Antiviral drugs used in Obstetrics and gynaecology
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Antiviral Drugs Used in Obstetrics and Gynaecology
Antiviral agents in OB/GYN are used primarily for herpesviruses (HSV, VZV, CMV), hepatitis B and C viruses, influenza, and HIV. Below is a systematic breakdown by indication.
1. Herpes Simplex Virus (HSV) in Pregnancy
HSV infection during pregnancy carries significant risk - neonatal herpes mortality exceeds 40% even with antiviral therapy. Treatment regimens in pregnancy differ from non-pregnant adults due to altered pharmacokinetics.
First-line agents: Acyclovir and Valacyclovir
Both are safe and FDA-acceptable in pregnancy. Acyclovir is a guanosine analogue that inhibits viral DNA polymerase after phosphorylation by viral thymidine kinase. Valacyclovir is the L-valyl ester prodrug of acyclovir with improved oral bioavailability.
CDC-Recommended Treatment of HSV During Pregnancy (Creasy & Resnik's Maternal-Fetal Medicine):
| Indication | Acyclovir | Valacyclovir |
|---|---|---|
| Primary/first-episode infection | 400 mg PO TID x 7-10 days | 1 g PO BD x 7-10 days |
| Symptomatic recurrent episode | 400 mg PO TID x 2 days, or 800 mg BD x 5 days | 500 mg PO BD x 3 days, or 1 g PO OD x 5 days |
| Daily suppression (from 36 weeks) | 400 mg PO TID | 500 mg PO BD |
Key points:
- Suppressive therapy from 36 weeks' gestation reduces the incidence of active lesions at term and the need for cesarean delivery
- Because the risk of neonatal herpes is greatest in mothers with a primary episode during pregnancy, antiviral treatment of all initial episodes of genital HSV in pregnancy is strongly recommended
- Acyclovir has been demonstrated safe for suppressive therapy for 6 years or longer
- Topical acyclovir is NOT recommended as it does not alter the course of infection
HSV Hepatitis in Pregnancy
Primary HSV hepatitis in pregnancy carries maternal and perinatal mortality rates of ~39%. IV acyclovir is the treatment of choice.
2. Varicella-Zoster Virus (VZV) in Pregnancy
VZV (chickenpox) can infect up to 2% of adults and has serious consequences in pregnancy:
- Congenital varicella syndrome (skin scarring, limb hypoplasia, ocular defects, CNS abnormalities) if primary infection in first 20 weeks
- Neonatal varicella - potentially fatal if maternal rash appears within 5 days before to 2 days after delivery
Treatment:
- Acyclovir / Valacyclovir - used for maternal varicella in pregnancy, particularly to reduce severity and prevent pneumonia
- Infants with suspected VZV exposure should receive varicella-zoster immune globulin (VariZIG) for prophylaxis OR treatment with acyclovir or valacyclovir
3. Cytomegalovirus (CMV)
CMV is the most common congenital infection and a leading cause of sensorineural hearing loss and neurodevelopmental disability. Primary CMV affects 1%-4% of seronegative women during pregnancy with a 30%-40% rate of fetal transmission.
Treatment:
- Ganciclovir (IV) - used for serious maternal CMV infections (hepatitis, end-organ disease). Data in pregnancy are sparse; it is unknown whether maternal treatment prevents fetal infection.
- Foscarnet (phosphonoformate) - an alternative for severe CMV infections; safety data in pregnancy are similarly sparse and its use is reserved for cases where ganciclovir is contraindicated (e.g., ganciclovir-resistant CMV).
- Valganciclovir (oral) - prodrug of ganciclovir; limited data in pregnancy.
- No vaccine is currently available; prevention relies on hygiene (hand washing after contact with saliva/urine).
4. Hepatitis B Virus (HBV) in Pregnancy
HBV is a major concern in pregnancy, with vertical transmission rates of 70%-90% in HBsAg+/HBeAg+ mothers without prophylaxis.
Antivirals used:
| Drug | Status in Pregnancy |
|---|---|
| Tenofovir disoproxil fumarate (TDF) | Preferred - a meta-analysis confirmed improved viral suppression, reduced mother-to-child transmission, no significant adverse maternal or fetal events |
| Telbivudine | Acceptable - same meta-analysis showed similar outcomes |
| Lamivudine | No longer preferred - high risk of viral resistance and cross-resistance to other antivirals; crosses placenta freely and found in breast milk at serum-equivalent concentrations; avoid in first trimester |
| Interferon-alpha (IFN-α) | Does NOT cross placenta; potential benefit vs. risk of immediate therapy vs. delayed post-delivery treatment must be weighed; not routinely recommended in pregnancy |
Women on chronic HBV therapy who become pregnant can continue treatment, but stage of liver disease and fetal risk must be weighed. All HBsAg-positive mothers' infants should receive HBV vaccine + hepatitis B immune globulin (HBIG) within 12 hours of birth.
5. Hepatitis C Virus (HCV) in Pregnancy
Direct-acting antivirals (DAAs) - e.g., sofosbuvir-based regimens - achieve cure rates >95% in the general population. However, current guidelines generally recommend deferring treatment until after delivery due to insufficient safety data in pregnancy. Referral to gastroenterology/infectious disease is recommended for HCV-positive pregnant women.
6. Influenza in Pregnancy
Pregnant women are at significantly higher risk for severe influenza and its complications (pneumonia, preterm birth, mortality).
Antivirals used:
| Drug | Notes |
|---|---|
| Oseltamivir (Tamiflu) | First-line; 75 mg BD x 5 days for treatment. Start within 48 hours of onset (but initiate even if >48 hrs). Also used for post-exposure prophylaxis: 75 mg OD x 7 days (extend to 10 days for household exposure) |
| Zanamivir (inhaled) | Approved alternative; safe in pregnancy |
| Peramivir (IV) | Approved alternative; safe in pregnancy |
| Amantadine | CONTRAINDICATED in pregnancy - associated with teratogenicity in animal models |
| Rimantadine | Generally avoided in pregnancy |
All three neuraminidase inhibitors (oseltamivir, zanamivir, peramivir) are considered safe. Antiviral treatment is most effective within 48 hours of symptom onset, but a pending or negative test should NOT delay treatment if clinical suspicion is high.
7. HIV in Pregnancy
Antiretroviral therapy (ART) is the cornerstone of preventing mother-to-child transmission (MTCT) of HIV.
Goals of ART in pregnancy:
- Suppress maternal viral load to undetectable levels (reduces MTCT risk to <1%)
- Maintain maternal health
- Provide post-exposure prophylaxis to the neonate
Key antiretroviral classes used:
| Class | Examples | Notes |
|---|---|---|
| NRTIs (backbone) | Tenofovir + emtricitabine/lamivudine | Preferred; lamivudine & tenofovir show comparable birth defect prevalence (~2.8%) per the US Antiretroviral Pregnancy Registry |
| INSTIs | Dolutegravir, raltegravir | Preferred third agents; rapid viral suppression |
| PIs (boosted) | Atazanavir/ritonavir, darunavir/ritonavir | Alternative options |
| NNRTIs | Efavirenz | Historically avoided in first trimester but now generally considered acceptable |
| Zidovudine (AZT) | IV intrapartum in selected high-risk cases | Classic PACTG 076 regimen component |
Neonatal prophylaxis: Infants born to HIV-positive mothers should receive antiretroviral prophylaxis (typically zidovudine ± nevirapine ± lamivudine) starting within hours of birth, with duration based on maternal viral load and risk stratification.
Summary Table
| Virus | Drug | Route | Use in Pregnancy |
|---|---|---|---|
| HSV | Acyclovir | Oral/IV | First-line; treatment + suppression |
| HSV | Valacyclovir | Oral | First-line; treatment + suppression |
| VZV | Acyclovir/Valacyclovir | Oral/IV | Maternal chickenpox; neonatal VZV |
| CMV | Ganciclovir | IV | Severe maternal CMV (limited data) |
| CMV | Foscarnet | IV | Severe/resistant CMV (limited data) |
| HBV | Tenofovir (TDF) | Oral | Preferred for HBV suppression |
| HBV | Telbivudine | Oral | Acceptable alternative |
| HBV | Lamivudine | Oral | No longer preferred (resistance) |
| HBV | IFN-alpha | SC/IM | Used cautiously; does not cross placenta |
| Influenza | Oseltamivir | Oral | First-line treatment + prophylaxis |
| Influenza | Zanamivir | Inhaled | Safe alternative |
| Influenza | Peramivir | IV | Safe alternative |
| Influenza | Amantadine | - | CONTRAINDICATED (teratogenic) |
| HIV | Multiple ART combinations | Oral/IV | Mandatory throughout pregnancy |
Sources: Creasy & Resnik's Maternal-Fetal Medicine: Principles and Practice (Tables 50.3, chapters on viral infections in pregnancy); Berek & Novak's Gynecology; Andrews' Diseases of the Skin (HSV chapter).
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