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Pregnancy and neonatal outcomes in women with HIV-1 exposed to integrase inhibitors, protease inhibitors and non-nucleoside reverse transcriptase inhibitors: an observational study

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Abstract

Purpose

Recommended regimens for pregnant women with HIV-1 are composed of two nucleoside reverse transcriptase inhibitors (NRTI) plus either a ritonavir-boosted protease inhibitor (PI) or an integrase strand transfer inhibitor (ISTI), with non-nucleoside reverse transcriptase inhibitors (NNRTI) representing an alternative drug class. The study’s purpose was to compare these three options in terms of pregnancy outcomes.

Methods

Data from a national observational study of pregnant women with HIV-1 were used. The analysis included all pregnancies reported between 2008 and 2018, ending in live births and exposed within 32 weeks of gestation to three-drug regimens composed of a NRTI backbone plus a PI, a NNRTI or a ISTI, without class switching during pregnancy. Clinical and laboratory outcomes were evaluated in univariate and multivariable analyses.

Results

Overall, 794 exposed pregnancies were analyzed (PI 78.4%, NNRTI 15.4%, ISTI 6.2%). Almost all outcomes had similar rates in the three groups. Women who received PI in pregnancy were less likely to be virologically suppressed at third trimester. PI use was associated with higher bilirubin and triglyceride levels, and ISTI use with a lower rate of low birthweight. The differences in viral suppression at third trimester and in low birthweight were not maintained in multivariable analyses that were adjusted for confounders.

Discussion

We found no major differences in a wide range of outcomes relevant for pregnant women with HIV. Such results are reassuring, and this information may be helpful in a context of preconception counseling when therapeutic choices for pregnancy are discussed between women and care providers.

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Acknowledgements

We thank Cosimo Polizzi and Alessandra Mattei of the Istituto Superiore di Sanità in Rome, Italy, for providing technical secretarial for this study. We also thank Ernesto Costabile for providing assistance as documentalist. No compensation was provided for these contributions.

The Italian Group on Surveillance of Antiretroviral Treatment in Pregnancy:

Project coordinators: M. Floridia, M. Ravizza, E. Tamburrini.

Participants: M. Ravizza, E. Tamburrini, F. Di Lorenzo, G. Sterrantino, M. Meli, I. Campolmi, F. Vichi, B. Del Pin, R. Marocco, C. Mastroianni, V.S. Mercurio, D. Zanaboni, G. Guaraldi, G. Nardini, C. Stentarelli, B. Beghetto, A.M. Degli Antoni, A. Molinari, M.P. Crisalli, A. Donisi, A. Ruggieri, M. Piepoli, V. Cerri, G. Zuccotti, V. Giacomet, C. Madia, L. Paradiso, F. Forlanini, G. Placido, P. Milini, F. Savalli, F. Sabbatini, D. Francisci, C. Papalini, L. Bernini, P. Grossi, L. Rizzi, G. Maso, M. Bernardon, S. Bussolaro, I. Della Pietà, A. Sorz, A. Meloni, A. Chiodo, M. Dedoni, F. Ortu, P. Piano, A. Citernesi, I. Bordoni Vicini, K. Luzi, A. Spinillo, M. Roccio, A. Vimercati, D. Calabretti, S. Gigante, B. Guerra, F. Cervi, G. Simonazzi, E. Margarito, M.G. Capretti, C. Marsico, G. Faldella, M. Sansone, P. Martinelli, A. Agangi, A. Capone, G.M. Maruotti, C. Tibaldi, L. Trentini, T. Todros, G. Masuelli, V. Frisina, V. Savasi, E. Cardellicchio, C. Giaquinto, M. Fiscon, E. Rubino, L. Franceschetti, R. Badolato, M.A. Forleo, B. Tassis, G.C. Tiso, O. Genovese, C. Cafforio, C. Pinnetti, G. Liuzzi, A.M. Casadei, A.F. Cavaliere, M. Cellini, A.M. Marconi, S. Dalzero, M. Ierardi, S.C. Simonetti, N. Alfieri, S. Agrati, C. Polizzi, A. Mattei, M.F. Pirillo, R. Amici, C.M. Galluzzo, S. Donnini, S. Baroncelli, M. Floridia.

SIGO-HIV Group National Coordinators: P. Martinelli, M. Ravizza.

Funding

This work (currently not funded) was supported in the past by public research grants (ref.: H85E08000200005) from the Italian Medicines Agency (AIFA). The funder had no role in study design, data collection, data analysis, manuscript preparation and/or publication decision. No funding was received for this work from any of the following organizations: National Institutes of Health (NIH); Wellcome Trust; and the Howard Hughes Medical Institute (HHMI).

Author information

Authors and Affiliations

  1. National Center for Global Health, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy

    Marco Floridia

  2. Department of Obstetrics and Gynaecology, DMSD San Paolo Hospital Medical School, University of Milan, Milan, Italy

    Serena Dalzero & Marina Ravizza

  3. Department of Pediatrics, Luigi Sacco Hospital and University of Milan, Milan, Italy

    Vania Giacomet

  4. Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy

    Enrica Tamburrini

  5. Catholic University of the Sacred Heart, Rome, Italy

    Enrica Tamburrini

  6. Department of Obstetrics and Neonatology, Città della Salute e della Scienza Hospital, University of Turin, Turin, Italy

    Giulia Masuelli

  7. Department of Obstetrics and Gynaecology, Luigi Sacco Hospital and University of Milan, Milan, Italy

    Valeria Savasi

  8. Department of Obstetrics and Gynaecology, IRCCS S. Matteo, Pavia, Italy

    Arsenio Spinillo

  9. Obstetrics and Gynecology Unit, Fondazione IRCCS Ospedale Maggiore Policlinico di Milano, Milan, Italy

    Beatrice Tassis

  10. Department of Obstetrics and Gynecology, ASST Spedali Civili, Brescia, Italy

    Laura Franceschetti

  11. Department of Infectious Diseases and Hepatology, Azienda Ospedaliera di Parma, Parma, Italy

    Anna Maria Degli Antoni

  12. Department of Neurosciences, Reproductive and Dentistry Science, University Federico II, Naples, Italy

    Matilde Sansone

  13. Department of Medical Specialties, Infectious Diseases Clinic, University of Modena and Reggio Emilia, Modena, Italy

    Giovanni Guaraldi

  14. Department of Biomedical and Human Oncological Science (DIMO), 2nd Unit of Obstetrics and Gynaecology, University of Bari, Bari, Italy

    Antonella Vimercati

  15. Department of Surgical Sciences, Division of Gynaecology and Obstetrics, University of Cagliari, Cagliari, Italy

    Alessandra Meloni

Authors
  1. Marco Floridia
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  2. Serena Dalzero
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  3. Vania Giacomet
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  4. Enrica Tamburrini
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  5. Giulia Masuelli
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  6. Valeria Savasi
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  7. Arsenio Spinillo
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  8. Beatrice Tassis
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  9. Laura Franceschetti
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  10. Anna Maria Degli Antoni
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  11. Matilde Sansone
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  12. Giovanni Guaraldi
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  13. Antonella Vimercati
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  14. Alessandra Meloni
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  15. Marina Ravizza
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Consortia

The Italian Group on Surveillance of Antiretroviral Treatment in Pregnancy

Contributions

MF, SD and VG designed the study; MF drafted and finalized the manuscript, and was responsible for statistical analysis; SD, VG, ET, GM, VS, AS, BT, LF, ADA, MS, GG, AV, AM and MR substantially contributed to acquisition of data and critical revision of the manuscript. All the authors approved the final version to be published.

Corresponding author

Correspondence to Marco Floridia.

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Conflict of interest

None to declare. None of the authors has a commercial or other association, financial interest, activity, relationship or association that might pose a conflict of interest. The corresponding author had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Ethical approval

Ethics approval was obtained from the Ethics Committee of the I.N.M.I. Lazzaro Spallanzani in Rome (ref. deliberation 578/2001, September 28, 2001).

Additional information

The members are listed in acknowledgement of text.

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Floridia, M., Dalzero, S., Giacomet, V. et al. Pregnancy and neonatal outcomes in women with HIV-1 exposed to integrase inhibitors, protease inhibitors and non-nucleoside reverse transcriptase inhibitors: an observational study. Infection 48, 249–258 (2020). https://doi.org/10.1007/s15010-019-01384-5

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  • DOI: https://doi.org/10.1007/s15010-019-01384-5

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