HIV and hepatitis in pregnancy
Hepatitis B, hepatitis C and HIV in pregnancy: serology, transmission and prevention
These three blood-borne viruses are common in Pakistan, where unsafe injections spread hepatitis C and B. CPSP asks you to read hepatitis B serology, to name the factor that decides whether the baby is infected, and to explain how vaccine, immunoglobulin and antiviral drugs prevent transmission.
Hepatitis B virus: the essentials
- Partly double-stranded DNA virus that replicates through an RNA intermediate using reverse transcriptase. Its DNA forms cccDNA in the hepatocyte nucleus, which antivirals cannot remove, so infection relapses when drugs stop and can reactivate with rituximab.
- Not very cytopathic: liver injury comes from CD8 T cells killing infected hepatocytes. Babies infected at birth are immune tolerant (very high DNA, normal ALT).
- Spread by blood, sex and mother to child. Needlestick risk from an infected source: HBV about 30%, HCV 3%, HIV 0.3%.
- Extrahepatic: serum sickness-like prodrome (immune complexes), membranous nephropathy, polyarteritis nodosa; HCC even without cirrhosis (viral DNA integration, HBx protein).
Reading hepatitis B serology
| Marker | Meaning |
|---|---|
| HBsAg | Infected now; present over 6 months means chronic |
| Anti-HBs | Immune; alone means vaccinated (vaccine is recombinant HBsAg only); 10 mIU/mL or more is protective |
| IgM anti-HBc | Acute infection; the only marker in the window period |
| IgG anti-HBc | Ever infected (with anti-HBs: past infection, immune) |
| HBeAg | Active replication, high infectivity |
| HBV DNA | Best quantitative measure of infectivity |
- HBsAg positive, HBeAg negative, but high DNA and raised ALT: precore mutant. HBsAg positive, HBeAg negative, low DNA, normal ALT: inactive (HBeAg-negative) chronic infection.
- Hepatitis D is a defective RNA virus needing HBsAg for its envelope; superinfection accelerates cirrhosis.
Hepatitis B in pregnancy
- Screen every woman at booking with HBsAg; if positive, check HBeAg, HBV DNA and liver tests.
- Most transmission happens at birth from maternal blood and secretions; a minority is in utero when DNA is very high.
- Untreated risk: 70–90% if HBeAg positive, much lower if anti-HBe positive. Acute hepatitis B near term carries high risk.
- Age decides chronicity: about 90% of babies infected at birth become chronic, under 5% of adults. Maternal HBeAg crosses the placenta and induces T-cell tolerance.
| Measure | How it works |
|---|---|
| Hepatitis B vaccine at birth, then routine EPI doses | Active immunity, takes weeks |
| HBIG (with vaccine, within 12 hours, different thigh) | Passive ready-made anti-HBs neutralises virus at once |
| Tenofovir from 28–32 weeks if HBV DNA over 200,000 IU/mL (or HBeAg positive without DNA testing) | Lowers maternal viraemia, preventing in utero and intrapartum infection |
- Babies under 2,000 g respond poorly: the birth dose is not counted and three further doses are given.
- Breastfeeding is allowed once the baby has vaccine and HBIG. The vaccine is not live and is safe in any trimester.
- Test the baby at 9–12 months with HBsAg and anti-HBs (anti-HBc may be maternal IgG for up to 18–24 months).
Hepatitis C
- RNA flavivirus; RNA polymerase lacks proofreading, so quasispecies and a hypervariable envelope (E2) escape antibodies: 70–85% become chronic and there is no vaccine.
- In Pakistan it is the commonest cause of chronic liver disease, spread mainly by reused syringes, unsafe procedures and unscreened blood; genotype 3 predominates.
- Anti-HCV shows exposure; HCV RNA PCR confirms current infection. Direct-acting antivirals (sofosbuvir-based, about 12 weeks) cure over 90% but are not used in pregnancy. Ribavirin is teratogenic: contraception during and for 6 months after, for men too.
- Vertical transmission about 5% if RNA positive, higher with HIV co-infection and high viral load. Avoid fetal scalp electrodes and fetal blood sampling; caesarean section gives no benefit; breastfeeding is allowed.
- Pregnancy dampens T-cell attack: ALT falls and RNA rises, with a postpartum flare.
- Babies: HCV RNA after 2 months, or antibody at 18 months (maternal antibody persists until then).
HIV in pregnancy
- Retrovirus; gp120 binds CD4 then the CCR5 or CXCR4 co-receptor; gp41 mediates fusion. Homozygous CCR5 delta-32 confers resistance.
- Maternal plasma viral load is the strongest determinant of transmission: under 1% on suppressive ART, 15–45% untreated. Start ART as early as possible (integrase inhibitors such as dolutegravir lower the load fastest).
- Other risk factors: membranes ruptured over 4 hours, chorioamnionitis, invasive procedures, preterm birth, breastfeeding without ART.
- Delivery is planned by the viral load at 36 weeks: vaginal birth if undetectable, caesarean section if high. IV zidovudine in labour crosses the placenta to give the fetus pre-exposure cover when the load is detectable.
- Infant diagnosis needs HIV PCR (nucleic acid test), because maternal IgG persists up to 18 months. Adults are screened with a fourth-generation antigen/antibody assay (p24 antigen shortens the window).
- Absolute CD4 count falls in pregnancy by haemodilution while the CD4 percentage stays stable.
- Nevirapine causes rash with hepatotoxicity, especially in women with CD4 above 250. HIV-2 is intrinsically resistant to NNRTIs.
- Undetectable equals untransmittable: a partner with a sustained undetectable load does not transmit sexually.
Remember Hepatitis B: the baby is infected at birth, so protect at birth. HIV: the mother's viral load decides.
Exam trap Anti-HBc in an infant may be maternal IgG; judge the baby by HBsAg and anti-HBs.
Exam trap An infant of an HIV-positive mother cannot be diagnosed by antibody tests before 18 months.
Test yourself on this topic
5 of the 77 questions in our bank on this topic. Choose an answer to see why every option is right or wrong.
A pregnant woman with HIV and a CD4 count of 420 cells/µL is started on a regimen containing nevirapine. Three weeks later she has fever, a widespread rash and an ALT of 900 U/L. Which known risk of this drug explains her illness?
Answer: Severe hepatotoxicity with rash
Nevirapine can cause severe, sometimes fatal, hepatotoxicity and skin reactions, usually in the first weeks of therapy. The risk is much higher in women with CD4 counts above 250 cells/µL, which includes many pregnant women. This is why nevirapine is no longer a preferred drug for women starting treatment. Lactic acidosis is linked to older NRTIs, crystal nephropathy to indinavir, and marrow suppression to zidovudine.
Nevirapine toxicity
- NNRTI
- Hepatitis + rash in early weeks
- Risk higher in women with CD4 > 250
- Single doses select resistance
Remember Nevirapine: liver and skin, worst in women with good CD4.
Exam trap A good CD4 count raises, not lowers, the risk of nevirapine hepatotoxicity in women.
Why the other options are wrong
- Lactic acidosis from mitochondrial damage Linked to older NRTIs such as stavudine.
- Crystal nephropathy with renal colic Linked to indinavir.
- Bone marrow suppression with anaemia Linked to zidovudine.
- Abacavir-type HLA hypersensitivity A different drug and HLA type.
In the labour room, a baby born to an HBsAg- and HBeAg-positive mother receives hepatitis B immunoglobulin into one thigh and the first vaccine dose into the other. How does the immunoglobulin protect the baby during the first weeks of life?
Answer: Ready-made anti-HBs neutralises the virus
Hepatitis B immunoglobulin is pooled human plasma with a high titre of anti-HBs. It gives immediate passive immunity by binding and neutralising virus the baby has been exposed to at delivery. The vaccine takes weeks to induce the baby's own anti-HBs, so the two are complementary. Immunoglobulin has no antiviral enzyme action and does not activate T cells.
HBIG vs vaccine
- HBIG: passive, immediate
- Vaccine: active, takes weeks
- Give both, different sites
- Within 12 hours of birth
Remember Borrowed antibody now, own antibody later.
Exam trap Giving both into the same site can reduce the vaccine response; use separate limbs.
Why the other options are wrong
- It stimulates the baby to make anti-HBs That is the role of the vaccine (active immunity).
- It blocks the viral reverse transcriptase That is how tenofovir acts.
- It activates the baby's cytotoxic T cells Passive antibody does not prime T cells.
- It induces interferon in the hepatocytes Interferon is not induced by immunoglobulin.
A 30-year-old woman at 26 weeks is HBsAg and HBeAg positive with an HBV DNA of 3 × 10⁷ IU/mL and normal liver tests. Which drug is started at about 28 weeks to reduce transmission to her baby?
Answer: Tenofovir disoproxil
In women with a high HBV DNA, a nucleotide analogue given from the late second or early third trimester lowers the viral load at delivery and reduces failure of neonatal immunoprophylaxis. Tenofovir disoproxil is preferred because it is potent, has a high barrier to resistance and has a large body of pregnancy safety data. Entecavir lacks adequate pregnancy data, interferon is contraindicated in pregnancy, and ribavirin is teratogenic and not active against HBV.
HBV antiviral in pregnancy
- High HBV DNA in mother
- Start tenofovir at 28–32 weeks
- Continue until after delivery
- Baby still needs vaccine + HBIG
Remember Tenofovir is the pregnancy drug for HBV.
Exam trap Antiviral therapy adds to, but never replaces, birth-dose vaccine and immunoglobulin.
Why the other options are wrong
- Entecavir Little pregnancy safety data.
- Pegylated interferon alfa Contraindicated in pregnancy (antiproliferative).
- Ribavirin Teratogenic and used for HCV, not HBV.
- Adefovir Weak, with more renal toxicity and resistance.
A 20-week pregnant staff nurse in a dialysis unit is anti-HBs negative and has never been vaccinated against hepatitis B. Which statement about giving her hepatitis B vaccine now is correct?
Answer: It is safe: it contains no live virus
The hepatitis B vaccine contains recombinant HBsAg produced in yeast. It is a non-infectious subunit vaccine and cannot cause infection in the mother or fetus. A non-immune pregnant woman at ongoing risk of exposure should therefore be vaccinated. Live vaccines such as MMR and varicella are the ones avoided in pregnancy.
HBV vaccine in pregnancy
- Recombinant HBsAg subunit
- Non-infectious
- Give if at risk, any trimester
- Avoid live vaccines instead
Remember No live virus, no fetal risk.
Exam trap Do not confuse inactivated or subunit vaccines with live attenuated ones.
Why the other options are wrong
- It must wait until after delivery No need to delay; she remains at risk.
- Only immunoglobulin may be given Immunoglobulin is for after an exposure, not ongoing protection.
- It is safe only in the third trimester Safe in any trimester.
- It risks infecting the fetus A subunit vaccine cannot infect anyone.
A pregnant woman is found to have HIV-2 rather than HIV-1 infection. Which class of antiretroviral drugs is ineffective against her virus?
Answer: Non-nucleoside reverse transcriptase inhibitors
HIV-2 reverse transcriptase has a different structure at the binding pocket used by non-nucleoside inhibitors, so nevirapine and efavirenz do not inhibit it. NRTIs, integrase inhibitors such as dolutegravir and some boosted protease inhibitors do work. HIV-2 is also less transmissible to the baby than HIV-1, but it still needs an effective regimen.
HIV-2
- Intrinsically resistant to NNRTIs
- Nevirapine, efavirenz ineffective
- Use NRTIs + integrase inhibitor
- Lower vertical transmission than HIV-1
Remember HIV-2: no NNRTIs.
Exam trap Standard HIV-1 viral load assays may not detect HIV-2.
Why the other options are wrong
- Nucleoside reverse transcriptase inhibitors Active against HIV-2.
- Integrase strand-transfer inhibitors Active against HIV-2.
- Boosted protease inhibitors Some are active against HIV-2.
- All classes work equally well NNRTIs do not work against HIV-2.
Where this sits in the CPSP syllabus
- Obstetrics & Gynaecology, Paper 2: Infection in obstetrics and gynaecology, Hepatitis B and C and HIV in pregnancy: transmission and prevention