Clinical trial NCT02692027: Same-day ART Initiation Versus Standard of Care After Positive HIV-test Result in Rural Lesotho
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV Infection
Keywords: Community-based initiation of antiretroviral therapy
Home-based HIV testing and counseling
Lesotho
Sub-sahara Africa
antiretroviral therapy
AIDS
Test and treat
Lead sponsor: Swiss Tropical & Public Health Institute
Sponsor class: OTHER
Collaborators: name: SolidarMed - Swiss Organization for Health in Africa
name: Ministry of Health, Lesotho
name: District Health Management Team of Butha-Buthe, Lesotho
name: University of Basel
name: University of Geneva, Switzerland
First posted: 2016-02-25
Enrollment: 276
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: HEALTH_SERVICES_RESEARCH

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Linkage to care
timeFrame: 90 days
measure: Viral suppression
timeFrame: 12 months
Secondary outcomes:
measure: 1-year retention in care
timeFrame: 12 months
measure: Viral suppression under ART
timeFrame: 6 months after ART initiation
measure: Change in body weight
timeFrame: 12 months
measure: Change in CD4 cell count
timeFrame: 12 months
measure: Change in haemoglobin
timeFrame: 12 months
measure: New clinical WHO stage 3 or 4 events
timeFrame: 12 months
Other outcomes:
Locations:
city: Butha-Buthe
country: Lesotho
facility: Butha-Buthe District Hospital
Study officials:
affiliation: Swiss Tropical & Public Health Institute
name: Niklaus D Labhardt, MD, MIH
role: PRINCIPAL_INVESTIGATOR
affiliation: Swiss Tropical & Public Health Institute
name: Tracy R Glass, PhD
role: STUDY_CHAIR
References:
citation: 90-90-90 An ambitious treatment target to help end the AIDS epidemic. UNAIDS / JC2684 (accessed October 30th 2014 at www.unaids.org) 2014.
citation: Cohen MS, Chen YQ, McCauley M, Gamble T, Hosseinipour MC, Kumarasamy N, Hakim JG, Kumwenda J, Grinsztejn B, Pilotto JH, Godbole SV, Mehendale S, Chariyalertsak S, Santos BR, Mayer KH, Hoffman IF, Eshleman SH, Piwowar-Manning E, Wang L, Makhema J, Mills LA, de Bruyn G, Sanne I, Eron J, Gallant J, Havlir D, Swindells S, Ribaudo H, Elharrar V, Burns D, Taha TE, Nielsen-Saines K, Celentano D, Essex M, Fleming TR; HPTN 052 Study Team. Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med. 2011 Aug 11;365(6):493-505. doi: 10.1056/NEJMoa1105243. Epub 2011 Jul 18.
citation: TEMPRANO ANRS 12136 Study Group; Danel C, Moh R, Gabillard D, Badje A, Le Carrou J, Ouassa T, Ouattara E, Anzian A, Ntakpe JB, Minga A, Kouame GM, Bouhoussou F, Emieme A, Kouame A, Inwoley A, Toni TD, Ahiboh H, Kabran M, Rabe C, Sidibe B, Nzunetu G, Konan R, Gnokoro J, Gouesse P, Messou E, Dohoun L, Kamagate S, Yao A, Amon S, Kouame AB, Koua A, Kouame E, Ndri Y, Ba-Gomis O, Daligou M, Ackoundze S, Hawerlander D, Ani A, Dembele F, Kone F, Guehi C, Kanga C, Koule S, Seri J, Oyebi M, Mbakop N, Makaila O, Babatunde C, Babatounde N, Bleoue G, Tchoutedjem M, Kouadio AC, Sena G, Yededji SY, Assi R, Bakayoko A, Mahassadi A, Attia A, Oussou A, Mobio M, Bamba D, Koman M, Horo A, Deschamps N, Chenal H, Sassan-Morokro M, Konate S, Aka K, Aoussi E, Journot V, Nchot C, Karcher S, Chaix ML, Rouzioux C, Sow PS, Perronne C, Girard PM, Menan H, Bissagnene E, Kadio A, Ettiegne-Traore V, Moh-Semde C, Kouame A, Massumbuko JM, Chene G, Dosso M, Domoua SK, N'Dri-Yoman T, Salamon R, Eholie SP, Anglaret X. A Trial of Early Antiretrovirals and Isoniazid Preventive Therapy in Africa. N Engl J Med. 2015 Aug 27;373(9):808-22. doi: 10.1056/NEJMoa1507198. Epub 2015 Jul 20.
citation: 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.
citation: Jones A, Cremin I, Abdullah F, Idoko J, Cherutich P, Kilonzo N, Rees H, Hallett T, O'Reilly K, Koechlin F, Schwartlander B, de Zalduondo B, Kim S, Jay J, Huh J, Piot P, Dybul M. Transformation of HIV from pandemic to low-endemic levels: a public health approach to combination prevention. Lancet. 2014 Jul 19;384(9939):272-9. doi: 10.1016/S0140-6736(13)62230-8. Epub 2014 Apr 14.
citation: Guideline on When to Start Antiretroviral Therapy and on Pre-Exposure Prophylaxis for HIV. Geneva: World Health Organization; 2015 Sep. Available from http://www.ncbi.nlm.nih.gov/books/NBK327115/
citation: Hull M, Lange J, Montaner JS. Treatment as prevention--where next? Curr HIV/AIDS Rep. 2014 Dec;11(4):496-504. doi: 10.1007/s11904-014-0237-5.
citation: Delva W, Abdool Karim Q. The HIV epidemic in Southern Africa - Is an AIDS-free generation possible? Curr HIV/AIDS Rep. 2014 Jun;11(2):99-108. doi: 10.1007/s11904-014-0205-0.
citation: MacCarthy S, Hoffmann M, Ferguson L, Nunn A, Irvin R, Bangsberg D, Gruskin S, Dourado I. The HIV care cascade: models, measures and moving forward. J Int AIDS Soc. 2015 Mar 2;18(1):19395. doi: 10.7448/IAS.18.1.19395. eCollection 2015.
citation: Yehia BR, Stephens-Shields AJ, Fleishman JA, Berry SA, Agwu AL, Metlay JP, Moore RD, Christopher Mathews W, Nijhawan A, Rutstein R, Gaur AH, Gebo KA; HIV Research Network. The HIV Care Continuum: Changes over Time in Retention in Care and Viral Suppression. PLoS One. 2015 Jun 18;10(6):e0129376. doi: 10.1371/journal.pone.0129376. eCollection 2015.
citation: Kranzer K, Govindasamy D, Ford N, Johnston V, Lawn SD. Quantifying and addressing losses along the continuum of care for people living with HIV infection in sub-Saharan Africa: a systematic review. J Int AIDS Soc. 2012 Nov 19;15(2):17383. doi: 10.7448/IAS.15.2.17383.
citation: Mills EJ, Nachega JB, Ford N. Can we stop AIDS with antiretroviral-based treatment as prevention? Glob Health Sci Pract. 2013 Mar 21;1(1):29-34. doi: 10.9745/GHSP-D-12-00053. eCollection 2013 Mar.
citation: Piot P, Abdool Karim SS, Hecht R, Legido-Quigley H, Buse K, Stover J, Resch S, Ryckman T, Mogedal S, Dybul M, Goosby E, Watts C, Kilonzo N, McManus J, Sidibe M; UNAIDS-Lancet Commission. Defeating AIDS--advancing global health. Lancet. 2015 Jul 11;386(9989):171-218. doi: 10.1016/S0140-6736(15)60658-4. Epub 2015 Jun 24. No abstract available.
citation: Nachega JB, Uthman OA, del Rio C, Mugavero MJ, Rees H, Mills EJ. Addressing the Achilles' heel in the HIV care continuum for the success of a test-and-treat strategy to achieve an AIDS-free generation. Clin Infect Dis. 2014 Jul;59 Suppl 1(Suppl 1):S21-7. doi: 10.1093/cid/ciu299.
citation: Naik R, Doherty T, Jackson D, Tabana H, Swanevelder S, Thea DM, Feeley FG, Fox MP. Linkage to care following a home-based HIV counselling and testing intervention in rural South Africa. J Int AIDS Soc. 2015 Jun 8;18(1):19843. doi: 10.7448/IAS.18.1.19843. eCollection 2015.
citation: Parker LA, Jobanputra K, Rusike L, Mazibuko S, Okello V, Kerschberger B, Jouquet G, Cyr J, Teck R. Feasibility and effectiveness of two community-based HIV testing models in rural Swaziland. Trop Med Int Health. 2015 Jul;20(7):893-902. doi: 10.1111/tmi.12501. Epub 2015 Apr 2.
citation: Clouse K, Pettifor AE, Maskew M, Bassett J, Van Rie A, Behets F, Gay C, Sanne I, Fox MP. Patient retention from HIV diagnosis through one year on antiretroviral therapy at a primary health care clinic in Johannesburg, South Africa. J Acquir Immune Defic Syndr. 2013 Feb 1;62(2):e39-46. doi: 10.1097/QAI.0b013e318273ac48.
citation: Gerdts SE, Wagenaar BH, Micek MA, Farquhar C, Kariaganis M, Amos J, Gimbel S, Pfeiffer J, Gloyd S, Sherr K. Linkage to HIV care and antiretroviral therapy by HIV testing service type in Central Mozambique: a retrospective cohort study. J Acquir Immune Defic Syndr. 2014 Jun 1;66(2):e37-44. doi: 10.1097/QAI.0000000000000081.
citation: Labhardt ND, Motlomelo M, Cerutti B, Pfeiffer K, Kamele M, Hobbins MA, Ehmer J. Home-based versus mobile clinic HIV testing and counseling in rural Lesotho: a cluster-randomized trial. PLoS Med. 2014 Dec 16;11(12):e1001768. doi: 10.1371/journal.pmed.1001768. eCollection 2014 Dec.
citation: Okeke NL, Ostermann J, Thielman NM. Enhancing linkage and retention in HIV care: a review of interventions for highly resourced and resource-poor settings. Curr HIV/AIDS Rep. 2014 Dec;11(4):376-92. doi: 10.1007/s11904-014-0233-9.
citation: Govindasamy D, Meghij J, Kebede Negussi E, Clare Baggaley R, Ford N, Kranzer K. Interventions to improve or facilitate linkage to or retention in pre-ART (HIV) care and initiation of ART in low- and middle-income settings--a systematic review. J Int AIDS Soc. 2014 Aug 1;17(1):19032. doi: 10.7448/IAS.17.1.19032. eCollection 2014.
citation: Posse M, Baltussen R. Costs of providing food assistance to HIV/AIDS patients in Sofala province, Mozambique: a retrospective analysis. Cost Eff Resour Alloc. 2013 Aug 28;11(1):20. doi: 10.1186/1478-7547-11-20.
citation: Govindasamy D, Ford N, Kranzer K. Risk factors, barriers and facilitators for linkage to antiretroviral therapy care: a systematic review. AIDS. 2012 Oct 23;26(16):2059-67. doi: 10.1097/QAD.0b013e3283578b9b.
citation: Amstutz A, Brown JA, Ringera I, Muhairwe J, Lejone TI, Klimkait T, Glass TR, Labhardt ND. Engagement in Care, Viral Suppression, Drug Resistance, and Reasons for Nonengagement After Home-Based Same-Day Antiretroviral Therapy Initiation in Lesotho: A Two-Year Follow-up of the CASCADE Trial. Clin Infect Dis. 2020 Dec 17;71(10):2608-2614. doi: 10.1093/cid/ciz1126.
citation: Labhardt ND, Ringera I, Lejone TI, Amstutz A, Klimkait T, Muhairwe J, Glass TR. Effect and cost of two successive home visits to increase HIV testing coverage: a prospective study in Lesotho, Southern Africa. BMC Public Health. 2019 Nov 1;19(1):1441. doi: 10.1186/s12889-019-7784-z.
citation: Labhardt ND, Ringera I, Lejone TI, Klimkait T, Muhairwe J, Amstutz A, Glass TR. Effect of Offering Same-Day ART vs Usual Health Facility Referral During Home-Based HIV Testing on Linkage to Care and Viral Suppression Among Adults With HIV in Lesotho: The CASCADE Randomized Clinical Trial. JAMA. 2018 Mar 20;319(11):1103-1112. doi: 10.1001/jama.2018.1818.
citation: Labhardt ND, Ringera I, Lejone TI, Masethothi P, Thaanyane T, Kamele M, Gupta RS, Thin K, Cerutti B, Klimkait T, Fritz C, Glass TR. Same day 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 (CASCADE trial). BMC Public Health. 2016 Apr 14;16:329. doi: 10.1186/s12889-016-2972-6.