Melanie Thompson, MD AIDS Research Consortium of Atlanta

Simoni, et.al. Topics in HIV Medicine, 2003

 Drug levels were a strong correlate of protection (OR 12.9, p<0.001) ◦ 92% reduction in risk with adequate drug levels

 To improve treatment outcomes through evidence-based recommendations for ◦ Maximizing treatment adherence ◦ Optimizing entry into and retention in care

 How much is enough? ◦ Early studies found 90-95% adherence needed to maintain viral suppression 1 ◦ Different regimens may require different thresholds of adherence for success 2  How is adherence measured and monitored? ◦ Multiple modalities for measurement ◦ No “gold standard” for measurement or monitoring  How can adherence be improved? ◦ Multiple levels for intervention: structural, behavioral, ART regimen, challenges on of special situations (e.g. homelessness, co-morbidities) 1 Patterson, AIDS, 2000; 2 Maggiolo, CID, 2005

Gardner et al. Clin Infect Dis 2011;52. 19% VL<50 c/mL

 NO BRAINER #1: If you can’t access care, you cannot access ART – so adherence is irrelevant  Timely entry into care is hampered by late diagnosis…in the USA

 Not being diagnosed  Stigma, fear of discrimination  Cost: time off work, visit and med costs  Distrust in health care system  Multiple “hurdles” to enter a clinic or practice ◦ Residency requirements ◦ Adequate documentation of residence or citizenship ◦ Distance from home or job ◦ Ability to take off time from work  Other competing “life events”: no time for HIV

 NO BRAINER #2: Continuous access to care is necessary for access to ART  Structural barriers to continuous care ◦ Clinic location, hours, rules ◦ Patient’s job, childcare requirements ◦ Cost for visit and medication (including “co-pay”)  Individual barriers ◦ Competing life factors: housing, food, childcare ◦ Co-morbidities: substance abuse, depression, concurrent diseases requiring subspecialist care ◦ Poverty and chaos

 “The empiric data necessary to make strong recommendations regarding the most efficacious way to improve ART adherence are currently lacking.”  “In response to this dearth…a common response from experts has been to recommend strategies based on  methodologically limited data  research from adherence in other fields  empirically demonstrated correlates of adherence  clinical experience Simoni et al. Topics in HIV Medicine 2003:11(6)

 Treatment adherence guidelines have never before been created; research is of varied quality  The science of treatment adherence is cross- cutting, including virology, pharmacology, behavioral science, sociology, technology, and health care implementation and delivery  Entry into and retention in care are an essential component of antiretroviral treatment success, but are complex and have not been well studied

 Treatment adherence strategies are contextual and may have different outcomes depending on populations and health care settings  Attempt to make global recommendations requires recognition of structural and cultural challenges as well as resource limitations

 Funding by IAPAC and the US NIH Office of AIDS Research  Invitation of international leaders in antiretroviral therapy and treatment adherence to convene an expert panel  Creation of draft outline  Appointment of section and topic leaders

 Decisions about appropriate methodology  Decisions regarding recommendations (consensus)  Drafting of document  Publication of guidelines document  Publication of implementation materials as “tool kit”

 Systematic literature review ◦ Collaboration with CDC’s Prevention Research Synthesis including 45,000 citations between 1996 and 5/2011 ◦ Development of literature review strategy  Scope of review: 1996 was beginning of access to HAART  Sources of literature  Inclusion criteria and key words

 Evidence grading process o Hybrid system using selected elements of GRADE o Literature quality scoring by 2 independent consultants o Panel ultimately responsible for assigning grade  Generation of recommendations by consensus ◦ Strength of recommendation assigned by panel ◦ Justification of recommendations based upon evidence

 Background & Rationale: Jean Nachega & Melanie Thompson  Methodology: Larry Chang  Monitoring and Measurement of Adherence: Robert Gross  Interventions to Promote Adherence: Michael Mugavero  Special Topics: Victoria Cargill  Issues Specific To Resource-limited Settings: Catherine Orrell

 Interventions to Promote Adherence ◦ Entry into and retention in care: John Bartlett ◦ Antiretroviral treatment strategies: Michael Mugavero ◦ Behavioral interventions: K. Rivet Amico ◦ Structural interventions: Chris Gordon ◦ Adherence tools: Jim Scott

 Special Topics Affecting Adherence ◦ Substance use: Rick Altice ◦ Concurrent medical conditions: Princy Kumar ◦ Homelessness: David Bangsberg ◦ Mental health: Michael Stirrett ◦ Incarceration: Curt Beckwith ◦ Children and adolescents: Adele Webb ◦ Pregnancy: Jean Nachega

Frederick Altice, MDBernard Hirschel, MDCatherine Orrell, MD K. Rivet Amico, PhDCharles Holmes, MDCelso Ramos-Filho MD David Bangsberg, MDTim HornRobert Remien, PhD Magda Barini-Garcia, MDShoshana Kahana, PhDJames Scott, Pharm D John Bartlett, MDPeter Kilmarx, MDJane Simoni, MD Curt Beckwith, MDPrincy Kumar, MDKimberly Smith, MD Victoria Cargill, MDCindy Lyles, PhDMichael Stirratt, PhD Larry Chang, MDRafael Mazin, MDMelanie Thompson, MD Vanessa Elharrar, MDHenry Masur, MDEvelyn Tomaszewski, MSW Tia Frazier, RNMichael Mugavero, MDMarco Vitoria, MD Christopher Gordon, PhDPeter Mugyenyi, MDAdele Webb, MD Robert Gross, MDJean Nachega, MD

Dec 2010: Formative Meeting Jan 2011: First Panel Meeting: draft outline, writing teams Feb-Apr 2011: Define Methodology Apr-July 2011: Literature Review and Evidence Grading July-Sept 2011: Drafting of Manuscript Publication!

 IAPAC: Jose Zuniga PhD, Angela Knudson  CDC Prevention Research Synthesis Project: Cindy Lyles PhD  Literature Review and Evidence Grading: Jennifer Johnsen MD MPH, Laura Bernard MPH, Kathryn Muessig MPH  Funding: US National Institutes of Health, Office of AIDS Research