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

AIDS and Behavior (2019) 23:2522–2531 https://doi.org/10.1007/s10461-019-02624-3 ORIGINAL PAPER Slow Acceptance of Universal Antiretroviral Therapy (ART) Among Mothers Enrolled in IMPAACT PROMISE Studies Across the Globe L. Stranix‑Chibanda1,4 · S. Brummel2 · J. Pilotto3 · M. Mutambanengwe4 · V. Chanaiwa4 · T. Mhembere4 · M. Kamateeka5 · J. Aizire5 · G. Masheto6 · R. Chamanga7 · M. Maluwa8 · S. Hanley9 · E. Joao10 · G. Theron11 · N. Nevrekar12 · M. Nyati13 · B. Santos14 · L. Aurpibul15 · M. Mubiana‑Mbewe16 · R. Oliveira17 · T. Anekthananon18 · P. Mlay19 · K. Angelidou2 · C. Tierney2 · L. Ziemba2 · A. Coletti20 · K. McCarthy20 · M. Basar21 · N. Chakhtoura22 · R. Browning23 · J. Currier24 · M. G. Fowler25 · P. Flynn26 · for the PROMISE study team Published online: 9 August 2019 © The Author(s) 2019 Abstract 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. Keywords Treat All · Universal ART· Women with HIV 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 * L. Stranix‑Chibanda lstranix@uzchs‑ctrc.org Extended author information available on the last page of the article 13 Vol:.(1234567890) criteria for ART initiation, assessing vertical HIV transmission during pregnancy and post-delivery, infant safety and maternal health. Universal ART Approach The current World Health Organization (WHO) recommendation for women diagnosed with HIV infection in pregnancy is to initiate life-long triple ART regardless of clinical or immunological staging [2]. This “Treat All” approach was informed in 2015 by the START trial [3] which demonstrated that universal ART initiation reduces the risk of HIV disease progression. Previously, concerns had been voiced about the acceptability of this approach, given the prevailing perception in communities that ART was reserved for people who were sick with low CD4 counts based on prior guidance [1, 2]. Similarly, the practicality of delivering such a strategy on a public scale and the ability of women to adhere to satisfactory levels had been questioned because of multiple operational challenges [4–7]. AIDS and Behavior (2019) 23:2522–2531 PROMISE Response to START Study Results Upon release of the START study results in July 2015, the PROMISE randomized interventions were immediately halted, and universal ART was recommended by the study team to all participants. Since the uptake of life-long ART would be relevant to ART programs that would soon incorporate this change, quantitative data were collected in a systematic manner from these asymptomatic women with high CD4 counts enrolled in a clinical trial across diverse global settings. We assessed the uptake of universal ART and present reasons to either accept or decline the recommendation. 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 2523 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. Participant Tracing and Information‑Giving About the START Study Results Figure 1 illustrates the timeline of events surrounding the action taken in response to the release of the START study results. The PROMISE study team directed sites to actively contact participants to return to the clinic to receive important information that could influence their decision to remain in follow-up. The rate of return was tracked at each site to ensure a timely response. The study team provided a structured script of simple ta (...truncated)