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Observational Study
. 2025 Jan 24;17(2):157.
doi: 10.3390/v17020157.

Immune Modulation Related to High-Dose Valacyclovir Administration for Primary Cytomegalovirus Infection in Pregnancy: An Insight into Virus Behavior and Maternal Serology

Marco De Santis  1   2 , Silvio Tartaglia  1 , Chiara Cerra  3 , Daniela Visconti  1 , Piero Valentini  4   5 , Antonio Lanzone  1   2 , Lucia Masini  1   2 , Rosaria Santangelo  6   7
Affiliations
Observational Study

Immune Modulation Related to High-Dose Valacyclovir Administration for Primary Cytomegalovirus Infection in Pregnancy: An Insight into Virus Behavior and Maternal Serology

Marco De Santis et al. Viruses. .

Abstract

Cytomegalovirus (CMV) infection during pregnancy poses significant maternal and fetal health risks. Valacyclovir, an antiviral drug, has been explored as a therapeutic option for managing primary CMV infections in pregnant women. This study investigates the effects of valacyclovir therapy on immune response maturation against CMV, maternal antibody levels, and viral replication during treatment. We conducted a retrospective observational study involving pregnant women diagnosed with primary CMV infection and presenting in utero infection who received high-dose valacyclovir therapy (8 g/day). A group started the therapy at diagnosis, while another group started only after positive amniocentesis. Maternal antibody levels (IgM, IgG, and IgG avidity) and PCR for CMV testing (in blood, urine, and saliva) were measured longitudinally during the second and third trimesters. Our findings indicate that early valacyclovir therapy is related to lower avidity levels over time and a delay in reaching a high IgG avidity level (18.22 ± 1.21 weeks) compared to the patients who started Valacyclovir during the second trimester after positive amniocentesis (14.52 ± 1.64 weeks; p = 0.066). The therapy does not condition the overall concentration of maternal CMV-specific IgM and IgG. While high-dose VCV does not directly target the mechanism of IgG avidity maturation, it can interfere with this process by reducing the viral load and antigen presentation, influencing IgG avidity maturation. Further research is needed to elucidate the long-term implications of potential immunological modulation induced by Valacyclovir and to optimize early diagnosis and the right treatment protocol during pregnancy.

Keywords: IgG avidity; cytomegalovirus; immune system; pregnancy; valacyclovir.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Patterns of specific anti-CMV IgM (left) and IgG (right) titers progress during pregnancy between the women undergoing VCV from diagnosis until delivery (Group A) and those who started the therapy after positive amniocentesis in the second trimester of pregnancy (Group B).
Figure 2
Figure 2
IgG avidity maturation trend in the population of pregnant patients presenting primary CMV infection undergoing high-dose VCV therapy.
Figure 3
Figure 3
IgG avidity progress between women with a positive PCR for CMV DNA in amniotic fluid treated with VCV from the diagnosis of primary CMV infection throughout the pregnancy (Group A, in red) and women who started the therapy after positive amniocentesis (Group B, in blue).
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