Prevalence of neurotoxicity symptoms among postpartum women on isoniazid preventive therapy and efavirenz-based treatment for HIV: an exploratory objective of the IMPAACT P1078 randomized trial
Authors: Mandima Patricia , Baltrusaitis Kristin , Montepiedra Grace , Aaron Lisa , Mathad Jyoti , Onyango-Makumbi Carolyne , Nyati Mandisa , Ngocho James , Chareka Gift , Ponatshego Ponego , Masheto Gaerolwe , McCarthy Katie , Jean-Philippe Patrick , Gupta Amita , Stranix-Chibanda Lynda ,   for the IMPAACT P1078 T. B. APPRISE study team, Saloojee Haroon , El-Sadr Wafaa , Harrington David , Levine Jonathan B. , Marshall Mary Faith , Mokgatlhe Lucky , Munderi Paula , Nunn Andrew , Singh Jerome Amir , Kwagala Betty , Mwinga Alwyn , Sow Papa Salif , Hill Catherine , Ellner Jerrold J. , John-Stewart Grace , Joffe Steven , Murray Barbara E. , Robb Merlin L. , Kabugho Enid , Wabwire Deo , Kaganzi Hellen , Maena Joel , Kataike Hajira , Marote Emmie , Mutambanengwe Mercy , Nematadzira Teacler , Maonera Suzen , Chanaiwa Vongai , Mbengeranwa Tapiwa , Maturure Sukunena , Mhembere Tsungai , Abrahams Nasreen , Cassim Haseena , Mathiba Ruth , Coetzee Joan , Louw Jeanne , Smuts Marlize , Rossouw Lindie , Rossouw Magdel , de Vaal Celeste , Mbaba Sharon , du Preez Karen , Verheye-Dua Frieda , Shao Aisa , Njau Boniface , Sakasaka Philoteus , Semvua Seleman , Kakhu Tebogo J. , Ralegoreng Thuto , Omoz-Oarhe Ayotunde , Chakalisa Unoda , Suryavanshi Nishi , Patil Sandesh , Nevrekar Neetal , Bharadwaj Renu , Kulkarni Vandana , Tongprasert Fuanglada , Sudjaritruk Tavitiya , Khamrong Chintana , Janjing Prapaporn , Pierre Marie Flore , Aristhomene Maria Linda , Lespinasse Dominique , Dumont Emelyne , LeBlanc Rebecca , Loftis Amy James , Kim Soyeon , Shapiro David , Tierney Camlin , Rexroad Vivian , Browning Renee 
Published: January 2023

Abstract
Background
This exploratory analysis investigates the prevalence and risk factors of neurocognitive toxicity in postpartum women on HIV treatment in response to a concern of an Isoniazid Preventive Therapy (IPT)/Efavirenz interaction.

Trial Design
Pregnant women on HIV treatment from countries with high TB prevalence were randomized in IMPAACT P1078 to 28 weeks of IPT started either during pregnancy or at 12 weeks postpartum. Partway through study implementation, the Patient Health Questionnaire 9, the cognitive complaint questionnaire, and the Pittsburg Sleep Quality Index were added to evaluate depression, cognitive function, and sleep quality at postpartum weeks. Screening for peripheral neuropathy was conducted throughout the study.

Methods
We summarized percentages of women with depression symptoms, cognitive dysfunction, poor sleep quality and peripheral neuropathy and assessed the association of 11 baseline risk factors of neurotoxicity using logistic regression, adjusted for gestational age stratum.

Results
Of 956 women enrolled, 749 (78%) had at least one neurocognitive evaluation. During the postpartum period, the percentage of women reporting at least mild depression symptoms, cognitive complaint and poor sleep quality peaked at 13%, 8% and 10%, respectively, at 12 weeks, and the percentage of women reporting peripheral neuropathy peaked at 13% at 24 weeks. There was no evidence of study arm differences in odds of all four neurotoxic symptoms.

Conclusions
Timing of IPT initiation and EFV use were not associated with symptoms of neurotoxicity. Further study is advised to formally assess risk factors of neurotoxicity.