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

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.

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.

Study Overview

• Status: Completed
• Conditions: HIV
• Intervention / Treatment: Combination product: Package of HIV care; Combination product: Standard HIV care

Detailed Description

PRAN is an open-label trial of 1000 Treatment-Naive PLHIV aged 16 years or more.

1. 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.
2. 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.
3. 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,
4. 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,
5. To assess the cost-effectiveness of this package of care intervention.

• Study Type: Interventional
• Enrollment (Actual): 1073
• Phase: Phase 4

Contacts and Locations

Study Locations

• Nepal
  • Bharatpur, Nepal
    • Bharatpur District Hospital
  • Dang, Nepal
    • Rapti Sub Regional Hospital
  • Kailālī, Nepal
    • Seti Zonal Hospital
  • Kailālī, Nepal
    • Tikapur Hospital
  • Kanchanpur, Nepal
    • Mahakali Zonal Hospital
  • Kathmandu, Nepal
    • Tribhuvan University Teaching Hospital
  • Kathmandu, Nepal
    • National Academy of Medical Science (NAMS), Bir Hospital
  • Pokhara, Nepal
    • Western Regional Hospital
  • Sunsari, Nepal
    • B.P. Koirala Institute of Health Sciences
  • Bagmati
    • Kathmandu, Bagmati, Nepal
      • Sukraraj Tropical & Infectious Disease Control Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Package of HIV care; 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; 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.; Other Names: Screening and management of opportunistic infection, Rapid ART initiation and Enhanced adherence support
Experimental: Standard HIV care; 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; 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).

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cryptococcal antigen	Burden of serum cryptococcal antigen positive in PLHIV with CD4 < 100/mL	Week 48
Immune Reconstitution Inflammatory Syndrome (IRIS)	Burden of IRIS	Week 48
CD4 cell count	Changes in CD4 cell count	Week 48

Collaborators and Investigators

• Sponsor: National Centre for AIDs and STD Control, Nepal
• Collaborators: Karolinska Institutet; B.P. Koirala Institute of Health Sciences; Tribhuvan University Teaching Hospital, Institute Of Medicine.; National Academy of Medical Sciences, Nepal; Expertise France; Bharatpur Eye Hospital; Sukraraj Tropical and Infectious Disease Hospital; Rapti Sub-regional Hospital; Western Regional Hospital; Seti Zonal Hospital; Tikapur Hospital; Mahakali Zonal Hospital
• Investigators: Principal Investigator: Basu Dev Pandey, MD, PhD, National Centre for AIDS and STD Control; Principal Investigator: Bir B Rawal, MA, National Centre for AIDS and STD Control; Principal Investigator: Rajan K Bhattarai, MPH, Save the Children; Principal Investigator: Rajya Shree Nyachhyon Kunwar, MBBS, MPH, National Centre for AIDS and STD Control/ Global Fund Programs; Principal Investigator: Upendra Shrestha, MPH, National Centre for AIDS and STD Control/ Global Fund Programs; Principal Investigator: Rajesh Khanal, MSc, National Centre for AIDS and STD Control/ Global Fund Programs; Principal Investigator: Marie Lagrange-Xelot, MD, Expertise France; Principal Investigator: Tristan Delory, MD, Expertise France; Principal Investigator: Anna Mia Ekstrom, MD, MPH, PhD, Dept of Infectious Diseases Karolinska University Hospital & Dept of Public Health (Global Health/IHCAR), Karolinska Institutet, Stockholm; Principal Investigator: Tara Nath Pokharel, MD, MPH, National Centre for AIDS and STD Control; Principal Investigator: Keshab Deuba, MMSc, PhD, National Centre for AIDS and STD Control/ Global Fund Programs

Publications and helpful links

General Publications

• INSIGHT START Study Group; Lundgren JD, Babiker AG, Gordin F, Emery S, Grund B, Sharma S, Avihingsanon A, Cooper DA, Fatkenheuer G, Llibre JM, Molina JM, Munderi P, Schechter M, Wood R, Klingman KL, Collins S, Lane HC, Phillips AN, Neaton JD. Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection. N Engl J Med. 2015 Aug 27;373(9):795-807. doi: 10.1056/NEJMoa1506816. Epub 2015 Jul 20.
• Guidelines for Managing Advanced HIV Disease and Rapid Initiation of Antiretroviral Therapy. Geneva: World Health Organization; 2017. No abstract available. Available from http://www.ncbi.nlm.nih.gov/books/NBK475977/
• Molina JM, Grund B, Gordin F, Williams I, Schechter M, Losso M, Law M, Ekong E, Mwelase N, Skoutelis A, Wiselka MJ, Vandekerckhove L, Benfield T, Munroe D, Lundgren JD, Neaton JD; INSIGHT START study group. Which HIV-infected adults with high CD4 T-cell counts benefit most from immediate initiation of antiretroviral therapy? A post-hoc subgroup analysis of the START trial. Lancet HIV. 2018 Apr;5(4):e172-e180. doi: 10.1016/S2352-3018(18)30003-1. Epub 2018 Jan 16.

Study record dates

Study Major Dates

• Study Start (Actual): January 22, 2018
• Primary Completion (Actual): December 24, 2019
• Study Completion (Actual): December 24, 2019

Study Registration Dates

• First Submitted: October 11, 2018
• First Submitted That Met QC Criteria: October 26, 2018
• First Posted (Actual): October 29, 2018

Study Record Updates

• Last Update Posted (Actual): September 21, 2020
• Last Update Submitted That Met QC Criteria: September 18, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: Acquired Immunodeficiency Syndrome; mHealth; Package of care; Rapid Initiation of antiretroviral therapy; Advanced HIV disease; Management of advance HIV disease
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases; HIV Infections; Acquired Immunodeficiency Syndrome
• Other Study ID Numbers: 525; NPL-H-SCF (Other Identifier: The Global Fund to Fight AIDS, Tuberculosis and Malaria)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No