ArticleThe Journal of infectious diseases2015
HIV protease inhibitor use during pregnancy is associated with decreased progesterone levels, suggesting a potential mechanism contributing to fetal growth restriction.
Article in The Journal of infectious diseases, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04087239 (HIV Exposure, Disease Acquisition and Progression Among Children), which is not on this map. Cited by 66 papers, 3 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
HIV Exposure, Disease Acquisition and Progression Among Children: Role of Maternal Immunogenetics, Viral Genetic Diversity, HAART Exposure, Co-morbidities and Psycho-Social Status: (UZ-CHS Birth Cohort)
Who cites it
66 citing papers in PubMed, 3 syntheses or guidelines pooled it, 121 citations in OpenAlex.
- Comparative risk of adverse perinatal outcomes associated with classes of antiretroviral therapy in pregnant women living with HIV: systematic review and meta-analysis.Frontiers in medicine · 2024Pooled it
- Adverse perinatal outcomes associated with prenatal exposure to protease-inhibitor-based versus non-nucleoside reverse transcriptase inhibitor-based antiretroviral combinations in pregnant women with HIV infection: a systematic review and meta-analysis.BMC pregnancy and childbirth · 2023Pooled it
- Association between maternal HIV infection and low birth weight and prematurity: a meta-analysis of cohort studies.BMC pregnancy and childbirth · 2015Pooled it
- Risk Factors for Adverse Birth Outcomes in the PROMISE 1077BF/1077FF Trial.Journal of acquired immune deficiency syndromes (1999) · 2019Trial
- Estradiol Levels Are Altered in Human Immunodeficiency Virus-Infected Pregnant Women Randomized to Efavirenz-Versus Lopinavir/Ritonavir-Based Antiretroviral Therapy.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2018Trial
- Benefits and Risks of Antiretroviral Therapy for Perinatal HIV Prevention.The New England journal of medicine · 2016Trial
- Perinatal outcomes associated with antiretroviral therapy for pregnant women living with HIV: an umbrella review.EClinicalMedicine · 2026Review
- From Pharmacovigilance Signals to Mechanistic Phenotypes: Integrating ADMET, PK/PD, and Network Context to Interpret Antiviral Safety in Pregnancy.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Brief Report: Is Gestational Exposure to HIV and Protease Inhibitors Associated With Timing of Pubertal Onset?Journal of acquired immune deficiency syndromes (1999) · 2026Article
- Target trials of preconception switch from nevirapine or efavirenz-based antiretroviral therapy to dolutegravir-based antiretroviral therapy on adverse birth and maternal outcomes.AIDS (London, England) · 2025Article
- Joining the dots: maternal cytomegalovirus, HIV and the placenta.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2025Review
- Comorbidities in pregnant South African women living with HIV and associations with adverse birth outcomes: a prospective cohort study.BMC pregnancy and childbirth · 2025Article
- Defining Appropriate Comparator Populations for Placental Pathology for Pregnant People With HIV.International journal of surgical pathology · 2025Article
- Growth-promoting hormonal alterations in pregnant women living with HIV receiving dolutegravir-based antiretroviral treatment are associated with lower infant 1-year weight z-scores.Frontiers in pediatrics · 2025Article
- Antiretroviral Therapy at Conception Leads to Lower Peripheral CD49aJournal of immunology research · 2025Article
- The Negative Impact of Maternal HIV Infection on Birth Outcomes-Myth or Reality?Pathogens (Basel, Switzerland) · 2024Article
- Placental progesterone and its receptor in HIV-infected pre-eclamptic women.Histochemistry and cell biology · 2024Article
- New insights on the potential effect of progesterone in Covid-19: Anti-inflammatory and immunosuppressive effects.Immunity, inflammation and disease · 2023Review
- Metabolomic profiling of preterm birth in pregnant women living with HIV.Metabolomics : Official journal of the Metabolomic Society · 2023Article
- Adverse perinatal outcomes attributable to HIV in sub-Saharan Africa from 1990 to 2020: Systematic review and meta-analyses.Communications medicine · 2023Article
6 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundProtease inhibitor (PI)-based combination antiretroviral therapy (cART) is administered during pregnancy to prevent perinatal human immunodeficiency virus (HIV) transmission. However, PI use has been associated with adverse birth outcomes, including preterm delivery and small-for-gestational-age (SGA) births. The mechanisms underlying these outcomes are unknown. We hypothesized that PIs contribute to these adverse events by altering progesterone levels.
methodsPI effects on trophoblast progesterone production were assessed in vitro. A mouse pregnancy model was used to assess the impact of PI-based cART on pregnancy outcomes and progesterone levels in vivo. Progesterone levels were assessed in plasma specimens from 27 HIV-infected and 17 HIV-uninfected pregnant women.
resultsPIs (ritonavir, lopinavir, and atazanavir) but not nucleoside reverse transcriptase inhibitors (NRTIs) or nonnucleoside reverse transcriptase inhibitors reduced trophoblast progesterone production in vitro. In pregnant mice, PI-based cART but not dual-NRTI therapy was associated with significantly lower progesterone levels that directly correlated with fetal weight. Progesterone supplementation resulted in a significant improvement in fetal weight. We observed lower progesterone levels and smaller infants in HIV-infected women receiving PI-based cART, compared with the control group. In HIV-infected women, progesterone levels correlated significantly with birth weight percentile.
conclusionsOur data suggest that PI use in pregnancy may lead to lower progesterone levels that could contribute to adverse birth outcomes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.