Early Antiretroviral Therapy in Resource Limited Settings ("EARLI") Study

Location: Mbarara, Uganda

Principal Investigators: Dr. Diane Havlir, UCSF and Prof. Moses Kamya, Makerere University

Other Investigators: Dr. Vivek Jain, UCSF; Dr. Elvin Geng, UCSF; Dr. Edwin Charlebois, UCSF; Dr. Gideon Amanyire, Mulago-Mbarara Joint AIDS Program; Dr. James G. Kahn, UCSF.

Study Coordinator: Dr. Dathan Byonanebye, IDRC

ClinicalTrials.gov Identifier: NCT01479634

After dramatic progress in recent years, HIV care for patients in resource limited settings stands at a crossroads. Governments, non-governmental organizations and charitable foundations are placing increasing scrutiny on the programmatic costs associated with delivering antiretroviral therapy (ART). Given these realities, if the global ART roll-out is to continue successfully, we must develop innovative new ways of providing HIV care and ART that are more efficient, more cost-effective, and tightly integrated within country-level health systems. We must treat more patients with fewer resources, and we need sustainable, simple models for ART delivery.

These goals can be accomplished building on several existing knowledge points. First, initiating ART at earlier disease stages and at higher CD4+ cell counts may prevent irreversible immunologic damage, prevent opportunistic infections and non-AIDS-associated morbidities, and may prevent death. Second, ART initiation at higher CD4+ cell counts is less complex, triggers fewer complications, and is less costly to healthcare systems. Third, patients responding to therapy and doing well require fewer physician-administered follow-up visits. This can allow for "task-shifting" to non-MD providers, and the establishment of tiered healthcare delivery down the spectrum of medical acuity. Fourth, the lack of HIV plasma RNA (viral load) monitoring is responsible for major structural problems in how we deliver ART, causing delays in recognizing ART failure, preventing clinicians from diagnosing HIV drug resistance, and making the decision to switch a patient to a new ART regimen very error-prone.

The EARLI study (Early Antiretroviral Therapy in Resource Limited Settings, NCT01479634) is attempting to generate data that will allow us to address all of these challenges and priorities. EARLI is a 3-year, non-randomized, open-label study of up to 400 ART-naïve patients with CD4+ T-cell counts above 250 cells/uL. The study will assess the virologic efficacy and overall costs associated with delivering ART to this high CD4+ T-cell count patient population under a "streamlined" model of care, which includes a limited visit schedule, follow-up visits performed largely by non-MD health care workers, and clinical monitoring that includes the performance of viral load. The EARLI study clinic is located in the Bwizibwera Level-IV Health Center in Mbarara District, Southwestern Uganda. Enrolled participants are given Truvada® and efavirenz or an alternate standard ART regimen depending on the baseline CD4+ T-cell count.

The EARLI study enrolled its first participants in November 2011, and is expected to continue follow-up of these patients through mid-2015.