U.S. Public Health Service Perinatal Guidelines This slide set is based on the Centers for Disease Control and Prevention. U.S. Public Health Service Task Force’s Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV-1 Transmission in the United States, April 2009. The most current version of the guidelines is available online at www.aidsinfo.nih.gov Recommendations for the Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women for Maternal Health and to Reduce Perinatal HIV-1 Transmission in the United States April 2009 April 2009: AETC National Resource Center

About This Presentation U.S. Public Health Service Perinatal Guidelines About This Presentation These slides were developed using the April 2009 guidelines. The intended audience is clinicians involved in the care of patients with HIV infection. Users are cautioned that, because of the rapidly changing field of HIV care, this information could become out of date quickly. Finally, it is intended that these slides be used as prepared, without changes in either content or attribution. Users are asked to honor this intent. – AETC National Resource Center http://www.aidsetc.org 2 April 2009 www.aidsetc.org April 2009: AETC National Resource Center April 2009: AETC National Resource Center

U.S. Public Health Service Perinatal Guidelines Table of Contents Topic Lessons from Clinical Trials Preconception Counseling and Care Management of Pregnant Women with HIV-Infected Male Partner Antepartum Management Intrapartum Management Postpartum Management Neonatal Postnatal Care Slide Number 6 11 14 16 53 60 64 April 2009 www.aidsetc.org April 2009: AETC National Resource Center

U.S. Public Health Service Perinatal Guidelines Introduction U.S. recommendations have evolved over 25 years With universal prenatal HIV counseling and testing, ARV prophylaxis, scheduled cesarean section delivery, and avoidance of breast-feeding, perinatal HIV infection has diminished to <2% in the United States The guidelines and slides update the July 8, 2008, recommendations The most recent information is available from the AIDSinfo website: http://aidsinfo.nih.gov April 2009 www.aidsetc.org April 2009: AETC National Resource Center

New Information Includes: U.S. Public Health Service Perinatal Guidelines 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) April 2009 www.aidsetc.org April 2009: AETC National Resource Center 5

U.S. Public Health Service Perinatal Guidelines Lessons from Clinical Trials of ARV Interventions to Reduce Perinatal HIV Transmission April 2009: AETC National Resource Center

ARVs: Mechanisms of Action U.S. Public Health Service Perinatal Guidelines ARVs: Mechanisms of Action ARVs reduce perinatal transmission by several mechanisms: Decreasing maternal viral load Preexposure and postexposure infant prophylaxis Combined antepartum, intrapartum, and infant ARV prophylaxis is recommended Please refer to the Perinatal Guidelines pgs. 4-5 April 2009 www.aidsetc.org April 2009: AETC National Resource Center

International Studies: Short-Course Regimens to Prevent Transmission U.S. Public Health Service Perinatal Guidelines International Studies: Short-Course Regimens to Prevent Transmission Combination ARV regimens are more effective than 1-drug therapy Longer duration of antepartum ARV prophylaxis is more effective than shorter duration Should start prophylaxis at least by 28 weeks If no maternal antepartum therapy, administer ARVs during labor and delivery, and to the infant Less effective than if antepartum ARVs also given Please refer to the Perinatal Guidelines pgs. 4-7 April 2009 www.aidsetc.org April 2009: AETC National Resource Center

U.S. Public Health Service Perinatal Guidelines International Studies: Short-Course Regimens to Prevent Transmission (2) If no maternal therapy, give postnatal infant ARV prophylaxis with a minimum of ZDV for 6 weeks In the United States: Adding single-dose NVP to standard combination antepartum ARV therapy is not recommended No additional efficacy; may cause NVP resistance Breast-feeding is not recommended for HIV-infected women (including those receiving suppressive combination ART) Safe, affordable, and feasible alternatives are available and culturally acceptable Please refer to the Perinatal Guidelines pgs. 4-7 April 2009 www.aidsetc.org April 2009: AETC National Resource Center

Transmission and Maternal HIV RNA U.S. Public Health Service Perinatal Guidelines 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 Please refer to the Perinatal Guidelines pgs. 4-7 10 10 April 2009 www.aidsetc.org April 2009: AETC National Resource Center

U.S. Public Health Service Perinatal Guidelines Preconception Counseling and Care for HIV-Infected Women of Childbearing Age April 2009: AETC National Resource Center

U.S. Public Health Service Perinatal Guidelines 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 Please refer to the Perinatal Guidelines pgs. 14-15 April 2009 www.aidsetc.org April 2009: AETC National Resource Center

U.S. Public Health Service Perinatal Guidelines 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) Please refer to the Perinatal Guidelines pgs. 14-15 April 2009 www.aidsetc.org April 2009: AETC National Resource Center

Management of the Pregnant Woman with an HIV-Infected Male Partner April 2009: AETC National Resource Center

Pregnant Woman with an HIV-Infected Male Partner U.S. Public Health Service Perinatal Guidelines 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 Please refer to the Perinatal Guidelines pg. 15 April 2009 www.aidsetc.org April 2009: AETC National Resource Center

Antepartum Care for HIV-Infected Women U.S. Public Health Service Perinatal Guidelines Antepartum Care for HIV-Infected Women April 2009: AETC National Resource Center

Use of ARVs during Pregnancy: General Principles U.S. Public Health Service Perinatal Guidelines 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 Please refer to the Perinatal Guidelines pgs. 16-17 April 2009 www.aidsetc.org April 2009: AETC National Resource Center

U.S. Public Health Service Perinatal Guidelines 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 Please refer to the Perinatal Guidelines pgs. 16-17 April 2009 www.aidsetc.org April 2009: AETC National Resource Center

HIV-Infected Pregnant Women Currently on ART U.S. Public Health Service Perinatal Guidelines 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 Please refer to the Perinatal Guidelines pgs. 18-19 April 2009 www.aidsetc.org April 2009: AETC National Resource Center

U.S. Public Health Service Perinatal Guidelines 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 Please refer to the Perinatal Guidelines pgs. 18-20 April 2009 www.aidsetc.org April 2009: AETC National Resource Center

U.S. Public Health Service Perinatal Guidelines 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 Please refer to the Perinatal Guidelines pgs. 19-20 April 2009 www.aidsetc.org April 2009: AETC National Resource Center

Women Not Currently on ARVs with History of Prophylaxis or Treatment U.S. Public Health Service Perinatal Guidelines 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 Please refer to the Perinatal Guidelines pgs. 17-18 April 2009 www.aidsetc.org April 2009: AETC National Resource Center

Special Considerations for ARV Use by Pregnant Women and Infants U.S. Public Health Service Perinatal Guidelines 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 Please refer to the Perinatal Guidelines pgs. 42-44 April 2009 www.aidsetc.org April 2009: AETC National Resource Center

Special Considerations for ARV Use (2) U.S. Public Health Service Perinatal Guidelines 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 Please refer to the Perinatal Guidelines pgs. 42-44 April 2009 www.aidsetc.org April 2009: AETC National Resource Center

Special Considerations for ARV Use (3) U.S. Public Health Service Perinatal Guidelines 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 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 3rd trimester; assess often for new symptoms Please refer to the Perinatal Guidelines pgs. 42-44 April 2009 www.aidsetc.org April 2009: AETC National Resource Center

U.S. Public Health Service Perinatal Guidelines Types of ARV Regimens NNRTI based (1 NNRTI + 2 NRTI backbone) PI based (1 or 2 PIs + 2 NRTI backbone) NRTI based (3 NRTIs: inferior virologic efficacy; consider if NNRTI- or PI-based regimen is not appropriate) April 2009 www.aidsetc.org April 2009: AETC National Resource Center

Current ARV Medications NRTI Abacavir (ABC) Didanosine (ddI) Emtricitabine (FTC) Lamivudine (3TC) Stavudine (d4T) Tenofovir (TDF) Zidovudine (AZT, ZDV) NNRTI Efavirenz (EFV) Delavirdine (DLV) Etravirine (ETR) Nevirapine (NVP) PI Atazanavir (ATV) Darunavir (DRV) Fosamprenavir (FPV) Indinavir (IDV) Lopinavir (LPV) Nelfinavir (NFV) Ritonavir (RTV) Saquinavir (SQV) Tipranavir (TPV) Entry Inhibitor Enfuvirtide (ENF, T-20) Maraviroc (MVC) Integrase Inhibitor Raltegravir (RAL) April 2009 www.aidsetc.org April 2009: AETC National Resource Center

Components of ART: Working Group Categories U.S. Public Health Service Perinatal Guidelines Components of ART: Working Group Categories Recommended Alternative Use in Special Circumstances Insufficient Data to Recommend Use Not Recommended Please refer to Table 3 of the guidelines. Table 3 provides recommendations about use of specific antiretroviral drugs in pregnancy as well as data on pharmacokinetics and toxicity in pregnancy. April 2009 www.aidsetc.org April 2009: AETC National Resource Center

ARV Recommendations: NRTIs U.S. Public Health Service Perinatal Guidelines ARV Recommendations: NRTIs Class concerns for NRTIs: lactic acidosis, mitochondrial toxicity Recommended Concerns in Pregnancy 3TC Extensive studies in pregnancy ZDV Alternative ABC Risk of hypersensitivity reaction; test for HLA-B*5701 before starting; do not use if positive for HLA-B*5701 ddI Lactic acidosis, sometimes fatal, with ddI + d4T FTC Slightly lower levels in 3rd trimester; no clear need to increase dosage d4T Same as ddI Please refer to Table 3 of the Perinatal Guidelines (pg.26-27) April 2009 www.aidsetc.org April 2009: AETC National Resource Center

ARV Recommendations: NRTIs (2) U.S. Public Health Service Perinatal Guidelines ARV Recommendations: NRTIs (2) Class concerns for NRTIs: lactic acidosis, mitochondrial toxicity Use in Special Circumstances Concerns in Pregnancy TDF Limited studies in pregnant women; concern for possible fetal bone effects; monitor for renal toxicity during pregnancy Please refer to the Perinatal Guidelines pg. 26-27 April 2009 www.aidsetc.org April 2009: AETC National Resource Center

ARV Recommendations: NNRTIs U.S. Public Health Service Perinatal Guidelines ARV Recommendations: NNRTIs Class concerns for NNRTIs: rash, hypersensitivity, hepatic toxicity Recommended Concerns in Pregnancy NVP Increased risk of potentially fatal liver toxicity if initiated at CD4 counts of >250/µL Use in Special Circumstances EFV FDA pregnancy class D; case reports of neural tube defects in humans with 1st trimester exposure Can be considered after 1st trimester If continued postpartum, ensure adequate contraception (concerns include drug interactions with hormonal contraceptives; risk of teratogenicity in fetus if woman becomes pregnant while taking EFV) Please refer to the Perinatal Guidelines pg. 27-28 April 2009 www.aidsetc.org April 2009: AETC National Resource Center

ARV Recommendations: NNRTIs (2) U.S. Public Health Service Perinatal Guidelines ARV Recommendations: NNRTIs (2) Class concerns for NNRTIs: rash, hypersensitivity, hepatic toxicity Insufficient Data to Recommend Use Concerns in Pregnancy ETR Insufficient data Not Recommended DLV Teratogenic in animals Please refer to the Perinatal Guidelines pg. 28 April 2009 www.aidsetc.org April 2009: AETC National Resource Center 32

ARV Recommendations: PIs U.S. Public Health Service Perinatal Guidelines ARV Recommendations: PIs Class concerns for PIs: hyperglycemia, diabetes, question of increased risk of preterm delivery Recommended Concerns in Pregnancy LPV/r* Optimal dosing of tablet formulation during pregnancy is uncertain Alternative ATV/r* Optimal dosing during pregnancy is uncertain IDV/r* May exacerbate hyperbilirubinemia in neonate NFV May require increased dosage in 3rd trimester SQV/r* Limited data on hard-gel and tablet formulations Please refer to the Perinatal Guidelines pgs. 28-30 * r = low-dose ritonavir April 2009 www.aidsetc.org April 2009: AETC National Resource Center

ARV Recommendations: PIs (2) U.S. Public Health Service Perinatal Guidelines ARV Recommendations: PIs (2) Insufficient Data to Recommend Use Concerns in Pregnancy DRV/r* No experience in pregnancy FPV/r* Limited experience in pregnancy TPV/r* Please refer to the Perinatal Guidelines pg. 30 * r = low-dose ritonavir April 2009 www.aidsetc.org April 2009: AETC National Resource Center

ARV Recommendations: Entry Inhibitors U.S. Public Health Service Perinatal Guidelines ARV Recommendations: Entry Inhibitors Insufficient Data to Recommend Use Concerns in Pregnancy ENF Minimal data in pregnancy MVC No experience in pregnancy Please refer to the Perinatal Guidelines pg. 30 April 2009 www.aidsetc.org April 2009: AETC National Resource Center

ARV Recommendations: Integrase Inhibitors U.S. Public Health Service Perinatal Guidelines ARV Recommendations: Integrase Inhibitors Insufficient Data to Recommend Use Concerns in Pregnancy RAL No experience in pregnancy Please refer to the Perinatal Guidelines pg. 31 36 36 April 2009 www.aidsetc.org April 2009: AETC National Resource Center

U.S. Public Health Service Perinatal Guidelines HIV/HBV Coinfection Screen for HBsAg Interferons not recommended during pregnancy If chronic HBV/HIV, and treatment required for either, use 3-drug regimen Include TDF + 3TC or FTC in ARV regimen Entecavir should not be used without fully suppressive anti-HIV ARV regimen (risk of ARV resistance) Please refer to the Perinatal Guidelines pgs. 36-37 April 2009 www.aidsetc.org April 2009: AETC National Resource Center

HIV/HBV Coinfection (2) U.S. Public Health Service Perinatal Guidelines HIV/HBV Coinfection (2) Postpartum, if treatment of HBV but not HIV indicated, consult with expert Risk of HBV flare with discontinuation of HBV-active ARVs Options include: Stop ARVs and start pegylated interferon-alfa Continue the 3-drug ARV regimen Please refer to the Perinatal Guidelines pgs. 36-37 April 2009 www.aidsetc.org April 2009: AETC National Resource Center

HIV/HBV Coinfection (3) U.S. Public Health Service Perinatal Guidelines HIV/HBV Coinfection (3) If HBV/HIV coinfected and treatment not required for either, consult with expert Options include: Antepartum 3-drug regimen including TDF + 3TC or FTC; discontinue postpartum (monitor closely for HBV flare) Antepartum 3-drug regimen without TDF + 3TC or FTC; discontinue postpartum Please refer to the Perinatal Guidelines pgs. 36-37 April 2009 www.aidsetc.org April 2009: AETC National Resource Center

HIV/HBV Coinfection (4) U.S. Public Health Service Perinatal Guidelines HIV/HBV Coinfection (4) Check transaminase levels 2 weeks after ARV initiation, at least monthly thereafter Infants: give HBIG and begin HBV vaccination series within 12 hours of birth Please refer to the Perinatal Guidelines pgs. 36-37 April 2009 www.aidsetc.org April 2009: AETC National Resource Center

U.S. Public Health Service Perinatal Guidelines HIV/HCV Coinfection Screen for HCV Interferons not recommended during pregnancy Ribavirin contraindicated during pregnancy (teratogenic) Coinfection increases risk of perinatal HCV transmission, and perhaps of HIV transmission Consider combination ART for all HCV/HIV pregnant women Please refer to the Perinatal Guidelines pgs. 37-38 April 2009 www.aidsetc.org April 2009: AETC National Resource Center

HIV/HCV Coinfection (2) U.S. Public Health Service Perinatal Guidelines HIV/HCV Coinfection (2) Check transaminase levels 2 weeks after ART initiation, at least monthly thereafter Mode of delivery based on considerations related to HIV infection alone Evaluate infants by HCV RNA testing (at 2-6 months) and/or HCV antibody testing (after age 15 months) Please refer to the Perinatal Guidelines pgs. 37-38 April 2009 www.aidsetc.org April 2009: AETC National Resource Center

Stopping ART during Pregnancy U.S. Public Health Service Perinatal Guidelines 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 Please refer to the Perinatal Guidelines pg. 38 April 2009 www.aidsetc.org April 2009: AETC National Resource Center

Failure of Viral Suppression U.S. Public Health Service Perinatal Guidelines 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 Please refer to the Perinatal Guidelines pg. 39 April 2009 www.aidsetc.org April 2009: AETC National Resource Center

Monitoring Woman and Fetus U.S. Public Health Service Perinatal Guidelines 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 34-36 weeks for decision on mode of delivery Please refer to the Perinatal Guidelines pgs. 41-42 April 2009 www.aidsetc.org April 2009: AETC National Resource Center

Monitoring Woman and Fetus (2) U.S. Public Health Service Perinatal Guidelines 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 Please refer to the Perinatal Guidelines pgs. 41-42 April 2009 www.aidsetc.org April 2009: AETC National Resource Center

ART and Pregnancy Outcome U.S. Public Health Service Perinatal Guidelines ART and Pregnancy Outcome Conflicting data: Are ARVs associated with adverse outcomes, especially preterm delivery? – Most U.S. data do not demonstrate increased risk Conflicting data: Does in utero ARV exposure cause mitochondrial dysfunction in neonates? – If so, appears to occur very rarely HIV-infected women should receive combination ART according to current guidelines Please refer to the Perinatal Guidelines pgs. 44-48 April 2009 www.aidsetc.org April 2009: AETC National Resource Center

ARV Resistance in Pregnancy U.S. Public Health Service Perinatal Guidelines ARV Resistance in Pregnancy Resistance to ARVs may: Decrease efficacy of perinatal prophylaxis Limit future maternal treatment options Limit treatment options in infected infants Please refer to the Perinatal Guidelines pgs. 50-52 April 2009 www.aidsetc.org April 2009: AETC National Resource Center

ARV Resistance Testing during Pregnancy U.S. Public Health Service Perinatal Guidelines ARV Resistance Testing during Pregnancy Recommended for: Women not currently on ARVs – before starting treatment or prophylaxis Women experiencing virologic failure or suboptimal VL suppression To maximize prevention of perinatal transmission, empiric ART can be started before test results are available, with adjustments made after results are known Please refer to the Perinatal Guidelines pgs. 50-52 April 2009 www.aidsetc.org April 2009: AETC National Resource Center

Management of ARV Resistance during Pregnancy U.S. Public Health Service Perinatal Guidelines Management of ARV Resistance during Pregnancy Women with ZDV resistance should still receive IV ZDV during labor, along with their ARV regimen Their infants should receive oral ZDV for 6 weeks Often, only wild-type virus is transmitted ZDV crosses placenta readily, with high levels in fetus Reduces genital HIV VL Consult pediatric HIV specialist Discontinue d4T in women taking ZDV Please refer to the Perinatal Guidelines pgs. 54-55 April 2009 www.aidsetc.org April 2009: AETC National Resource Center

Incidence of Resistance with Prophylactic Regimens U.S. Public Health Service Perinatal Guidelines 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 Please refer to the Perinatal Guidelines pg. 52 April 2009 www.aidsetc.org April 2009: AETC National Resource Center

Prevention of ARV Drug Resistance U.S. Public Health Service Perinatal Guidelines 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 Please refer to the Perinatal Guidelines pg. 55 April 2009 www.aidsetc.org April 2009: AETC National Resource Center

Intrapartum Care for HIV-Infected Women U.S. Public Health Service Perinatal Guidelines Intrapartum Care for HIV-Infected Women April 2009: AETC National Resource Center

Intrapartum ARV Therapy/Prophylaxis U.S. Public Health Service Perinatal Guidelines 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 Please refer to the Perinatal Guidelines pgs. 59-61 April 2009 www.aidsetc.org April 2009: AETC National Resource Center

Intrapartum ARV Therapy/Prophylaxis (2) U.S. Public Health Service Perinatal Guidelines 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 Please refer to the Perinatal Guidelines pgs. 59-61 April 2009 www.aidsetc.org April 2009: AETC National Resource Center

Intrapartum ARV Therapy/Prophylaxis (3) U.S. Public Health Service Perinatal Guidelines 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 Please refer to the Perinatal Guidelines pgs. 59-61 April 2009 www.aidsetc.org April 2009: AETC National Resource Center

HIV Transmission and Cesarean Delivery U.S. Public Health Service Perinatal Guidelines 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 Please refer to the Perinatal Guidelines pgs. 65-66 April 2009 www.aidsetc.org April 2009: AETC National Resource Center

Maternal Risks by Mode of Delivery U.S. Public Health Service Perinatal Guidelines 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 Please refer to the Perinatal Guidelines pgs. 66-67 April 2009 www.aidsetc.org April 2009: AETC National Resource Center

Other Intrapartum Management Issues U.S. Public Health Service Perinatal Guidelines 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 Please refer to the Perinatal Guidelines pg. 70 April 2009 www.aidsetc.org April 2009: AETC National Resource Center

Postpartum Management for HIV-Infected Women U.S. Public Health Service Perinatal Guidelines Postpartum Management for HIV-Infected Women April 2009: AETC National Resource Center

U.S. Public Health Service Perinatal Guidelines 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 Please refer to the Perinatal Guidelines pgs. 71-73 April 2009 www.aidsetc.org April 2009: AETC National Resource Center

Postpartum Follow-Up (2) U.S. Public Health Service Perinatal Guidelines 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) Please refer to the Perinatal Guidelines pgs. 71-73 April 2009 www.aidsetc.org April 2009: AETC National Resource Center

Postpartum Follow-Up (3) U.S. Public Health Service Perinatal Guidelines 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 Please refer to the Perinatal Guidelines pgs. 71-73 April 2009 www.aidsetc.org April 2009: AETC National Resource Center

Neonatal Postnatal Care U.S. Public Health Service Perinatal Guidelines Neonatal Postnatal Care April 2009: AETC National Resource Center

Infants Born to Mothers with Unknown HIV Infection Status U.S. Public Health Service Perinatal Guidelines 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 Please refer to the Perinatal Guidelines pgs. 75-80 April 2009 www.aidsetc.org April 2009: AETC National Resource Center

Infant ARV Prophylaxis U.S. Public Health Service Perinatal Guidelines 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 Please refer to the Perinatal Guidelines pgs. 75-80 April 2009 www.aidsetc.org April 2009: AETC National Resource Center

Infant ARV Prophylaxis (2) U.S. Public Health Service Perinatal Guidelines 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 Please refer to the Perinatal Guidelines pgs. 75-80 April 2009 www.aidsetc.org April 2009: AETC National Resource Center

Infant ARV Prophylaxis (3) U.S. Public Health Service Perinatal Guidelines 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 Please refer to the Perinatal Guidelines pgs. 75-80 April 2009 www.aidsetc.org April 2009: AETC National Resource Center

Initial Management of the HIV-Exposed Neonate U.S. Public Health Service Perinatal Guidelines Initial Management of the HIV-Exposed Neonate 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 Please refer to the Perinatal Guidelines pgs. 80-81 April 2009 www.aidsetc.org April 2009: AETC National Resource Center

Initial Management of the HIV-Exposed Neonate (2) U.S. Public Health Service Perinatal Guidelines 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 14-21 days, 1-2 months, and 4-6 months Some experts test at birth Please refer to the Perinatal Guidelines pg. 80-81 April 2009 www.aidsetc.org April 2009: AETC National Resource Center

Long-Term Follow-Up of ARV-Exposed Infants U.S. Public Health Service Perinatal Guidelines 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 Please refer to the Perinatal Guidelines pg. 82 April 2009 www.aidsetc.org April 2009: AETC National Resource Center

Guidelines Information U.S. Public Health Service Perinatal Guidelines Guidelines Information U.S. Public Health Service Perinatal Guidelines Working Group meets monthly, reviews clinical trials results, and updates the guidelines The published text is posted on www.aidsinfo.nih.gov April 2009 www.aidsetc.org April 2009: AETC National Resource Center

U.S. Public Health Service Perinatal Guidelines About This Slide Set This presentation was prepared by Susa Coffey, MD; Rebecca Fry, MSN, APN; Elaine Gross, RN, MS; Supriya Modey, MPH, MBBS; for the AETC National Resource Center in July 2008, and revised in April 2009 See the AETC National Resource Center website for the most current version of this presentation: http://www.aidsetc.org April 2009 www.aidsetc.org April 2009: AETC National Resource Center