Effectiveness of a combination strategy for linkage and retention in adult HIV care in Swaziland: The Link4Health cluster randomized trial

Abstract

BackgroundGaps in the HIV care continuum contribute to poor health outcomes and increase HIV transmission. A combination of interventions targeting multiple steps in the continuum is needed to achieve the full beneficial impact of HIV treatment.Methods and findingsLink4Health, a cluster-randomized controlled trial, evaluated the effectiveness of a combination intervention strategy (CIS) versus the standard of care (SOC) on the primary outcome of linkage to care within 1 month plus retention in care at 12 months after HIV-positive testing. Ten clusters of HIV clinics in Swaziland were randomized 1:1 to CIS versus SOC. The CIS included point-of-care CD4+ testing at the time of an HIV-positive test, accelerated antiretroviral therapy (ART) initiation for treatment-eligible participants, mobile phone appointment reminders, health educational packages, and noncash financial incentives. Secondary outcomes included each component of the primary outcome, mean time to linkage, assessment for ART eligibility, ART initiation and time to ART initiation, viral suppression defined as HIV-1 RNA < 1,000 copies/mL at 12 months after HIV testing among patients on ART ≥6 months, and loss to follow-up and death at 12 months after HIV testing. A total of 2,197 adults aged ≥18 years, newly tested HIV positive, were enrolled from 19 August 2013 to 21 November 2014 (1,096 CIS arm; 1,101 SOC arm) and followed for 12 months. The median participant age was 31 years (IQR 26–39), and 59% were women. In an intention-to-treat analysis, 64% (705/1,096) of participants at the CIS sites achieved the primary outcome versus 43% (477/1,101) at the SOC sites (adjusted relative risk [RR] 1.52, 95% CI 1.19–1.96, p = 0.002). Participants in the CIS arm versus the SOC arm had the following secondary outcomes: linkage to care regardless of retention at 12 months (RR 1.08, 95% CI 0.97–1.21, p = 0.13), mean time to linkage (2.5 days versus 7.5 days, p = 0.189), retention in care at 12 months regardless of time to linkage (RR 1.48, 95% CI 1.18–1.86, p = 0.002), assessment for ART eligibility (RR 1.20, 95% CI 1.07–1.34, p = 0.004), ART initiation (RR 1.16, 95% CI 0.96–1.40, p = 0.12), mean time to ART initiation from time of HIV testing (7 days versus 14 days, p < 0.001), viral suppression among those on ART for ≥6 months (RR 0.97, 95% CI 0.88–1.07, p = 0.55), loss to follow-up at 12 months after HIV testing (RR 0.56, 95% CI 0.40–0.79, p = 0.002), and death (N = 78) within 12 months of HIV testing (RR 0.80, 95% CI 0.46–1.35, p = 0.41). Limitations of this study include a small number of clusters and the inability to evaluate the incremental effectiveness of individual components of the combination strategy.ConclusionsA combination strategy inclusive of 5 evidence-based interventions aimed at multiple steps in the HIV care continuum was associated with significant increase in linkage to care plus 12-month retention. This strategy offers promise of enhanced outcomes for HIV-positive patients.Trial registrationClinicalTrials.gov NCT01904994.

Rapid initiation of antiretroviral therapy for people living with HIV

“…CD4 threshold to determine eligibility of ART differed across studies. In Elul 2017, McNairy 2017, Rosen 2016, and Stevens 2017, participants were eligible for ART if their CD4 count was less than 350 cells/mm 3 . Amanyire 2016 and Koenig 2017 started with the same threshold (350 cells/mm 3 ) but, following changes in national guidelines, changed the ART eligibility criteria during the study to include all participants with CD4 count fewer than 500 cells/mm 3 .…”

“…Elul 2017 offered ART on the first clinic visit; McNairy 2017 aimed to offer ART within seven days of diagnosis and Amanyire 2016 within 14 days of diagnosis. We have summarized the main characteristics of the included studies in Table 7.…”

“…b Downgraded by one for indirectness and qualitative heterogeneity. The largest studies, Elul 2017 and McNairy 2017, included individuals who were not eligible for antiretroviral therapy (ART) in denominators. The time of ART initiation varied across studies, with studies offering ART on the same day as diagnosis, within seven days or within 14 days.…”

“…Broad CIs containing clinically significant benefit and no effect. d One study (McNairy 2017), measured virological suppression at 12 months only in those participants who received ART for at least six months. We did not, therefore, include this study in the pooled estimate of effect.…”

“…f Not downgraded for imprecision. Significant heterogeneity within the forest plot explained as McNairy 2017 calculated viral suppression in a subpopulation of participants on ART for six months. g Downgraded by one for indirectness.…”