What is the recommended treatment regimen for a pregnant woman with Human Immunodeficiency Virus (HIV)?

HIV in Pregnancy: Oral Exam Case

Case Presentation

A 28-year-old G2P1 woman at 16 weeks gestation presents for her first prenatal visit. She was diagnosed with HIV-1 infection 3 years ago and has been on tenofovir/emtricitabine/lopinavir-ritonavir (TDF/FTC/LPV/r) with good viral suppression (undetectable viral load for the past year). Her CD4 count is 450 cells/mm³. She asks whether she should continue her current regimen during pregnancy.

Key Questions to Address

1. Should this patient continue her current antiretroviral regimen?

No, this patient should be switched from tenofovir/emtricitabine to a zidovudine/lamivudine-based backbone, particularly given she is on lopinavir/ritonavir. 1

The BMJ guidelines provide a strong recommendation against the specific combination of TDF/FTC/LPV/r in pregnancy due to increased risks of early neonatal death, preterm delivery <34 weeks, and stillbirth compared to zidovudine/lamivudine-based regimens. 1

• For pregnant women on TDF/FTC combined with other antiretrovirals (not LPV/r), there is a weak recommendation to switch to zidovudine/lamivudine-based therapy 1
• The evidence is strongest and the recommendation most definitive when TDF/FTC is combined specifically with ritonavir-boosted lopinavir 1

2. What is the recommended antiretroviral regimen for this patient?

The recommended regimen is zidovudine 300 mg twice daily plus lamivudine combined with an appropriate third agent (such as ritonavir-boosted lopinavir, darunavir/ritonavir, atazanavir/ritonavir, efavirenz, or raltegravir). 1

Maternal dosing specifics: 2

• Zidovudine 300 mg orally twice daily in combination with other antiretrovirals 2
• Continue throughout pregnancy until labor onset 2

Intrapartum management: 1, 2

• During labor: IV zidovudine 2 mg/kg loading dose over 1 hour, followed by continuous infusion of 1 mg/kg/hour until umbilical cord clamping 1, 2
• Continue other antiretrovirals orally during labor 1

Neonatal prophylaxis: 1, 2

• Start within 12 hours of birth 2
• Zidovudine 2 mg/kg orally every 6 hours (or 1.5 mg/kg IV every 6 hours if unable to take oral) for 6 weeks 1, 2

3. When should antiretroviral therapy be initiated if the patient was treatment-naïve?

For treatment-naïve pregnant women with HIV-1 RNA >1000 copies/mL, initiate combination antiretroviral therapy (HAART) ideally after the first trimester, though therapy should not be delayed if the woman requires treatment for her own health. 1

Algorithm for treatment-naïve patients: 1

• CD4 <350 cells/mm³ OR symptomatic disease: Start HAART immediately regardless of trimester
• CD4 ≥350 cells/mm³ AND viral load >1000 copies/mL: Consider delaying until after first trimester (after 14 weeks) to minimize fetal exposure during organogenesis
• CD4 ≥350 cells/mm³ AND viral load <1000 copies/mL: May use zidovudine monotherapy starting after first trimester, OR initiate HAART

4. What are the exceptions where TDF/FTC might still be preferred?

Women may choose TDF/FTC-based regimens despite pregnancy in specific clinical scenarios: 1, 3

• Severe anemia (where zidovudine's hematologic toxicity is prohibitive) 1
• Lamivudine-resistant hepatitis B with high risk of vertical transmission 1, 3
• Documented zidovudine-resistant or lamivudine-resistant HIV 1
• Drug allergy or serious drug interactions with zidovudine/lamivudine 1
• Alternatives not available 1
• Strong patient preference for once-daily regimen (though most women prioritize avoiding neonatal death over pill burden) 1

5. What monitoring is required during pregnancy?

Monitoring schedule: 3

• HIV antibody testing every 2-3 months to confirm continued negative status (for PrEP patients) or viral suppression (for treatment patients) 3
• Assess medication adherence at each visit, as efficacy is highly dependent on daily adherence 3
• Monitor for hematologic toxicity, particularly with zidovudine (hemoglobin, granulocyte count) 2
• Viral load assessment to guide delivery planning (elective cesarean if >1000 copies/mL at 34-36 weeks) 1

6. What are the critical safety considerations with zidovudine?

Hematologic toxicity is the primary concern: 2

• Dose interruption required if: 2

  • Hemoglobin <7.5 g/dL or reduction >25% from baseline
  • Granulocyte count <750 cells/mm³ or reduction >50% from baseline

• Use with caution if baseline granulocyte count <1000 cells/mm³ or hemoglobin <9.5 g/dL 2

• Dose interruption does not eliminate need for transfusion in severe anemia 2

• Consider adjunctive epoetin alfa if marrow recovery occurs and resumption of therapy is needed 2

Renal impairment dosing: 2

• CrCl <15 mL/min or on dialysis: reduce to 100 mg every 6-8 hours 2

7. What are common pitfalls to avoid?

Critical errors to prevent:

• Never discontinue only some antiretrovirals - if stopping therapy in first trimester, stop all drugs simultaneously (or stop NRTIs 3-7 days after stopping NNRTIs due to long half-life) 1
• Do not use nevirapine in women with CD4 >250 cells/mm³ due to severe hepatotoxicity risk unless benefit clearly outweighs risk 1
• Do not delay treatment if maternal health requires it - the first trimester consideration applies only to women who don't need immediate therapy 1, 2
• Ensure accurate pediatric dosing calculations - prescribers must calculate dose based on body weight and not exceed adult doses 2
• Do not confuse tenofovir disoproxil fumarate (TDF) with tenofovir alafenamide (TAF) - the safety concerns may not apply equally to TAF 1

8. What about postpartum management?

Postpartum antiretroviral decisions: 1

• Women who started therapy solely for prevention of vertical transmission may discontinue after delivery if CD4 and clinical status don't warrant continued treatment 1
• When discontinuing, stop all drugs simultaneously (or NRTIs 3-7 days after NNRTIs) 1
• Women who require ongoing treatment for their own health should continue HAART postpartum 1
• Breastfeeding is contraindicated in the United States for HIV-infected mothers to avoid postnatal transmission risk 4

9. What is the evidence basis for these recommendations?

The PROMISE trial (2016) demonstrated: 1

• Similar efficacy in reducing vertical transmission between TDF/FTC/LPV/r and AZT/3TC-based regimens 1
• However, composite safety outcomes showed TDF/FTC/LPV/r increased early prematurity, stillbirth, and neonatal death compared to AZT/3TC regimens 1
• This led to the strong recommendation against TDF/FTC/LPV/r specifically 1

Historical context: 1

• PACTG protocol 076 established zidovudine's role in preventing vertical transmission, reducing transmission from 24.9% to 7.8% 1
• Zidovudine remains the mainstay of perinatal prevention 10+ years after initial trials 1

10. Are there newer alternatives to consider?

Integrase inhibitors show promise: 5

• Dolutegravir with tenofovir alafenamide/emtricitabine is recommended for pregnant women due to high antiviral efficacy and low adverse birth outcomes 6
• INSTI-based regimens achieve more rapid viral load suppression than NNRTI regimens 5
• A US cohort study showed no perinatal HIV transmission and no neural tube defects with INSTI use 5
• However, the strongest guideline evidence still supports zidovudine/lamivudine backbones 1

Important caveat: Descovy (emtricitabine/tenofovir alafenamide) is NOT approved for PrEP in cisgender women for prevention from receptive vaginal sex 6