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AETC NRC Slide Set

Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV Transmission in the United States.

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AETC NRC Slide Set

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  1. Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV Transmission in the United States HHS Panel on the Treatment of HIV-infected Pregnant Women and Prevention of Perinatal Transmission – A Working Group of the Office of AIDS Research Advisory Council AETC NRC Slide Set

  2. About This Presentation • These slides were developed from the March 28, 2014,revisions to the guidelines. • The goal of the guidelines is to provide guidance to HIV care practitioners. Because the field of HIV care is changing rapidly, users of this slide set are advised to check http://aidsinfo.nih.gov/guidelines/html/3/perinatal-guidelines/0 for updates. • 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 March 2014

  3. Table of Contents Topic Slide Number 4 6 24 106 116 122 145 • Introduction • Pre-Conception Counseling • Antepartum Care • Intrapartum Care • Postpartum Care • Care of the Neonate • Lessons Learned from Clinical Trials March 2014

  4. Introduction (1) • Providers considering the use of antiretrovirals (ARVs) for HIV-infected women during pregnancy must take into account: • ARV treatment (ART) for maternal HIV infection; and • ARV chemoprophylaxis to reduce the risk of perinatal transmission of HIV • With universal prenatal HIV counseling and testing, preconception care, ARV prophylaxis, scheduled C-section delivery (if indicated), and avoidance of breast-feeding, perinatal HIV infection has diminished to <2% in the United States. March 2014

  5. Introduction (2) Recommendations in these guidelines are based on scientific evidence and expert opinion and are rated using the system below: March 2014

  6. PRECONCEPTION COUNSELING AND CARE FOR HIV-INFECTED WOMEN OF CHILDBEARING AGE

  7. Preconception Counseling and Care (1) • Comprehensive family planning and preconception care is part of routine primary care and is recommended by CDC, ACOG,and other national organizations. • Purpose: • Prevention of unintended pregnancies • Optimization of maternal health prior to pregnancy • Prevention of perinatal transmission • Prevention of HIV transmission to anuninfected partner while trying to conceive March 2014

  8. Preconception Counseling and Care (2) Recommendations • Discuss childbearing intentions with all women of childbearing age on an ongoing basis throughout the course of their care. (AIII) • Include information about effective and appropriate contraceptive methods to reduce the likelihood of unintended pregnancy. (AI) March 2014

  9. Preconception Counseling and Care (3) • During preconception counseling, include information on safer sexual practices and elimination of alcohol, illicit drugs, and smoking, which are important for the health and of all women as well as for fetal/infant health, should pregnancy occur. (AII) • All HIV-infected women contemplating pregnancy should be on a maximally suppressive antiretroviral regimen. (AII) March 2014

  10. Preconception Counseling and Care (4) • When selecting or evaluating combination (cART) for HIV-infected women of childbearing age, consider the following (AII): • A regimen’s effectiveness • Hepatitis B virus disease status • Teratogenic potential of the drugs in the cARTregimen, should pregnancy occur • Possible adverse outcomes for the mother and fetus March 2014

  11. Preconception Counseling and Care (5) • Women who do not desire pregnancy should be offered contraception. • All available methods can be used, including hormonal contraception and intrauterine devices. • Interactions between some ARVs and hormonal contraceptives may lower contraceptive efficacy • Emergency contraception can be used as appropriate ̶ either pills or copper IUD • Again, be aware of potential interactions with ARVs that could lower contraceptive efficacy • Interactions between ARVs and ulipristal acetate have not been defined but are likely March 2014

  12. Drug Interactions between ARVs and Hormonal Contraceptives (CIII) (1) NNRTIs: March 2014

  13. Drug Interactions between ARVs and Hormonal Contraceptives (CIII) (2) RTV-Boosted PIs: March 2014

  14. Drug Interactions between ARVs and Hormonal Contraceptives (CIII) (3) RTV-Boosted PIs: March 2014

  15. Drug Interactions between ARVs and Hormonal Contraceptives (CIII) (4) PIs without RTV: March 2014

  16. Drug Interactions between ARVs and Hormonal Contraceptives (CIII) (5) PIs without RTV: March 2014

  17. Drug Interactions between ARVs and Hormonal Contraceptives (CIII) (6) Integrase Inhibitors: CCR5 Antagonist: March 2014

  18. Reproductive Options for HIV-Concordant and SerodiscordantCouples (1) For both concordant (both partners are HIV infected) and discordant couples: • Expert consultation is recommended so that approaches can be tailored to specific needs, which may vary from couple to couple. (AIII) • Partners should be screened for genital tract infections. (AII) • The HIV-infected partner should attain maximum viral suppression before attempting conception. (AIII) March 2014

  19. Reproductive Options for HIV-Concordant and Serodiscordant Couples (2) For discordant couples: • cART for the infected partner may not be fully protective against sexual transmission of HIV. • Periconception administration of antiretroviral preexposure prophylaxis (PrEP) for HIV-uninfected partners may offer an additional tool to reduce the risk of sexual transmission. (CIII) The utility of PrEP for the uninfected partner when the infected partner is receiving cART and has a suppressed viral load has not been studied. March 2014

  20. Reproductive Options for HIV-Concordant and SerodiscordantCouples (3) Discordant couples with HIV-infected female: • The safest conception option is artificial insemination, including the option of self-insemination with a partner’s sperm during the periovulatory period. (AIII) March 2014

  21. Reproductive Options for HIV-Concordant and Serodiscordant Couples (4) Discordant couples with HIV-infected male: • The use of donor sperm from an HIV-uninfected male with artificial insemination is the safest option. • When the use of donor sperm is unacceptable, the use of sperm preparation techniques coupled with either intrauterine insemination or in vitrofertilization should be considered. (AII) • Semen analysis is recommended for HIV-infected males before conception is attempted to prevent unnecessary exposure to infectious genital fluid when the likelihood of getting pregnant is low because of semen abnormalities. (AIII) March 2014

  22. Reproductive Options for HIV-Concordant and Serodiscordant Couples (5) • PericonceptionPrEP • Very few data to date on periconceptionPrEP; studies under way • Infected partner should be on ART with fully suppressed HIV viral load • Only combination tenofovir/emtricitabine is currently being studied in heterosexual PrEP trials • Couples should use condoms at all times except during periovulatory intercourse • No reported increase in congenital anomalies for children whose mothers were exposed to tenofovir or emtricitabine during pregnancy Review Table 4 “Clinical Trials of PrEP” for more information March 2014

  23. Reproductive Options for HIV-Concordant and Serodiscordant Couples (6) • Laboratory testing for HIV infection, baseline renal function, and chronic HBV infection should be performed before initiating PrEP. • HBV-uninfected individuals should be vaccinated. • Monitor for potential side effects such as renal dysfunction and clinical toxicities. • Frequent testing of HIV-uninfected partner; if result is HIV positive, discontinue PrEP to minimize drug resistance and refer for treatment. March 2014

  24. ANTEPARTUM CARE

  25. Principles of ARV Use during Pregnancy (1) • Initial evaluation of HIV-infected pregnant women should include assessment of HIV disease status and recommendations regarding initiation or modification of cART. (AIII) • All pregnant women should receive ART to prevent perinatal transmission regardless of HIV RNA and CD4 levels. (AI) • Combined antepartum, intrapartum, and infant ARV prophylaxis is recommended because ARV drugs reduce perinatal transmission by several mechanisms, including lowering maternal antepartum viral load and providing infant pre- and postexposure prophylaxis. (AI) March 2014

  26. Principles of ARV Use during Pregnancy (2) • The known benefits and potential risks of ARV use during pregnancy should be discussed with all HIV-infected women. (AIII) • In counseling patients, the importance of adherence to their ARV regimens should be emphasized. (AII) • ARV drug-resistance studies should be performed before starting or modifying ARV drug regimens in women whose HIV RNA is above the threshold for resistance testing. (AIII) • When HIV is diagnosed later in pregnancy, cART should be initiated promptly without waiting for results of resistance testing (BIII) *see Antiretroviral Drug Resistance and Resistance Testing in Pregnancy March 2014

  27. Principles of ARV Use during Pregnancy (3) • Coordination of services among prenatal care providers, primary care and HIV specialty care providers, and when appropriate, mental health and drug abuse treatment services, and public assistance programs, is essential to ensure that infected women adhere to their ARV drug regimens. (AIII) March 2014

  28. Clinician Consultation Center (formerly the National Perinatal HIV Hotline) (1-888-448-8765) For free clinical consultation for providers caring for HIV-infected women and their infants March 2014 August 2012

  29. General Principles of Drug Selection • Guidelines for use of cART for maternal health during pregnancy generally are the same as for women who are not pregnant • Some modifications based on concerns about specific ARVs during pregnancy • Consider benefits vs risks of ARV drug use during pregnancy • Ensure that at least 1 NRTI with high placental transfer is included in cART regimen for sufficient infant preexposure prophylaxis • Counsel women on the importance of close adherence to ARV regimen • Offer support services, mental health services, smoking cessation, and drug abuse treatment plans as indicated • Coordinate between HIV and OB specialists March 2014

  30. Teratogenicity (1) • All cases of ARV drug exposure during pregnancy should be reported to the Antiretroviral Pregnancy Registry at: http://www.APRegistry.com. (AIII) • Efavirenz (EFV): • Nonpregnant women of childbearing potential should undergo pregnancy testing before initiation of EFV and receive counseling about the potential risk to the fetus and desirability of avoiding pregnancy while on EFV-containing regimens. (AIII) • Alternative ARV regimens that do not include EFV should be strongly considered in women who are planning to become pregnant or are sexually active and not using effective contraception, assuming these alternative regimens are acceptable to the provider and are not thought to compromise the woman’s health. (BIII) March 2014

  31. Teratogenicity (2) • Because the risk of neural tube defects is restricted to the first 5-6 weeks of pregnancy and pregnancy is rarely recognized before 4-6 weeks of pregnancy, and unnecessary changes in ARV drugs during pregnancy may be associated with loss of viral control and increased risk of perinatal transmission, EFV can be continued in pregnant women receiving an EFV-based regimen who present for antenatal care in the first trimester, provided the regimen produces virologic suppression. (CIII) March 2014

  32. Teratogenicity (3) • Tenofovir: • No known teratogenicity • Possible decrease in length and head circumference following in utero exposure • Folate antagonists (eg, TMP-SMX) may have increased risk of birth defects during first-trimester use March 2014

  33. Nevirapine and Hepatic/Rash Toxicity (1) • Nevirapine (NVP)-based regimens should be initiated in women with CD4 counts >250 cells/µL only if the benefits outweigh the risks because of the drug’s potential for causing hepatic toxicity/hypersensitivity reaction. (AII) • Women who become pregnant while receiving NVP-containing regimens and who are tolerating the regimen can continue regardless of CD4 count. (AII) March 2014

  34. Nevirapine and Hepatic/Rash Toxicity (2) • Non-NVP ARVs should be considered for women with preexisting liver disease. • Data from 3,582 pregnant women in 20 studies did not find evidence of increased risk of NVP-related events compared with nonpregnant women. March 2014

  35. NRTI Drugs and Mitochondrial Toxicity • The combination of stavudine (d4T) and didanosine (ddl) should not be prescribed during pregnancy because of reports of lactic acidosis and maternal/neonatal mortality with prolonged use in pregnancy. (AII) • Mitochondrial dysfunction should be considered in uninfected children with perinatal exposure to ARV drugs who present with severe clinical findings, particularly neurological. (AII) • Long-term clinical follow-up is recommended for any child with in utero exposure to ARV drugs. (AIII) March 2014

  36. Combination ARV Drug Regimens and Pregnancy Outcome • Clinicians should be aware of a possible small increased risk of preterm birth in pregnant women receiving protease inhibitor (PI)-based ART; however, given the clear benefits of such regimens for both a women’s health and prevention of perinatal transmission, PIs should not be withheld for fear of altering pregnancy outcome. (AII) March 2014

  37. Recommendations for Use of ARVs during Pregnancy • In general, the same regimens as recommended for treatment of nonpregnant adults should be used in pregnant women unless there are known adverse effects for women, fetuses, or infants that outweigh benefits. (AIII) • Multiple factors must be considered when choosing a regimen for a pregnant woman including comorbidities, convenience, adverse effects, drug interactions, resistance testing results, pharmacokinetics (PK), and experience with use in pregnancy. (AII) • PK changes may lead to lower plasma drug levels of drugs and necessitate increased dosages, more frequent dosing, or boosting, especially of protease inhibitors. (AII) March 2014

  38. ART for Pregnant Women • All HIV-infected pregnant women should receive a potent combination ARV) regimen to reduce the risk of perinatal transmission of HIV. (AI) • The choice of regimen should take into account current adult treatment guidelines, what is known about the use of specific drugs in pregnancy, and the risk of teratogenicity. • Reducing HIV RNA to undetectable levels lowers the risk of perinatal transmission, lessens the need for elective C-section to reduce risk of HIV transmission, and reduces risk of ARV drug resistance in the mother. March 2014

  39. ART for Pregnant Women (2) • The decision as to whether to start the regimen in the first trimester or delay until 12 weeks’ gestation will depend on CD4 count, HIV RNA levels, and maternal conditions. (AIII) • Earlier initiation of a combination ARV regimen may be more effective in reducing transmission, but benefits must be weighed against potential fetal effects of first-trimester drug exposure. • Fetuses are most susceptible to potential teratogenic effects in the first trimester. • Although most transmission occurs late in pregnancy or during delivery, recent analyses suggest that early control of viral replication may be important. March 2014

  40. ART for Pregnant Women (3) • ARV drug-resistance studies should be performed before starting the ARV regimen if HIV RNA is above the threshold for resistance testing unless drug-resistance studies have already been performed. (AI) • If HIV is diagnosed later in pregnancy, the ARV regimen should be initiated promptly without waiting for the results of resistance testing. (BIII) March 2014

  41. ART for Pregnant Women (4) • If there is no evidence of resistance, combination ARV regimens that are preferred for the treatment of ART-naive HIV-infected pregnant women include: a dual NRTI combination (abacavir/lamivudine, tenofovir/emtricitabine or lamivudine, or zidovudine/lamivudine) and either a ritonavir-boosted protease inhibitor (ritonavir-boosted atazanavir or ritonavir-boosted lopinavir) or an NNRTI (efavirenz initiated after 8 weeks of pregnancy). (AIII) * Refer to Antiretroviral Drug Resistance and Resistance Testing in Pregnancy March 2014

  42. ART for Pregnant Women (5) • cART regimens should include at least 3 ARVs, as in nonpregnant adults • Generally, 2 NRTIs + 1 ritonavir-boosted PI or 2 NRTIs + 1 NNRTI • Individualize ARVs based on factors such as: • Woman’s ARV history • Possible ARV resistance • Comorbidities • PK changes in pregnancy, placental ARV transfer • Potential adverse effects on woman and on fetus • Experience in pregnancy March 2014

  43. ART for Pregnant Women (6) • Preferred Drugs or Drug Combinations • Clinical trial data in adults have demonstrated optimal efficacy and durability with acceptable toxicity and ease of use • Pregnancy-specific PK data are available to guide dosing • No established association with teratogenic effects or clinically significant adverse outcomes for mothers, fetuses, or newborns • Some recommended ARVs may have toxicity in animal studies that has not been verified in humans March 2014

  44. Initial ART for ARV-Naive Pregnant Women (1) Preferred 2-NRTI Backbone Regimens March 2014

  45. Initial ART for ARV-Naive Pregnant Women (2) Preferred PI Regimens March 2014

  46. Initial ART for ARV-Naive Pregnant Women (3) Preferred NNRTI Regimen March 2014

  47. Initial ART for ARV-Naive Pregnant Women (4) Alternative Regimens: Clinical trial data demonstrate efficacy in adults but experience in pregnancy is limited, data are lacking or incomplete on teratogenicity, or regimen is associated with dosing, formulation, toxicity, or interaction issues March 2014

  48. Initial ART for ARV-Naive Pregnant Women (5) Alternative PI Regimens March 2014

  49. Initial ART for ARV-Naive Pregnant Women (6) Alternative NNRTI Regimen Alternative Integrase Inhibitor Regimen March 2014

  50. Initial ART for ARV-Naive Pregnant Women (7) Insufficient Data to Recommend: Drugs and drug combinations are approved for use but lack sufficient pregnancy-specific PK or safety data Not Recommended: Inferior virologic response, potentially serious maternal or fetal safety concerns, or PK antagonism, or not recommended for ARV-naive nonpregnant populations March 2014

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