Findings from the first randomised controlled trial to date evaluating postpartum antiretroviral therapy (ART) for women with high CD4 cell counts (over 400 cells/mm3) highlight a critical need to increase treatment acceptance in this population. The research was presented at the 21st International AIDS Conference (AIDS 2016) in Durban, South Africa.
Despite counselling and prior exposure to intense ART education and HIV monitoring within a highly-resourced clinical trial setting, over a third of women declined ART when the offer of treatment was extended to all women in the study, needing more time to consider the benefits for their own health.
Effective implementation of the “treat all” approach recommended by the World Health Organization (WHO), requires addressing the significant challenges these findings raise.
The findings come from the Promoting Maternal and Infant Survival Everywhere (PROMISE 1077HS) study, carried out at 52 clinical research sites in Argentina, Botswana, Brazil, China, Haiti, Peru, Thailand and the United States.
The study was conducted between January 2010 and November 2014 to determine if health over the long term is better served by continuing or stopping ART after delivery among non-breastfeeding women with high CD4 cell counts who did not meet local criteria for starting ART.
PROMISE 1077HS results: continued postpartum treatment
The PROMISE study found that continuing ART after giving birth was safe and associated with reduced illness and infection in over 1600 young asymptomatic women with high CD4 cell counts, Judith Currier told participants at the conference on Thursday.
Virologic failure was high (23%) in this study and resistance testing suggested the need to improve adherence for the majority.
PROMISE 1077HS examined the effects of ART on postpartum maternal health; 1077FF and BF evaluated the effects of intrapartum and postpartum ART regimens on vertical HIV transmission as well as the effects of ART on postpartum maternal health in settings plus formula feeding (FF) or breastfeeding (BF).
Asymptomatic HIV-positive non-breastfeeding women with CD4 cell counts equal to or above 400 cells/mm3 before starting ART who began ART in pregnancy were randomised up to 42 days after delivery to continue or stop ART.
The primary composite endpoint included death, AIDS-defining illness and serious non-AIDS events. A post-hoc analysis evaluated WHO Stage 2 and 3 events.
Analyses reflect follow-up until July 2015. All participants were told about the findings of the START study and all were offered ART.
Of the 1652 women enrolled the median age was 27 and 28 years in the continue (827) and stop (825) arms, respectively. At entry the median CD4 cell count was 696 cells/mm3 and 695 cells/mm3, respectively. Median ART exposure before delivery was 19 weeks (IQR: 13-24) and 94% had a viral load under 1000 copies/ml.
After a median follow-up of 2.3 years, continued ART did not significantly reduce the risk of death, AIDS-defining illness or serious non-AIDS event. However, the risk of WHO Stage 2 and 3 events was halved in those randomised to continue ART: 39 (2.02 per 100 person-years) and 80 (4.36 per 100 person-years) events, respectively, HR: 0.47 (95% CI: 0.32-0.68), p < 0.001.
When the composite endpoint of death, AIDS-defining illness or serious non-AIDS event and WHO Stage 2 and 3 events was analysed, continued ART reduced the risk of reaching this endpoint by 44% (HR 0.56, 95% CI 0.41-0.78).
While toxicity rates in the continue arm were higher, the difference was not statistically significant.
Of the 827 women randomised to continue ART 23% (189) had confirmed virologic failure. One hundred and fifty-five (82%) had virologic testing, 103 (66%) had no evidence of resistance at the time of failure; of the 52 with evidence of failure 22 had resistance to one of the drugs in the failing regimen.
Dr Currier concluded in addition to supporting the use of continued ART for postpartum women (Option B+), interventions to improve adherence as well as studies to examine newer regimens with a high genetic barrier to resistance are needed to insure maximal long-term benefit.
Acceptance of early ART
The PROMISE study followed women until June 2015 when all women in the study were offered the opportunity to begin immediate antiretroviral treatment in response to the results of the START study. START showed that early treatment reduced mortality and illness; its findings have led to the WHO recommendation of `Treat All`.
Despite these findings Lynda Stranix-Chibanda, presenting on behalf of the IMPAACT/PROMISE trials, reported just over one-third of HIV-positive women when given the opportunity to start ART chose not to, notably after a single counselling session. They needed more time to consider the offer of starting ART for their own health. Dr Stranix-Chibanda stressed the importance of this for programme implementers in scaling up test-and-treat strategies.
Following the results of the START study the PROMISE study team let active participants know of the results strongly encouraging those not on ART to start treatment immediately to optimise their own health. Starting treatment carried no financial cost nor did the decision affect continued participation in the studies.
Dr Stranix-Chibanda presented a summary of the participants’ responses and their reasons for accepting or declining early ART.
A mixed methods approach was used to collect responses from participants getting the START information. Staff contacted participants asking them to return to the clinic. Using a structured script START results were given and understanding assessed. During a client-centred counselling session those not on ART were advised to accept the offer to start ART. Women chose their primary reason for accepting or declining the offer of early ART from a set of closed options.
Of the 1483 (35%) women not on ART and advised to start ART, 984 (66%) accepted and just over a third 499 (34%) declined.
Acceptance rates varied among the 14 countries ranging from 100% maximum, a mean of 66% and a minimum of 37%.
Reasons given for declining ART (1077BF/FF and 1077HS) included wanting more time to consider (44% and 33% respectively) and feeling well and knowing they had a high CD4 cell count (13% and18%, respectively). Among those accepting early ART, 46% and 43% respectively did so because of health concerns while 35% and 36% respectively did because of the protocol team’s recommendation.
With continued counselling, however, the proportion of women who remain off ART decreases with each visit supporting the important need for more time.
Currier J et al. Randomized trial of stopping or continuing ART among post-partum women with pre-ART CD4≥ 400 cells/mm3 (PROMISE 1077HS). 21st International AIDS Conference, Durban, abstract THAB0103LB, 2016.
Stranix-Chibanda L et al. Low acceptance of early antiretroviral therapy (ART) among post-partum women enrolled in IMPAACT PROMISE studies across the globe. 21st International AIDS Conference, Durban, abstract THAB0106LB, 2016.