Prevention of Perinatal HIV Transmission

Transcription

1 Prevention of Perinatal HIV Transmission Emily Adhikari, MD Division of Maternal-Fetal Medicine Obstetrics and Gynecology University of Texas Southwestern Medical Center February 20, 2018

2 None

3 Understand the prenatal, intrapartum, and postnatal management of HIV and current controversies Describe first-line antiretroviral therapy (ART) regimens for use in pregnancy Describe the contraceptive options available to HIVinfected women State the reproductive options for safer conception among serodiscordant couples

4 CDC HIV Surveillance Report 2016

5 CDC 2014

6 People living with HIV CDC 2012

7 No. of baby seroconversions Lost to follow up Delivered elsewhere SAB/EAB/SB Delivered pregnancies, liveborn >24 weeks

8 Diagnosed >1 year prior to presentation Diagnosed 1 year prior to presentation * *Preliminary data

9 Number of seroconversions HIV-exposed babies Courtesy Mary Mallory, RN,PNP

10 Diagnoses of Perinatally Acquired HIV Infection among Children Born in the United States and Puerto Rico, Birth Years , by Area of Residence N = 345 Note. Data include persons with a diagnosis of HIV infection regardless of stage of disease at diagnosis. CDC 2015

11 JAMA Peds, 2017

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13 HIV Diagnostic Outcomes among Infants, by Time of Antiretroviral (ARV) Administration Birth Years United States and Puerto Rico CDC 2015

14 Intrauterine (before 36 weeks) ~20% of cases Detection of HIV in newborn at 1 2 days of life Peripartum ~80% of cases Onset of placental separation Mother-to-fetus microtransfusions Labor and rupture of membranes Detection of HIV at weeks to months of life

15 Minimize (eliminate) the risk of perinatal HIV transmission Optimize the health of the mother while minimizing adverse pregnancy outcomes Establish (or re-establish) HIV care during and after delivery Minimize interruptions in therapy and risk of viral resistance Plan for contraception or future safe conception

16 Without ART during pregnancy, the risk of transmission from mother to infant is 1 in 4. The risk of perinatal transmission can be <1% with: Highly active ART therapy (HAART) for mom (prior to conception ideally) Intrapartum AZT Elective Cesarean section as appropriate Formula feeding Infant prophylaxis

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19 Mofenson, NEJM,1999

20 Perinatal HIV Transmission Rate per 100 No ART ZDV alone 9.10 cart without PI 3.80 cart with PI Cooper, Combination ART for pregnant women with HIV, JAID Human Retrovir, 2002

21 CID, 2015

22 Without ART during pregnancy, the risk of transmission from mother to infant is 1 in 4. The risk of perinatal transmission can be <1% with: Highly active ART therapy (HAART) for mom (prior to conception ideally) Intrapartum AZT Elective Cesarean section as appropriate Formula feeding Infant prophylaxis

23 Intravenous (IV) zidovudine: Should be administered to women living with HIV with HIV RNA >1,000 copies/ml (or unknown HIV RNA) near delivery (AI), Is not required for women receiving ART regimens who have HIV RNA 50 copies/ml during late pregnancy and near delivery and no concerns regarding adherence to the ART regimen (BII).

24 CID, 2013

25 Obstetrics & Gynecology, 2017

26 Without ART during pregnancy, the risk of transmission from mother to infant is 1 in 4. The risk of perinatal transmission can be <1% with: Highly active ART therapy (HAART) for mom (prior to conception ideally) Intrapartum AZT Elective Cesarean section as appropriate Formula feeding Infant prophylaxis

27 Cesarean section recommended: For women with HIV RNA levels >1,000 near time of delivery Schedule at 38 weeks if for viral load; 39 weeks otherwise Benefits of Cesarean unclear after ROM or onset of labor, or for women with HIV RNA levels <1,000 on combination ARVs Trial of Labor after Cesarean (TOLAC)

28 In women with an HIV RNA >1,000 copies/ml or unknown HIV RNA level who present in spontaneous labor or with ruptured membranes, there is insufficient evidence to determine whether cesarean reduces the risk of perinatal HIV transmission. Management of women originally scheduled for cesarean delivery because of HIV infection who present in labor must be individualized at the time of presentation (BII).

29 Obstetrics & Gynecology, 2017

30 Maternal Factors High viral load Low CD4+ lymphocyte count Maternal systemic co-infections STDs: ulcerative diseases Maternal IV drug use No ART or prophylaxis

31 Obstetric Factors?Length of ruptured membranes Chorioamnionitis Vaginal delivery (if VL > 1000) Invasive procedures Infant Factors Prematurity Breastfeeding

32 How long is too long? Should I do a c-section after 4 hours of rupture? What if my patient is in active labor? What if my patient is remote from delivery?

33 AJOG, 1995

34 AIDS, 2001

35 AJOG, 2012

36 BJOG, 2016

37 Data on the association of duration of rupture of membranes (ROM) and perinatal transmission in the era of effective antiretroviral therapy (ART) are reassuring. BUT

38 JAIDS, 2002

39 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.

40 AIDSinfo.nih.gov

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42 AIDSinfo.nih.gov

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44 AIDSinfo.nih.gov

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46 Current practice at PHHS is to administer IV ZDV to all HIV-positive women regardless of viral load Continue oral ART regimen during labor Avoid invasive procedures Active management of labor Avoid methergine

47 Preterm Birth Drug interactions

48 Women taking antiretroviral therapy may be at increased risk for preterm delivery, low birth weight infants (<2500g) and small-for-gestational age infants (BW <10 th centile for GA). RR ranges in 19 studies reporting an association, but data are heterogeneous In 2 studies evaluating risk of spontaneous preterm birth in association with ART use: no association What about the PROMISE study?

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50 RCT of antepartum treatment regimens: ZDV alone, ZDV-based ART, TDF-based ART Efficacy outcomes: + Infant HIV at 1 week, infant HIVfree survival Safety outcomes: Maternal, infant safety outcomes, adverse pregnancy outcomes: Preterm delivery (<37wks), early preterm (<34wks) Low (<2500g) or very low (<1500g) infant birth weight

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52 Hypertensive disorders of pregnancy not recorded Strongly associated with adverse pregnancy outcomes (preterm birth, low birth weight, neonatal death, stillbirth) Spontaneous versus iatrogenic preterm birth TDF LPV/r interaction?

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54 In women who are receiving a cytochrome P450 (CYP) 3A4 enzyme inhibitor (e.g., a protease inhibitor, cobicistat), methergine should be used only if no alternative treatments for postpartum hemorrhage are available and the need for pharmacologic treatment outweighs the risks. If methergine is used, it should be administered in the lowest effective dose for the shortest possible duration (BIII).

55 Maternal Child Health postpartum visit (MFM clinic) Refer mother for continued HIV care Confirm ART dosage changes if needed postpartum (atazanavir) Monitor for adherence and postpartum depression HIV testing and follow-up of neonate and other children Follow-up of sexual/needle-sharing partners

56 Primary, gynecologic/obstetric, and family planning services Mental health services Substance abuse treatment Coordination of care through case management for the woman, her children, and other family members

57 HIV-infected women can use all available contraceptive methods For those on boosted PI regimen (atazanavir/ritonavir) : Implant, progestin-only pill, combined hormonal contraceptives = 2 DMPA = 1 IUD: Initiation = 1/2, Continuation = 1 Emergency contraception should be offered CDC, Medical Eligibility Criteria for Contraception 2016

58 Stewart, Interpregnancy HIV Control, AJOG, 2014

59 Adams, Clinical Infectious Diseases, 2015

60 Deliveries at Parkland between Jan 1, 2005 June 30, 2015 n = 579 deliveries Followed up to MFM clinic postpartum 465 (80%) Followed up to HIV clinic within 1 year postpartum 390 (67%) Median time to HIV clinic visit (days) 50 [29-103] Data presented as n (%) or median [Q1, Q3] as appropriate Unpublished data

61 ART for the infected partner until VL undetectable Consider pre-exposure prophylaxis (PrEP) Discordance between plasma and genital viral loads reported ARV drugs vary in ability to penetrate the genital tract Timed, peri-ovulatory Male intercourse with HIV: donor without sperm a artificial insemination condom after partner with HIV has achieved Sperm preparation techniques viral suppression on ART. Female with HIV: artificial insemination (partner s sperm) Semen analysis recommended to HIV-infected males before conception is attempted

62 Once daily Truvada: Start 1 month prior to attempting to conceive; continue for 1 month after conception Timed, periovulatory unprotected intercourse only (AFTER partner is fully suppressed) HIV, STDs, and pregnancy tests q3months (Cr q6 months) Check Hep B status, vaccinate Adherence is critical Anyone at ongoing risk of HIV acquisition is a candidate If new HIV infection documented during PrEP: stop PrEP and stop attempting to conceive. Refer to HIV specialist.

63 Pregnancy and breastfeeding are NOT contraindications Abstinence recommended during pregnancy Discuss symptoms, risk of acute HIV infection during pregnancy (and risk of vertical transmission). PrEP when the HIV-infected partner is receiving cart and suppressed has not been well studied

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65 Needs at Parkland: - PreP on formulary - Medical home for non-pregnant women in serodiscordant relationships on PreP Obstetrics & Gynecology, 2016

66 Summary Women with HIV are living longer and having more babies Elimination of perinatal transmission is possible Simplified ART regimens are recommended over Combivir/Kaletra Some areas of obstetrics still controversial Postpartum follow up is key Providers should inquire about patient and partner HIV status and offer safe conception counseling PrEP is recommended for women at high risk of HIV acquisition

67 Barbara McElwee, WHNP Scott Roberts, MD Vanessa Rogers, MD Linda Andoseh, NP Arti Barnes, MD Jeanne Sheffield, MD Casey Senter, MD Cece Cheng, MD Mary Ann Kelly, RN Don McIntire, PhD Catherine Eppes, MD Mary Mallory, RN, PNP