International HIV Antiretroviral Adherence, Resistance and Survival (UARTO)

• ClinicalTrials.gov Identifier: NCT01596322
• Recruitment Status: Completed
• First Posted: May 11, 2012
• Last Update Posted: October 31, 2017
• Sponsor: Massachusetts General Hospital
• Collaborators: University of California, San Francisco; Department of Health and Human Services; Mbarara University of Science and Technology; University of British Columbia; Dana-Farber Cancer Institute
• Information provided by (Responsible Party): Jessica Haberer, MD, Massachusetts General Hospital

Study Description

Brief Summary:

Real-time Wireless Adherence Monitoring to HIV Antiretroviral Therapy in Rural Uganda.

Condition or disease
HIV/AIDS

Detailed Description:

The investigators will study use a novel method of real-time wireless adherence monitoring in one of the best established multi-disciplinary HIV antiretroviral treatment cohorts in rural Africa. The investigators will advance our theoretical understanding of HIV antiretroviral adherence behavior, HIV pathogenesis, and to address the monitoring and prevention of HIV antiretroviral treatment failure. Based on a successful pilot study in rural Uganda and favorable cost-effective estimates, the investigators will deploy the Wisepill real-time wireless adherence monitoring system to objectively monitor adherence in real time. The investigators will determine to what extent social capital mitigates economic barriers to long-term adherence and determine if the pervasive impact of stigma on adherence operates through social capital (Aim 1). The investigators will determine the relationship between missed doses, low-level viremia (between 1 and 50 copies RNA/mL), inflammation, bacterial translocation, suboptimal CD4 response, and mortality (Aim 2). Finally, The investigators will examine the relationship between complex adherence patterns and viral failure to both inform selective viral load monitoring and to lay the foundation for the first-of-kind intervention to prevent viral failure after missed doses, but before viral rebound (Aim 3). The investigators will secure behavioral and biologic data over nine years of potential treatment by recruiting 500 additional people to our existing cohort in Mbarara, Uganda for a total of 750 participants.

Study Design

• Study Type: Observational
• Actual Enrollment: 750 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Novel Approaches to Monitoring and Utilizing Adherence to HIV Therapy in Uganda
• Actual Study Start Date: September 2004
• Actual Primary Completion Date: September 2015
• Actual Study Completion Date: September 2015

Groups and Cohorts

Group/Cohort
UARTO

Outcome Measures

Primary Outcome Measures :

1. Adherence to antiretroviral therapy [ Time Frame: real time (up to 7 years) ]
   Adherence is assessed through a medication event monitoring system which records every time the device is opened (e.g. for pill taking). Before June 2012, this data was stored on the device and downloaded monthly. After June 2012, this data is transmitted through cellular networks to a central server in real time.

Secondary Outcome Measures :

1. Correlates of adherence to antiretroviral therapy [ Time Frame: every four months ]
   Questionnaires are administered to participants regarding factors such as depression, stigma, food insecurity, reproductive health, and economic status.
2. Biological consequences of adherence (or incomplete adherence) [ Time Frame: every four months and during adherence interruptions ]
   Specimens are collected for immunologic and genetic testing at baseline and every four months, as well as during interruptions in adherence as detected by the real time adherence monitoring system.
3. Adherence to antiretroviral therapy by self report [ Time Frame: every four months ]
   Participants report their adherence over the previous 3 and 28 days by doses missed and visual analog scale.

Biospecimen Retention:   Samples With DNA

plasma, buffy coat, saliva

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Probability Sample

Study Population

HIV positive adults 18 years and older, who are ART naive and initiating ART at either Mbarara HIV clinic or Mulago HIV clinic in Uganda

Criteria

Inclusion Criteria:

• HIV positive patients over 18 years
• ART naive and initiating therapy at the Mbarara Immune Suppression Syndrome (ISS) Clinic
• Live within 60 kilometers of the clinic
• Women who have received a single dose of nevirapine for prevention of mother to child transmission, but have not received other ART, will be included

Exclusion Criteria:

• Patients who do initiate therapy during the course of the study recruitment
• Patients who decline or are unable to give consent

Contacts and Locations

Locations

Uganda

Mbarara ISS Clinic, Mulago HIV Clinic

Mbarara, Uganda

Sponsors and Collaborators

Massachusetts General Hospital

University of California, San Francisco

Department of Health and Human Services

Mbarara University of Science and Technology

University of British Columbia

Dana-Farber Cancer Institute

Investigators

• Principal Investigator: Jessica Haberer, MD; Massachusetts General Hospital

More Information

Publications of Results:

Altice FL, Friedland GH. The era of adherence to HIV therapy. Ann Intern Med. 1998 Sep 15;129(6):503-5. doi: 10.7326/0003-4819-129-6-199809150-00015. No abstract available.

Friedland GH, Williams A. Attaining higher goals in HIV treatment: the central importance of adherence. AIDS. 1999 Sep;13 Suppl 1:S61-72.

Sontag D, Richardson L. Doctors withhold H.I.V. pill regimen from some. N Y Times Web. 1997 Mar 2:1, 35. No abstract available.

Tchetgen E, Kaplan EH, Friedland GH. Public health consequences of screening patients for adherence to highly active antiretroviral therapy. J Acquir Immune Defic Syndr. 2001 Feb 1;26(2):118-29. doi: 10.1097/00042560-200102010-00003.

Wainberg MA, Friedland G. Public health implications of antiretroviral therapy and HIV drug resistance. JAMA. 1998 Jun 24;279(24):1977-83. doi: 10.1001/jama.279.24.1977.

Harries AD, Nyangulu DS, Hargreaves NJ, Kaluwa O, Salaniponi FM. Preventing antiretroviral anarchy in sub-Saharan Africa. Lancet. 2001 Aug 4;358(9279):410-4. doi: 10.1016/s0140-6736(01)05551-9.

Popp D, Fisher JD. First, do no harm: a call for emphasizing adherence and HIV prevention interventions in active antiretroviral therapy programs in the developing world. AIDS. 2002 Mar 8;16(4):676-8. doi: 10.1097/00002030-200203080-00025. No abstract available.

UNAIDS. Report on the global HIV/AIDS epidemic. Geneva: UNAIDS, 2002

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Chang JL, Tsai AC, Musinguzi N, Haberer JE, Boum Y, Muzoora C, Bwana M, Martin JN, Hunt PW, Bangsberg DR, Siedner MJ. Depression and Suicidal Ideation Among HIV-Infected Adults Receiving Efavirenz Versus Nevirapine in Uganda: A Prospective Cohort Study. Ann Intern Med. 2018 Aug 7;169(3):146-155. doi: 10.7326/M17-2252. Epub 2018 Jun 26.

• Responsible Party: Jessica Haberer, MD, Associate Professor, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT01596322
• Other Study ID Numbers: UARTO, R01 MH054907
• First Posted: May 11, 2012
• Last Update Posted: October 31, 2017
• Last Verified: October 2017

Keywords provided by Jessica Haberer, MD, Massachusetts General Hospital:

HIV/AIDS in resource limited setting; HIV treatment outcomes in resource limited setting; Adherence to HIV treatment in resource limited setting; ART resistance in resource limited setting

Additional relevant MeSH terms:

Acquired Immunodeficiency Syndrome; HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Immunologic Deficiency Syndromes; Immune System Diseases