1. ANTEPARTUM CARE

2. Pregnant Women Who Are ARV Naive (1)  Pregnant women with HIV infection should receive standard clinical, immunologic, and virologic evaluation.  Including hepatitis C and tuberculosis screening  All HIV-infected pregnant women should receive a potent combination ARV regimen to reduce the risk of perinatal transmission. (AI)  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. August 2012 2 www.aidsetc.org

3. Pregnant Women Who Are ARV Naive (2)  The choice of regimen should take into account current adult treatment guidelines, what is known about the use of the drugs during pregnancy, and the risk of teratogenicity. (see Guidelines Table 5)  Use a dual-NRTI backbone; 1 or more NRTIs should have high levels of transplacental passage: (AIII)  ZDV, 3TC, FTC, TFV, ABC  NVP can be used as a component of the regimen in pregnant women with CD4 counts <250 cells/µL. But NVP should only be used if the benefit clearly outweighs the risk of hepatic toxicity. (AII) August 2012 3 www.aidsetc.org

4. Pregnant Women Who Are ARV Naive (3)  The decision as to whether to start the regimen in the 1st trimester vs delay until 12 weeks’ gestation will depend on CD4 count, VL, and maternal conditions such as nausea and vomiting. (AIII)  Earlier initiation may be more effective in reducing risk of transmission, but benefits must be weighed against potential fetal effects.  Fetuses are most susceptible to potential teratogenic effects in the 1st trimester.  Although most transmission occurs late in pregnancy or during delivery, recent analyses suggest that early control of viral replication may be important. August 2012 4 www.aidsetc.org

5. Pregnant Women Who Are ARV Naive (4)  Conduct drug resistance testing before starting ARVs.  However, if HIV is diagnosed or the woman presents later in pregnancy, start the ARV regimen promptly and adjust, as needed, after resistance testing results are available. August 2012 5 www.aidsetc.org

6. Pregnant Women Who Are ARV Naive (5)  RAL has been suggested for women with a high viral load late in pregnancy because of its ability to rapidly suppress VL. But the safety and efficacy of RAL in this setting have not been evaluated.  Use of ZDV alone for prophylaxis is not optimal, but could be an option, combined with C-section delivery, for women with VL below <1,000 copies/mL who wish to reduce fetal exposure to ARVs. August 2012 6 www.aidsetc.org

7. Pregnant Women Who Are ARV Naive (6)  The regimen initiated during pregnancy can be modified after delivery to a simplified regimen with ARVs that are not used in pregnancy because of insufficient pregnancy safety data.  Drugs may be stopped after delivery in women who do not feel prepared to continue lifelong treatment.  Consult with the HIV care provider. August 2012 7 www.aidsetc.org

8. HIV-Infected Pregnant Women Who Are Currently Receiving Antiretroviral Therapy (1)  HIV-infected women who present for care in the 1st trimester should continue any effective ARV regimen. (AII)  Including:  Effective EFV-based regimens (CIII)  Effective NVP-based regimens (AIII)  Resistance testing should be performed on women with detectable viremia. (AI)  >500-1,000 copies/mL August 2012 8 www.aidsetc.org

9. HIV-Infected Pregnant Women Who Are Currently Receiving Antiretroviral Therapy (2)  Rationale for continuing EFV during pregnancy:  1st trimester exposure is not associated with a large increase in the risk of neural tube defects.  The risk of neural tube defects is limited to the first 5-6 weeks of pregnancy, before most pregnancies are recognized.  Treatment changes during pregnancy increase the risk of incomplete viral suppression at the end of pregnancy. August 2012 9 www.aidsetc.org

10. Pregnant Women Who Are ARV- Experienced (1)  Pregnant women with HIV infection who have received ARVs previously for prevention of perinatal transmission:  Rates of resistance appear to be low after prophylaxis with combination ART. But interpretation of resistance testing after treatment discontinuation is complex; resistance testing is most accurate if done while on ARVs or within 4 weeks of discontinuing ARVs.  Treatment failure has not been demonstrated with reinitiation of ART following prophylactic use in pregnancy. August 2012 10 www.aidsetc.org

11. Pregnant Women Who Are ARV- Experienced (2)  Pregnant women with HIV infection who have received ARVs previously for their own health:  Choice of ARV regimen is challenging and will vary by:  History of ART  Indication for stopping treatment  Efficacy of previous ART  Results of past and current resistance testing  Testing for HLA-B*5701 August 2012 11 www.aidsetc.org

12. Pregnant Women Who Are ARV- Experienced (3) Recommendations:  Obtain an accurate history of all prior ARV regimens used for treatment or prevention, including efficacy, tolerance, prior resistance testing, and adherence. (AIII)  Perform drug-resistance testing. (AIII)  Initiate therapy or prophylaxis promptly (without waiting for test results) in women who present late in pregnancy. (BIII) August 2012 12 www.aidsetc.org

13. Pregnant Women Who Are ARV- Experienced (4)  Consult specialists about the choice of regimen in women who previously received ART for their own health. (AIII)  Choose a combination ARV regimen based on results of resistance testing and prior history of ART. (AII)  Avoid drugs with teratogenic potential or known adverse potential for the mother. (AII) August 2012 13 www.aidsetc.org

14. Maternal and Fetal Monitoring during Pregnancy (1)  More frequent VL monitoring during pregnancy is recommended to identify women in whom the decline in VL is slower than expected.  Viral suppression generally achieved in 16-24 weeks in ARV-naive adherent individuals; rare cases take longer. August 2012 14 www.aidsetc.org

15. Maternal and Fetal Monitoring during Pregnancy (2)  Monitor VL:  At the initial visit (AI)  2-4 weeks after initiating or changing ARV regimen (BI)  Monthly until VL is undetectable (BIII)  At least every 3 months during pregnancy (BIII)  At 34-36 weeks’ gestation to inform decisions about mode of delivery (AIII) August 2012 15 www.aidsetc.org

16. Maternal and Fetal Monitoring during Pregnancy (3)  Monitor CD4 count:  At initial antenatal visit (AI)  At least every 3 months during pregnancy (BIII), or every 6 months in women on ART for more than 2-3 years who are adherent, clinically stable, and have sustained viral suppression (CIII) August 2012 16 www.aidsetc.org

17. Maternal and Fetal Monitoring during Pregnancy (4)  Perform genotypic drug resistance testing at baseline if VL >500-1,000 copies/mL, whether they are ARV naive or currently on ART. (AIII)  Repeat testing in women who have suboptimal viral suppression on ART or who have persistent viral rebound to detectable levels after prior viral suppression on an ARV regimen. (AIII) August 2012 17 www.aidsetc.org

18. Maternal and Fetal Monitoring during Pregnancy (5)  Monitor for complications of ART based on what is known about the adverse effects of the drugs in the regimen. (AIII)  Perform 1st-trimester ultrasound to confirm gestational age and to guide timing of scheduled C-section (if needed). (AII) August 2012 18 www.aidsetc.org

19. Maternal and Fetal Monitoring during Pregnancy (6)  Perform amniocentesis, if indicated, only after initiation of ART regimen and, if possible, when VL is undetectable. (BIII)  No perinatal transmission after amniocentesis have been reported in women on effective ART.  Small risk cannot be ruled out.  In women with detectable VL in whom amniocentesis is deemed necessary, consultation with an expert should be considered. August 2012 19 www.aidsetc.org

20. Failure of Viral Suppression (1)  Use a 3-pronged approach for management of suboptimal suppression of VL.  Assess for resistant virus (AII)  Assess adherence (AII)  Consult an expert for consideration of modifying the ARV regimen (AIII)  Treatment modification has been independently associated with HIV RNA >400 copies/mL during late pregnancy. August 2012 20 www.aidsetc.org

21. Failure of Viral Suppression (2)  Efficacy and safety of adding RAL to an ART regimen during late pregnancy in women with high VL or multiple drug-resistance mutations has not been evaluated and is not recommended.  The addition of a single drug to a failing regimen may further increase risk of resistance and loss of future effectiveness of RAL.  Cesarean delivery is recommended when RNA is >1,000 copies/mL near the time of delivery. (AII) August 2012 21 www.aidsetc.org

22. Resistance Testing during Pregnancy (1)  Drug resistance:  Is one of the major factors leading to treatment failure  May limit future maternal treatment options and decrease effectiveness of ARV prophylaxis during current and future pregnancies  Increased risk of resistance  During pregnancy with:  Nausea and vomiting  PK changes  Postpartum  After simultaneous discontinuation of drugs with different half-lives August 2012 22 www.aidsetc.org

23. Resistance Testing during Pregnancy (2) Recommendations:  Perform drug resistance studies before starting or modifying ART for all pregnant women with detectable VL prior to initiation of ART (AIII) and for those with detectable VL while on ART or suboptimal suppression after starting ART. (AII)  Start empiric ART for women who present during late pregnancy; adjust regimen as needed when results are available. (BIII) August 2012 23 www.aidsetc.org

24. Resistance Testing during Pregnancy (3)  Give all HIV-infected pregnant women maximally suppressive ART. (AII)  Provide counseling and support for adherence. (AII) August 2012 24 www.aidsetc.org

25. Stopping ARVs during Pregnancy (1)  Women who are on ART and present in the 1st trimester should continue therapy. (AII)  Although EFV should be avoided during the first trimester when possible, therapy should NOT be interrupted in women taking the drug who present in the 1st trimester. August 2012 25 www.aidsetc.org

26. Stopping ARVs during Pregnancy (2)  Discontinuation of ART during pregnancy may be indicated in some situations.  If ART is stopped acutely for severe or life- threatening toxicity, severe hyperemesis, or other acute illness that precludes oral intake, all ARV drugs should be stopped and reinitiated at the same time. (AIII) August 2012 26 www.aidsetc.org

27. Stopping ARVs during Pregnancy (3)  If an NNRTI-based regimen is being stopped electively, consider either:  Stopping NNRTI first and continue other ARVs for a period; or  Switching from an NNRTI to a PI before interruption; continue PI-based regimen for a period.  Optimum period of time is unknown. At least 7 days is recommended. (CIII)  For EFV-based regimens, some experts recommend up to 30 days. (CIII)  If NVP is restarted after >2 weeks, restart with the 2- week half-dose escalation period. (AII) August 2012 27 www.aidsetc.org