Browsing by Author "Onyango-Makumbi, Carolyne"

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    Individual and composite adverse pregnancy outcomes in a randomized trial on isoniazid preventative therapy among women living with human immunodeficiency virus
    (Oxford University Press, 2021-06-01) Theron, Gerhard; Montepiedra, Grace; Aaron, Lisa; McCarthy, Katie; Chakhtoura, Nahida; Jean-Philippe, Patrick; Zimmer, Bonnie; Loftis, Amy James; Chipato, Tsungai; Nematadzira, Teacler; Nyati, Mandisa; Onyango-Makumbi, Carolyne; Masheto, Gaerolwe; Ngocho, James; Tongprasert, Fuanglada; Patil, Sandesh; Lespinasse, Dominique; Weinberg, Adriana; Gupta, Amita
    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.
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    Isoniazid Preventive Therapy in HIV-Infected Pregnant and Postpartum Women
    (Massachusetts Medical Society, 2019-10-03) Gupta, Amita; Montepiedra, Grace; Aaron, Lisa; Theron, Gerhard; McCarthy, Katie; Bradford, Sarah; Chipato, Tsungai; Vhembo, Tichaona; Stranix-Chibanda, Lynda; Onyango-Makumbi, Carolyne; Masheto, Gaerolwe R.; Mmbaga, Blandina T.; Aurpibul, Linda; Bhosale, Ramesh; Mave, Vidya; Rouzier, Vanessa; Hesseling, Anneke; Shin, Katherine; Zimmer, Bonnie; Costello, Diane; Sterling, Timothy R.; Chakhtoura, Nahida; Jean-Philippe, Patrick; Weinberg, Adriana
    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.)