The update was based on data from an open-label clinical trial (ClinicalTrials.gov Identifier: NCT03960645) that included 33 virologically-suppressed pregnant adults with HIV-1 and no known substitutions associated with resistance to the individual components of Biktarvy. Study participants received Biktarvy once daily from the second or third trimester through postpartum. At baseline, the median CD4+ cell count was 558 cells/μL.

Findings showed viral suppression was maintained during pregnancy, at delivery, and through week 18 postpartum in the 32 participants who completed the study. The median change in CD4+ cell count from baseline to week 12 postpartum was 159 cells/μL. Twenty-nine neonates who received testing at birth and/or at 4 to 8 weeks after birth were reported to have negative/undetectable HIV-1 PCR results. 

In pregnant patients, viral load should be monitored closely as lower exposures of Biktarvy were observed during pregnancy compared with the postpartum period. According to the prescribing information, the exposure changes during pregnancy are not considered clinically significant in virologically suppressed pregnant individuals.

The overall safety profile of Biktarvy was consistent with that seen in previous studies; no new safety or tolerability concerns were observed with Biktarvy during pregnancy and postpartum.

“This label update marks an important milestone for Biktarvy, reinforcing its efficacy profile for pregnant [people living with HIV-1], an often understudied and most vulnerable community in clinical research,” said Jared Baeten, MD, PhD, Vice President, HIV Clinical Development, Gilead Sciences. “Not only is Biktarvy an alternative regimen for use in pregnancy, but people of childbearing potential can also remain on Biktarvy if they become pregnant.

Biktarvy is a 3-drug combination of bictegravir, an HIV-1 integrase strand transfer inhibitor, and emtricitabine and tenofovir alafenamide, both HIV-1 nucleoside analog reverse transcriptase inhibitors. It is supplied as a tablet in 2 dosage strengths: 30mg/120mg/15mg and 50mg/200mg/25mg. The recommended dosage for pregnant individuals is one 50mg/200mg/25mg tablet once daily.

Among women with a short cervix, the use of a cervical pessary did not result in a reduction in preterm birth risk when compared with usual care, according to data from a National Institutes of Health (NIH)-funded phase 3 study.

The unblinded, randomized, controlled TOPS trial (ClinicalTrials.gov Identifier: NCT02901626) enrolled 544 participants with a singleton pregnancy at risk for preterm delivery. These patients had a cervical length of 20mm or less and were at gestations of 16 weeks through 24 weeks.

Study participants were randomly assigned to receive either a cervical pessary (n=280) or usual care (n=264; vaginal progesterone if they met the criteria per local standard of care). The primary endpoint was the number of participants with preterm delivery or fetal death at less than 37 weeks.

Findings showed no significant difference between the groups; the primary endpoint occurred in 45.5% (127/280) of the pessary group and 45.6% (120/264) of the usual care group (relative risk, 1.00; 95% CI, 0.83-1.20). The study was stopped early because the risk of fetal or newborn death appeared to be higher in those who received the pessary compared with those who did not (13.3% vs 6.8%; relative risk, 1.94 [95% CI, 1.13-3.32]).

It was noted that participants in the usual care group were more likely to receive cervical cerclage, which may have influenced the outcome of the study.

The Food and Drug Administration has made a final decision to withdraw the approval of Makena (hydroxyprogesterone caproate) and its generic equivalents, based on a postmarketing study that failed to show clinical benefit.

In 2011, the FDA granted accelerated approval to Makena to reduce the risk of preterm birth in women with a singleton pregnancy who have a history of singleton spontaneous preterm birth. The approval was based on data from a placebo-controlled trial that showed weekly injections of Makena reduced the rate of recurrent preterm delivery in high-risk women. The proportion of patients who delivered preterm at less than 37 weeks was 37.1% for the Makena arm and 54.9% for the control arm (treatment difference, -17.8% [95% CI, -28.0, -7.4]). No overall survival difference was observed in this trial due to the higher rate of miscarriages and stillbirths in the Makena arm.

As part of this approval, the Company was required to conduct a confirmatory trial (PROLONG; ClinicalTrials.gov Identifier: NCT01004029), which included 1710 patients randomly assigned to receive weekly injections of Makena or placebo. Results showed that the trial did not meet the coprimary endpoints. The incidence of preterm delivery at less than 35 weeks was 11.0% for the Makena-treated group and 11.5% for placebo (P =.72). In addition, no statistical differences in the rates of neonatal mortality and morbidity were observed between the groups (5.4% for Makena vs 5.2% for placebo; P =.84). According to the manufacturer, the difference in results was influenced by the study population, as the first trial included a higher risk population than the PROLONG study. 

A review of these findings by the FDA’s Obstetrics, Reproductive, and Urologic Drugs Advisory Committee resulted in the panel voting in favor of the Agency pursuing the withdrawal of Makena from the US market.

Today’s announcement by the FDA’s Commissioner Robert M. Califf, MD and the FDA’s Chief Scientist Namandjé Bumpus, PhD effectively ends the lawful distribution of Makena in the US.

“It is tragic that the scientific research and medical communities have not yet found a treatment shown to be effective in preventing preterm birth and improving neonatal outcomes, particularly in light of the fact that this serious condition has a disparate impact on communities of color, especially Black women,” said Califf. “Fundamentally, however, the touchstone of FDA drug approval is a favorable benefit-risk assessment; without that favorable assessment, the drug should not have the status of being FDA-approved.”

HealthDay News — Induction of labor in uncomplicated pregnancies during weeks 37 to 41 of gestation is associated with lower education performance in children, according to a study published online February 22 in Acta Obstetricia et Gynecologica Scandinavica.

Renée J. Burger, from the University of Amsterdam, and colleagues studied the influence of elective induction of labor for each week of gestation from 37 to 42 weeks on offspring school performance at 12 years of age. The analysis included 226,684 liveborn children (2003 to 2008) from uncomplicated pregnancies.

The researchers found that for each gestational age up to 41 weeks, induction of labor was associated with decreased school performance scores vs nonintervention (at 37 weeks: −0.05 standard deviation when adjusted for confounding factors). Fewer children after induction of labor reached higher secondary school level vs those with nonintervention (at 38 weeks: 48 vs 54%; adjusted odds ratio, 0.88).

“This is to our knowledge the first study using a fetus-at-risk approach to compare school performance at age 12 after induction of labor and nonintervention in low-risk term pregnancies, simulating the dilemma often faced in clinical practice,” the authors write. “Clinicians should balance the advantages and disadvantages of induction of labor and incorporate long-term outcomes in counseling and decisions around induction of labor.”

One author disclosed financial ties to the pharmaceutical industry.

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Chen Liu, from the Columbia University Mailman School of Public Health in New York City, and colleagues estimated the prevalence of mistreatment by health care professionals during childbirth in a representative multistate sample. The cross-sectional study included survey data collected from respondents to the 2020 Pregnancy Risk and Monitoring System in 6 states and New York City. The sample included 4458 postpartum individuals representative of 552,045 people with live births in seven jurisdictions in 2020.

The researchers found that 13.4% of participants reported experiencing mistreatment during childbirth, with being “ignored, refused request for help, or failed to respond in a timely manner” the most common type of mistreatment (7.6%). Factors associated with experiencing mistreatment were: being lesbian, gay, bisexual, transgender, or queer identifying; being Medicaid-insured or unmarried; having obesity before pregnancy, an unplanned caesarean birth, or a history of substance use disorder; experiencing intimate partner or family violence; having a mood disorder; or giving birth during the COVID-19 public health emergency. Ambiguous associations were seen for mistreatment with race and ethnicity, age, education level, rural or urban geography, immigration status, and household income.

“We found that mistreatment during childbirth was a common experience. To our knowledge, evidence of effective interventions to improve respectful maternity care in the US is scant,” the authors write.

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A single oral dose of azithromycin was found to significantly lower the risk of maternal sepsis or death among women planning a vaginal delivery, according to new data published in The New England Journal of Medicine.

The National Institutes of Health (NIH)-led phase 3 study (A-PLUS; ClinicalTrials.gov Identifier: NCT03871491) included 29,278 women who were in labor at 28 weeks’ gestation or more and who were planning a vaginal delivery. Between September 2020 and August 2022, study participants were randomly assigned to receive either a single 2g oral dose of azithromycin or placebo during labor. The primary endpoints of the study were the incidence of maternal death or sepsis, as well as the incidence of intrapartum/neonatal death or sepsis. 

Within the first 6 weeks after delivery, the incidence of maternal sepsis or death was 1.6% in the azithromycin arm compared with 2.4% in the placebo arm, with a relative risk of 0.67 (95% CI, 0.56-0.79; P <.001). Findings showed the maternal primary outcome was mainly driven by the difference in the incidence of sepsis between the azithromycin and placebo arms (1.5% vs 2.3%, respectively), with a relative risk of 0.65 (95% CI, 0.55-0.77).

While treatment with azithromycin significantly lowered the risk of maternal sepsis or death compared with placebo, the analysis demonstrated little effect on neonatal death or sepsis (10.5% vs 10.3%), with a relative risk of 1.02 (95% CI, 0.95-1.09; P =.56).

The study was originally designed to enroll up to 34,000 women. However, during an interim analysis, the trial was stopped early due to the clear maternal benefit based on a recommendation from the data and safety monitoring committee.

“These findings have the potential to change clinical practice by providing a safe, effective and low-cost approach to reduce the global burden of maternal sepsis and death,” said Diana W. Bianchi, MD, director of NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the primary funder of the trial. “We urgently need effective strategies to prevent pregnancy-related infections, which account for roughly 10% of maternal deaths worldwide.”

References

1. Single-dose antibiotic prevents maternal sepsis and death. News release. National Institutes of Health. Accessed February 9, 2023. https://www.nih.gov/news-events/news-releases/single-dose-antibiotic-prevents-maternal-sepsis-death.
2. Tita AT, Carlo WA, McClure EM, et al. Azithromycin to prevent sepsis or death in women planning a vaginal birth. N Engl J Med. Published online February 9, 2023. doi:10.1056/NEJMoa2212111

HealthDay News — Initiation of oxycodone vs codeine is not associated with an increased risk for persistent opioid use after delivery overall, but increased risk is seen after vaginal delivery, according to a study published online July 31 in CMAJ, the journal of the Canadian Medical Association.

Jonathan S. Zipursky, MD, PhD, from the Sunnybrook Health Sciences Centre in Toronto, and colleagues conducted a population-based cohort study involving people who filled a prescription for codeine or oxycodone within 7 days of hospital discharge after delivery between September 1, 2012, and June 30, 2020. The primary outcome was persistent opioid use, for which the risk was compared for those who initiated oxycodone vs codeine.

A total of 70,607 people who filled an opioid prescription within 7 days of discharge were identified during the 8-year study period: 21,308 and 49,299 (30.2 and 69.8%) received codeine and oxycodone, respectively. Receipt of oxycodone was not associated with persistent opioid use compared with receipt of codeine (relative risk, 1.04; 95% CI, 0.91 to 1.20). After vaginal delivery, there was an association noted between oxycodone and persistent use (relative risk, 1.63; 95% CI, 1.31 to 2.03), but this was not seen after cesarean delivery (relative risk, 0.85; 95% CI, 0.73 to 1.00).

“Awareness of these factors and others related to persistent use may help clinicians tailor opioid prescribing while ensuring adequate analgesia after delivery,” the authors write.

Several authors disclosed ties to biopharmaceutical companies; several authors receive payment for expert testimony or providing medicolegal opinions relating to analgesics.

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HealthDay News — An increase in 39-week induction rates and a decrease in cesarean delivery (CD) rates were seen following publication of A Randomized Trial of Induction vs Expectant Management (ARRIVE) in August 2018, according to a research letter published online August 10 in JAMA Network Open.

Rachel Wood, MD, from Brigham and Women’s Hospital in Boston, and colleagues examined whether publication of the ARRIVE trial in August 2018, which revealed that low-risk nulliparous patients who were induced at 39 weeks of gestation had a reduced risk for CD, was associated with observable obstetric practice changes in the US. Data were obtained for 2,860,942 births (66 and 34% from the pre-ARRIVE and post-ARRIVE periods, respectively).

The researchers observed an immediate increase in 39-week induction rates after the dissemination period, with a 39-week induction rate of 15.0% compared with an expected 13.8% based on trends during the pre-ARRIVE period (adjusted incident rate ratio [aIRR], 1.10); CD rates were significantly lower than expected (24.7 vs 25.1%; aIRR, 0.988). Significant ongoing temporal changes included an increase of 0.009 39-week inductions and a decrease of 0.0014 CDs per month.

“These findings suggest that the publication of the ARRIVE trial was associated with an increase in 39-week induction rates and a reduction in CD rates for low-risk nulliparous patients across the US,” the authors write.

Several authors disclosed ties to the biomedical and medical technology industries.

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Emily H. Adhikari, MD, from the University of Texas Southwestern Medical Center in Dallas, and colleagues conducted a single-center, cluster randomized trial involving individuals with a gestational age of 37 weeks or more, cervical dilation of 2cm or less, intact membranes, and indication for delivery. A total of 1322 women were randomly assigned to vaginal misoprostol in 33 clusters and 1224 were randomly assigned to oral misoprostol in 37 clusters between May 24, 2021, and September 19, 2022; misoprostol regimens were followed by a standardized oxytocin protocol.

The researchers found that the primary outcome of vaginal delivery at first induction attempt did not differ between induction regimens and occurred in 78.1 and 77.2% of the vaginal and oral misoprostol arms, respectively. Tachysystole with fetal heart rate changes occurred less often in the vaginal vs the oral misoprostol arms (3.5 vs 5.9%). There was no significant difference noted between the groups in time to delivery. In the vaginal group, oxytocin was required less often before delivery (68.8 vs 78.4%).

“Use of a vaginal misoprostol compared with an oral misoprostol protocol for induction of labor in term gravid patients with intact membranes and cervical dilation of 2cm or less did not result in increased vaginal delivery,” the authors write.

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