HIV-ExposedNeonate 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 to combination 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 April 2009www.aidsetc.org43

Initial Management of the HIV-Exposed Neonate (2) Begin PCP prophylaxis (TMP-SMX) at 6 weeks, after completion of ZDV regimen, unless HIV has been ruled out Diagnosis of HIV infection in neonates: virologic tests (HIV DNA or RNA) ◦ Age days, ◦ 1-2 months, and ◦ 4-6 months ◦ Some experts test at birth April 2009www.aidsetc.org44

Long-Term Follow-Up of ARV-Exposed Infants Children with significant organ system abnormalities of unknown etiology: evaluate for mitochondrial dysfunction 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 gynecologic evaluation with Pap tests April 2009www.aidsetc.org45

Infant Feeding Infant Feeding

It Takes An Island! Public Health Prevention programs Screening Diagnosis Contact tracing Linkage to care Case management Psychosocial services STD screening/treatment Clinical Care Medical evaluation OB evaluation HIV OI prevention/treatment ARV treatment Nutrition Counseling Education (pt and family) Psychosocial support Adherence/retention Palliative care Policy Makers Leadership Resource appropriation Coordination/administration Communication Stigma reduction Community Psychosocial support Family support and respite Funding Community education Stigma reduction Spiritual care Best Outcome