Same-day ART Initiation Versus Standard of Care After Positive HIV-test Result in Rural Lesotho

Study Overview
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Brief Summary
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The CASCADE-trial is a two-armed open-label randomized controlled trial conducted in rural Lesotho. Participants who were tested HIV-positive during community-based HIV testing and counseling campaigns are randomized to the intervention or control arm. Allocation is 1:1 with parallel assignment. Participants in the control arm follow the standard of care after a community-based HIV test result: They are referred to the nearest clinic where they will receive baseline laboratory testing and adherence counseling. After at least 2 clinic visits for adherence counseling they can start anti-retroviral therapy (ART). After ART-initiation they have to attend monthly follow-up at the clinic for drug refill. Individuals randomized to the intervention arm are proposed same day community-based ART initiation combined with less frequent follow-up visits. The primary outcomes are linkage to care at 3 months and viral suppression at 12 months after having tested HIV-positive during the community-based HIV testing and counseling campaigns.

Detailed Description
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A published version of the trial protocol can be downloaded at: http://bmcpublichealth.biomedcentral.com/articles/10.1186/s12889-016-2972-6 Background In November 2014 the Joint United Nations Programme on HIV/AIDS (UNAIDS) published the 90-90-90 targets for 2020 (UNAIDS 2014). The strategy aims at a massive scale-up in coverage of antiretroviral therapy (ART) among individuals infected with HIV. Based on accumulated evidence that viral suppression through successful ART reduces the risk of transmission(Cohen 2011), it is expected that - if achieved - the 90-90-90 targets would lead to a reduction of the yearly global HIV-incidence from 2 million currently to 500'000 by 2020 (Jones 2014). In 2015 two randomized controlled trials showed the benefit of starting ART as early as possible for infected individuals - even if CD4-cell counts were above the threshold of 500 cells/mL (TEMPRANO 2015; INSIGHT START 2015), leading the World Health Organization (WHO) to recommend that anyone infected with HIV should start ART as soon as possible after diagnosis (WHO 2015). A seek-test-treat strategy bears, however, unprecedented challenges in settings where HIV is hyperendemic and resources may be limited (Hull 2014; Delva 2015). The Continuum of Care Cascade (the cascade) involves the steps HIV-infected individuals have to take in order to achieve viral suppression. It starts with knowing one's HIV status, continues with linkage to care after a positive HIV test, initiation of ART, uninterrupted continuation of ART (retention in care and adherence to medication), and ends with viral suppression (MacCarthy 2015). Already prior to announcement of the seek-test-and-treat approach, weaknesses in the cascade often hampered the effectiveness of HIV programs in resource-rich as well as resource-poor settings (Yehia 2015; Kratzer 2012). In Sub-Saharan Africa the care cascade is still far from the 90-90-90 targets with only 29% of infected individuals estimated to be on ART and virally suppressed in 2013. In order to achieve the UNAIDS targets innovative, effective, and practical approaches for improving the care cascade are thus urgently needed (Mills 2013; Piot 2015). Linkage to care after an initial positive HIV test has been described as the Achilles' heel of the care cascade (Nachega 2014). Most studies from Sub-Saharan Africa report linkage rates lower than 50% (Naik 2015; Parker 2015; Clouse 2013; Gerdts 2014). In a cluster-randomized trial comparing home-based with mobile-clinic HIV testing and counselling (HTC) in Lesotho, only 25% of newly tested HIV-positive individuals accessed care within one month after the test (Labhardt 2014). Several interventions have been shown to improve linkage to care, such as point-of-care CD4 count directly after a positive HIV test, immediate start of cotrimoxazole prophylaxis, incentives such as food-assistance, extended post-test counselling during home-visits, or community-workers accompaniment. However, controlled studies testing programmatic intervention packages for improving linkage to care are still largely lacking (Okeke 2014; Govindasamy 2014). Furthermore, it must be noted that interventions, such as patient-accompaniment or food support are resource intensive and may work in small NGO-driven projects, but are not sustainable on a larger scale (Posse 2013). In a systematic review addressing barriers for linkage to care, transport cost and distance were the most frequently cited factors for patients not enrolling in care after a positive HIV test (Govindasamy 2012). Objective of the trial This CASCADE trial tests the effectiveness of same day home-based ART initiation after a positive HIV test in combination with a reduction of the frequency of follow-up visits to the clinic as a pragmatic and programmatically feasible approach to improve linkage to care, retention in care, and viral suppression. It is a two-armed open-label randomized controlled trial. Allocation is 1:1 with parallel assignment. The intervention is targeted to individuals who tested HIV-positive during community-based HTC. Recruitment and participants Participants will be recruited during community-based HTC campaigns in the district of Butha-Buthe, in northern Lesotho. Home-based HTC campaigns will be conducted for an anticipated period of 3 months beginning at the end of February in the catchment areas of six health care facilities - four nurse-led health centers, one missionary and one public hospital. Three teams consisting of 4 lay counsellors, each supervised by one professional counsellor and a nurse visit all households in randomly pre-selected areas proposing HTC to all household members. If a household member tests HIV positive during the HTC campaign and eligible for the CASCADE trial, he/she will be randomized to one of the two arms.

Official Title
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Same Day Community-based ART Initiation Versus Clinic-based Pre-ART Assessment and Counselling for Individuals Newly Tested HIV-positive During Community-based HIV Testing in Rural Lesotho - a Randomized Controlled Trial

Conditions
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HIV Infection

Intervention / Treatment
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* Other: Same-day ART initiation
* Other: Standard of care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV infection newly diagnosed during community-based HTC-campaigns Never been on triple-ART Lives and/or works in the district of Butha-Buthe and declares to seek follow-up at one of the 6 health facilities involved in the study Signed written informed consent Exclusion Criteria: Pregnant or breast-feeding Already enrolled in chronic care for another disease, such as tuberculosis or diabetes Clinical WHO-stage 4 or active tuberculosis Positive cryptococcal antigen test

Ages Eligible for Study
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Minimum Age: 18 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: Health Services Research
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard of care<br>Standard of care in Lesotho. ART-initiation after at least two clinic visits for pre-ART counseling and monthly follow-up visits at the clinic thereafter. | Other: Standard of care<br>* Individuals found HIV-positive during the community-based HIV testing campaigns and randomized to the control arm receive post-test counselling and a referral letter with an appointment at their chosen health facility. On the first visit to the clinic, the participant receives laboratory assessment and a first adherence counselling session. The participant must then return to the clinic to receive his/her laboratory results and to undergo a second adherence counselling session. Once the participant has started ART, the first and second follow-up visits are scheduled for 14 and 28 days after ART initiation, respectively. Thereafter, follow-up visits are scheduled monthly until 6 months after ART initiation. If the participant is clinically stable, clinical follow-up visits may then be spaced to 3-monthly intervals, but refills of ART must still be collected on a monthly basis.<br>|
| Experimental: Same-day ART initiation with less frequent follow-up visits<br>Proposition of same-day ART initiation with less frequent follow-up visits thereafter. | Other: Same-day ART initiation<br>* Participants tested HIV-positive during community-based HIV testing and randomized to the intervention group receive post-test counseling and on-the-spot clinical and laboratory assessment. Directly after the positive HIV-test result the study nurse assesses the participant clinically and performs point-of-care laboratory baseline testing. Thereafter, the participant receives a standardized short adherence counselling. After adherence counseling the participant is offered to start ART immediately. Those who decide to start ART during the visit or intend to start within seven days will receive a 30 day ART-supply and an follow-up appointment at the clinic within 12 to 16 days. In order to reduce travel time and transport cost, participants who are clinically stable, will have their follow-up visits and ART refills more widely spaced with appointments at 6 weeks, 3, 6, (9) and 12 months after ART initiation.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Linkage to care | Linkage to care within 3 months after having been tested HIV positive during the HTC-campaign. A patient is considered to have linked to care if he/she attends the clinic at least once within 90 days after HIV diagnosis. | 90 days | 
| Viral suppression | Viral suppression 12 months after positive HIV test result. Viral suppression is defined as a viral load <100 copies/mL between 11 and 14 months after diagnosis of HIV-infection. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1-year retention in care | Proportion confirmed dead (death record at clinic or confirmed by a first-grade relative), lost to follow-up (not attending the clinic 11-14 months after HIV-test and not confirmed dead), and retained in care (on ART, attends the clinic) | 12 months | 
| Viral suppression under ART | Viral load <100 copies/mL among those who started ART 5-7 months after ART-initiation. | 6 months after ART initiation | 
| Change in body weight |  | 12 months | 
| Change in CD4 cell count |  | 12 months | 
| Change in haemoglobin |  | 12 months | 
| New clinical WHO stage 3 or 4 events |  | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Community-based initiation of antiretroviral therapy, Home-based HIV testing and counseling, Lesotho, Sub-sahara Africa, antiretroviral therapy, AIDS, Test and treat