Adapting and pilot testing an evidence-based ARV adherence intervention for China

1. Adapting and pilot testing an evidence-based ARV adherence intervention for China Ann B. Williams, Honghong Wang, Xianhong Li, Kris Fennie, Jane Burgess UCLA School of Nursing & Xiangya School of NursingLos Angeles, California, U.S.A. & Changsha, Hunan, China

2. HIV/AIDS Medication Adherence Challenges • Lifetime duration of treatment • Frequent (& serious) adverse drug effects • AIDS stigma

3. In order to achieve the optimal virologic, immunologic, and clinical outcomes possible with HAART, the level of adherence required is over 90%. (Bartlett, 2002; Paterson et al., 2000; Singh et al., 1999) This is the equivalent of missing 1 dose per month on a once-a-day regimen. Only 6% of patients report full adherence, with a mean level of 56% adherence. (Murphy et al., 2003) Adherence may be the variable determining HAART failure or success. (Knobel et al., 1999) While patients report a preference for once-a-day dosing, research suggests adherence rates are no better for QD dosing. (Stone et al., 2004) Adherence required… …and adherence achieved

4. Emerging Resistance PROBABILITY OF SELECTING FOR RESISTANT STRAINS MOST DANGEROUS PLACE: PARTIAL SUPPRESSION 0% 100% SUPPRESSION OF VIRAL REPLICATION

5. Viral Virulence Viral Resistance Effective drug potency PATIENTADHERENCE PRESERVATION OF IMMUNE FUNCTION AND DELAY IN DEISEASE PROGRESSION Rate of viral replication Intracellular drug concentration Host Factors Systemic drug concentration Pharmacokinetics

6. Background: ATHENA Intervention • A home-based adherence intervention delivered by a nurse and peer educator team. • Demonstrated efficacy in the northeastern U.S. in a randomized controlled trial.

7. Clinician Characteristics Patient Characteristics Regimen Characteristics Adherence Illness Characteristics

8. A focus limited to personal behavior change leads to a programmatic emphasis on individual responsibility for health, at the cost of an examination of individual response-ability, or the capacity of the individual for responding to his or her personal needs or the challenges posed by the environment. Meredith Minkler Health education, health promotion and the open society: An historical perspective. HEQ, 16: 17-30, 1989

9. Social Context Clinician Characteristics Patient Characteristics Regimen Characteristics Adherence Illness Characteristics

10. Intervention • Home visit by a peer counsellor and a nurse • Once a week, first 3 months • Bi-weekly, months 4-6 • Once a month, months 7-12 • Visits last 15 minutes to one hour

11. Results Selected characteristics of ATHENA participants at baseline* *These characteristics did not differ significantly between the intervention and control groups.

12. ResultsSubjects with ≥ 90% adherence 33 82 40% 24 64 38% 24 66 36% 19 60 32% 19 61 31% 16 44 36% 33 79 42% 18 68 27% 14 64 22% 14 60 23% 12 54 22% 9 37 24% A greater proportion of subjects in the intervention group had adherence greater than 90% at each time point compared to the control group. The difference over time is significant (Extended Mantel-Haenszel Test: 5.80, p=.02)

13. Summary Results • The intervention group maintained a higher proportion of subjects with adherence greater than 90% over time compared to the control group (p=.02). • A statistically significant intervention effect on viral load or CD4+ count was not seen. • There was an statistically signifcant association between >90% adherence and an undetectable viral load over time (p<.03).

14. Conclusions • Home visits from a nurse and peer counselor significantly improved medication adherence compared to usual care. • The proportion of individuals with medication adherence >90% was unacceptably low in both control and experimental groups.

15. ATHENA to Ai Sheng NuoReaching around the GlobeNurses working together to help patients take lifesaving medication

16. Purpose • To adapt the ATHENA intervention to the social and cultural context of Hunan Province • To conduct a pilot test of the adapted intervention

17. HIV/AIDS in Hunan Province • HIV/AIDS cases reported through 2010: 10,794 • Patients are: • Rural • Poor • High prevalence of IDU (40% of PLWHA)

18. HIV/AIDS in Hunan Province • Free treatment (ARVs) is available • Medication adherence is a challenge • Evidence-based interventions to support adherence are limited and were developed for use in different social, cultural, and economic environments.

19. Adaptation Framework • The ADAPT-ITT Model • 8 sequential steps • Qualitative and quantitative data

20. Step 1: Assessment • Cross sectional survey • 7 China CARES sites • 308 respondents • 20% reported <90% adherence • Associated with current heroin use

21. Step 1: Assessment • Qualitative data • Stigma • Family relationships and responsibility • Guilt

22. Step 2: Choosing ATHENA • Freirian philosophy • Well suited to Chinese culture • Emphasizes community context • Known in China Process Action Reflection Action

23. Administration Demonstrating the intervention Reviewing original manuals Consider applicability to Hunan context Production Identify core elements Peer educators Dialogue Reflection Produce plan for adaptation Emphasis on family Group activities Step 3 and 4

24. Step 5: Expert review • PLWHA, families, and HCWs reviewed proposed intervention • Concerns: Risk for disclosure & stigma

25. Step 6: IntegrationATHENA to Ai Sheng Nuo

26. Love, Life, Promise • Ai Sheng Nuo • Family emphasis • Decreased frequency of home visits • More structured patient education • Option for group activities

27. Step 7: Training & developing manual

28. Step 8: Pilot testingMethods • Randomized controlled pilot • July 2010 – August 2012 • Randomized to intervention or control • Intervention: Monthly visits and interim phone contact plus standard clinic support • Control: Standard clinic support

29. Study Sites: Hunan Province • 11th largest province of China, situated in the southeast. • Commercial sex work and injection drug use are highly prevalent. • Two clinical sites, in Hengyang City and Changsha. • Comprehensive evaluation and ARV when indicated. • However, mental health screening and treatment are not routinely available.

30. Pilot study: SubjectsEligibility • Living with HIV/AIDS • Attending one of the two clinical sites • Self-reporting adherence <90% to prescribed ARVs or to pre-ARV medications (TMP-SMX, multi vitamins)

31. Pilot study: Measures • A 7-day visual analogue scale • Social Support Rating Scale • Center for Epidemiological Studies Depression Scale (Chinese) • HIV/AIDS Related Stigma Scale.

32. Pilot study: Data collection • Data were collected in structured face-to-face interviews conducted at the time of a regularly scheduled clinical visit. • Information regarding ARV regimen, treatment duration, time of diagnosis, CD4 count and HIV-RNA from medical record review. • Baseline, 6 months, 12 months

33. Results: SubjectsN = 114 ARV status at baseline • 57 reporting <90% adherence to pre-ARV meds • 57 reporting <90% adherence to ARV Presumed HIV transmission routes • 36% IDU • 40% Heterosexual contact • 11% MTM sexual contact • 2% Transfusion • 11% Unclear

34. Results: Subjects Male: 82 (72%) Female: 32 (28%) Age < 30 32 (28%) 30 – 45 57 (50%) > 45 25 (22%) Married 59 (52%) High school or college 46 (40%) Stably Employed 32 (28%)

35. Results: Subjects • Past or current drug abuse 35 (31%) • Has disclosed HIV status 84 (75%) • 2 years or less since diagnosis 90 (82%) • CD4 <350 cells/mm3 87 (98%)

36. Results: Subjects • ARV regimens • AZT + 3TC + NVP or EFV • D4T + 3TC + NVP or EFV • AZT + LPV/r + 3TC • LPV/r + TDF + 3TC

37. Depressive symptoms at baseline • 66% scored 16 or greater on the CESD-C • Those in the ARV prep treatment stage were more likely to report significant depressive symptomatology than those for whom ARV had already been prescribed. (OR = 2.84, 95% CI 1.26, 6.38; p = 0.01)

38. Factors independently associated with depressive symptoms • History of drug use OR 4.10 (1.11, 15.15) p=.03 • High perception of stigma 1.06 (1.02, 1.09) p=.001 • Lack of stable employment 3.23 (1.01, 10.00) p=.05 • Lack of social support 1.10 (1.03, 1.19) p=.02

39. ResultsSubjects with > 90% adherence A greater proportion of subjects in the intervention group had adherence greater than 90% at both time points compared to the control group. The difference over time is significant (Extended Mantel-Haenszel Test: 8.8,p=.003)

40. Pilot Test • Biological measures: • No difference between groups: • Quantitative HIV-RNA • CD4 counts • Results of ARV resistance studies • No resistance at baseline by standard genotype • Ultra Deep Sequencing ongoing

41. Other findings • Adherence barriers identified: • Medication side effects • Fear of disclosure • Knowledge deficits • Poor family relationships

42. Conclusions • Structured approach facilitates adaptation of evidence based interventions. • In spite of significant cultural differences, adaptation is possible. • Key barriers to ARV adherence appear to be universal. • Strategies to improve adherence may differ somewhat, but home based interventions are effective.

43. Future Directions • Logistics: Mobile communication technology. • Content: address mental health issues, especially depression. • Cost of intervention.