HIV in Pregnancy: Comprehensive Post-Graduate Review

Based on WHO, NACO (India EVTHS Guidelines 2024), BHIVA 2025, ACOG, and Creasy & Resnik's Maternal-Fetal Medicine

1. EPIDEMIOLOGY AND MOTHER-TO-CHILD TRANSMISSION (MTCT)

Timing of vertical transmission (untreated):

2. SCREENING AND DIAGNOSIS

2.1 Who to Screen

• Serodiscordant couples
• Women in high-prevalence areas
• Women with recent STI
• Women with symptoms of acute HIV infection
• New partners during pregnancy
• Women in direct-in-labour (DIL) scenarios with unknown status

2.2 Diagnostic Tests

Generation of HIV Tests:

• 4th generation (4G) combination test: Detects HIV-1/2 antibodies AND HIV-1 p24 antigen simultaneously. Preferred in pregnancy. Positive window period starts as early as 2 weeks post-exposure (vs. 3-4 weeks for 3G Ab tests). This is the standard for antenatal screening.
• Rapid Diagnostic Tests (RDTs): Antibody-based; used at point-of-care. NACO uses a 3-test serial algorithm: ELISA/CMIA as screening, then 2 rapid immunochromatographic tests for confirmation.

NACO Algorithm for HIV Diagnosis (India):

1. Test 1 (Screening): ELISA or CMIA (4th generation preferred) - if reactive, proceed
2. Test 2: Rapid immunodot test - if reactive, proceed
3. Test 3: Rapid immunodot test (different antigen) - if reactive = HIV confirmed

• Any discordance → Western Blot or NAT (nucleic acid testing)
• Window period: Repeat in 6 weeks if high-risk exposure with initial negative

In Labour (Direct-in-Labour / DIL cases):

• Expedited/rapid point-of-care HIV testing within 1 hour of arrival is mandatory
• Result must be available before delivery when possible
• If reactive on rapid test → initiate ART/ARV prophylaxis immediately without waiting for full confirmation
• All DIL cases with unknown status screened for HIV + syphilis at labour room entry

2.3 Additional Investigations at Diagnosis

3. MANAGEMENT IN THE ANTENATAL PERIOD

3.1 Counseling (Pre-test and Post-test)

• Nature of the test, window period, implications
• Confidentiality assurance
• Partner disclosure discussion
• Consent (written in India)

• Staged disclosure, breaking news sensitively
• Implications for her health, the pregnancy, the baby
• Absolute importance of ART adherence
• Partner testing and disclosure support
• Contraception counseling for future pregnancies
• Reassurance: with ART, MTCT <1-2%
• Infant feeding counseling (context-specific)
• Linkage to ART centre, psychosocial support

3.2 ART Initiation - "Test and Treat" (Universal ART)

3.3 NACO 2024 Preferred First-Line ART Regimen (India)

Note: Previously TLE (TDF + 3TC + Efavirenz 600mg) was the NACO first-line. The transition to TLD (with DTG) is now the preferred regimen per updated NACO/EVTHS 2024 guidelines, consistent with WHO 2021 update. DTG is preferred over EFV as the third agent.

• INSTI (Integrase Strand Transfer Inhibitor) - high barrier to resistance
• Once-daily dosing - improves adherence
• Better tolerated than EFV (fewer CNS side effects)
• Faster viral suppression
• No significant teratogenicity signal in updated data (2019 Tsepamo study revised downward; risk of NTD is approximately 0.1% when started periconception - acceptable given HIV risks)
• However: Folic acid 5mg/day should be given to all pregnant WLHIV, especially if on DTG in first trimester

• Early 2018 Botswana data showed NTD signal (~0.9%)
• Subsequent larger analysis (Tsepamo 2019, 2022) showed NTD rate ~0.1% (background rate ~0.05%) - risk small and benefit far outweighs risk
• WHO recommends DTG for all women including those who could become pregnant
• BHIVA 2025 recommends supplementation with 5mg folic acid peri-conceptionally and in first trimester

• TDF + 3TC + EFV 400/600mg (TLE) - still acceptable
• Atazanavir/ritonavir (ATV/r) or Darunavir/r (DRV/r) based regimens - if INSTI resistance
• Avoid LPV/r if possible (higher preterm birth risk vs other PIs)
• Zidovudine (AZT) can replace TDF in renal dysfunction (eGFR <50)
• In HBV co-infection: TDF/TAF + FTC/3TC must be part of the regimen (active against both HIV and HBV)

3.4 Monitoring in Antenatal Period

• At initiation of ART
• Every 4 weeks until undetectable, then every 2 months
• Mandatory at 36 weeks gestation - guides mode of delivery decision
• At delivery

• Baseline at booking (first trimester)
• Repeat at 6 months if baseline <350 cells/mm³
• Not routinely repeated if suppressed on ART and CD4 >350

• LFTs at 2 and 4 weeks after ART initiation, then regularly (BHIVA 2025)
• Renal function (TDF nephrotoxicity)
• CBC (AZT-containing regimens → anaemia)
• Early GDM screening (all PI-containing regimens and DTG → modest GDM risk)
• BP and urine protein (pre-eclampsia risk slightly increased)
• Screen and treat STIs (syphilis, gonorrhoea, chlamydia, BV)
• Mental health screening (depression, IPV)

• Defer until viral suppression achieved (VL undetectable)
• If unavoidable → multidisciplinary discussion + consider IV AZT peri-procedure

• Screen all WLHIV for TB at every visit
• If active TB diagnosed → start TB treatment first, then ART within 2-8 weeks
• Preferred ATT regimen: standard RHEZ - rifampicin, isoniazid, ethambutol, pyrazinamide
• ART backbone: TDF + 3TC + DTG (DTG dose may need adjustment with rifampicin - double DTG dose to 50mg BD with rifampicin-containing regimens, per NACO)
• IPT: safe in pregnancy; rule out active TB first

• All standard vaccines per national schedule
• Avoid live vaccines if CD4 <200 (MMR, varicella)
• Influenza (inactivated) - recommended
• COVID-19 vaccination - recommended
• Pneumococcal vaccine if CD4 <200

• TDF/FTC (Truvada) - safe in pregnancy
• Indicated if serodiscordant relationship with detectable/unknown VL partner, recent STI, IDU

4. INTRAPARTUM MANAGEMENT

4.1 Mode of Delivery

4.2 Intrapartum ART

• Continue oral ART throughout labour - do NOT stop the woman's regular regimen
• IV Zidovudine (ZDV) intrapartum infusion: Recommended by BHIVA/ACOG when VL ≥1000 copies/mL (or if mode of delivery is uncertain/emergency):
  • Loading dose: AZT 2 mg/kg IV over 1 hour
  • Maintenance: AZT 1 mg/kg/hour IV until cord clamping
  • In resource-limited settings (NACO): IV AZT may not be universally available; prioritize continued oral ART
• Direct-in-Labour (DIL) with unknown HIV status: Expedited testing → if reactive → start ART immediately (oral TLD or at minimum single-dose NVP + AZT/3TC if no TLD available)

4.3 Obstetric Practices in Labour

• Duration of ruptured membranes is a risk factor for MTCT (especially if VL is not suppressed)
• With fully suppressed VL (<50 copies/mL), the risk from prolonged ROM is minimal

4.4 Intrapartum in Caesarean Section

• Perform elective CS at 38-39 weeks (before labour onset, before ROM)
• Emergency CS: Continue IV AZT infusion
• Standard antibiotic prophylaxis (cefazolin at induction; metronidazole if indicated)
• Minimise contact with maternal blood; avoid uterine exteriorization unnecessarily
• Standard haemostasis

5. POSTPARTUM (PUERPERIUM) MANAGEMENT

5.1 Maternal Management

• ALL WLHIV continue lifelong ART postpartum - do not stop
• BHIVA 2025 Grade 1A recommendation: lifelong ART for all
• Enhanced support and follow-up in first 3 months postpartum (high risk of adherence lapse)
• First MDT HIV review: within 4-6 weeks of delivery
• Review at 6-week postnatal visit: VL, ART adherence, mental health, contraception, infant feeding

• Screen for postnatal depression (Edinburgh Postnatal Depression Scale)
• Assess for IPV (intimate partner violence)
• Peer support, counselor linkage

• Dual protection (condom + another method) for all WLHIV
• All methods generally available; drug interactions matter:
  • EFV + combined OCP → decreased OCP efficacy (liver enzyme induction)
  • DTG-based ART: minimal interaction with hormonal contraceptives
  • Depo-Provera (DMPA): effective, no significant interaction
  • IUD (copper or LNG): very effective, suitable
  • Implant (etonogestrel): check for drug interactions with PI/NNRTI-based ART
• Avoid estrogen-only pills with EFV (significant reduction in EE levels)
• Discuss permanent contraception if family complete

• Safe to try for next pregnancy when VL undetectable and stable
• Partner testing and PrEP if serodiscordant

5.2 Infant Feeding

• Breastfeeding is recommended when ART is available and maternal VL is suppressed, because the overall benefits (nutrition, protection from infections, maternal bonding) outweigh the small residual MTCT risk from breastfeeding
• NACO 2024 (India): Breastfeed exclusively for 6 months, continue with complementary foods from 6 months; wean by 12 months (or when safe alternative feeding is available)
• Exclusive breastfeeding (EBF) + maternal ART → MTCT during breastfeeding reduced to <1-2%
• Mixed feeding (breast + formula) is MORE dangerous than EBF as it increases gut permeability
• Formula feeding (replacement feeding): Only recommended when AFASS criteria are met: Affordable, Feasible, Acceptable, Safe, Sustainable
  • In India/LMICs: AFASS criteria are rarely met → breastfeeding with ART preferred
  • In high-income countries (BHIVA 2025): Formula feeding recommended for all WLHIV when maternal VL is detectable or unknown; breastfeeding acceptable if VL undetectable and woman is fully counseled and supported

• Formula feeding recommended as default
• Breastfeeding only if VL <50 copies/mL, on stable ART, full MDT support
• Do NOT resume breastfeeding after a gastroenteritis episode in infant
• Infant gastroenteritis → pause breastfeeding, discuss with paediatricians

5.3 Neonatal/Infant Management

Neonatal ARV Prophylaxis - NACO India Protocol:

• Syrup Nevirapine (NVP) 2 mg/kg/dose once daily x 6 weeks

• Syrup NVP 2 mg/kg once daily x 12 weeks

• Triple therapy (presumptive HIV treatment): AZT + 3TC + NVP (at treatment doses) x 6 weeks
• Some guidelines: AZT 4 mg/kg/dose BD + 3TC 2 mg/kg/dose BD + NVP 4-6 mg/kg/dose once daily

• Start at 6 weeks of age
• Continue until HIV infection is excluded (final negative EID test at 18 months)
• This protects against PCP (Pneumocystis jirovecii pneumonia), the most common OI in HIV-exposed infants

Early Infant Diagnosis (EID) - HIV Testing Schedule (NACO India):

Note: Maternal HIV antibodies persist until ~15-18 months in infant - therefore antibody tests are unreliable for diagnosis until 18 months. DNA PCR (nucleic acid testing on DBS) is the gold standard for EID.

• Sensitivity of HIV DNA PCR reaches 96% by 4 weeks in non-breastfeeding infants
• Sensitivity at birth: ~38-65% (higher for in-utero infection)
• Presumptive clinical diagnosis (CD4 <25%, severe OI) can be used to initiate treatment if EID unavailable

• Repeat confirmatory test immediately (second DBS)
• If confirmed → start treatment-dose ART (LPV/r + AZT + 3TC for infants <3 years; per paediatric HIV guidelines)
• Refer to paediatric HIV specialist
• Notify for national surveillance

• Continue prophylaxis as scheduled
• Continue serial testing as above
• At 18 months: sero-reversion (negative antibody test) confirms uninfected status

6. PREVENTION OF HIV ACQUISITION IN PREGNANCY (PrEP)

• TDF 300mg + FTC 200mg (Truvada) once daily - safe in pregnancy and breastfeeding
• Indications: Serodiscordant couple (partner VL detectable/unknown), sex worker, IDU, recent STI
• Discuss with NACO ART center; available under programme
• Counsel on dual protection (PrEP + condoms)

7. SPECIAL CLINICAL SCENARIOS

Newly Diagnosed in Late Pregnancy / at Labour

• Initiate ART on the SAME day as diagnosis - do not delay
• Include IV AZT intrapartum if VL unknown or high
• Intensive counseling; provide 1-month ART supply
• Rapid linkage to ART center postpartum

Woman on ART Presenting in Pregnancy with Detectable VL

• Check adherence first
• Resistance testing if VL >500-1000 copies/mL
• Do not switch while awaiting resistance results - optimize adherence
• If adherence good and VL still high → likely resistance → expert consultation

HIV + Tuberculosis Co-infection

• Most common OI in pregnancy in India
• Start TB treatment first; add ART within 2-8 weeks (sooner if CD4 <50)
• Rifampicin-based ATT significantly reduces DTG levels → use DTG 50mg BD (double dose)
• Monitor LFTs closely (hepatotoxicity risk compound)
• IPT not given if on active TB treatment

HIV + Hepatitis B Co-infection

• ART must include TDF + 3TC or FTC (both active against HBV)
• Do NOT stop ART postpartum → risk of HBV reactivation flare
• Newborn: HBV vaccine within 24 hrs + HBIG (hepatitis B immunoglobulin)

Opportunistic Infections in Pregnancy

• PCP: TMP-SMX is safe in pregnancy (avoid near term - neonatal jaundice risk)
• Cryptococcal meningitis: Liposomal amphotericin B (avoid fluconazole in 1st trimester)
• CMV retinitis: IV Ganciclovir (teratogenic in first trimester - expert guidance)
• Toxoplasmosis: Pyrimethamine + sulfadiazine (avoid in 1st trimester - pyrimethamine is folate antagonist)

8. WHO ELIMINATION TARGETS (Global & India NACO 2024)

• MTCT rate of HIV <5% in breastfeeding populations
• New paediatric HIV cases from MTCT: ≤50 per 100,000 live births
• Congenital syphilis: ≤50 per 100,000 live births

• ≥95% ANC-1 coverage
• ≥95% HIV testing coverage in pregnant women
• ≥95% syphilis testing coverage
• ≥95% ART coverage for pregnant WLHIV
• ≥95% neonatal ARV prophylaxis coverage

9. SUMMARY CARE CASCADE (NACO India)

Pregnant woman → ANC registration
        ↓
HIV screening (RDT/ELISA + syphilis RDT + HBsAg) at 1st ANC
        ↓
   Reactive → Confirmatory testing at ICTC (3-test algorithm)
        ↓
   Confirmed HIV positive → Link to ART centre (SAME DAY)
        ↓
Baseline investigations (VL, CD4, LFT, RFT, TB screen, coinfections)
        ↓
Initiate TLD (TDF+3TC+DTG) immediately - LIFELONG
        ↓
Monthly ANC monitoring (VL at 4 weeks, 12 weeks, 36 weeks, delivery)
        ↓
Intrapartum: Continue ART + IV AZT if VL ≥1000 + Avoid invasive procedures
Mode of delivery by VL at 36 weeks
        ↓
Delivery → Immediate neonatal NVP prophylaxis within 6 hours
        ↓
Postpartum: Continue maternal ART lifelong + NVP to infant 6-12 weeks
+ Breastfeeding with ART (India) or formula (high-income settings)
+ Cotrimoxazole prophylaxis to infant from 6 weeks
        ↓
EID at birth, 6w, 6m, 12m, 18m → Final sero-status confirmed at 18m

• Creasy & Resnik's Maternal-Fetal Medicine, 9th Ed. (Chapter 49: Management of HIV During Pregnancy)
• National Guidelines for Elimination of Vertical Transmission of HIV and Syphilis (NACO/MoHFW India, 2024)
• BHIVA Guidelines on Management of HIV in Pregnancy and Postpartum Period (2025)
• WHO Consolidated Guidelines on ARV Drugs (2021 update)
• ACOG Practice Bulletin on HIV in Pregnancy (2018, reaffirmed)
• IAS-USA Panel 2024 [PMID 39616604]
• Lancet 2025: Maternal viral load and perinatal HIV transmission [PMID 40652949]
• Lancet HIV 2025: Probability of vertical HIV transmission [PMID 40753992]