Rapid initiation of antiretroviral therapy for people living with HIV

Background Despite antiretroviral therapy (ART) being widely available, HIV continues to cause substantial illness and premature death in low‐and‐middle‐income countries. High rates of loss to follow‐up after HIV diagnosis can delay people starting ART. Starting ART within seven days of HIV diagnosis (rapid ART initiation) could reduce loss to follow‐up, improve virological suppression rates, and reduce mortality. Objectives To assess the effects of interventions for rapid initiation of ART (defined as offering ART within seven days of HIV diagnosis) on treatment outcomes and mortality in people living with HIV. We also aimed to describe the characteristics of rapid ART interventions used in the included studies. Search methods We searched CENTRAL, the Cochrane Database of Systematic Reviews, MEDLINE, Embase, and four other databases up to 14 August 2018. There was no restriction on date, language, or publication status. We also searched ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform, and websites for unpublished literature, including conference abstracts. Selection criteria We included randomized controlled trials (RCTs) that compared rapid ART versus standard care in people living with HIV. Children, adults, and adolescents from any setting were eligible for inclusion. Data collection and analysis Two review authors independently assessed the eligibility of the studies identified in the search, assessed the risk of bias and extracted data. The primary outcomes were mortality and virological suppression at 12 months. We have presented all outcomes using risk ratios (RR), with 95% confidence intervals (CIs). Where appropriate, we pooled the results in meta‐analysis. We assessed the certainty of the evidence using the GRADE approach. Main results We included seven studies with 18,011 participants in the review. All studies were carried out in low‐ and middle‐income countries in adults aged 18 years old or older. Only one study included pregnant women. In all the studies, the rapid ART intervention was offered as part of a package that included several cointerventions targeting individuals, health workers and health system processes delivered alongside rapid ART that aimed to facilitate uptake and adherence to ART. Comparing rapid ART with standard initiation probably results in greater viral suppression at 12 months (RR 1.18, 95% CI 1.10 to 1.27; 2719 participants, 4 studies; moderate‐certainty evidence) and better ART uptake at 12 months (RR 1.09, 95% CI 1.06 to 1.12; 3713 participants, 4 studies; moderate‐certainty evidence), and may improve retention in care at 12 months (RR 1.22, 95% CI 1.11 to 1.35; 5001 participants, 6 studies; low‐certainty evidence). Rapid ART initiation was associated with a lower mortality estimate, however the CIs included no effect when compared to standard of care (RR 0.72, 95% CI 0.51 to 1.01; 5451 participants, 7 studies; very low‐certainty evidence). It is uncertain whether rapid ART has an effect on modification of ART treatment regimens as data are lacking (RR 7.89, 95% CI 0.76 to 81.74; 977 participants, 2 studies; very low‐certainty evidence). There was insufficient evidence to draw conclusions on the occurrence of adverse events. Authors' conclusions RCTs that include initiation of ART within one week of diagnosis appear to improve outcomes across the HIV treatment cascade in low‐ and middle‐income settings. The studies demonstrating these effects delivered rapid ART combined with several setting‐specific cointerventions. This highlights the need for pragmatic research to identify feasible packages that assure the effects seen in the trials when delivered through complex health systems. Plain language summary available in English Français Effects of starting antiretroviral therapy within one week of diagnosis on people living with HIV What is the aim of this review? The aim was to determine whether starting antiretroviral therapy (ART) within one week of HIV diagnosis (rapid ART) resulted in a lower risk of dying or better suppression of the virus in people's blood than standard care; as well as studying the effect of this intervention on whether people start taking ART and continue to be engaged in care after 12 months. Key messages Offering ART to people living with HIV (PLWH) within one week of diagnosis probably increases the number of people initiating the therapy at 12 months and the number of PLWH whose virus has been suppressed in the blood at 12 months. It may also improve the number of people who are still in contact with healthcare services at 12 months. We don't know the effect this has on people dying. We found that several other changes need to be made alongside rapid ART for services to achieve these outcomes. What was studied in the review? HIV is a leading cause of death worldwide. Although more people are taking ART than ever before, there is a large percentage of PLWH who are not being treated. One of the reasons identified is the long period between being diagnosed with HIV and starting ART. Rapid ART has been proposed as a way to increase the number of PLWH being started on ART and improve HIV‐related outcomes. What are the main results of the review? We found seven studies that met the inclusion criteria of the review and assessed the effect of rapid ART on PLWH. Rapid ART probably increases the number of people being initiated on ART at 12 months and the number of PLWH with no detectable virus in their blood at 12 months (moderate‐certainty evidence). Based on low‐certainty evidence, rapid ART may increase the number of PLWH being retained in care. We don't know whether rapid ART has an effect on the number of deaths (very low‐certainty evidence). We found that if healthcare services aim to offer ART within a week of diagnosis, changes to how these systems operate will need to be made. How up to date is the review? We searched for relevant trials up to 14 August 2018. Authors' conclusions Implications for practice Overall, interventions that include rapid initiation of antiretroviral therapy (ART) appear to improve outcomes across the HIV treatment cascade, at least in the short term. Those implementing this intervention should consider the cointerventions and health system modifications required to facilitate rapid delivery of ART and ensure effectiveness. Implications for research Now that rapid ART is being implemented widely, researchers need to consider what the best modes of implementation are, how to adapt health systems and what cointerventions to offer within resource constraints in order to support patients to accept ART, and link to care and remain engaged in care in the long term. Pragmatic research that helps define ‘treatment readiness', explores cointerventions that are feasible, and defines treatment delivery modes within complex health system interventions will help specify how to implement rapid ART