Original Article

Effect of Integrase Strand Transfer Inhibitor Use on Time to HIV Viral Suppression before Delivery

Authors: Oriel A. Nissim, MD, Marjorie C. Spitznagel, MD, Stephanie E. Kirk, PharmD, Jessica L. Tarleton, MD, MPH, Gweneth B. Lazenby, MD, MSCR

Abstract

Objectives: We sought to determine whether pregnant individuals with human immunodeficiency virus (HIV) prescribed integrase strand transfer inhibitor (INSTI) antiretrovirals (ARVs) achieve viral suppression faster than individuals taking non-INSTI regimens and to determine whether there were differences in viral suppression at delivery among INSTI ARVs.

Methods: This is a retrospective cohort study of pregnant individuals with HIV who delivered a live infant during the study period (January 1, 2009–December 31, 2020). Patients’ ARV therapy (ART) was classified as including INSTI or non-INSTI. We compared the proportion of individuals with viral suppression at delivery by group and individual INSTI ARVs using χ2 and Fisher exact tests. A log rank test was used to compare time to viral suppression on ARVs.

Results: During the study period, 168 individuals delivered a live infant. Most of the patients were diagnosed as having HIV before pregnancy and had taken ARVs before conception (76%), but fewer than half had an undetectable viral load at the first antenatal visit (45%). During pregnancy, 46% were prescribed INSTI and 54% were prescribed non-INSTI ARVs. Most had an undetectable HIV RNA viral load at delivery (75% INSTI and 72% non-INSTI, P = 0.7). The time to viral suppression was similar between groups (log rank test P = 0.43). Viral suppression at delivery was similar among INSTI ARVs: raltegravir (53%), elvitegravir (88%), dolutegravir (73%), and bictegravir (88%) (P = 0.13).

Conclusions: Despite recommendations to prescribe INSTI in pregnancy for rapid viral suppression, we did not find a significant difference in time to viral suppression when pregnant individuals were taking non-INSTI ARVs. We did not find that one INSTI ARV was superior for viral suppression.
Posted in: Infectious Disease136 Acquired Immunodeficiency Syndrome (AIDS) And Human Immunodeficiency Virus (HIV) Infection17

This content is limited to qualifying members.

Existing members, please login first

If you have an existing account please login now to access this article or view purchase options.

Purchase only this article ($25)

Create a free account, then purchase this article to download or access it online for 24 hours.

Purchase an SMJ online subscription ($75)

Create a free account, then purchase a subscription to get complete access to all articles for a full year.

Purchase a membership plan (fees vary)

Premium members can access all articles plus recieve many more benefits. View all membership plans and benefit packages.

References

1. Lockman S, Brummel SS, Ziemba L, et al. Efficacy and safety of dolutegravir with emtricitabine and tenofovir alafenamide fumarate or tenofovir disoproxil fumarate, and efavirenz, emtricitabine, and tenofovir disoproxil fumarate HIV antiretroviral therapy regimens started in pregnancy (IMPAACT 2010/VESTED): a multicentre, open-label, randomised, controlled, phase 3 trial. Lancet 2021; 397:1276–1292.
 
2. HHS Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in adults and adolescents with HIV. https://clinicalinfo.hiv.gov/sites/default/files/guidelines/documents/adult-adolescent-arv/guidelines-adult-adolescent-arv.pdf. Updated March 23, 2023. Accessed August 30, 2021.
 
3. Cahn P, Madero JS, Arribas JR, et al. Dolutegravir plus lamivudine versus dolutegravir plus tenofovir disoproxil fumarate and emtricitabine in antiretroviral-naive adults with HIV-1 infection (GEMINI-1 and GEMINI-2): week 48 results from two multicentre, double-blind, randomised, noninferiority, phase 3 trials. Lancet 2019;393:143–155.
 
4. American College of Obstetricians and Gynecologists. ACOG Committee Opinion No. 751: labor and delivery management of women with human immunodeficiency virus infection. Obstet Gynecol 2018;132:e131–e137.
 
5. Panel on Treatment of Pregnant Persons with HIV Infection and Prevention of Perinatal Transmission. Recommendations for the use of antiretroviral drugs in pregnant persons with HIV infection and interventions to reduce perinatal HIV transmission in the United States. https://clinicalinfo.hiv.gov/en/guidelines/perinatal/recommendations-arv-drugs-pregnancy-overview. Updated January 31, 2023. Accessed August 30, 2021.
 
6. Hanna DB, Hessol NA, Golub ET, et al. Increase in single-tablet regimen use and associated improvements in adherence-related outcomes in HIV-infected women. J Acquir Immune Defic Syndr 2014;65:587–596.
 
7. Sax PE, Meyers JL, Mugavero M, et al. Adherence to antiretroviral treatment and correlation with risk of hospitalization among commercially insured HIV patients in the United States. PloS One 2012;7:e31591.
 
8. World Health Organization. Updated recommendations on HIV prevention, infant diagnosis, antiretroviral initiation and monitoring. https://www.who.int/publications/i/item/9789240022232. Published March 17, 2021. Accessed August 30, 2021.
 
9. Podany AT, Scarsi KK, Fletcher CV. Comparative clinical pharmacokinetics and pharmacodynamics of HIV-1 integrase strand transfer inhibitors. Clin Pharmacokinet 2017;56:25–40.
 
10. Zash R, Jacobson DL, Diseko M, et al. Comparative safety of dolutegravir-based or efavirenz-based antiretroviral treatment started during pregnancy in Botswana: an observational study. Lancet Glob Health 2018;6:e804–e810.
 
11. Zash R, Makhema J, Shapiro RL. Neural-tube defects with dolutegravir treatment from the time of conception. N Engl J Med 2018;379:979–981.
 
12. Zash R, Holmes L, Diseko M, et al. Neural-tube defects and antiretroviral treatment regimens in Botswana. N Engl J Med 2019;381:827–840.
 
13. Momper JD, Best BM, Wang J, et al. Elvitegravir/cobicistat pharmacokinetics in pregnant and postpartum women with HIV. AIDS 2018;32:2507–2516.
 
14. Rahangdale L, Cates J, Potter J, et al. Integrase inhibitors in late pregnancy and rapid HIV viral load reduction. Am J Obstet Gynecol 2016;214:385. e1-385.e7.
 
15. Badell ML, Sheth AN, Momplaisir F, et al. A multicenter analysis of elvitegravir use during pregnancy on HIV viral suppression and perinatal outcomes. Open Forum Infect Dis 2019;6:ofz129.
 
16. van der Galien R, Ter Heine R, Greupink R, et al. Pharmacokinetics of HIV-integrase inhibitors during pregnancy: mechanisms, clinical implications and knowledge gaps. Clin Pharmacokinet 2019;58:309–323.
 
17. Song I, Borland J, Arya N, et al. Pharmacokinetics of dolutegravir when administered with mineral supplements in healthy adult subjects. J Clin Pharmacol 2015;55:490–496.
 
18. Swindells S, Andrade-Villanueva JF, Richmond GJ, et al. Long-acting cabotegravir and rilpivirine for maintenance of HIV-1 suppression. N Engl J Med 2020;382:1112–1123.
 
19. Margolis DA, Gonzalez-Garcia J, Stellbrink HJ, et al. Long-acting intramuscular cabotegravir and rilpivirine in adults with HIV-1 infection (LATTE-2): 96-week results of a randomised, open-label, phase 2b, non-inferiority trial. Lancet 2017;390:1499–1510.