1. Determinants of long term adherence to antiretroviral drugs among adults followed over 54 months in Dakar (Senegal) M. Ciss 1, A. Desclaux 2, K. Diop 3, M.B. Fall 3 Laniece 4, B. Ndiaye 3, I. Ndoye 5, K. Sow 6 1. Laboratory of Drugs Control, Dakar, Senegal 2. Laboratory of Human Ecology and Anthropology, University of Aix-Marseille 3, Aix en Provence, France 3. Central Pharmacy of Fann National Hospital, Dakar, Senegal 4. French Cooperation / Multisectorial Aids Control Program, Dakar, Senegal 5. National Multisectorial Aids Control Program, Dakar, Senegal 6. Aids Control Division, Ministry of Health, Dakar, Senegal

2. Adherence in African resource limited settings Results of several recent studies : –levels of adherence comparable to those observed in industrialized countries may be achieved –but often compromised by the cost of antiretroviral therapies, identified as the first barrier to adherence Very few data on long term adherence to HAART in African context (longitudinal assessment)

3. Access to HAART in Senegal West African with a low and stable HIV prevalence Public Initiative launched in 1998 HAART delivered Patient’s financial participation for ART: –From 1998 to 2000: at least 35 US$ / month –From 2001 to 2003: ART delivered free of charge for those in need –Since December 2003: ART free for all

4. Assessment of adherence in the Senegalese Program Study objective -to assess adherence through a quantitative approach -to identify the main determinants of poor adherence Study design - a 54-month prospective observational cohort study conducted from November 1999 to April 2004

5. Study population and methods Study population : all the adult patients belonging to the first 180 enrolled patients and monitored medically at least 30 days beyond the 1st November of 1999. Methods : Individual interviews conducted by the pharmacist at each dispensation (every two months at least) based on a questionnaire Adherence level estimated over the last 30 days, on the patients’ stated consumption and on the proportion of the prescribed dose returned unused Estimation of adherence: stated number of tablets taken X 100 % number of tablets prescribed High adherence defined as a mean monthly adherence ≥ 95%

6. Results 167 eligible subjects Participation rate: 95% (n=159) 22 died (14%) and 7 withdrew (4%) over the 6820 patient-months of observation 5029 patient-months documented for adherence Median length of follow-up in the ART program: 23 months, IQR [13-36] 80 of the 159 patients were enrolled in clinical trials during 18 months (ANRS 12-04 and 12-06 studies)

7. Baseline patients’ characteristics Sex ratio 1,1:1 Mean age: 38 years CDC stage at D0: 6% stage A 40% stage B 54% stage C Mean viral load (log 10 ): 5.44 copies/ml Mean CD4 cell count: 160 / ml Antiretroviral naive patients: 93% Married patients: 44% Mean number of children per patient: 2.7 Never been to school: 33% of patients Unemployed patients: 40% Median monthly income: 25 US$ 43% of patients without any income

8. Prescribed ART therapies 8 available molecules : AZT, 3TC, DDI, D4T IDV, NFV EFZ, NVP Most current combinations over the 54 months of observation: –Dual therapies NRTI : 4.8% –Triple tritherapies with IDV : 38.7% or NFV : 2.9% –Triple therapies with EFZ : 50.1% or NVP : 3.5% Modifications of treatment among 29% of patients

9. Adherence estimation Mean monthly adherence : 90.2% (IQR : 96 -100%) among 159 patients over 54 months During 80% of the documented months, the stated adherence was 95% or over Probability of being “highly adherent” (95% of the doses or more stated as taken) : 0.78 with 95% CI (0.74 – 0.81)

10. Mean monthly adherence according to ARV therapy duration among 159 patients followed from November 1999 to April 2004.

11. Distribution of causes of prolonged treatment interruptions (>6 days) according to year of follow-up (N=159)

12. Main determinants of long term adherence Bio-clinical and sociological determinants studied using a logistic regression taking into account the correlation structure of the data (GEE population-averaged model)

13. High adherence determinants Univariate analysis (Wald p-value) Multivariate analysis Age at inclusion0.62not included Gender0.18not significant Clinical centre0.83not included Distance of residence (less than 50 km vs 50 km or more) 0.46not included Monthly patient revenues (at D0) Cat. : 0, ≤127 US$, >127 US$ 0.61not included

14. High adherence determinants Univariate analysis (p-value) Multivariate analysis CD4 categories at D0 (< 200 ; 200 to 349; ≥350) 0.02not significant log 10 viral load at D00.51not significant CDC disease stages at inclusion (A vs B or C) <10 -4 OR=0.41 95% CI [0.20-0.86] P=0.018 Antiretroviral therapy monthly cost (18 US$ or less vs more) 0.34OR=0.74 95% CI [0.55-0.99] P=0.046 Type of regimen (not PI- vs PI-containing) 0.012OR=0.46 95% CI [0.26-0.83] p<10 -2

15. High adherence determinants Univariate analysis (p-value) Multivariate analysis Treatment duration<10 -4 Among patients receiving not PI-containing regimen from M13 to M24 vs M1 to M12 OR=0.52 95% CI [0.37-0.74] p<10 -3 from M25 to M36 vs M1 to M12 OR=0.36 95% CI [0.25-0.74] p<10 -3 from M37 to M48 vs M1 to M12 OR=0.28 95% CI [0.17-0.51] p<10 -3 from M49 to M68 vs M1 to M12 OR=0.26 95% CI [0.16-0.42] p<10 -3

16. Main factors related to poor adherence Symptomatic HIV infection at D0 or before (CDC stage B ou C) Duration of treatment Cost of ART combination Protease inhibitor-containing regimen None of the socio-demographic charasteristics (age, gender, location of residence, level of revenues)

17. Conclusions High levels of stated adherence over a 4 year follow- up Strategies to reinforce adherence : –Treat early symptomatic people –Set up affordable prices for ART (free++) –Choose a simple and well tolerated ART combination as first-line regimen (for HIV-1 infected patients, PI seem less accepted than NNRTI) –Implement measures to reinforce adherence over time (individual therapeutic education/counselling, talk groups, home and hospital visits)

18. Collaborations and partnerships Fann National Hospital S. Ba, D. Ball, K. Diop, C. Fall, M.B. Keita Fall, B. Ndiaye, M. Ndiaye, O. Sylla, A. Thiam National Drugs Control Laboratory M. Ciss Aids Control Division, Ministry of Health K. Sow French Cooperation / PMLS / IRD UR 36 I. Lanièce Multisectorial Aids Control Program FL. Mbodj, I. Ndoye IRD UR 36 B. Taverne, J.F. Etard, E. Delaporte Aix-Marseille University - Laboratory of Human Ecology and Anthropology / IRD UR 36 A. Desclaux Fundings ANRS, IRD, PMLS, MAE, UE