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

HIV Clinical Trial

— PRAN  

Official title:

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03723525
• Other study ID #: 525
• Secondary ID: NPL-H-SCF
• Status: Completed
• Phase: Phase 4
• Start date: January 22, 2018
• Est. completion date: December 24, 2019

Study information

• Verified date: September 2020
• Source: National Centre for AIDs and STD Control, Nepal
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1073
• Est. completion date: December 24, 2019
• Est. primary completion date: December 24, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• HIV
• HIV Infections

Intervention

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.
• 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).

Locations

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

Sponsors (13)

Lead Sponsor	Collaborator
National Centre for AIDs and STD Control, Nepal	B.P. Koirala Institute of Health Sciences, Bharatpur Eye Hospital, Expertise France, Karolinska Institutet, Mahakali Zonal Hospital, National Academy of Medical Sciences, Nepal, Rapti Sub-regional Hospital, Seti Zonal Hospital, Sukraraj Tropical and Infectious Disease Hospital, Tikapur Hospital, Tribhuvan University Teaching Hospital, Institute Of Medicine., Western Regional Hospital

Country where clinical trial is conducted

Nepal, 

References & Publications (3)

Guidelines for Managing Advanced HIV Disease and Rapid Initiation of Antiretroviral Therapy. Geneva: World Health Organization; 2017. No abstract available. — View Citation

INSIGHT START Study Group, Lundgren JD, Babiker AG, Gordin F, Emery S, Grund B, Sharma S, Avihingsanon A, Cooper DA, Fätkenheuer 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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Cryptococcal antigen	Burden of serum cryptococcal antigen positive in PLHIV with CD4 < 100/mL	Week 48
Other	Immune Reconstitution Inflammatory Syndrome (IRIS)	Burden of IRIS	Week 48
Other	CD4 cell count	Changes in CD4 cell count	Week 48
Primary	Mortality	All-cause mortality over the first 24 weeks after starting ART	Week 24
Secondary	Retention in treatment	PLHIV alive and on ART over the first 48 weeks after starting ART	Week 48
Secondary	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
Secondary	Morbidity	Incidence of opportunistic infection and immune reconstitution inflammatory syndrome (IRIS)	Week 48
Secondary	Viral load suppression	PLHIV and on ART who have a suppressed viral load (<1000 copies/mL)	Week 48
Secondary	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
Secondary	Mortality	All-cause mortality over the first 96 weeks after starting ART	Week 48
Secondary	Hospitalization	Hospital inpatient episodes and total days admitted	0-48