Adverse perinatal outcomes associated with protease inhibitor-based antiretroviral therapy in pregnant women living with HIV: A systematic review and meta-analysis

Cowdell, Imogen; Beck, Katharina; Portwood, Clara; Sexton, Harriet; Kumarendran, Mary; Brandon, Zoe; Kirtley, Shona; Hemelaar, Joris

doi:10.1016/j.eclinm.2022.101368

Cited by 21 publications

(23 citation statements)

References 67 publications

(170 reference statements)

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“…Two infants (2%) in the present study were stillborn. This compares to a national rate of 0.85% between 2007 and 2015 (20). We did not find an association between preterm birth or birth weight and late booking, antenatal diagnosis, late treatment initiation, use of protease inhibitors, high viral load at booking, or low CD4 count.…”

Section: Discussioncontrasting

confidence: 74%

“…Untreated maternal HIV infection is associated with an increased risk of adverse perinatal outcomes, including preterm birth, low birth weight, small for gestational age (SGA), and stillbirth (12). Maternal cART improves maternal health and reduces vertical HIV transmission, but the impact on adverse perinatal outcomes has been controversial and may vary by ART regimen and timing of ART initiation (13)(14)(15)(16)(17)(18)(19)(20)(21). Current best practice for the care of pregnant WLHIV in the UK is guided by the British HIV Association (BHIVA) guidelines (3).…”

Section: Introductionmentioning

confidence: 99%

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Trends in management and outcomes of pregnant women living with HIV between 2008–2013 and 2014–2019: A retrospective cohort study

Brandon

Chakravarti²,

Hemelaar³

2022

Front. Med.

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BackgroundDespite major advances in the care of pregnant women living with HIV (WLHIV), they remain at increased risk of adverse pregnancy outcomes. This study assesses recent developments in management and outcomes of pregnant WLHIV at a tertiary obstetric unit in the United Kingdom.MethodsWe conducted a retrospective cohort study of WLHIV delivering at the John Radcliffe Hospital, Oxford, during 2008–2019. Detailed data was collected for maternal, virological, obstetric, and perinatal characteristics. To determine changes over time, data from the periods 2008–13 and 2014–19 were compared.ResultsWe identified 116 pregnancies in 94 WLHIV. Between 2008–2013 and 2014–2019, the rate of preconception HIV diagnosis increased from 73 to 90% (p = 0.021) and the proportion of WLHIV on combination ART (cART) at conception increased from 54 to 84% (p = 0.001). The median gestation at which cART was initiated antenatally decreased from 22+1 to 17+1 weeks (p = 0.003). In 2014-2019, 41% of WLHIV received non-nucleoside reverse transcriptase inhibitor-based cART, 37% protease inhibitor-based cART, and 22% of cART regimens contained an integrase inhibitor. The proportion of WLHIV with a viral load <50 copies/mL at delivery rose from 87 to 94% (p = 0.235). Sixty-six percent of WLHIV delivered by Cesarean section, with a significant decrease over time in the rate of both planned (62–39%, p = 0.016) and actual (49–31%, p = 0.044) elective Cesarean. Perinatal outcomes included one case of perinatal HIV transmission (0.86%), 11% preterm birth, 15% small-for-gestational-age, and 2% stillbirth. There was an association between a viral load >50 copies/mL at delivery and preterm delivery (p = 0.0004).ConclusionVirological, obstetric, and perinatal outcomes of WLHIV improved during the study period. Implementation of national guidance has led to an increase in preconception diagnosis and treatment, earlier initiation of antenatal treatment, a reduction in the number of women with a detectable viral load at delivery, and an increase in vaginal deliveries.

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Section: Discussioncontrasting

confidence: 74%

Section: Introductionmentioning

confidence: 99%

Trends in management and outcomes of pregnant women living with HIV between 2008–2013 and 2014–2019: A retrospective cohort study

Brandon

Chakravarti²,

Hemelaar³

2022

Front. Med.

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“…Our study did not show a higher risk for most of the adverse perinatal outcomes after prenatal exposure to PI-based combination compared to NNRTI-based combination. However, our review suggests a signi cant increased risk of VSGA, similarly reported in another recent review [15]. The risk of PTB initially reported is not clearly demonstrated [10, 18, 30, 31, 40, 43-45, 47-56, 58], with signi cant between-studies heterogeneity.…”

Section: ) Conclusionsupporting

confidence: 61%

“…It remains crucial to fully assess their associated perinatal outcomes to optimise ART strategies in pregnant women worldwide, but more particularly in sub-Saharan Africa, where both maternal HIV prevalence and rates of adverse perinatal outcomes are high [5]. Several studies have reported an increased risk of adverse perinatal outcomes after prenatal exposure to antiretroviral Page 3/44 combinations, depending on the antiretroviral drug classes used [9][10][11][12][13][14][15][16]. PI-regimens still remain an important alternative option for pregnant women in 2022 that still need to be fully understood, due to con icting results.…”

mentioning

confidence: 99%

“…PI-regimens still remain an important alternative option for pregnant women in 2022 that still need to be fully understood, due to con icting results. Indeed, several studies have reported an association between PI-based combinations and preterm birth, while other studies have not found similar results [12,[15][16][17][18].Therefore, we conducted a systematic review and meta-analysis aimed to assess the risk of adverse perinatal outcomes associated with PI-based combination use during pregnancy compared to NNRTI-based combination.2) Methods…”

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confidence: 99%

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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

Saint-Lary

Bénevent

Damase‐Michel

et al. 2022

Preprint

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Background: About 1.3 million pregnant women lived with HIV and were eligible to receive antiretroviral therapy (ART) worldwide in 2021. The World Health Organization recommends protease inhibitors (PI)-based regimen as second or third-line during pregnancy. With remaining pregnant women exposed to PIs, there is still an interest to assess whether this treatment affects perinatal outcomes. Adverse perinatal outcomes after prenatal exposure to PI-based ART remain conflicting: some studies report an increased risk of preterm birth (PTB) and low-birth-weight (LBW), while others do not find these results. We assessed adverse perinatal outcomes associated with prenatal exposure to PI-based compared with non-nucleoside reverse transcriptase (NNRTI)-based ART. Methods: We performed a systematic review searching PubMed, Reprotox, Clinical Trial Registry (clinicaltrials.gov) and abstracts of HIV conferences between 01/01/2002 and 29/10/2021. We used Oxford and Newcastle-Ottawa scales to assess the methodological quality. Studied perinatal outcomes were spontaneous abortion, stillbirth, congenital abnormalities, PTB (<37 weeks of gestation), very preterm birth (VPTB, <32 weeks of gestation), LBW (<2500 grs), very low-birth-weight (VLBW, <1500g), small for gestational age (SGA) and very small for gestational age (VSGA). The association between prenatal exposure to PI-based compared to NNRTI-based ART was measured for each adverse perinatal outcome using random-effect meta-analysis to estimate pooled relative risks (RR) and their corresponding 95% confidence intervals (CI). Pre-specified analyses were stratified according to country income and study quality assessment, and summarized when homogeneous. Results: Out of the 49,171 citations identified, our systematic review included 32 published studies, assessing 45,427 pregnant women. There was no significant association between prenatal exposure to PIs compared to NNRTIs for VPTB, LBW, SGA, stillbirth, and congenital abnormalities. However, it was inconclusive for PTB, and PI-based ART is significantly associated with an increased risk of VSGA (sRR 1.41 [1.08-1.84]; I2=0%) compared to NNRTIs. Conclusions: We did not report any significant association between prenatal exposure to PIs vs NNRTIs-based regimens for most of the adverse perinatal outcomes, except for VSGA significantly increased (+41%). The evaluation of antiretroviral exposure on pregnancy outcomes remains crucial to fully assess the benefice-risk balance, when prescribing ART in women of reproductive potential with HIV. PROSPERO number: CRD42022306896.

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Antiretroviral Therapy in Pregnancy: A 2023 Review of the Literature

Goulding,

Meeks,

Shay

et al. 2024

Curr HIV/AIDS Rep

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Adverse perinatal outcomes associated with protease inhibitor-based antiretroviral therapy in pregnant women living with HIV: A systematic review and meta-analysis

Cited by 21 publications

References 67 publications

Trends in management and outcomes of pregnant women living with HIV between 2008–2013 and 2014–2019: A retrospective cohort study

Trends in management and outcomes of pregnant women living with HIV between 2008–2013 and 2014–2019: A retrospective cohort study

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

Antiretroviral Therapy in Pregnancy: A 2023 Review of the Literature

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