Slow Acceptance of Universal Antiretroviral Therapy (ART) Among Mothers Enrolled in IMPAACT PROMISE Studies Across the Globe

Citation: 
L. Stranix-Chibanda, S. BrummelJ. Pilotto, M. Mutambanengwe, V. Chanaiwa, T. Mhembere, M. Kamateeka, J. Aizire, G. Masheto, R. Chamanga, M. Maluwa, S. Hanley, E. Joao. G. Theron, N. Nevrekar, M. Nyati, B. Santos, L. Aurpibul, M. Mubiana-Mbewe, R. Oliveira, T. Anekthananon, P. Mlay, K. Angelidou, C. Tierney, L. Ziemba, A. Coletti, K.Mc, C, rthy, M. Basar, N. Chakhtoura, R. Browning, J. Currier, M. G. Fowler, P. Flynn.
Publication year: 
2019

 

The PROMISE trial enrolled asymptomatic HIV-infected pregnant and postpartum women not eligible for antiretroviral treatment (ART) per local guidelines and randomly assigned proven antiretroviral strategies to assess relative efficacy for perinatal prevention plus maternal/infant safety and maternal health. The START study subsequently demonstrated clear benefit in initiating ART regardless of CD4 count. Active PROMISE participants were informed of results and women not receiving ART were strongly recommended to immediately initiate treatment to optimize their own health. We recorded their decision and the primary reason given for accepting or rejecting the universal ART offer after receiving the START information. One-third of participants did not initiate ART after the initial session, wanting more time to consider. Six sessions were required to attain 95% uptake. The slow uptake of universal ART highlights the need to prepare individuals and sensitize communities regarding the personal and population benefits of the “Treat All” strategy.

 

 

Introduction

Previous Antiretroviral Strategies for Pregnant Women

Prior to 2016, ART was reserved for HIV-infected pregnant women with signs of immunosuppression or clinical AIDS [1]. Women who were not immunocompromised received antiretroviral prophylaxis consisting of mono-, dual or triple antiretroviral regimens throughout pregnancy, and they or their infants received prophylaxis during lactation. Significant resources were invested in educating communities about the immunological threshold for ART initiation and increasing access to CD4 cell testing in maternity clinics. The PROMISE study was a strategy trial designed to compare these antiretroviral strategies among asymptomatic HIV-infected pregnant women who did not meet country criteria for ART initiation, assessing vertical HIV transmission during pregnancy and post-delivery, infant safety and maternal health.

 

 

Methods

PROMISE Study Design

PROMISE was conducted at 70 research sites in 15 countries within sub-Saharan Africa, Asia and the Americas. A total of 5400 asymptomatic HIV-infected pregnant women with high CD4 counts (above 350 cells/mm3 or the treatment threshold at that time) were assigned to different ARV strategies and followed for HIV disease progression, vertical transmission and safety. In settings where maternal ART and replacement feeding was standard, eligible women were randomized within 6 weeks of delivery to continue or stop ART and remain in follow-up for intense monitoring of HIV disease progression and adverse events in a protocol named 1077HS (for HAART standard) [8]. In settings where maternal ART was not standard for the prevention of vertical transmission, separate protocols were conducted—1077FF and 1077BF—in formula feeding and breastfeeding settings, respectively. Within 1077FF/BF, pregnant women were randomized to triple ART or prophylaxis with zidovudine throughout pregnancy and delivery in the Antepartum Component plus single dose nevirapine at delivery followed by a 2 week “tail” of tenofovir/emtricitabine [9]. Women who did not access HIV services in pregnancy could join the study around the time of delivery. Eligible mothers were randomized after delivery in the Postpartum Component to receive or not receive maternal ART. Once the period of risk for vertical transmission was over—at delivery for 1077FF and after weaning or after 18 months of study intervention, whichever came first, for 1077BF—women receiving ART were randomized in the Maternal Health Component to continue or stop ART. Enrolled women who were not eligible for subsequent randomizations were followed in an observational cohort through study completion.

Participants were followed at least quarterly to monitor clinical, immunological and virologic status. Women randomly assigned to not take ART started ART once country criteria for treatment initiation were met. Women remained in PROMISE follow-up regardless of ART status.