Vaginal Self-Sampling for Human Papillomavirus Infection as a Primary Cervical Cancer Screening Tool in a Haitian Population

Human papillomavirus (HPV) testing as primary cervical cancer screening has not been studied in Caribbean women. We tested vaginal self-collection versus physician cervical sampling in a population of Haitian women

Using a composite maternal-infant outcome measure in tuberculosis prevention studies among pregnant women

CITATION: Montepiedra, G. et al. 2021. Using a Composite Maternal-Infant Outcome Measure in Tuberculosis-Prevention Studies Among Pregnant Women. Clinical infectious diseases, 73(3):587–e593. doi:10.1093/cid/ciaa1674The original publication is available at https://academic.oup.com/cid/Background: Tuberculosis (TB-)-preventive therapy (TPT) among pregnant women reduces risk of TB in mothers and infants, but timing of initiation should consider potential adverse effects. We propose an analytical approach to evaluate the risk-benefit of interventions. Methods: A novel outcome measure that prioritizes maternal and infant events was developed with a 2-stage Delphi survey, where a panel of stakeholders assigned scores from 0 (best) to 100 (worst) based on perceived desirability. Using data from TB APPRISE, a trial among pregnant women living with human immunodeficiency virus (WLWH) that randomized the timing of initiation of isoniazid, antepartum versus postpartum, was evaluated. Results: The composite outcome scoring/ranking system categorized mother-infant paired outcomes into 8 groups assigned identical median scores by stakeholders. Maternal/infant TB and nonsevere adverse pregnancy outcomes were assigned similar scores. Mean (SD) composite outcome scores were 43.7 (33.0) and 41.2 (33.7) in the antepartum and postpartum TPT initiation arms, respectively. However, a modifying effect of baseline antiretroviral regimen was detected (P = .049). When women received nevirapine, composite scores were higher (worse outcomes) in the antepartum versus postpartum arms (adjusted difference, 14.3; 95% confidence interval [CI], 2.4-26.2; P = .02), whereas when women received efavirenz there was no difference by timing of TPT (adjusted difference, .62; 95% CI, -3.2-6.2; P = .53). Conclusions: For TPT, when used by otherwise healthy persons, preventing adverse events is paramount from the perspective of stakeholders. Among pregnant WLWH in high-TB-burden regions, it is important to consider the antepartum antiretroviral regimen taken when deciding when to initiate TPT. Clinical Trials Registration. NCT01494038 (IMPAACT P1078).https://academic.oup.com/cid/article/73/3/e587/5955952?login=truePublishers versio

Pregnancy outcomes of women conceiving on antiretroviral therapy (ART) compared to those commenced on ART during pregnancy

CITATION: Theron, G. et al. 2021. Pregnancy Outcomes of Women Conceiving on Antiretroviral Therapy (ART) Compared to Those Commenced on ART During Pregnancy. Clinical infectious diseases, 73(2): e312–e320. doi:10.1093/cid/ciaa805The original publication is available at https://academic.oup.com/cid/Background: Globally, the number of infected women of childbearing age living with human immunodeficiency virus (HIV) and conceiving on antiretroviral therapy (ART) is increasing. Evidence of ART safety at conception and during pregnancy and adverse pregnancy outcomes remains conflicting. The Promoting Maternal and Infant Survival Everywhere (PROMISE) 1077 breastfeeding (BF) and formula feeding (FF) international multisite trials provide an opportunity to examine the impact of ART at conception on pregnancy outcomes with subsequent pregnancies. Methods: The PROMISE 1077BF/1077FF trials were designed to address key questions in the management of HIV-infected women who did not meet clinical guidelines for ART treatment during the time of the trials. After the period of risk of mother-to-child transmission was over, women were randomized to either continue or discontinue ART. We compared subsequent pregnancy outcomes of nonbreastfeeding women randomized to continue ART following delivery, or breastfeeding women randomized to continue ART following breastfeeding cessation who conceived while on ART to women randomized to discontinue ART, who restarted ART after pregnancy was diagnosed. Results: Pregnancy outcomes of 939 subsequent pregnancies of 826 mothers were recorded. The intention-to-treat analyses showed increased incidence of low birth weight (<2500 g) for women who conceived while on ART (relative risk, 2.65 [95% confidence interval {CI}, 1.20-5.81]), and also a higher risk of spontaneous abortion, stillbirth, or neonatal death (hazard ratio, 1.40 [95% CI, .99-1.98]) compared to women who restarted ART after they were found to be pregnant during trial follow-up. Conclusions: We found an increased risk for adverse pregnancy outcomes in women conceiving on ART, emphasizing the need for improved obstetric and neonatal care for this group. Clinical trials registration: NCT01061151.https://academic.oup.com/cid/article/73/2/e312/5860458?login=truePublishers versio

Individual and composite adverse pregnancy outcomes in a randomized trial on isoniazid preventative therapy among women living with human immunodeficiency virus

CITATION: Theron, G. et al. 2021. Individual and Composite Adverse Pregnancy Outcomes in a Randomized Trial on Isoniazid Preventative Therapy Among Women Living With Human Immunodeficiency Virus. Clinical infectious diseases, 72(11):e784–e790. doi:10.1093/cid/ciaa1482The original publication is available at https://academic.oup.com/cid/Background: International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) P1078, a randomized noninferiority study designed to compare the safety of starting isoniazid preventive therapy (IPT) in women living with human immunodeficiency virus (HIV) either during pregnancy or after delivery, showed that IPT during pregnancy increased the risk of composite adverse pregnancy outcomes, but not individual outcomes. Many known factors are associated with adverse pregnancy outcomes: these factors' associations and effect modifications with IPT and pregnancy outcomes were examined. Methods: Pregnant women living with HIV from 8 countries with tuberculosis incidences >60/100 000 were randomly assigned to initiate 28 weeks of IPT either during pregnancy or at 12 weeks after delivery. Using univariable and multivariable logistic regression and adjusting for factors associated with pregnancy outcomes, composite and individual adverse pregnancy outcome measures were analyzed. Results: This secondary analysis included 925 mother-infant pairs. All mothers were receiving antiretrovirals. The adjusted odds of fetal demise, preterm delivery (PTD), low birth weight (LBW), or a congenital anomaly (composite outcome 1) were 1.63 times higher among women on immediate compared to deferred IPT (95% confidence interval [CI], 1.15-2.31). The odds of fetal demise, PTD, LBW, or neonatal death within 28 days (composite outcome 2) were 1.62 times higher among women on immediate IPT (95% CI, 1.14-2.30). The odds of early neonatal death within 7 days, fetal demise, PTD, or LBW (composite outcome 3) were 1.74 times higher among women on immediate IPT (95% CI, 1.22-2.49). Conclusions: We confirmed higher risks of adverse pregnancy outcomes associated with the initiation of IPT during pregnancy, after adjusting for known risk factors for adverse pregnancy outcomes.https://academic.oup.com/cid/article/72/11/e784/5913421?login=truePublishers versio

Isoniazid Preventive Therapy in HIV-Infected Pregnant and Postpartum Women

CITATION: Gupta, A. et al. 2019. Isoniazid Preventive Therapy in HIV-Infected Pregnant and Postpartum Women. The New England Journal of Medicine, 381(14):1333-1346. doi:10.1056/NEJMoa1813060The original publication is available at https://www.nejm.org/BACKGROUND: The safety, efficacy, and appropriate timing of isoniazid therapy to prevent tuberculosis in pregnant women with human immunodeficiency virus (HIV) infection who are receiving antiretroviral therapy are unknown. METHODS: In this multicenter, double-blind, placebo-controlled, noninferiority trial, we randomly assigned pregnant women with HIV infection to receive isoniazid preventive therapy for 28 weeks, initiated either during pregnancy (immediate group) or at week 12 after delivery (deferred group). Mothers and infants were followed through week 48 after delivery. The primary outcome was a composite of treatment-related maternal adverse events of grade 3 or higher or permanent discontinuation of the trial regimen because of toxic effects. The noninferiority margin was an upper boundary of the 95% confidence interval for the between-group difference in the rate of the primary outcome of less than 5 events per 100 person-years. RESULTS: A total of 956 women were enrolled. A primary outcome event occurred in 72 of 477 women (15.1%) in the immediate group and in 73 of 479 (15.2%) in the deferred group (incidence rate, 15.03 and 14.93 events per 100 person-years, respectively; rate difference, 0.10; 95% confidence interval [CI], −4.77 to 4.98, which met the criterion for noninferiority). Two women in the immediate group and 4 women in the deferred group died (incidence rate, 0.40 and 0.78 per 100 person-years, respectively; rate difference, −0.39; 95% CI, −1.33 to 0.56); all deaths occurred during the postpartum period, and 4 were from liver failure (2 of the women who died from liver failure had received isoniazid [1 in each group]). Tuberculosis developed in 6 women (3 in each group); the incidence rate was 0.60 per 100 person-years in the immediate group and 0.59 per 100 person-years in the deferred group (rate difference, 0.01; 95% CI, −0.94 to 0.96). There was a higher incidence in the immediate group than in the deferred group of an event included in the composite adverse pregnancy outcome (stillbirth or spontaneous abortion, low birth weight in an infant, preterm delivery, or congenital anomalies in an infant) (23.6% vs. 17.0%; difference, 6.7 percentage points; 95% CI, 0.8 to 11.9). CONCLUSIONS: The risks associated with initiation of isoniazid preventive therapy during pregnancy appeared to be greater than those associated with initiation of therapy during the postpartum period. (Funded by the National Institutes of Health; IMPAACT P1078 TB APPRISE ClinicalTrials.gov number, NCT01494038. opens in new tab.)https://www.nejm.org/doi/full/10.1056/NEJMoa1813060Publisher’s versio

Etravirine pharmacokinetics in HIV-infected pregnant women

__Background__ The study goal was to describe etravirine pharmacokinetics during pregnancy and postpartum in HIV-infected women. __Methods__ IMPAACT P1026s and PANNA are on-going, non-randomized, open-label, parallel-group, multi-center phase-IV prospective studies in HIV-infected pregnant women. Intensive steady-state 12-h pharmacokinetic profiles were performed from 2nd trimester through postpartum. Etravirine was measured at two labs using validated ultra performance liquid chromatography (detection limits: 0.020 and 0.026 mcg/mL). __Results__ Fifteen women took etravirine 200 mg twice-daily. Etravirine AUC0-12 was higher in the 3rd trimester compared to paired postpartum data by 34% (median 8.3 vs. 5.3 mcg*h/mL, p = 0.068). Etravirine apparent oral clearance was significantly lower in the 3rd trimester of pregnancy compared to paired postpartum data by 52% (median 24 vs. 38 L/h, p = 0.025). The median ratio of cord blood to maternal plasma concentration at delivery was 0.52 (range: 0.19-4.25) and no perinatal transmission occurred. __Conclusion__ Etravirine apparent oral clearance is reduced and exposure increased during the third trimester of pregnancy. Based on prior dose-ranging and safety data, no dose adjustment is necessary for maternal health but the effects of etravirine in utero are unknown. Maternal health and infant outcomes should be closely monitored until further infant safety data are available. __Clinical Trial registration:__ The IMPAACT protocol P1026s and PANNA study are registered at ClinicalTrials.gov under NCT00042289 and NCT00825929

Prevention of HIV-1 transmission through breastfeeding: efficacy and safety of maternal antiretroviral therapy versus infant nevirapine prophylaxis for duration of breastfeeding in HIV-1-infected women with high CD4 cell count (IMPAACT PROMISE): a randomized, open label, clinical trial.

CAPRISA, 2018.Abstract available in pdf

Factors Associated with Birth Spacing and Contraceptive Use in Leogane, Haiti

<p>AbstractAbstractAbstractAbstract Abstract</p><p>Spacing the inter-pregnancy interval to more than two years reduces maternal and neonatal morbidity and mortality. Modern contraceptive use can reduce maternal morbidity and mortality by contributing to birth spacing and reducing the total fertility rate. This study is designed to understand the factors associated with appropriate birth spacing and the barriers to modern contraceptive use in Leogane, Haiti. A cross sectional survey of 552 reproductive age women in Leogane proper was performed from June to July of 2011. Univariate, multivariate, and logisitic regressions were used to analyze the data. The results demonstrate the importance of education, employment status, contraceptive use and stable relationships in influencing appropriate birth spacing. Women who spaced their births tended to have less complications compared to women who did not, however this difference was not statistically significant. Barriers to contraceptive use were cultural factors such as religion, and low socioeconomic status. However, contraceptive use was positively influenced by education and partner acceptance of contraceptives. These findings indicate that family programs focused on educating women and their partners on the benefits of contraception and birth spacing would be successful in Leogane, Haiti.</p>Thesi

Laparotomy to laparoscopy: Changing trends in the surgical management of ectopic pregnancy in a tertiary care teaching hospital

To review the changing trends in the surgical management of ectopic pregnancy and to evaluate the effect of an ongoing training program for resident surgeons on the rate and success of laparoscopic surgery. Retrospective chart review (Canadian Task Force classification II-3). University tertiary medical center. One thousand forty-six patients with ectopic pregnancy treated at Jackson Memorial Hospital from January 1, 1995, through December 31, 2004. A formal, ongoing laparoscopic training program was established in 1999. The rate of laparoscopy, laparotomy, and conversion for each year was compared with the baseline year of 1995 and between the years before and after the establishment of the training program. Four hundred sixty-eight laparotomies and 578 laparoscopies were successfully completed. The laparoscopic approach rate has increased from 40.9% in 1995 to 86.3% in 2004. By year 2000 and thereafter, significantly more ectopic surgeries were approached through the laparoscope compared with in 1995 (p<.01). By 2000 and thereafter, significantly less conversions occurred compared with the baseline year of 1995 (4.0% vs 18.5%; p = .01). Laparoscopy became the primary approach for the management of ectopic pregnancy in part because of resident participation in an ongoing laparoscopy training program