Early HIV Therapy in Patients With High CD4 Cell Counts (EARLI)

• 48-Week Efficacy [ Time Frame: When all participants reach 48 weeks on study ] [ Designated as safety issue: No ]
  Proportion of patients with virologic suppression (HIV-1 plasma RNA ≤400 copies/cc) at 48 weeks, stratified by study arm.
  
  
• Programmatic Costs [ Time Frame: When all participants reach 48 weeks on study ] [ Designated as safety issue: No ]
  Total estimated costs of provider time, medications, diagnostic testing, and healthcare facility infrastructure per patient treated with ART for one year, stratified by study arm
  
  

• 96-Week and 144-Week Efficacy [ Time Frame: When all particiants reach 96 and 144 weeks on study, respectively ] [ Designated as safety issue: No ]
  Proportion of patients with virologic suppression (HIV-1 plasma RNA ≤400 copies/cc) at 96 and 144 weeks, stratified by study arm.
  
  
• Predictors of Retention in Care [ Time Frame: When all participants reach 48 weeks on study, then again 144 weeks on study ] [ Designated as safety issue: No ]
  Factors statistically significantly associated with attendance at all scheduled clinical visits throughout the first 48 weeks of ART, and throughout the full 144 week study period, stratified by study arm.
  
  
• Adverse Event Rates [ Time Frame: When all participants reach 48 weeks on study, then again at 144 weeks ] [ Designated as safety issue: Yes ]
  Describe grade 3 or 4 toxicities (defined by NIH DAIDS scale) that occur throughout the first 48 weeks of ART, and throughout the full 144 week study period, stratified by study arm. These will be assessed by active and passive ascertainment and clinical verification, stratified by study arm.
  
  
• Medication Adherence [ Time Frame: When all participants reach 48 weeks on study ] [ Designated as safety issue: No ]
  Proportion of total medication doses taken by patients at 48 weeks, assessed by pharmacy refill records, stratified by study arm.
  
  

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 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.

We propose here a pilot study that will address and investigate all of the above critical issues. This study will focus exclusively on asymptomatic patients with CD4 cell counts ≥250 cells/uL. These relatively healthier individuals are well suited to a more streamlined approach to ART delivery and healthcare provision.

Primary Objectives:

A. To evaluate the 48 week efficacy of ART initiated in asymptomatic individuals with high CD4+ cell counts (CD4+ > 250 cells/uL) and provided in a "streamlined" mode of care.

B. To evaluate the programmatic costs of streamlined ART delivery to asymptomatic high CD4+ count individuals.

Secondary Objectives:

A. To evaluate the 96 week efficacy of ART initiated in high CD4+ cell count individuals.

B. To identify predictors of retention in care among high CD4+ cell count ART initiators.

C. To assess adverse events among high CD4+ cell count ART initiators. D. To assess medication adherence among high CD4+ cell count ART initiators.