Impact of Immediate Versus South African Recommendations Guided ART Initiation on HIV Incidence

Study Overview
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Brief Summary
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This trial is evaluating a public health intervention strategy trial which aims to reduce the incidence of HIV at a population-level. The proposed strategy is a two steps process: Extensive HIV counselling and testing, and comprehensive prevention programme among a target population Immediate ART initiation after HIV diagnosis, irrespective of CD4 count criteria. The underlaying trial hypothesis is that HIV testing followed by immediate ART initiation of all HIV-infected individuals will prevent onward transmission and reduce HIV incidence in the population. This is a cluster randomised controlled trial with a total of 22 communities used as the units for randomisation. Enrolment of a population of 22 000 individuals among which 4 400 are expected to be HIV-Infected.

Detailed Description
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The trial objective is to estimate the effect of ART initiated immediately after HIV diagnosis on the reduction in incidence of new HIV infections in the general population. It will be conducted in two phases: First phase: aiming to evaluate the feasibility and acceptability of extensive HIV testing and early ARV treatment initiation on a subset of the target population (Hlabisa sub-district in KwaZulu Natal, South Africa); completion on February 2014. Second phase: full implementation of the trial in the target population from May 2014. The proposed intervention has two components : Component 1 Test: HIV counselling and testing, and comprehensive prevention programme among the entire target population Component 2 Treat: ART treatment initiation for HIV infected individuals following two strategies control group: ART initiation when eligible for treatment as per WHO guidelines intervention group: immediate ART initiation regardless of immunological and clinical staging

Official Title
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A Cluster Randomised Trial Comparing the Impact of Immediate Versus South African Recommendations Guided ART Initiation on HIV Incidence. The ARNS 12249 TasP (Treatment as Prevention) Trial in Hlabisa Sub-district, KwaZulu-Natal, South Africa.

Conditions
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HIV Infection

Intervention / Treatment
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* Drug: Immediate ARV treatment initiation with TDF/FTC/EFV
* Other: South African recommendation guided ARV (TDF/FTC/EFV) initiation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 16 and more Member of a household in the designated cluster within the Hlabisa sub-district of KwaZulu Natal in South Africa Able and willing to give written informed consent for trial participation and/or HIV counselling and testing

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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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Immediate ARV treatment initiation<br>Initiation of ARV treatment regardless of participants's immunological and clinical staging | Drug: Immediate ARV treatment initiation with TDF/FTC/EFV<br>* All HIV-infected adults will be offered ART regardless of their immunological and clinical staging. The first line regimen proposed will be Atripla (R), a fixed dose combination containing tenofovir disoproxil (245 mg)/emtricitabine (200 mg)/efavirenz (600 mg)(FTC/TDF/EFV). The dosing will be 1 tablet OD.<br>|
| Other: South African recommendation guided ARV initiation<br>HIV-infected individuals will be assessed clinically and immunologically and when eligible for treatment as per South African guidelines will be offered ART | Other: South African recommendation guided ARV (TDF/FTC/EFV) initiation<br>* HIV-infected adult participants will be eligible for ART as per the South African guidelines (August 2011) if: CD4 count ≤ 350 cells/mm3 irrespective of clinical symptoms WHO clinical stage 3 or 4 irrespective of CD4 count MDR or XDR TB The first line regimen proposed will be Atripla (R), a fixes dose combination containing tenofovir disoproxil (245 mg)/emtricitabine (200 mg)/efavirenz (600 mg)(TDF/FTC/EFV). The dosing will be 1 tablet OD.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Uptake of initial and repeat HIV counselling and testing (Feasibility phase) | Percentage of the target population tested for HIV | 14 months | 
| Uptake of ARV treatment among HIV-infected individuals (Feasibility phase) | Percentage of HIV-infected patients followed-up in the trial clinics receiving ARV treatment when eligible | 14 months | 
| HIV infection incidence | Serology will be done on Dry Blood Spot collected during repeated surveys | 4 years after enrolment initiation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sexual partnerships | Percentage of participants reporting a certain number of sexual partnerships in the last 12 months | Repeated measure every 6 months during follow-up | 
| Safe sex and condom use | Percentage of participants using a male condom with their partner during the last sexual intercourse | Repeated measure every 6 months during follow-up | 
| Quality of life | the EQ-5D scale among the whole sample the Patient Reported Outcomes Quality Of Life specific to HIV (PROQOL-HIV) instrument and the HIV/AIDS stigma instrument for PLWHA (HASI-P) tool among HIV-infected participants | Repeated measure every 6 months during follow-up | 
| Health care use and health care expenditures | Percentage of participants reporting health care visits (primary care centre, pharmacy, hospitalisation) in the past four weeks and cost incurred | Repeated measure every 6 months during follow-up | 
| Stigma at community level | Percentage of participants agreeing that people in the community do not blame people for having HIV Percentage of participants agreeing that people in the community avoid people with HIV | Repeated measure every 6 months during follow-up | 
| Adherence to ART | Measured three-monthly using a visual analogue scale, pill identification test and pill count | Repeated measure every 6 months during follow-up | 
| Retention | Proportion of HIV-infected participants still under active follow-up in the trial at key timepoints | Repeated measure every 6 months during follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, Prevention, Treatment, South Africa