Antiretroviral Therapy in Pregnancy

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Antiretroviral Therapyin Pregnancy

• Jane Hitti, MD, MPH
• University of Washington

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2006 Approved Antiretrovirals

• Nucleoside / tide reverse transcriptase
  inhibitors
• Zidovudine
• Didanosine
• Zalcitabine
• Stavudine
• Lamivudine
• Abacavir
• Emtricitabine
• Tenofovir
• Non-nucleoside reverse transcriptase inhibitors
• Delavirdine
• Nevirapine
• Efavirenz

• Protease inhibitors
• Indinavir
• Saquinavir
• Nelfinavir
• Amprenavir
• Fosamprenavir
• Lopinavir
• Atazanavir
• Ritonavir
• Fusion inhibitors
• Enfuvirtide

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Fusion Inhibitors
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Fusion Inhibitors
Reverse Transcriptase Inhibitors
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Fusion Inhibitors
Protease Inhibitors
Reverse Transcriptase Inhibitors
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HIV Treatment Options During Pregnancy

• Almost all women receive 3-drug regimens
• Protease inhibitor 2 nucleoside analogs
• Triple nucleosides
• NNRTI regimens used less frequently
• ZDV monotherapy rarely used

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What are the goals of HIV treatment during
pregnancy?

• 1. Optimal medical care for the mother
• Avoid induction of viral resistance with
  suboptimal regimen
• 2. Reduction or prevention of perinatal
  transmission
• Zidovudine monotherapy acceptable
• Include zidovudine in any multi-drug regimen if
  possible
• 3. Avoid toxicity to mother or fetus

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Antiretroviral drugs in pregnancy

• Risks
• Unknown long-term effects on fetus
• Pharmacokinetics not known for some drugs
• Effect of ZDV or brief ART for maternal health

• Benefits
• Low viral load minimizes HIV transmission risk
• ART benefits mother

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Case Planning a pregnancy

• Ms W is a 30 year old woman with chronic
  hypertension, diabetes, morbid obesity and HIV.
  She has irregular menses and has never been
  pregnant, but wishes to have children.
• HIV RNA 3,000 CD4 gt 500
• Hypertension and diabetes are poorly controlled

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Management

• What is the most important change she needs to
  make in her health status before becoming
  pregnant?
• Suppress viral load to undetectable
• OR
• Optimize control of her hypertension and diabetes

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Outcome

• Ms W began ovulating regularly and conceived
  shortly after her endocrinologist prescribed
  metformin.
• She was hospitalized for complications of
  diabetes and hypertension for the last 12 weeks
  of her pregnancy.
• She had a healthy girl at 36 weeks gestation.
• Her daughter is HIV negative.

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Case Drug toxicity

• 29 year old Latina G1P0 diagnosed with HIV in
  this pregnancy. 5 weeks after starting
  nevirapine-containing ART (28 weeks gestation)
  she develops RUQ pain and nausea.
• Liver function tests abnormal
• Jaundice

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Drug toxicity, cont'd

• What is the best management plan?
• Stop all antiretroviral therapy
• OR
• Follow closely and wait to see what happens

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Drug toxicity Outcome

• Liver function abnormalities improved within 2
  weeks of stopping ART.
• She re-started ZDV monotherapy and delivered by
  Cesarean.
• Her daughter is HIV-negative.

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Case Virologic failure

• 43 year old Liberian immigrant, G7P4, newly
  diagnosed as HIV early in pregnancy. Starts on
  3-drug ART regimen. Viral loads are as follows
• Baseline 25,000 copies/mL
• 4 weeks after starting ART 31,000 copies/mL

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Virologic failure, cont'd

• Pt acknowledges occasional missed meds says she
  will do better
• 8 wk viral load 51,000
• HIV genotype no resistance mutations

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Virologic failure, cont'd

• Patient misses several appointments and appears
  again at 35 weeks' gestation. She acknowledges
  that she has not ever taken ART medications.
• What are the options for management now?

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Adherence to ART during after pregnancy

• 445 pregnant women in observational cohort with
  follow-up to 1 yr postpartum
• Adherence self-report in pregnancy, 6, 24 48
  wks PP
• Perfect adherence no missed doses in past 4 days

Bardeguez et al, CROI Abstract 706
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Adherence during after pregnancy
Perfect adherence
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Predictors of poor adherence in pregnancy

• Predictive
• Initiated ART prior to pregnancy
• AIDS
• Missed prenatal vitamins
• Alcohol or marijuana
• Depression

• Not predictive
• Age
• Race / ethnicity
• Education
• Planned pregnancy
• Regimen intensity
• Pill burden
• Meal restrictions

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Antiretroviral Pregnancy Registry

• Prospective reports of exposure to any
  antiretroviral agent during pregnancy
• Phone [phone], ext. 58465

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Resources

• HIV / AIDS Treatment Guidelines
• www.aidsinfo.nih.gov
• Antiretroviral Pregnancy Registry
• pregnancyregistry.gsk.com/antiretroviral.html