HIV in Pregnancy - A Complete Guide for MS Finals

1. Epidemiology and Background

• Without any intervention, HIV mother-to-child transmission (MTCT) occurs in ~25% of pregnancies, rising to ~40% if breastfeeding continues to 12 months.
• Since the landmark PACTG 076 trial (1994) - which showed ZDV monotherapy reduced MTCT from 25% to 8% - the world has seen a dramatic decline.
• With modern combination ART throughout pregnancy and no breastfeeding, MTCT is now <1% in high-income settings.
• Globally, ~2,000 HIV-exposed infants are born daily; 90% of cases are in sub-Saharan Africa.
• Nearly all pediatric HIV infection today is through perinatal transmission (not horizontal).

2. Pathophysiology of MTCT - Timing and Mechanisms

• High maternal viral load (most important)
• Low CD4+ count / immunosuppression
• Viral characteristics: chemokine receptor tropism (R5 vs. X4), resistance patterns
• Obstetric variables: delivery mode, duration of ROM, chorioamnionitis
• Seroconversion during pregnancy or breastfeeding (high-risk window)
• Co-infections: syphilis, other STIs, CMV
• Drug abuse, heterosexual transmission from high-risk partner

3. Screening in Pregnancy

CDC 3-Step Testing Algorithm:

CDC Recommendations for HIV Testing in Laboratories (Creasy & Resnik, Fig. 49.4)

• If positive → Step 2
• If negative → HIV-negative (done)

• Distinguishes HIV-1 from HIV-2 (treatment implications differ)
• If negative/indeterminate → Step 3

• Detects acute HIV-1 infection or confirms false positive

When to Repeat Testing:

• High-risk women (seropositive partner, high-prevalence area): repeat in 3rd trimester
• STI diagnosed or symptoms of acute HIV: repeat immediately
• Expedited testing during labor for women at increased risk who were not retested in 3rd trimester
• In labor with unknown status: rapid HIV test (result within 1 hour)

4. PrEP in Pregnancy

• Regimen: Tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) oral combination
• Indications: Condomless sex with a partner with detectable/unknown HIV RNA, recent STI, injection drug use
• Safe in pregnancy and postpartum/breastfeeding period

5. Baseline Workup After HIV Diagnosis in Pregnancy

• CD4+ T-cell count
• HIV RNA viral load (quantitative PCR)
• Resistance testing (genotype) - before ART initiation if viral load >500-1000 copies/mL
• Hepatitis B and C serology (affects ART choice)
• Full STI screen (syphilis, gonorrhea, chlamydia)
• TB screening (affects ART timing)
• CBC, LFTs, renal function

6. ART in Pregnancy - When to Start

• ART-naive woman: Start as soon as possible after diagnosis (ideally by end of 1st trimester)
• Already on ART: Continue the same regimen (if virologically suppressed and no teratogenicity concerns)
• Do NOT interrupt ART postpartum - continue lifelong

7. ART Regimen Selection in Pregnancy

Preferred Backbone: 2 NRTIs

Preferred 3rd Agent: INSTI (Integrase Strand Transfer Inhibitor)

Drugs to AVOID in Pregnancy:

Special Situation - High Viral Load Presenting Late:

• Consider raltegravir as part of the regimen (proven more rapid VL suppression than other ARVs in this scenario) - per DHHS 2025

8. Monitoring During Pregnancy

9. Mode of Delivery

• Historically: IV ZDV (2 mg/kg loading then 1 mg/kg/hr) was given during labor to all HIV-positive women
• Current recommendation: If VL is consistently undetectable on cART, IV ZDV is NOT required - continue current oral ART regimen through labor and delivery
• IV ZDV is still recommended when VL is detectable/unknown near delivery or when ART was not received

• Avoid fetal scalp electrodes (FSE) - breach skin barrier
• Avoid fetal scalp blood sampling
• Minimize instrumental delivery
• Avoid amniotomy unless necessary
• Minimize episiotomy

10. Postpartum Management

• Continue ART lifelong (WHO Option B+, DHHS recommendation) - do NOT stop after delivery
• Monitor viral load 6 weeks postpartum
• Emotional support, adherence counseling
• Contraception counseling (note: some ARVs interact with hormonal contraceptives - particularly boosted PIs and NNRTIs can reduce efficacy of combined oral contraceptives)

11. Infant Feeding

12. Neonatal Management

Neonatal ARV Prophylaxis vs. Presumptive Therapy

• ZDV alone for 4-6 weeks

• Received no antepartum ART, OR
• Received only intrapartum ART, OR
• Had suboptimal viral suppression (VL ≥50 copies/mL) within 4 weeks of delivery, OR
• Had acute/primary HIV infection during pregnancy or breastfeeding

• ZDV + 3TC + Nevirapine (3 doses NVP in first week of life + 6 weeks ZDV) - shown more efficacious than ZDV alone
• Or a full 3-drug regimen at treatment doses

Neonatal HIV Diagnosis (Serial NAAT):

• Birth (within 48 hours): Detects in utero infection
• 14-21 days: Detects intrapartum infection (may be negative at birth)
• 1-2 months
• 4-6 months

13. Effects of HIV/ART on Pregnancy Outcomes

Maternal HIV Effects:

• Generally asymptomatic during pregnancy in high-income countries
• Advanced disease: risk of reactivating CMV, toxoplasmosis, HSV
• Higher risk of STIs (syphilis, HTLV-1, Hep C co-infections in endemic areas)

ART Effects on Fetus/Neonate:

14. Summary of Risk Reduction - A Framework

No treatment           → MTCT risk 25-40%
ZDV monotherapy        → MTCT risk ~8% (PACTG 076)
Elective C/S alone     → MTCT risk ~2% (pre-HAART era)
cART + vaginal birth   → MTCT risk <1%
cART + no breastfeed   → MTCT risk <0.1% (approaching zero)

15. Recent Evidence to Know (2024-2025)

16. Exam High-Yield Points - Quick Bullets

• The 4th-generation test (p24 Ag + Ab) diagnoses HIV 2 weeks earlier than older tests
• Opt-out testing has significantly improved uptake in pregnancy
• MTCT risk without treatment: 25% (pregnancy alone), 40% (including breastfeeding to 12 months)
• MTCT risk with optimal modern cART: <1%
• Preferred ART in pregnancy (2025): DTG or BIC + TDF/FTC (or TAF/FTC)
• Elective C/S at 38 weeks is indicated when VL ≥1,000 copies/mL near delivery
• IV ZDV intrapartum is NOT needed if VL is undetectable on cART
• Neonatal prophylaxis: ZDV x 4-6 weeks (low risk) OR 3-drug ART (high risk)
• Infant diagnosis: DNA/RNA PCR at 48 hrs, 14-21 days, 1-2 months, 4-6 months (NOT antibody test before 18 months)
• Breastfeeding in US/UK: Formula feeding preferred; with undetectable maternal VL, breastfeeding now an option per 2025 DHHS counseling guidelines
• LPV/r is associated with preterm birth - use DRV/r or ATV/r if PI needed
• Do not stop ART postpartum - continue lifelong