Management of HIV in Pregnancy

Iris C. Colón, MDAssociate ChiefMaternal-Fetal Medicine Dept. of Obstetrics and GynecologySanta Clara Valley Medical Center

Case Presentation

25y/o Hispanic woman G2P1 at 13+2 weeks referred for HIV positive result on prenatal labs.

Prior uncomplicated pregnancy 8 years ago. New partner with history of drug use. Pap smear at outside clinic LSIL.

Objectives

Discuss the latest advances in the management of HIV in pregnancy.

Discuss the risk of mother-to-infant transmission. Understand current guidelines of antiretroviral

regimens and the modifications during pregnancy. Promoted obstetric practices that will aid in the

reduction of perinatal transmission.

* I have no conflict of interest disclosures.

Outline

Historical Perspective Epidemiology HIV Testing Standards for Treatment in Pregnancy

– Cornerstones and Goals– HAART– Maternal Evaluation

Outline

Prevention of Perinatal Transmission– Pharmaceutical Interventions– Surgical Interventions

Modification of Obstetric Practices

Historical Perspective

June 5, 1981 – MMWR

Reports on 5 homosexual men diagnosed with P. carinii pneumonia.

Subsequently, etiologic agent discovered, diagnostic tests developed, public health interventions instituted and pharmaceutical agents developed.

Epidemiology

1.2 million living with HIV in the USA in 2009.– 20% are undiagnosed– 25% are women

40,000 new cases in 2009: 10,000 in women and 166 in children <13 y/o.

Epidemiology

200,000 women with HIV in the US.

Majority of infected women are at the peak of reproduction (14-45 years).

African-American and Hispanic women account for over 80% of new cases.

Estimates of New HIV Infections, by Race/Ethnicity, Risk Group, and Gender for the Most Affected US Populations, 2009Prejean J, et al. Estimated HIV incidence in the United States, 2006-2009. PLoS One 2001;6(8):1-13. www.cdc.gov

Epidemiology

7,000 pregnancies/yr complicated by HIV in United States.

Vast majority of pediatric infections are secondary to vertical transmission.

100-200 infants in the US infected annually. Many of these infections involve women who

were not tested early enough in pregnancy or who did not receive prevention services.

Pediatric AIDS (PACTG 076) Trial

Evaluated safety and efficacy of zidovudine

(ZDV,AZT,Retrovir) vs placebo in HIV infected pregnant patients.

ZDV during pregnancy and labor, and neonate for 6 weeks of life.

Reduction of transmission rate from

25% to 8%.

HIV Testing

Serostatus should be determined as early in pregnancy as possible.

The Institute of Medicine –

“Universal HIV testing with patient notification as a routine component of prenatal care”.

ACOG, AAP and the CDC support this recommendation.

HIV Testing

Why universal screening? Attempts to identify those “at risk” fail to

identify some infected patients. Avoids stereotyping and stigmatizing.

HIV Testing:ACOG Committee Opinion 2004

Universal screening via opt-out approach. Repeat testing in the 3rd trimester to women in areas

of high prevalence, those known to be at high risk for infection, and those that declined testing earlier.

Use conventional HIV testing in the 3rd trimester. Use rapid HIV testing in labor for women with

undocumented HIV status. If rapid HIV test is positive, initiate anti-retrovirals

prophylaxis (with consent).

Standards for Treatment in Pregnancy

Pregnancy should not be a barrier to the most potent HIV therapies.

HAART – highly active antiretroviral therapy

Available since 1996 – serious side effects but very effective in reducing viral load and improving prognosis.

Standards for Treatment in Pregnancy

HAART is recommended for all pregnant women to prevent perinatal transmission and for treatment of maternal HIV disease.

Cornerstones of monitoring : viral loads and CD4 counts.

The goal in pregnancy is to maintain a viral load under 1000 copies/ml.

HAART

Original regimens described in 1996.

Regimens include 2 nucleoside/nucleotide RT inhibitors plus a third agent from either protease inhibitor, non-nucleoside RT inhibitor, or fusion inhibitor.

HAART

Nucleoside RT Inhibitors

Zidovudine (ZDV,AZT)*

Lamiduvine (Epivir, 3TC)*

Zalcitabine (ddC, HIVID)

Didanosine (ddi, Videx)

Staduvine (Zerit, d4T)

Abacabir (Ziagen, ABC)

Nucleotide RT Inhibitors

Tenofovir DF (Viread)

Fusion Inhibitor

Enfuvirtide (Fuzeon)

Non-nucleoside RT Inhibitors

Nevirapine (Viramune)

Delavirdine (Rescriptor)

Efavirenz (Sustiva)

Protease Inhibitors

Indinavir (Crixivan)

Ritonavir (Norvir)

Saquinavir (Fortovase)

Nelfinavir (Viracept)

Amprenavir (Agenerase)

Lopinavir/Ritonavir (Kaletra)*

HAART

Adherence to therapy is crucial – failure to do so results in developing resistant virus.

Regimens usually “spare” one class of agent.

HAART: Pregnancy Considerations

ZDV should be used as component of HAART regimens.

Overall, nucleoside RT inhibitors well tolerated and not teratogenic. But avoid staduvine and didanosine (lactic acidosis).

Efavirenz – contraindicated due to teratogenicity in monkeys and myelomeningoceles in humans.

Indinavir – may predispose to nephrolithiasis. Nevirapine – hepatotoxicity.

Maternal Evaluation

Multidisciplinary team approach to care. Detailed history and physical exam. Routine prenatal laboratory tests (including STD

screening, Pap smear, PPD). Hepatitis B and C testing. Renal and liver function tests. Viral load Lymphocyte subset determination (CD4 counts). Ultrasounds: dating, anatomy, and growth.

Maternal Evaluation

CD4 count <200/mm³ : P. carinni prophylaxis with sulfamethoxazole/trimethoprim (Bactrim).

CD4 count <50/mm³ : Mycobacterium avium complex (MAC) prophylaxis with azithromycin (Zithromax) and ophthalmology consult.

Hepatitis C: 33% of HIV patients are coinfected. Increased risk of liver toxicity from HAART.

Case follow-up

March:Viral load 25,823 copies/ml, CD4 count 100Started on HAART – Lamivudine/Zidovudine (Epivir/AZT) and Lopinavir/Ritonavir (Kaletra)Sulfamethoxazole/trimethoprim prophylaxis

April:Viral load 103 copies/ml, CD4 count 150LSIL – Colposcopy multiple condylomatous cervical lesions

Prevention of Perinatal Transmission

Vertical transmission is the most common cause of HIV infection in children - 90% of cases.

Rates vary widely worldwide from 10-60%, depending on breastfeeding, viral loads and obstetric practices.

In US – 1000 children/yr infected through birth prior to PACTG 076 regimen.

In the year 2009 – down to 131 cases.

AIDS cases due to the perinatal transmission of HIV infection, by year of diagnosis, 2001–2005, United States cdc.gov

Race/ethnicity of children (<13 years) with AIDS diagnosed during 2005 (includes all children with a diagnosis of AIDS, not just those who contracted HIV perinatally) cdc.gov

Perinatal Transmission

70-80% at delivery and 20-30% in utero.

Possible mechanisms:

Microtransfusions during contractions

Ascension through the cervix and vagina during parturition

Exposure to secretions and blood at delivery

Absorption through infant’s GI tract

Perinatal Transmission

Supporting evidence:

Increased infection with increased duration of ruptured membranes

Reduced rates of transmission with elective cesarean delivery

Strongest predictor of perinatal transmission:

maternal viral load

Perinatal Transmission

Pharmacological Interventions

HAART ZDV regimen as per PACTG 076 regimen

PACTG 076 Regimen

Timing of ZDV

Antepartum

Labor & Delivery

Neonatal

ZDV Regimen

100mg ZDV PO, 5 times/day, start 14 wks

IV load dose 2mg/kg, then continuous 1mg/kg/hr until delivery

Syrup at 2mg/kg q 6hrs for 6 weeks, start 8-12 hrs after birth.

Intrapartum ZDV

Intravenous ZDV is no longer required for patients receiving combination HAART who have viral load <400– Department of Health and Human Services, Panel

on Prevention of Perinatal Transmission 7/31/12

Perinatal Transmission

Surgical Interventions

Data from two prospective studies ( French and Swiss), an international randomized trial and a meta-analysis using 15 prospective cohort studies indicate that there is a significant relationship between mode of delivery and vertical transmission.

Perinatal Transmission

Data from these studies was collected prior to HAART and without data regarding viral load.

Scheduled cesarean delivery reduces the likelihood of vertical transmission of HIV compared with either unscheduled cesarean section or vaginal delivery.

Holds true whether or not the patient receives ZDV.

ACOG’s Committee Opinion 2000

Patients should be counseled that in the absence of antiretroviral therapy, risk of vertical transmission in 25%.

With ZDV, the risk is reduced to 5-8%. ZDV plus scheduled cesarean delivery, risk reduced

to 2%. Viral load <1000 copies/ml – risk 2% (even without

scheduled cesarean delivery). No combination of therapies can guarantee a 0%

transmission rate.

ACOG’s Committee Opinion 2000

Viral load > 1000 copies/ml – counsel regarding the potential benefit of scheduled cesarean delivery.

No reduction in the transmission rate if C/S performed after onset of labor or rupture of membranes.

Patient’s autonomy in deciding the route of delivery must be respected.

ACOG’s Committee Opinion 2000

Patients should receive IV ZDV, starting 3 hours preoperatively.

Use prophylactic antibiotics. Schedule cesarean section at 38 weeks. Avoid amniocentesis for fetal lung maturity

determination. Use most recent viral load to direct counseling.

Case follow-up

June, July and August:

Viral load <75 copies/ml, CD4 count 120

August

Vaginal delivery at term

Modification of Obstetric Practices

Determine HIV serostatus in women who present in labor with no prenatal care.

Minimize breaks in fetal skin. Avoid invasive procedures. Minimize infant exposure to maternal blood

and secretions.

Modification of Obstetric Practices

Forceps or vacuum extraction: use as obstetric indications dictate.

Avoid vaginal trauma. Avoid fetal scalp electrodes and fetal scalp

punctures for pH. No artificial rupture of membranes (risk of

transmission increases after rupture for 4-12 hours).

Modification of Obstetric Practices

Clear infant’s airway with mechanical (not DeLee) suction.

Remove all maternal body fluids from infant’s skin immediately.

Clean baby’s skin with soap and water ASAP and prior to venipuncture, injections and application of ophthalmic prophylaxis.

Modification of Obstetric Practices

Breastfeeding is contraindicated in US. Postpartum care – contraception, pap smear.

Resources for Updated Guidelines

aidsinfo.nih.gov hivatis.org cdc.gov

Summary

HIV screening should be included in the routine panel of prenatal screening tests for all pregnant women.

Pregnancy should not be a barrier to the most potent HIV therapies.

The goal in pregnancy is to maintain the viral load at <1,000 copies/ml.

Multidisciplinary team approach to the care of pregnant women with HIV.

Perinatal transmission rates can be reduced from 25% to 2% if HIV is detected and treated early in pregnancy.

ONE TEST / TWO LIVES

Questions?

References

Minkoff H. Human Immunodeficiency Virus Infection in Pregnancy. Obstet Gynecol 2003;101:797-810.

Clark W, Lindsay M. Contemporary Management of Human Immunodeficiency Virus Infection During Pregnancy. The Female Patient 2002;27:10-16.

American College of Obstetricians and Gynecologists. Prenatal and Perinatal Human Immunodeficiency Virus Testing: Expanded Recommendations. ACOG Committee Opinion No. 304. Washington: American College of Obstetricians and Gynecologists, 2004.

References

American College of Obstetricians and Gynecologists. Scheduled Cesarean Delivery and the Prevention of Vertical Transmission of HIV Infection. ACOG Committee Opinion No. 234. Washington: American College of Obstetricians and Gynecologists, 2000.

American College of Obstetricians and Gynecologists. Joint Statement on Human Immunodeficiency Virus Screening. ACOG Statement of Policy. Washington: American College of Obstetricians and Gynecologists, 1999, reaffirmed 2006.

References

Minkoff H. Human Immunodeficiency Virus. Creasy/Resnick: Maternal-Fetal Medicine 1999:725-735.

Connor E, et al. Reduction of Maternal-Infant Transmission of Human Immunodeficiency Virus Type 1 with Zidovudine Treatment. Pediatric AIDS Clinical Trials Group Protocol 076 Study Group. N Engl J Med 1994:331:1173-1180

References

American College of Obstetricians and Gynecologists. Human Immunodeficiency Virus and Acquired Immunodeficiency Syndrome and Women of Color. ACOG Committee Opinion No. 414. Washington: American College of Obstetricians and Gynecologists, 2008.

American College of Obstetricians and Gynecologists. Human Immunodeficiency Virus. ACOG Committee Opinion No. 389. Washington: American College of Obstetricians and Gynecologists, 2007.

References

Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission. 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, July 31, 2012. http://aidsinfo.nih.gov

Duff P, Sweet R, Edwards R. Maternal and Fetal Infections. Creasy/Resnick:Maternal-Fetal Medicine 2009:770-773.