Adherence to ARV Treatment and Prevention to End AIDS

Transcription

1 Adherence to ARV Treatment and Prevention to End AIDS David Bangsberg, MD, MPH Director Massachusetts General Hospital Center for Global Health Associate Professor Harvard Medical School Visiting Professor Mbarara University of Science and Technology November, 2011

2

3 [In sub-saharan Africa].the potential short term gains from reducing individual morbidity and mortality may be far outweighed by the potential for the long term spread of drug resistance. In Africa, a higher proportion of patients are likely to fall into the category of potential poor adherers unless resource intensive adherence programmes are available. Antiretroviral therapy in Africa Warren Stevens, Steve Kaye, Tumani Corrah BMJ 2004;328:

4 Bell-shaped Adherence and Resistance Curve Increasing probability of selecting mutation Inadequate Drug Pressure To Select Resistant Virus Drug Pressure Selects Resistant Virus Increasing Adherence

5 Bangsberg et al J. Antimicrob Chem; (5): Resistance Risk by Adherence and Regimen Class

6 A Single Tablet Regimen is Associated with Higher Adherence and Viral Suppression than Multiple Tablet Regimens in Homeless and Marginally Housed Individuals. Bangsberg et al AIDS Mean Aherence Proportion VL< '0-49' '50-<75' '75-<80' '80-<90' '90-100' Month FDC EFV/TDF/FTC NNRTI PI RPI Adherence Category FDC EFV/TDF/FTCF r-pi Unannounced pill count adherence STR 86% vs other 73% p=0.001 Proportion VL<400 c/ml STR 69% vs other 47% p=0.034

7 Meta-Analysis of Barriers to Adherence in Africa and North America Mills et al JAMA 2006:296: Systematic review of adherence 28,689 patients in 228 studies North America Brazil, Uganda, Cote d Ivoire, South Africa, Malawi, Bostwana, Costa Rica, Romania Resource-Rich Country 54.7% (95CI: %) Resource-Poor Country 77.1% (95CI:67.3%-85.6%)

8

9 A Social Model of Adherence for sub-saharan Africa Ware et al PLoS Medicine 2009 Improving Health

10 A Social Model of Adherence for sub-saharan Africa Ware et al PLoS Medicine 2009 Improving Health Resource Scarcity Resource Scarcity

11 A Social Model of Adherence for sub-saharan Africa Ware et al PLoS Medicine 2009 Improving Health Resource Scarcity Relationships as resources to overcome economic obstacles to adherence Social Capital Adherence fulfills responsibility to helpers and preserve relationships as a resource Resource Scarcity

12 A Social Model of Adherence for sub-saharan Africa Ware et al PLoS Medicine 2009 Improving Health Resource Scarcity Relationships as resources to overcome economic obstacles to adherence Social Capital Adherence fulfills responsibility to helpers and preserve relationships as a resource Resource Scarcity

13 A Social Model of Adherence for sub-saharan Africa Ware et al PLoS Medicine 2009 Improving Health Resource Scarcity Relationships as resources to overcome economic obstacles to adherence Social Capital Adherence fulfills responsibility to helpers and preserve relationships as a resource Resource Scarcity

14 Modest Decline in Adherence Over Time in Uganda Byakika-Tusiime et al. AIDS Behavior participants on ART for 2-42 months Unannounced pill count adherence 98.3% Declinining adherence: Each month 0.93 odds of sustaining >95% adherence (p =.003)

15 Structural and Economic Barriers to Adherence Transportation Tuller et al AIDS and Beh 2009 Hardon et al AIDS Care 2007 Rosen et al S.African Med J 2007 Food insecurity Tsai et al Soc Sci Med 2011 Weiser et al AIDS 2011 Weiser PLoS One 2010 Tuller et al PLoS One 2010 Miller el al Aids and Behavior 2010 Weiser JAIDS 2009

16 Frequency and Duration of Treatment Interruptions >48hrs over 24 weeks Oyugi et al AIDS 2007 Interruptions > 48 hours 199 interruptions 62 people (64%) Mean # interruptions/person 2.0 ±2.9 (S.D) Mean duration (days) for those who have interruptions 11.5 ±9.2 (S.D) Interruptions account for 90% of all missed doses

17 Duration of MEMS Defined Treatment Interruption and Probability of NNRTI Virologic Failure Parienti et al PLoS One 2008 n=72 Estimated probability of viral control + Controls O Cases Estimated 95% confidence interval Longer interval of treatment discontinuation in days

18 Real-time Adherence Monitoring Haberer et al AIDS and Behavior 2010 Wisepill Adherence Monitor

19 Real-time Adherence Monitoring Haberer et al AIDS and Behavior 2010

20 Real-time Adherence Monitoring Haberer et al AIDS and Behavior 2010

21 Weekly Short Message Service Reminders Improve Adherence in Kenya Lester et al. Lancet 2010 How are you? N=528 SMS Control p Self-reported adherence >95% Viral suppression <400 copies/ml 62% 50% % 48%.04 Pop-Eleches et al. AIDS 2011 This is your reminder N=431 Weekly Daily Control Proportion >90% MEMS adherent 63% p=.01 50% p=.92 47%

22 Treatment as Prevention Dose response: HIV RNA-transmission Quinn et al NEJM 2000 Comprehensive HIV testing and treatment may bring Ro <1 Granich et al Lancet 2009 ART 92% reduction in transmission Donnell et al Lancet 2010 ART 96% reduction in transmission Cohen NEJM 2012

23 Treatment as Prevention Challenges Can we get everyone tested, treated, and retained? Geng Jama 2008, Gardner CID 2011; Bassett JAIDS 2009, AIDS 2010; Katz AIDS 2010; Rosen PLoS Med 2011 Will healthy people adhere as well as ill people? Will adherence be sustained? Tusiime AIDS Beh 2009 Can health systems expand access under fiscal constraints Geng PLoS One 2011

24 At Front Lines, AIDS War Is Falling Apart Donald McNeil Jr, May 9, 2010 Dinavance Kamukama, 28, front right, with her cousins in Kampala, Uganda. She is on a waiting list for AIDS medication.

25 Diminishing Availability of Publicly Funded Slots for Antiretroviral Initiation Among ART-eligible HIV-infected Patients in Uganda Geng et al PLoS One 2010 Weekly Number of Patients Starting ART by Stakeholder Frequency apr jul oct jan apr2010 PEPFAR Global Fund-MOH FTF

26 Decrease in Multinational Funding Slots Delays Time to ART Start Geng et al PLoS One 2010

27 Pre-exposure Prophylaxis: ARV in HIV negatives to Prevent HIV Acquisition Partners TDF2 Caprisa 004 IPREX Fem-PREP Voice MTN-003 (oral tenofovir) 62-73% reduction 63% reduction 39% reduction 44% reduction 0% reduction 0% reduction

28 CAPRISA 004: Adherence is critical for efficacy against HIV High (>80% gel adherence) n=336 (38%) 54% efficacy Intermediate (50-80% adherence) n=181 (20%) 38% efficacy Low (<50% gel adherence) n=367 (42%) 28% efficacy Abdool Karim et al, Science 2010

29 HIV Biomedical Prevention Studies Study Population Adherence Diaphragm and gel High risk women 49% self report West Africa TNF Female sex workers 60% clinic pill count Tanzania Acyclovir High-risk women 50% took 90% Caprisa High-risk women 72% applicator count IPREX MSM <50% detectable drug level Fem-PREP/Voice High-risk women Unknown Partners in Prevention Acyclovir Stable discordant couples 80% reported >90% Partners PREP Stable discordant couples % electronic monitoring and unannounced pill count

30 Excellent Adherence PrEP Adherence Explained by Relationship Dynamics Ware et al IAPAC 2011 PrEP Resolves Tension in a Committed HIV Discordant Sexual Relationship Discordance dilemma PREP adherence is opportunity to mitigate tension and strengthen relationship

31 Excellent Adherence PrEP Adherence Explained by Relationship Dynamics Ware et al IAPAC 2011 PrEP Resolves Tension in a Committed HIV Discordant Sexual Relationship Discordance dilemma Love PREP adherence is opportunity to mitigate tension and strengthen relationship

32 Corollary: Relationship Discord Threatens PrEP Adherence Ware et al (IAPAC2010) PrEP Can Create Tension in a Previously Committed HIV Discordant Sexual Relationship PREP is a reminder of discordance dilemma in setting of mistrust or threat to the relationship Discord and Distrust PREP nonadherence becomes mechanism to express discord

33 PrEP Adherence During Relationship Discord and Distrust Courtesy of Fran Priddy IAVI

34 Africans don t know what Western time is, and do not know what you are talking about, when asked to take drugs at specific times. Andrew Natsios USAID Administrator

35 How to Take ARVs on Time in Rural Uganda Without a Watch: John s Adherence Story Maier et al PLOS 2006 No education Works as a farmer. Lives with his brother, sister-in-law, and three nieces in a three room mud-walled house without electricity. Owns a lantern, bed, sofa, bike, and a radio, but no watch. HIV in April 2005 and started generic D4T/3TC/NVP (Triomune) after disseminated herpes zoster and Kaposi s sarcoma CD4 count of 151

36

37 Electronic medication monitor record of time of bottle openings for am and pm doses.

38 Adherence 90% of doses within 10 minutes of 7:20 90% of doses within 17 minutes of 7:20 pm Overall adherence 98.9%

39

40 John s Adherence: 0-9 and months Initial MEMS assessment (August 2005 to April 2006 (9 months)) Subsequent MEMS assessment (May 2006 to January 2007 (9 months))

41 Conclusions Adherence-resistance relationships are regimen specific and dynamic; patterns matter Simpler and more potent regimens associated with favorable outcomes ARV adherence in sub-saharan Africa is excellent Fragile balance of social capital to overcome routine structural and economic barriers to care. Return of treatment ARV waitlists will have an unpredictable impact on adherence ARV prevention will depend on adherence in a poorly understood context

42 Acknowledgements Andrew Moss, PhD Tom Coates, PhD Bruce Walker, MD Jessica Haberer, MD, MS Peter Hunt, MD Jeff Martin, MD Conrad Muzoora, MMED Anna Baylor, MD Steven Deeks, MD Mwbesa Bwana, MD Isaac Kigorzi, MD Norma Ware, PhD Richard Harrigan, PhD Lloyd Marshall UCSF UCLA MGH/Harvard MGH/Harvard UCSF UCSF Mbarara University of Science and Technology MGH UCSF Mbarara University of Science and Technology Mbarara University of Science and Technology Harvard Medical School University of British Columbia Wisepill, Cape Town Funding Mark and Lisa Schwartz Foundation NIMH RO ; Michael Stirratt, PhD and Chris Gordon, PhD