High rates of viral suppression in adults and children with high CD4+ counts using a streamlined ART delivery model in the SEARCH trial in rural Uganda and Kenya

Abstract

Introduction: The 2015 WHO recommendation of antiretroviral therapy (ART) for all HIV-positive persons calls for treatment initiation in millions of persons newly eligible with high CD4+ counts. Efficient and effective care models are urgently needed for this population. We evaluated clinical outcomes of asymptomatic HIV-positive adults and children starting ART with high CD4+ counts using a novel streamlined care model in rural Uganda and Kenya.Methods: In the 16 intervention communities of the HIV test-and-treat Sustainable East Africa Research for Community Health Study (NCT01864603), all HIV-positive individuals irrespective of CD4 were offered ART (efavirenz [EFV]/tenofovir disoproxil fumarate + emtricitabine (FTC) or lamivudine (3TC). We studied adults (≥fifteen years) with CD4 ≥ 350/μL and children (two to fourteen years) with CD4 > 500/μL otherwise ineligible for ART by country guidelines. Clinics implemented a patient-centred streamlined care model designed to reduce patient-level barriers and maximize health system efficiency. It included (1) nurse-conducted visits with physician referral of complex cases, (2) multi-disease chronic care (including for hypertension/diabetes), (3) patient-centred, friendly staff, (4) viral load (VL) testing and counselling, (5) three-month return visits and ART refills, (6) appointment reminders, (7) tiered tracking for missed appointments, (8) flexible clinic hours (outside routine schedule) and (9) telephone access to clinicians. Primary outcomes were 48-week retention in care, viral suppression (% with measured week 48 VL ≤ 500 copies/mL) and adverse events.Results: Overall, 972 HIV-positive adults with CD4+ ≥ 350/μL initiated ART with streamlined care. Patients were 66% female and had median age thirty-four years (IQR, 28–42), CD4+ 608/μL (IQR, 487–788/μL) and VL 6775 copies/mL (IQR, <500–37,003 c/mL). At week 48, retention was 92% (897/972; 2 died/40 moved/8 withdrew/4 transferred care/21/964 [2%] were lost to follow-up). Viral suppression occurred in 778/838 (93%) and 800/972 (82%) in intention-to-treat analysis. Grade III/IV clinical/laboratory adverse events were rare: 95 occurred in 74/972 patients (7.6%). Only 8/972 adults (0.8%) switched ART from EFV to lopinavir (LPV) (n = 2 for dizziness, n = 2 for gynaecomastia, n = 4 for other reasons). Among 83 children, week 48 retention was 89% (74/83), viral suppression was 92% (65/71) and grade III/IV adverse events occurred in 4/83 (4.8%).Conclusions: Using a streamlined care model, viral suppression, retention and ART safety were high among asymptomatic East African adults and children with high CD4+ counts initiating treatment.Clinical Trial Number: NCT01864603

HIV programmatic outcomes following implementation of the ‘Treat‐All’ policy in a public sector setting in Eswatini: a prospective cohort study

“…The association was more pronounced for patients presenting with advanced HIV disease, and the effect of CD4 cell count varied with time under SOC, with higher hazard early during treatment. Notably, under Treat-All, outcomes for patients with high CD4 cell counts were similar to those for patients with 201 to 350 cells/mm 3 , a pattern confirmed by two other Treat-All trials [31,32] but in contrast to findings from the Western Cape, South Africa, where attrition was increased for CD4 >500 cells/mm 3 [33].…”

“…Overall retention was comparable to ART programmes in low-and middle-income countries [65] and two Treat-All trials in Southern Africa [32,33]. However, point estimates of retention tended to be lower than under SOC, than previous retention estimates from this setting before the introduction of Treat-All [38] and than in a streamlined combination intervention trial in Eastern Africa [31]. Similarly to another Treat-All trial in South Africa [32], 6% of patients never returned for a clinic visit after ART initiation (vs. 3% under SOC).…”

“…The impact of changing ART eligibility criteria in RLS is poorly understood because of the lack of recent programme data , the gap between supporting health policies and efficient operationalization and inconclusive treatment outcome data from ongoing Treat‐All trials . Eswatini (formerly Swaziland) is one of the few countries that piloted the Treat‐All policy before it became a WHO recommendation in 2016 .…”

Effectiveness of interventions for unstable patients on antiretroviral therapy in South Africa: results of a cluster‐randomised evaluation

“…Differentiated HIV care has been proposed to provide appropriate care to different populations within clinics. The modest body of rigorous evidence on differentiated care to date, however, largely focuses on strategies for stable patients [30][31][32][33][34][35][36]. Far less has been written about strategies for unstable patients, a population much harder to manage.…”

Isoniazid Preventive Therapy Completion in the Era of Differentiated HIV Care

“…All participants were receiving differentiated HIV care consisting of nurse triage, quarterly ART visits, and patient-centered care at five government-sponsored clinics in rural Uganda. 15 Screening and frequency of clinic visits for IPT were conducted per Uganda Ministry of Health (MOH) guidelines. 14 Patients started on IPT (INH with B6) returned to clinic for a 2-week assessment for possible side effects and then monthly thereafter for 5 months.…”