Prevention of Perinatal HIV Transmission in 2016 · Prevention of Perinatal HIV ... Avoid methergine . Preterm Birth Drug interactions ... What about the PROMISE study?

Emily Adhikari, MD Division of Maternal-Fetal Medicine

Obstetrics and Gynecology University of Texas Southwestern Medical Center

February 20, 2018

Prevention of Perinatal HIV Transmission

None

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 HIV-

infected women

State the reproductive options for safer conception

among serodiscordant couples

CDC HIV Surveillance Report 2016

CDC 2014

CDC 2012

People living with HIV

0

20

40

60

80

100

120

2011 2012 2013 2014 2015 2016 2017

Lost to follow up

Delivered elsewhere

SAB/EAB/SB

Delivered pregnancies,liveborn >24 weeks

2 2 1 No. of baby seroconversions

0 0 0 1

0

20

40

60

80

100

120

2011 2012 2013 2014 2015 2016 2017

Diagnosed >1 year prior topresentation

Diagnosed ≤ 1 year prior to presentation

*Preliminary data

*

0

20

40

60

80

100

120

140

2011 2012 2013 2014 2015 2016 2017

HIV-exposed babies

1 1 2 0 2 2 Number of seroconversions 2

Courtesy Mary Mallory, RN,PNP

Note. Data include persons with a diagnosis of HIV infection regardless of stage of disease at diagnosis.

Diagnoses of Perinatally Acquired HIV Infection among Children Born in the United

States and Puerto Rico, Birth Years 2009–2013, by Area of Residence

N = 345

CDC 2015

JAMA Peds, 2017

HIV Diagnostic Outcomes among Infants, by Time of Antiretroviral (ARV)

Administration Birth Years 2009–2013—United States and Puerto Rico

CDC 2015

● 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

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

● 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

Mofenson, NEJM,1999

24.50

9.10

3.80

1.20 0.00

5.00

10.00

15.00

20.00

25.00

30.00

1993 1994 1999 2002

Perinatal HIV Transmission Rate per 100

Cooper, Combination ART for pregnant women with HIV, JAID Human Retrovir, 2002

ZDV alone

cART without PI

cART with PI

No ART

CID, 2015

● 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

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).

CID, 2013

Obstetrics & Gynecology, 2017

● 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

● 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)…

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).

Obstetrics & Gynecology, 2017

● Maternal Factors

● High viral load

● Low CD4+ lymphocyte count

● Maternal systemic co-infections

● STDs: ulcerative diseases

● Maternal IV drug use

● No ART or prophylaxis

● Obstetric Factors

● ?Length of ruptured membranes

● Chorioamnionitis

● Vaginal delivery (if VL > 1000)

● Invasive procedures

● Infant Factors

● Prematurity

● Breastfeeding

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?

AJOG, 1995

AIDS, 2001

AJOG, 2012

BJOG, 2016

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

JAIDS, 2002

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.

www.aidsinfo.nih.gov

2.19.18 AIDSinfo.nih.gov

2.19.18 AIDSinfo.nih.gov

2.19.18 AIDSinfo.nih.gov

● 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

Preterm Birth Drug interactions

● Women taking antiretroviral therapy may be at

increased risk for preterm delivery, low birth

weight infants (<2500g) and small-for-gestational

age infants (BW <10th centile for GA).

● RR ranges 1.2 - 3.4 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?

● RCT of antepartum treatment regimens: ZDV alone,

ZDV-based ART, TDF-based ART

● Efficacy outcomes: + Infant HIV at 1 week, infant HIV-

free 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

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?

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).

● 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

● 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

● 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

Stewart, Interpregnancy HIV Control, AJOG, 2014

Adams, Clinical Infectious Diseases, 2015

Unpublished data

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]

Deliveries at Parkland between Jan 1, 2005 – June 30, 2015

Data presented as n (%) or median [Q1, Q3] as appropriate

● 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

Female with HIV: artificial insemination (partner’s sperm)

Male with HIV: donor sperm with artificial insemination

• Sperm preparation techniques

• Semen analysis recommended to HIV-infected males before conception is attempted

Timed, peri-ovulatory intercourse without a condom after partner with HIV has achieved viral suppression on ART.

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.

● 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

https://dctakesonhiv.com/prep/african_american_women

Needs at Parkland: - PreP on formulary - Medical home for non-pregnant women in serodiscordant relationships on PreP

Obstetrics & Gynecology, 2016

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

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