Package of Care to Improve Retention in ART and Mortality Among Treatment Naive HIV Infected Individuals

Study Overview
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Brief Summary
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This is a cluster randomized trial to determine whether a package of care including rapid antiretroviral therapy (ART) initiation, as compared to standard ART initiation, improves mortality, retention in care and viral suppression among treatment naive people living with HIV (PLHIV) in Nepal. Package of care includes immediate screening and treatment of opportunistic infections (OIs), rapid ART initiation and enhanced retention in care using mobile health (mHealth) and weekly/biweekly home-based adherence/ retention support linked to community care centre. Standard of care includes screening and management of common OIs, baseline assessment (CD4, viral load and other tests), antiretroviral drugs and ART follow up.

Detailed Description
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PRAN is an open-label trial of 1000 Treatment-Naive PLHIV aged 16 years or more. To evaluate whether a package of care including rapid ART initiation [diagnosis and management of opportunistic infection (OI), rapid ART initiation and enhanced adherence support] is more effective in reducing morbidity and mortality, as compared to standard ART initiation, among ART naïve PLHIV in Nepal. To evaluate whether a package of care including rapid ART initiation is more effective in improving retention in HIV treatment, as compared to standard ART initiation, among ART naïve PLHIV in Nepal. To evaluate whether a package of care including rapid ART initiation improves viral suppression among ART naïve PLHIV in Nepal to a higher extent than standard ART initiation, To evaluate whether the different components of care act synergistically to improve mortality, retention in care and viral suppression among treatment Naive PLHIV, as compared to standard ART initiation, To assess the cost-effectiveness of this package of care intervention.

Official Title
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Evaluation of World Health Organization (WHO) Recommendations on Test and Treat Strategy, Managing Advanced HIV Disease and Rapid Initiation of ART Among People Living With HIV in Nepal: A Cluster Randomized Trial.

Conditions
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HIV

Intervention / Treatment
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* Combination Product: Package of HIV care
* Combination Product: Standard HIV care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age greater than or equal to 16 years Diagnosed with HIV-infection ART-naive Consent for study participation Exclusion Criteria: Age less than or equal to 15 years Any previous use of ART

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Package of HIV care<br>Screening and management (Preventive / Pre-emptive therapies dosages) of different opportunistic infections (OI), Rapid antiretroviral therapy (ART) initiation and Enhanced adherence support. | Combination Product: Package of HIV care<br>* A. Screening and management (Preventive / Pre-emptive therapies dosages) of different opportunistic infections (OI). Detail information mentioned in the manual (refer to uploaded protocol). B. Rapid ART Initiation PLHIV without suspicion or active OI: Initiate ART within seven days or same day after HIV serology disclosure PLHIV with suspicion or active OI: Defer initiation if clinical symptoms suggest tuberculosis or cryptococcal meningitis. Detail information mentioned in the manual (refer to uploaded protocol). C. Enhanced Adherence/Retention Support: mHealth: Receive text messages in mobile regarding appointment reminder (pill pick up, CD4 test, viral load test, early infant diagnosis (EID) test etc.) and general awareness messages (positive prevention, the importance of regular health check-up etc.). PLHIV with advanced HIV disease will also receive weekly/biweekly home-based adherence/ retention support linked to community care centre and community home-based care.<br>* Other names: Screening and management of opportunistic infection, Rapid ART initiation and Enhanced adherence support;|
| Experimental: Standard HIV care<br>Screening and management of common OIs, basic health assessment (CD4, viral load and other tests), ARV drugs and follow up. | Combination Product: Standard HIV care<br>* Standard of HIV care includes screening and management of OI (OI- tuberculosis (TB), bacterial pneumonia, herpes, and candidiasis), baseline assessment (CD4 and other blood tests- complete blood count, hemoglobin, platelets, liver function test, renal function test, urine for albumin, chest x-ray), at 6 months CD4 test, viral load (twice a year) and then on a yearly basis, additional lab test at 3 months, 6 months, antiretroviral (ARV) toxicity monitoring like hemoglobin (Zidovudine), Serum Glutamic-Pyruvic Transaminase (Nevirapine/Efavirenz), Creatinine (Tenofovir), prophylaxis (Co-trimoxazole preventive therapy CD4<350 and WHO stage III and IV and Isoniazid preventive therapy if eligible) and ART / follow up (generally monthly/ bimonthly).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality | All-cause mortality over the first 24 weeks after starting ART | Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Retention in treatment | PLHIV alive and on ART over the first 48 weeks after starting ART | Week 48 | 
| Adherence to ART | Adherence will be assessed on a monthly basis (total pills taken by patient in last month/ total pills prescribed to patient in last month). | Week 0-48 | 
| Morbidity | Incidence of opportunistic infection and immune reconstitution inflammatory syndrome (IRIS) | Week 48 | 
| Viral load suppression | PLHIV and on ART who have a suppressed viral load (<1000 copies/mL) | Week 48 | 
| Cost effectiveness of Package of care | Intervention cost will be calculated from estimates of the per-patient quantity of services used in delivery of package of care. Cost per death prevented and cost per DALY gained. | Week 48 | 
| Mortality | All-cause mortality over the first 96 weeks after starting ART | Week 48 | 
| Hospitalization | Hospital inpatient episodes and total days admitted | 0-48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Package of care, Rapid Initiation of antiretroviral therapy, Advanced HIV disease, mHealth, Acquired Immunodeficiency Syndrome, Management of advance HIV disease