Early HIV Treatment and Survival Over Six Years of Observation in the ANRS 12249 Treatment as Prevention Trial

Kathy Baisley; Joanna Orne-Gliemann; Joseph Larmarange; Melanie Plazy; Dami Collier; Jaco Dreyer; Thobeka Mngomezulu; Kobus Herbst; Willem Hanekom; Francois Dabis; Mark J. Siedner; Collins Iwuji

Disclosures

HIV Medicine. 2022;23(8):922-928. 

In This Article

Abstract and Introduction

Abstract

Objectives: Population-based universal test and treat (UTT) trials have shown an impact on population-level virological suppression. We followed the ANRS 12249 TasP trial population for 6 years to determine whether the intervention had longer-term survival benefits.

Methods: The TasP trial was a cluster-randomized trial in South Africa from 2012 to 2016. All households were offered 6-monthly home-based HIV testing. Immediate antiretroviral therapy (ART) was offered through trial clinics to all people living with HIV (PLHIV) in intervention clusters and according to national guidelines in control clusters. After the trial, individuals attending the trial clinics were transferred to the public ART programme. Deaths were ascertained through annual demographic surveillance. Random-effects Poisson regression was used to estimate the effect of trial arm on mortality among (i) all PLHIV; (ii) PLHIV aware of their status and not on ART at trial entry; and (iii) PHLIV who started ART during the trial.

Results: Mortality rates among PLHIV were 9.3/1000 and 10.4/1000 person-years in the control and intervention arms, respectively. There was no evidence that the intervention decreased mortality among all PLHIV [adjusted rate ratio (aRR) = 1.10, 95% confidence interval (CI) = 0.85–1.43, p = 0.46] or among PLHIV who were aware of their status but not on ART. Among individuals who initiated ART, the intervention decreased mortality during the trial (aRR = 0.49, 95% CI = 0.28–0.85, p = 0.01), but not after the trial ended.

Conclusions: The 'treat all' strategy reduced mortality among individuals who started ART but not among all PLHIV. To achieve maximum benefit of immediate ART, barriers to ART uptake and retention in care need to be addressed.

Introduction

South Africa has the largest HIV epidemic in the world, with an estimated 7.5 million people living with HIV (PLHIV) and 5.2 million on antiretroviral treatment (ART) in 2019.[1] Although HIV-related mortality has reduced significantly with increased ART uptake, 22% of deaths in 2018 were attributable to HIV.[2]

Clinical trials have shown the beneficial effect of early ART initiation on morbidity and mortality.[3,4] Consequently, regardless of CD4 count, ART is now a global standard of care[5] and was adopted by South Africa in September 2016.[6] However, the impact of this 'treat all' strategy on population-level HIV mortality within programmatic settings is unknown. Several recent cluster-randomized trials have demonstrated the potential of universal test and treat (UTT; i.e. the combination of universal testing campaigns and 'treatment for all') for population-level impact.[7] The SEARCH trial in Uganda and Kenya found that UTT improved population-level viral suppression and reduced mortality among PLHIV, but had no effect on HIV incidence.[8] By contrast, the MaxART trial in Eswatini found that 'treat all' improved population-level viral suppression but had no impact on mortality.[9]

The ANRS 12249 Treatment as Prevention (TasP) trial in rural South Africa compared immediate ART with standard-of-care (SOC) ART initiation. The trial found no effect on HIV incidence, although viral suppression was high among individuals who started ART.[10] The effect on mortality among PLHIV has not been examined. Although the TasP trial ended in June 2016, the cohort continued to be followed in the Africa Health Research Institute's (AHRI) demographic surveillance.[11] We undertook these analyses to address the question of whether a 'treat all' policy in rural South Africa provides long-term survival benefits among PLHIV.

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