1. IMPLEMENTING CLINICAL RECOMMENDATIONS: ART STRATEGIES, TOOLS, AND HEALTHY SYSTEMS/SERVICE DELIVERY RECOMMENDATIONS 11-14: ADHERENCE John G. Bartlett Johns Hopkins University School of Medicine May 2012www.iapac.org

2. THE CONTINUUM OF HIV CARE -- US MMWR (60), 2011 Of all with HIV infection, 850,000 individuals do not have suppressed HIV RNA (72%) 100% 75% 50% 25% 80% 77% 66% 89% 77%

3. Among regimens of similar efficacy and tolerability, once-daily regimens are recommended for treatment-naive patients beginning ART (II B). Switching treatment-experienced patients receiving complex or poorly tolerated regimens to once-daily regimens is recommended, given regimens with equivalent efficacy (III B). Among regimens of equal efficacy and safety, fixed-dose combinations are recommended to decrease pill burden (III B). ART STRATEGIES

4. Reminder devices and use of communication technologies with an interactive component are recommended (I B). Education and counseling using specific adherence-related tools is recommended (I A). ADHERENCE TOOLS FOR PATIENTS

5. EDUCATION AND COUNSELING INTERVENTIONS Individual one-on-one ART education is recommended (II A). Providing one-on-one adherence support to patients through 1 or more adherence counseling approaches is recommended (II A). Group education and group counseling are recommended; however, the type of group format, content, and implementation cannot be specified on the basis of the currently available evidence (II C). Multidisciplinary education and counseling intervention approaches are recommended (III B). Offering peer support may be considered (III C).

6. THE NON-VALUE OF PILL COUNTS: FEM-PrEP (Van Damme. NEJM 2012) Trial: Randomized, double-blind placebo-controlled trial in 2,120 HIV negative women in South Africa. Results Placebo TDF/FTC n=1,058 n=1,062 Adherence report 95% 95% Pill counts 88%88% TDF levels >10 ng/mL Failure -----15% No failure -----24%

7. WHAT TO START Guideline Backbone3 rd Drug DHHS, IAS-USA TDF/FTCEFV, RAL, BritishATV/r, DRV/r European TDF/FTCEFV, NVP ABC/3TCATF/r DRV/r LPV/r, RAL WHO TDF/3TCEFV, NVP AZT/3TC

8. ART REGIMEN: REGIMEN SELECTION Goal: NDV, avoid resistance, ADR Factors in the decision: Baseline resistance test Co-morbidities: Core, Renal, HBC, Pregnancy, Psychological issues Potency: Undefeated regimens Urgency: Pregnancy, HIVAN, AIDS, Primary HIV Resistance to resistance: FOTO (EFV) and PI/r Cost and coverage

9. WHAT TO START: PILL BURDEN Regimen x/d Pills EFV/TDF/FTC* 1 1 ATV/r/2 NRTIs 13 DRV/r/2 NRTIs 1 4 RAL/2 NRTIs 2 3 *RPV/TDF/FTC

10. Study 236-102: ATRIPLA VS. QUAD IN TREATMENT-NAÏVE (N=700): HIV-1 RNA < 50 copies/mL (Sax P. 2012 CROI. Abstr. 101) +3.6%, 95% CI 3.6 (-1.6% to +8.8%) CD4+ change: Quad + 239 vs. EFV +206 c/mm 3 (p=0.009) Sax P, et al. 19th CROI; Seattle, WA; March 5-8, 2012. Abst. 101.

11. COST OF CARE Contemporary costs/yr. (AIDS 2010;24:2705) HAART $12,000 (72%) Meds (other) $ 2,100 In-patient $ 600 Out-patient $ 400 Total (Meds) $ 16,600 Growth: 40,000/yr survival + T&T all: $800 million

12. 12 US PATENT EXPIRATIONS DLV SQV RTV IDV AZT ddI d4TABC3TC ddCTDF AZT/3TC NVP AZT/3TC/ABC ABC/3TC NFV 05 07 06 08 09 10 11 12 13 14 15 16 17 18 ATV 19 20 21 22 23 TDF/FTC VVC* (SP) LPV/RTV tabs MVC TPV DRV LPV/ RTV caps ETR RPV EFV RAL 2022-5 EVG RTV boosting GS7340 = 2025 CVC= 2023+ 12

13. FREQUENCY OF RESISTANCE MUTATIONS WITH VIROLOGIC FAILURE ClassTrialsResistance mutations PI/r7 1/255 (0.4%) NNRTI369/213 (32%) II268/102 (67%) CCR51113/29 (45%)

14. DHHS GUIDELINES 2012 VLCD4 Pre ART3-6 mos. 3-6 mos. StartBaselineBaseline 2-8 wks*----------- On ART3-6 mos.3-12 mos. *week VL (log 10 c/mL 1-0.75-1 4 1.5-2 8-16<500 24-48<50

15. P4P4P: THE STATUS OF PAYING PATIENTS FOR SELF CARE Practice: Widespread and international Incentives: Cash, groceries, lottery tickets, meal tickets. Conditions: Chronic – smoking, obesity, BP control, diabetes, HIV HIV trial: HPTN 65 – Controlled trial, (unblinded) HIV test – $25, Enroll in care – $70, NDV – $280/yr (1.7% of HIV care cost) Status: Widely practiced, no one wants to talk about it.

16. A TEST OF FINANCIAL INCENTIVES TO IMPROVE WARFARIN ADHERENCE (VOLPP KG. BMC HEALTH SYS RES 2008;8:272)

17. THE POWER OF HOPE (Harris J, De Angelis. JAMA 2012;300:2912) “With a deeper understanding of the science of care, physicians will increasingly realize that a meaningful patient-physician relationship leaves each patient better able to adhere to the treatment plan.”

18. HEALTHCARE OUTCOMES IN HIV: REDUCING DISPARITIES (MOORE R. CID; IN PRESS) Issue: Major issue in HIV care is retention in care and adherence Method: Moore Clinic data 1995-2010 N=6,366 Pt/yrs 27,941 Demographics: B – 77%, F – 34% Risk: IDU-45%; MSM – 30% Insurance: Private – 15% Results: Calculated life expectancy at age 28 yrs = 73.4 yrs for all groups – race, gender and risk

19. HEALTHCARE OUTCOMES IN HIV: REDUCING DISPARITIES (MOORE R. CID; IN PRESS) Issue: Major issue in HIV care is retention in care and adherence Method: Moore Clinic data 1995-2010 N=6,366 Pt/yrs 27,941 Demographics: B – 77%, F – 34% Risk: IDU-45%; MSM – 30% Insurance: Private – 15% Results: Calculated life expectancy at age 28 yrs = 73.4 yrs for all groups – race, gender and risk

20. VL FOR 3 HIV RISK CATEGORIES OVER TIME (MOORE RD. CID 2012; IN PRESS)

21. ART ADHERENCE IAPAC GUIDANCE: Scientifically validated systematic approaches Regimen selection: Drugs that will work (science) Drugs patients will take (art) Factors to consider: Documentation metric: VL Impact of patent expiration Cost-support services P4P4P Clinic viral load