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      Uptake of Home-Based HIV Testing, Linkage to Care, and Community Attitudes about ART in Rural KwaZulu-Natal, South Africa: Descriptive Results from the First Phase of the ANRS 12249 TasP Cluster-Randomised Trial

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          Abstract

          Background

          The 2015 WHO recommendation of antiretroviral therapy (ART) for all immediately following HIV diagnosis is partially based on the anticipated impact on HIV incidence in the surrounding population. We investigated this approach in a cluster-randomised trial in a high HIV prevalence setting in rural KwaZulu-Natal. We present findings from the first phase of the trial and report on uptake of home-based HIV testing, linkage to care, uptake of ART, and community attitudes about ART.

          Methods and Findings

          Between 9 March 2012 and 22 May 2014, five clusters in the intervention arm (immediate ART offered to all HIV-positive adults) and five clusters in the control arm (ART offered according to national guidelines, i.e., CD4 count ≤ 350 cells/μl) contributed to the first phase of the trial. Households were visited every 6 mo. Following informed consent and administration of a study questionnaire, each resident adult (≥16 y) was asked for a finger-prick blood sample, which was used to estimate HIV prevalence, and offered a rapid HIV test using a serial HIV testing algorithm. All HIV-positive adults were referred to the trial clinic in their cluster. Those not linked to care 3 mo after identification were contacted by a linkage-to-care team. Study procedures were not blinded.

          In all, 12,894 adults were registered as eligible for participation (5,790 in intervention arm; 7,104 in control arm), of whom 9,927 (77.0%) were contacted at least once during household visits. HIV status was ever ascertained for a total of 8,233/9,927 (82.9%), including 2,569 ascertained as HIV-positive (942 tested HIV-positive and 1,627 reported a known HIV-positive status). Of the 1,177 HIV-positive individuals not previously in care and followed for at least 6 mo in the trial, 559 (47.5%) visited their cluster trial clinic within 6 mo. In the intervention arm, 89% (194/218) initiated ART within 3 mo of their first clinic visit. In the control arm, 42.3% (83/196) had a CD4 count ≤ 350 cells/μl at first visit, of whom 92.8% initiated ART within 3 mo. Regarding attitudes about ART, 93% (8,802/9,460) of participants agreed with the statement that they would want to start ART as soon as possible if HIV-positive. Estimated baseline HIV prevalence was 30.5% (2,028/6,656) (95% CI 25.0%, 37.0%). HIV prevalence, uptake of home-based HIV testing, linkage to care within 6 mo, and initiation of ART within 3 mo in those with CD4 count ≤ 350 cells/μl did not differ significantly between the intervention and control clusters. Selection bias related to noncontact could not be entirely excluded.

          Conclusions

          Home-based HIV testing was well received in this rural population, although men were less easily contactable at home; immediate ART was acceptable, with good viral suppression and retention. However, only about half of HIV-positive people accessed care within 6 mo of being identified, with nearly two-thirds accessing care by 12 mo. The observed delay in linkage to care would limit the individual and public health ART benefits of universal testing and treatment in this population.

          Trial registration

          ClinicalTrials.gov NCT01509508

          Abstract

          Collins Iwuji and colleagues report implementation indicators and early health outcomes from the first phase of a cluster-randomized trial of immediate antiretroviral therapy to all HIV-positive individuals in rural KwaZulu-Natal, South Africa.

          Author Summary

          Why Was This Study Done?
          • A study in stable sexual partners in which one partner was HIV-positive and the other partner was HIV-negative (and both partners had disclosed to each other) showed that if the HIV-positive partner was on antiretroviral therapy, there was a 96% reduction in HIV transmission from the HIV-positive partner to the HIV-negative partner.

          • However, we do not know if antiretroviral therapy prescribed to HIV-positive individuals in the general population—and where individuals might not disclose their HIV status to sexual partners—would have a similar impact on HIV transmission.

          • It is important to determine whether prescribing antiretroviral therapy to all HIV-positive individuals is more effective at decreasing HIV transmission than starting individuals on antiretroviral therapy only once their HIV has progressed to the point at which local HIV treatment guidelines currently recommend that HIV-positive individuals start treatment.

          What Did the Researchers Do and Find?
          • We designed an experiment to investigate whether antiretroviral therapy can reduce new HIV infections in the general population, and piloted the trial in ten communities in KwaZulu-Natal, South Africa, to check whether starting HIV-positive individuals on antiretroviral therapy directly after diagnosis is feasible and acceptable.

          • We visited people in their homes, offered HIV rapid tests every six months to all individuals 16 years and older, and referred identified HIV-positive individuals to trial clinics, where they were offered antiretroviral therapy either regardless of their CD4 count (intervention group) or when they were treatment-eligible per current national guidelines (control group).

          • During the two-year study, we contacted 9,927 (77%) of 12,894 eligible individuals and ascertained the HIV status of 80% of contacted women and 75% of contacted men.

          • HIV-positive status was ascertained for 1,339 adults who were not previously in care; 1,177 were followed in the trial at least 6 mo after referral, of whom 559 (47.5%) engaged with care within this period.

          What Do These Findings Mean?
          • Our findings show good acceptance of home-based HIV testing in rural South Africa but highlight the challenges in reaching adequate numbers of people to offer HIV tests to, especially among men.

          • We also found that linkage to care was slower than expected, but amongst those who reached the clinics, uptake of antiretroviral therapy was high, with the majority of individuals achieving good control of the virus.

          • Our study informs health care professionals, planners, and policy makers about the challenges that need to be addressed to achieve the UNAIDS target of 90% of people living with HIV aware of their HIV diagnosis, 90% on antiretroviral therapy, and 90% achieving good control of the virus, with testing and treatment offered to all.

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          Most cited references30

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          Prevention of HIV-1 infection with early antiretroviral therapy.

          Antiretroviral therapy that reduces viral replication could limit the transmission of human immunodeficiency virus type 1 (HIV-1) in serodiscordant couples. In nine countries, we enrolled 1763 couples in which one partner was HIV-1-positive and the other was HIV-1-negative; 54% of the subjects were from Africa, and 50% of infected partners were men. HIV-1-infected subjects with CD4 counts between 350 and 550 cells per cubic millimeter were randomly assigned in a 1:1 ratio to receive antiretroviral therapy either immediately (early therapy) or after a decline in the CD4 count or the onset of HIV-1-related symptoms (delayed therapy). The primary prevention end point was linked HIV-1 transmission in HIV-1-negative partners. The primary clinical end point was the earliest occurrence of pulmonary tuberculosis, severe bacterial infection, a World Health Organization stage 4 event, or death. As of February 21, 2011, a total of 39 HIV-1 transmissions were observed (incidence rate, 1.2 per 100 person-years; 95% confidence interval [CI], 0.9 to 1.7); of these, 28 were virologically linked to the infected partner (incidence rate, 0.9 per 100 person-years, 95% CI, 0.6 to 1.3). Of the 28 linked transmissions, only 1 occurred in the early-therapy group (hazard ratio, 0.04; 95% CI, 0.01 to 0.27; P<0.001). Subjects receiving early therapy had fewer treatment end points (hazard ratio, 0.59; 95% CI, 0.40 to 0.88; P=0.01). The early initiation of antiretroviral therapy reduced rates of sexual transmission of HIV-1 and clinical events, indicating both personal and public health benefits from such therapy. (Funded by the National Institute of Allergy and Infectious Diseases and others; HPTN 052 ClinicalTrials.gov number, NCT00074581.).
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            Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection

            New England Journal of Medicine, 373(9), 795-807
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              A Trial of Early Antiretrovirals and Isoniazid Preventive Therapy in Africa.

              In sub-Saharan Africa, the burden of human immunodeficiency virus (HIV)-associated tuberculosis is high. We conducted a trial with a 2-by-2 factorial design to assess the benefits of early antiretroviral therapy (ART), 6-month isoniazid preventive therapy (IPT), or both among HIV-infected adults with high CD4+ cell counts in Ivory Coast.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                PLoS Med
                PLoS Med
                plos
                plosmed
                PLoS Medicine
                Public Library of Science (San Francisco, CA USA )
                1549-1277
                1549-1676
                9 August 2016
                August 2016
                : 13
                : 8
                : e1002107
                Affiliations
                [1 ]Africa Centre for Population Health, University of KwaZulu-Natal, Durban, South Africa
                [2 ]Research Department of Infection and Population Health, University College London, London, United Kingdom
                [3 ]Centre INSERM U1219 Bordeaux Population Health, Université de Bordeaux, Bordeaux, France
                [4 ]Institut de Santé Publique, d’Epidémiologie et de Développement, Centre INSERM U1219 Bordeaux Population Health, Université de Bordeaux, Bordeaux, France
                [5 ]Centre Population & Développement UMR 196, Université Paris Descartes, Institut de Recherche pour le Développement, Paris, France
                [6 ]School of Nursing and Public Health, University of KwaZulu-Natal, Durban, South Africa
                [7 ]Agence Nationale de Recherches sur le Sida et les Hépatites Virales, Paris, France
                [8 ]Human Health and Development and Global Health Research Institute, Faculty of Medicine, University of Southampton, Southampton, United Kingdom
                University of Bern, SWITZERLAND
                Author notes

                I have read the journal's policy and the authors of this manuscript have the following competing interests: CI has received honoraria for services rendered to Gilead Sciences. CR is employed by the ANRS. MLN is a member of the Editorial Board of PLOS Medicine. All other authors declare no competing interests.

                Conceived and designed the experiments: CI FT NO JOG CR MLN FD. Performed the experiments: CI FT NO JOG MLN FD. Analyzed the data: JL FT RT. Contributed reagents/materials/analysis tools: JL FT RT. Wrote the first draft of the manuscript: CI JOG. Contributed to the writing of the manuscript: CI FT NO JOG JL CR MLN FD. Enrolled patients: CI NO. Agree with the manuscript’s results and conclusions: CI FT RT NO JOG JL CR MLN FD. All authors have read, and confirm that they meet, ICMJE criteria for authorship.

                ‡ These authors are joint senior authors on this work.

                ¶ Membership of the ANRS 12249 TasP trial group is provided in the Acknowledgments.

                Author information
                http://orcid.org/0000-0001-7097-700X
                http://orcid.org/0000-0002-1614-8857
                Article
                PMEDICINE-D-15-03328
                10.1371/journal.pmed.1002107
                4978506
                27504637
                ecbcc45d-247b-4a0c-9eb4-c72da154d25c
                © 2016 Iwuji et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 5 November 2015
                : 28 June 2016
                Page count
                Figures: 2, Tables: 3, Pages: 18
                Funding
                Funded by: The French National Agency for Aids and Viral Hepatitis Research (ANRS)
                Award ID: 12249
                Funded by: Deutsche Gesellschaft für Internationale Zusammenarbeit (GIZ) GmbH
                Award ID: 81151938
                Funded by: International Initiative for Impact Evaluation
                Funded by: funder-id http://dx.doi.org/10.13039/100004334, Merck;
                Funded by: funder-id http://dx.doi.org/10.13039/100005564, Gilead Sciences;
                Funded by: funder-id http://dx.doi.org/10.13039/100004440, Wellcome Trust;
                Award ID: 097410/Z/11/Z
                The French National Agency for Aids and Viral Hepatitis Research (ANRS) is the sponsor and co-funder of the trial; http://www.anrs.fr (ANRS 12249). The study received additional support from the Deutsche Gesellschaft für Internationale Zusammenarbeit (GIZ) GmbH; https://www.giz.de/en/html/index.html (81151938). The research was also co-funded by the International Initiative for Impact Evaluation, Inc. (3ie), a grantee of the Bill & Melinda Gates Foundation; http://www.3ieimpact.org. The trial is conducted with the support of Merck & Co. Inc. and Gilead Sciences that provided the Atripla drug supply. The Africa Centre for Population Health receives core funding from the Wellcome Trust, which provides the platform for the population- and clinic-based research at the Centre; https://wellcome.ac.uk (097410/Z/11/Z). CR is a representative of the ANRS and contributed to the design, interpretation, and writing of the manuscript.
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                Custom metadata
                Data can be accessed through the URL https://data.africacentre.ac.za following registration and completion of a data access agreement. In addition, there is a contractual obligation on the part of the Africa Centre for Population Health as agreed with the trial sponsor and the funders to place the project data in the public domain through a data repository for scientific purposes one year after the main publication of the full trial results on HIV incidence.

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