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Safety of tenofovir during pregnancy: early growth outcomes and hematologic side effects in HIV-exposed uninfected infants

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Abstract

Intrauterine exposure to zidovudine-based combination antiretroviral therapy (cART) can cause severe anemia within the first weeks of life. Tenofovir disoproxil fumarate (TDF)–based regimens may have less hematologic side effects but may affect growth parameters. This study aimed to assess the safety of TDF for prevention of mother-to-child transmission (PMTCT) in HIV-exposed uninfected infants regarding early growth outcomes and hematologic side effects. Our retrospective observational cohort study included children born (n = 232) to HIV-infected mothers (n = 228) on cART. Blood counts were compared at birth, 4–6 weeks, and 3, 12 and 18 months of age. Growth parameters were measured at birth and 12 and 18 months of age. Data were analyzed according to treatment group (TDF and non-TDF cART regimes). The median hemoglobin (Hgb) was significantly lower in the non-TDF-based group at birth (15.4 g/dl vs. 16.9 g/dl; **p = 0.002) and at 4–6 weeks of age (9.9 g/dl vs. 10.4 g/dl; **p = 0.004). The mean corpuscular volume was higher in the non-TDF-based group (109 fl vs. 105 fl; ***p < 0.001) as well at 4–6 weeks (102 fl vs. 95 fl; ***p < 0.001). In the TDF-based group, a higher proportion of neutropenia (grade 2 and higher) compared to the non-TDF-group (21.4% vs. 11%; *p = 0.015) was observed at three months of age. This effect was transient. There was no difference in growth.

Conclusions: TDF appears to have no major side effects in our cohort. Transient anemia was observed more commonly with non-TDF regimens. However, our research suggests a potential delayed effect of TDF on neutrophils at 3 months of age.

What is Known:

• TDF is suspected to affect the growth of HIV-exposed uninfected infants.

• Non-TDF-based cART regimes for prevention of mother-to-child transmission of HIV often result in transient anemia in the infant.

What is New:

• TDF appears to have no major side effects regarding the growth of HIV-exposed uninfected infants.

• Our research suggests a potential delayed effect of TDF on neutrophils at 3 months of age in these infants.

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Abbreviations

3TC:

Lamivudine

ABC:

Abacavir

ANC:

Absolute neutrophil count

APR:

Antiretroviral Pregnancy Registry

ATV:

Atazanavir

BMD:

Bone mineral density

BMI:

Body mass index

cART:

Combination antiretroviral therapy

C-section:

Cesarean section

d4T:

Stavudine

FTC:

Emtricitabine

FPV:

Fosamprenavir

HCAZ:

z-Scores for head circumference

Hgb:

Hemoglobin

HIV:

Human immunodeficiency virus

IQR:

Interquartile ranges

IV:

Intravenously

LA:

z-Scores for length

LPV:

Lopinavir

MACDP:

Metropolitan Atlanta Congenital Defects Program

MCV:

Mean corpuscular volume

NNRTI:

Non-nucleoside reverse transcriptase inhibitor

NRTIs:

Nucleoside reverse transcriptase inhibitors

NVP:

Nevirapine

PI:

Protease inhibitor

PMTCT:

Prevention of mother-to-child transmission

r:

Ritonavir

RAL:

Raltegravir

RKI:

Robert Koch Institute

SQV:

Saquinavir

TAF:

Tenofovir alafenamide fumarate

TDF:

Tenofovir disoproxil fumarate

WAZ :

z-Scores for weight

ZDV :

Zidovudine

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Acknowledgments

The authors would like to thank the participants in this study. They would also like to thank Nikola Hanhoff for her important contribution to the statistical analysis for this paper.

Funding

Dr. Seidel was a participant in the BIH-Charité Clinical Scientist Program funded by the Charité-Universitätsmedizin Berlin and the Berlin Institute of Health.

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Authors

Contributions

VS, KW, and CFS conceived and designed the research and study process; VS, KW, WH, RK, and CFS responsible for data collection; VS and CB analyzed the data; VS drafted the manuscript; VS and RCR edited and revised the manuscript. All authors read and approved the final manuscript.

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Correspondence to Vera Seidel.

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The authors declare that they have no conflict of interest.

Ethical approval

The study had local ethics committee (EA1/378/16) approval. No written informed consent was required for the retrospective analyses of routine clinical parameters.

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Communicated by Nicole Ritz

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Seidel, V., Weizsäcker, K., Henrich, W. et al. Safety of tenofovir during pregnancy: early growth outcomes and hematologic side effects in HIV-exposed uninfected infants. Eur J Pediatr 179, 99–109 (2020). https://doi.org/10.1007/s00431-019-03481-x

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