Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Trials
Published in: Trials 1/2013

Open Access 01-12-2013 | Study protocol

Evaluation of the impact of immediate versus WHO recommendations-guided antiretroviral therapy initiation on HIV incidence: the ANRS 12249 TasP (Treatment as Prevention) trial in Hlabisa sub-district, KwaZulu-Natal, South Africa: study protocol for a cluster randomised controlled trial

Authors: Collins C Iwuji, Joanna Orne-Gliemann, Frank Tanser, Sylvie Boyer, Richard J Lessells, France Lert, John Imrie, Till Bärnighausen, Claire Rekacewicz, Brigitte Bazin, Marie-Louise Newell, François Dabis, ANRS 12249 TasP study group

Published in: Trials | Issue 1/2013

Login to get access

Abstract

Background

Antiretroviral therapy (ART) suppresses HIV viral load in all body compartments and so limits the risk of HIV transmission. It has been suggested that ART not only contributes to preventing transmission at individual but potentially also at population level. This trial aims to evaluate the effect of ART initiated immediately after identification/diagnosis of HIV-infected individuals, regardless of CD4 count, on HIV incidence in the surrounding population. The primary outcome of the overall trial will be HIV incidence over two years. Secondary outcomes will include i) socio-behavioural outcomes (acceptability of repeat HIV counselling and testing, treatment acceptance and linkage to care, sexual partnerships and quality of life); ii) clinical outcomes (mortality and morbidity, retention into care, adherence to ART, virologic failure and acquired HIV drug resistance), iii) cost-effectiveness of the intervention. The first phase will specifically focus on the trial’s secondary outcomes.

Methods/design

A cluster-randomised trial in 34 (2 × 17) clusters within a rural area of northern KwaZulu-Natal (South Africa), covering a total population of 34,000 inhabitants aged 16 years and above, of whom an estimated 27,200 would be HIV-uninfected at start of the trial. The first phase of the trial will include ten (2 × 5) clusters. Consecutive rounds of home-based HIV testing will be carried out. HIV-infected participants will be followed in dedicated trial clinics: in intervention clusters, they will be offered immediate ART initiation regardless of CD4 count and clinical stage; in control clusters they will be offered ART according to national treatment eligibility guidelines (CD4 <350 cells/μL, World Health Organisation stage 3 or 4 disease or multidrug-resistant/extensively drug-resistant tuberculosis). Following proof of acceptability and feasibility from the first phase, the trial will be rolled out to further clusters.

Discussion

We aim to provide proof-of-principle evidence regarding the effectiveness of Treatment-as-Prevention in reducing HIV incidence at the population level. Data collected from the participants at home and in the clinics will inform understanding of socio-behavioural, economic and clinical impacts of the intervention as well as feasibility and generalizability.

Trial registration

Clinicaltrials.gov: NCT01509508; South African Trial Register: DOH-27-0512-3974.
Appendix
Available only for authorised users
Literature
1.
2.
Quinn TC, Wawer MJ, Sewankambo N, Serwadda D, Li C, Wabwire-Mangen F, Meehan MO, Lutalo T, Gray RH: Viral load and heterosexual transmission of human immunodeficiency virus type 1. Rakai Project Study Group. N Engl J Med. 2000, 342: 921-929. 10.1056/NEJM200003303421303.CrossRefPubMed
3.
Garcia PM, Kalish LA, Pitt J, Minkoff H, Quinn TC, Burchett SK, Kornegay J, Jackson B, Moye J, Hanson C, Zorrilla C, Lew JF: Maternal levels of plasma human immunodeficiency virus type 1 RNA and the risk of perinatal transmission. Women and Infants Transmission Study Group. N Engl J Med. 1999, 341: 394-402. 10.1056/NEJM199908053410602.CrossRefPubMed
4.
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: Prevention of HIV-1 Infection with Early Antiretroviral Therapy. N Engl J Med. 2011, 365: 493-505. 10.1056/NEJMoa1105243.CrossRefPubMedPubMedCentral
5.
Tanser F, Bärnighausen T, Grapsa E, Zaidi J, Newell ML: High coverage of ART associated with decline in risk of HIV acquisition in rural KwaZulu-Natal, South Africa. Science. 2013, 339: 966-971. 10.1126/science.1228160.CrossRefPubMedPubMedCentral
6.
The HIV Modelling Consortium Treatment as Prevention Editorial Writing Group: HIV treatment as prevention: models, data, and questions–towards evidence-based decision-making. PLoS Med. 2012, 9: e1001259-10.1371/journal.pmed.1001259.CrossRefPubMedCentral
7.
Granich RM, Gilks CF, Dye C, De Cock KM, Williams BG: Universal voluntary HIV testing with immediate antiretroviral therapy as a strategy for elimination of HIV transmission: a mathematical model. Lancet. 2009, 373: 48-57. 10.1016/S0140-6736(08)61697-9.CrossRefPubMed
8.
Dodd PJ, Garnett GP, Hallett TB: Examining the promise of HIV elimination by ‘test and treat’ in hyperendemic settings. AIDS. 2010, 24: 729-735. 10.1097/QAD.0b013e32833433fe.CrossRefPubMedPubMedCentral
9.
Eaton JW, Johnson LF, Salomon JA, Barnighausen T, Bendavid E, Bershteyn A, Bloom DE, Cambiano V, Fraser C, Hontelez JA, Humair S, Klein DJ, Long EF, Phillips AN, Pretorius C, Stover J, Wenger EA, Williams BG, Hallett TB: HIV treatment as prevention: systematic comparison of mathematical models of the potential impact of antiretroviral therapy on HIV incidence in South Africa. PLoS Med. 2012, 9: e1001245-10.1371/journal.pmed.1001245.CrossRefPubMedPubMedCentral
10.
Hontelez JAC, Lurie MN, Bärnighausen T, Bakker R, Baltussen R, Tanser F, Hallett TB, Newell M-L, De Vlas SJ: Treatment as prevention for HIV in South Africa: different models show consistency in occurrence, but difference in timing of elimination and the overall impact of the intervention. J Int AIDS Soc. 2012, 15 (Suppl 3):
11.
Kitahata MM, Gange SJ, Abraham AG, Merriman B, Saag MS, Justice AC, Hogg RS, Deeks SG, Eron JJ, Brooks JT, Rourke SB, Gill MJ, Bosch RJ, Martin JN, Klein MB, Jacobson LP, Rodriguez B, Sterling TR, Kirk GD, Napravnik S, Rachlis AR, Calzavara LM, Horberg MA, Silverberg MJ, Gebo KA, Goedert JJ, Benson CA, Collier AC, Van Rompaey SE, Crane HM: Effect of early versus deferred antiretroviral therapy for HIV on survival. N Engl J Med. 2009, 360: 1815-1826. 10.1056/NEJMoa0807252.CrossRefPubMedPubMedCentral
12.
Sterne JA, May M, Costagliola D, De Wolf F, Phillips AN, Harris R, Funk MJ, Geskus RB, Gill J, Dabis F, Miro JM, Justice AC, Ledergerber B, Fatkenheuer G, Hogg RS, Monforte AD, Saag M, Smith C, Staszewski S, Egger M, Cole SR: Timing of initiation of antiretroviral therapy in AIDS-free HIV-1-infected patients: a collaborative analysis of 18 HIV cohort studies. Lancet. 2009, 373: 1352-1363.CrossRefPubMed
13.
Anglaret X, Minga A, Gabillard D, Ouassa T, Messou E, Morris B, Traore M, Coulibaly A, Freedberg KA, Lewden C, Menan H, Abo Y, Dakoury-Dogbo N, Toure S, Seyler C: AIDS and non-AIDS morbidity and mortality across the spectrum of CD4 cell counts in HIV-infected adults before starting antiretroviral therapy in Cote d’Ivoire. Clin Infect Dis. 2012, 54: 714-723. 10.1093/cid/cir898.CrossRefPubMed
14.
15.
Welz T, Hosegood V, Jaffar S, Batzing-Feigenbaum J, Herbst K, Newell ML: Continued very high prevalence of HIV infection in rural KwaZulu-Natal, South Africa: a population-based longitudinal study. AIDS. 2007, 21: 1467-1472. 10.1097/QAD.0b013e3280ef6af2.CrossRefPubMed
16.
Tanser F, Barnighausen T, Cooke GS, Newell ML: Localized spatial clustering of HIV infections in a widely disseminated rural South African epidemic. Int J Epidemiol. 2009, 38: 1008-1016. 10.1093/ije/dyp148.CrossRefPubMedPubMedCentral
17.
Zaidi J, Grapsa E, Tanser F, Newell M, Bärnighausen T: HIV prevalence trends after scale-up of antiretroviral treatment: a population-based study in a poor rural community in KwaZulu-Natal. J Int AIDS Soc. 2012, 15 (Suppl 3):
18.
Barnighausen T, Tanser F, Newell ML: Lack of a decline in HIV incidence in a rural community with high HIV prevalence in South Africa, 2003–2007. AIDS Res Hum Retroviruses. 2009, 25: 405-409. 10.1089/aid.2008.0211.CrossRefPubMedPubMedCentral
19.
Barnighausen T, Wallrauch C, Welte A, McWalter TA, Mbizana N, Viljoen J, Graham N, Tanser F, Puren A, Newell ML: HIV incidence in rural South Africa: comparison of estimates from longitudinal surveillance and cross-sectional cBED assay testing. PLoS One. 2008, 3: e3640-10.1371/journal.pone.0003640.CrossRefPubMedPubMedCentral
20.
Tanser F, Bärnighausen T, Newell M: Identification of Localized Clusters of High HIV Incidence in a Widely Disseminated Rural South African Epidemic: A Case for Targeted Intervention Strategies. 2011, Boston, MA (USA): 18th Conference on Retroviruses and Opportunistic Infections (CROI), Abstract 137
21.
Houlihan CF, Bland RM, Mutevedzi PC, Lessells RJ, Ndirangu J, Thulare H, Newell ML: Cohort Profile: Hlabisa HIV Treatment and Care Programme. Int J Epidemiol. 2011, 40: 318-326. 10.1093/ije/dyp402.CrossRefPubMed
22.
Maheswaran H, Thulare H, Stanistreet D, Tanser F, Newell ML: Starting a home and mobile HIV testing service in a rural area of South Africa. J Acquir Immune Defic Syndr. 2012, 59: e43-e46. 10.1097/QAI.0b013e3182414ed7.CrossRefPubMedPubMedCentral
23.
Tanser F, Hosegood V, Barnighausen T, Herbst K, Nyirenda M, Muhwava W, Newell C, Viljoen J, Mutevedzi T, Newell ML: Cohort Profile: Africa Centre Demographic Information System (ACDIS) and population-based HIV survey. Int J Epidemiol. 2008, 37: 956-962. 10.1093/ije/dym211.CrossRefPubMed
24.
Tanser F, Hosegood V, Benzler J, Solarsh G: New approaches to spatially analyse primary health care usage patterns in rural South Africa. Trop Med Int Health. 2001, 6: 826-838. 10.1046/j.1365-3156.2001.00794.x.CrossRefPubMed
25.
Goldie SJ, Yazdanpanah Y, Losina E, Weinstein MC, Anglaret X, Walensky RP, Hsu HE, Kimmel A, Holmes C, Kaplan JE, Freedberg KA: Cost-effectiveness of HIV treatment in resource-poor settings–the case of Cote d’Ivoire. N Engl J Med. 2006, 355: 1141-1153. 10.1056/NEJMsa060247.CrossRefPubMed
26.
Hontelez JA, De Vlas SJ, Tanser F, Bakker R, Barnighausen T, Newell ML, Baltussen R, Lurie MN: The impact of the new WHO antiretroviral treatment guidelines on HIV epidemic dynamics and cost in South Africa. PLoS One. 2011, 6: e21919-10.1371/journal.pone.0021919.CrossRefPubMedPubMedCentral
27.
Grosskurth H, Mosha F, Todd J, Mwijarubi E, Klokke A, Senkoro K, Mayaud P, Changalucha J, Nicoll A, Ka-Gina G, Newell J, Mugeye K, Mabey D, Hayes R: Impact of improved treatment of sexually transmitted diseases on HIV infection in rural Tanzania: randomised controlled trial. Lancet. 1995, 346: 530-536. 10.1016/S0140-6736(95)91380-7.CrossRefPubMed
28.
Tanser F, Barnighausen T, Hund L, Garnett GP, McGrath N, Newell ML: Effect of concurrent sexual partnerships on rate of new HIV infections in a high-prevalence, rural South African population: a cohort study. Lancet. 2011, 378: 247-255. 10.1016/S0140-6736(11)60779-4.CrossRefPubMedPubMedCentral
29.
30.
National Department of Health: Clinical guidelines for the management of HIV/AIDS in adults and adolescents. 2010, Republic of South Africa: Department of Health
31.
Chaiyachati K, Hirschhorn LR, Tanser F, Newell ML, Barnighausen T: Validating five questions of antiretroviral nonadherence in a public-sector treatment program in rural South Africa. AIDS Patient Care STDS. 2010, 25: 163-170.
32.
Boyer S, Clerc I, Bonono CR, Marcellin F, Bile PC, Ventelou B: Non-adherence to antiretroviral treatment and unplanned treatment interruption among people living with HIV/AIDS in Cameroon: Individual and healthcare supply-related factors. Soc Sci Med. 2011, 72: 1383-1392. 10.1016/j.socscimed.2011.02.030.CrossRefPubMed
33.
Carrieri P, Cailleton V, Le Moing V, Spire B, Dellamonica P, Bouvet E, Raffi F, Journot V, Moatti JP: The dynamic of adherence to highly active antiretroviral therapy: results from the French National APROCO cohort. J Acquir Immune Defic Syndr. 2001, 28: 232-239.CrossRefPubMed
34.
Spire B, Carrieri P, Sopha P, Protopopescu C, Prak N, Quillet C, Ngeth C, Ferradini L, Delfraissy JF, Laureillard D: Adherence to antiretroviral therapy in patients enrolled in a comprehensive care program in Cambodia: a 24-month follow-up assessment. Antivir Ther. 2008, 13: 697-703.PubMed
35.
Duracinsky M, Herrmann S, Berzins B, Armstrong AR, Kohli R, Le Coeur S, Diouf A, Fournier I, Schechter M, Chassany O: The development of PROQOL-HIV: an international instrument to assess the health-related quality of life of persons living with HIV/AIDS. J Acquir Immune Defic Syndr. 2012, 59: 498-505. 10.1097/QAI.0b013e318245cafe.CrossRefPubMed
36.
Duracinsky M, Lalanne C, Le Coeur S, Herrmann S, Berzins B, Armstrong AR, Lau JT, Fournier I, Chassany O: Psychometric validation of the PROQOL-HIV questionnaire, a new health-related quality of life instrument-specific to HIV disease. J Acquir Immune Defic Syndr. 2012, 59: 506-515. 10.1097/QAI.0b013e31824be3f2.CrossRefPubMed
37.
Holzemer WL, Uys LR, Chirwa ML, Greeff M, Makoae LN, Kohi TW, Dlamini PS, Stewart AL, Mullan J, Phetlhu RD, Wantland D, Durrheim K: Validation of the HIV/AIDS Stigma Instrument - PLWA (HASI-P). AIDS Care. 2007, 19: 1002-1012. 10.1080/09540120701245999.CrossRefPubMed
38.
Ukoumunne OC, Carlin JB, Gulliford MC: A simulation study of odds ratio estimation for binary outcomes from cluster randomized trials. Stat Med. 2007, 26: 3415-3428.CrossRefPubMed
39.
Mancl LA, DeRouen TA: A covariance estimator for GEE with improved small-sample properties. Biometrics. 2001, 57: 126-134. 10.1111/j.0006-341X.2001.00126.x.CrossRefPubMed
40.
Attia S, Egger M, Muller M, Zwahlen M, Low N: Sexual transmission of HIV according to viral load and antiretroviral therapy: systematic review and meta-analysis. Aids. 2009, 23 (11): 1397-1404. 10.1097/QAD.0b013e32832b7dca.CrossRefPubMed
41.
Anglemyer A, Rutherford GW, Baggaley RC, Egger M, Siegfried N: Antiretroviral therapy for prevention of HIV transmission in HIV-discordant couples. Cochrane Database Syst Rev. 2011, 8: CD009153-PubMed
42.
World Health Organisation: Recommendations for a public health approach. Guidance on Couples HIV Testing and Counselling including Antiretroviral Therapy for Treatment and Prevention in Serodiscordant Couples. 2012, Geneva: World Health Organisation, In
43.
World Health Organisation: Recommendations for a public health approach. Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection. 2013, Geneva: World Health Organisation, In
44.
Chi BH, Cantrell RA, Zulu I, Mulenga LB, Levy JW, Tambatamba BC, Reid S, Mwango A, Mwinga A, Bulterys M: Adherence to first-line antiretroviral therapy affects non-virologic outcomes among patients on treatment for more than 12 months in Lusaka, Zambia. Int J Epidemiol. 2009, 38 (3): 746-756. 10.1093/ije/dyp004.CrossRefPubMedPubMedCentral
45.
Maqutu D, Zewotir T, North D, Naidoo K, Grobler A: Factors affecting first-month adherence to antiretroviral therapy among HIV-positive adults in South Africa. Afr J AIDS Res. 2010, 9 (2): 117-124. 10.2989/16085906.2010.517478.CrossRefPubMedPubMedCentral
46.
Uy J, Armon C, Buchacz K, Wood K, Brooks JT: Initiation of HAART at higher CD4 cell counts is associated with a lower frequency of antiretroviral drug resistance mutations at virologic failure. J Acquir Immune Defic Syndr. 2009, 51 (4): 450-453. 10.1097/QAI.0b013e3181acb630.CrossRefPubMed
47.
Barnighausen T, Bloom DE, Humair S: Economics of antiretroviral treatment vs. circumcision for HIV prevention. Proceedings of the National Academy of Sciences of the United States of America. 2012, 109 (52): 21271-21276. 10.1073/pnas.1209017110.CrossRefPubMedPubMedCentral
Metadata
Title
Evaluation of the impact of immediate versus WHO recommendations-guided antiretroviral therapy initiation on HIV incidence: the ANRS 12249 TasP (Treatment as Prevention) trial in Hlabisa sub-district, KwaZulu-Natal, South Africa: study protocol for a cluster randomised controlled trial
Authors
Collins C Iwuji
Joanna Orne-Gliemann
Frank Tanser
Sylvie Boyer
Richard J Lessells
France Lert
John Imrie
Till Bärnighausen
Claire Rekacewicz
Brigitte Bazin
Marie-Louise Newell
François Dabis
ANRS 12249 TasP study group
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Trials / Issue 1/2013
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/1745-6215-14-230

Other articles of this Issue 1/2013

Trials 1/2013 Go to the issue

Study protocol

Study of Optimal Replacement of Thyroxine in the ElDerly (SORTED): protocol for a mixed methods feasibility study to assess the clinical utility of lower dose thyroxine in elderly hypothyroid patients: study protocol for a randomized controlled trial

Study protocol

Improving the application of a practice guideline for the assessment and treatment of suicidal behavior by training the full staff of psychiatric departments via an e-learning supported Train-the-Trainer program: study protocol for a randomized controlled trial

Study protocol

A pilot study of intraocular use of intensive anti-inflammatory; triamcinolone acetonide to prevent proliferative vitreoretinopathy in eyes undergoing vitreoretinal surgery for open globe trauma; the adjuncts in ocular trauma (AOT) trial: study protocol for a randomised controlled trial

Methodology

Process evaluations for cluster-randomised trials of complex interventions: a proposed framework for design and reporting

Study protocol

The UP-TECH project, an intervention to support caregivers of Alzheimer’s disease patients in Italy: study protocol for a randomized controlled trial

Study protocol

Effects of different information brochures on women’s decision-making regarding mammography screening: study protocol for a randomized controlled questionnaire study