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C Staehelin, O Keiser, A Calmy, R Weber, M Cavassini, L Elzi, P Schmid, E Bernasconi, H Furrer

Response to Antiretroviral Therapy in HIV Patients of Sub Saharan African Origin in the Swiss HIV Cohort Study. C Staehelin, O Keiser, A Calmy, R Weber, M Cavassini, L Elzi, P Schmid, E Bernasconi, H Furrer and the Swiss HIV Cohort Study Supported by the Swiss National Science Foundation.

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C Staehelin, O Keiser, A Calmy, R Weber, M Cavassini, L Elzi, P Schmid, E Bernasconi, H Furrer

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  1. Response to Antiretroviral Therapy in HIV Patients of Sub Saharan African Origin in the Swiss HIV Cohort Study C Staehelin, O Keiser, A Calmy, R Weber, M Cavassini, L Elzi, P Schmid, E Bernasconi, H Furrer and the Swiss HIV Cohort Study Supported by the Swiss National Science Foundation

  2. Background / Objective • Situation on cART • Response to cART • Time to undetectable RNA • Time to viral rebound • Increase in CD4 count • Mortality • Intent to stay on cART

  3. Sub-Saharan African (SSA) vs Northwest European Patients (NWE) 4376 3707 • Treatment naive starting triple ART • Exclusion if • - unboosted saquinavir • planned treatment interruption • structured treatment interruption, pregnancy • active iv drug use • Analysed: SSA 598; NWE 3109

  4. Total study participants: 3707 SSA NWE p - value (598, 16%) (3109, 84%) Female sex (64%) 384 700 (23%) <0.001 Presumed HIV transmission 541 heterosexual (90%) 1094 (35%) - MSM 9 (2%) 1445 (46%) - <0.001 ivdu 2 (0.3%) 447 (14%) - blood products 16 (3%) 23 (1%) - other/unknown 29 (5%) 91 (3%) - 39(34 -47) <0.001 23 (26-37) Age at start cART (yrs) CD4 at start cART 208 (96 - 332) 0.02 189 (107-284) 4.72 (3.9-5.2) Log HIV RNA at start cART 4.9 (4.2-5.4) <0.001 10 HBs Ag positive 64 (10.7 %) 141 (4. 5 %) <0.001 (3.3%) HCV serology positive 19 615 (20%) <0.001 AIDS at start ARV 22% 19% 0.14 Baseline Patient Characteristics

  5. Study participants: 3707 SSA NWE p - value (n= 598 ) (n=3109 ) Follow - up (yrs) after start cART 4.0 (1.9 - 6.7) 5.2 (2.2 - 8.8) <0.001 Initial therapy, total NRTI 3% 2% - PI based 34% 43% - <0.001 PI/r based 19% 26% - NNRTI based 42% 27% - Initial therapy n=424 n=1700 if cART start > 1999 NRTI 4% 3% - <0.001 PI based 19% 13% - PI/r based 22% 38% - - NNRTI based 54% 43% Follow-up Time and Treatment Regimens

  6. Study participants: 3707 SSA NWE p - value (n= 598) (n=3109) Discontinued 148 (25%) 653 (21%) 0.04 Reason for discontinuation - death 9% 36% - moved to foreign country 24% 8% <0.001 - withdrew from SHCS 22% 19% - no response to several invitations 41% 33% - other 4% 2% Discontinuation in SHCS

  7. 500 400 300 Increase in CD4 counts 200 100 0 p= 0.4 0.2 0.4 0.4 1 year 2 years 3 years 4 years 1 year 2 years 3 years 4 years SS Africa NW Europe CD4 increase

  8. Time to HIV RNA < 50c/ml Log rank p=0.16 1.00 0.75 0.50 0.25 0.00 0 6 12 18 24 30 36 analysis time (months) Number at risk NWE 3109 1258 586 414 324 267 231 SSA 598 201 115 84 72 57 48 NW Europe SS Africa Cox Regression Time to HIV RNA <50 c/ml Cox Regression Time to HIV RNA <50 SSA, p=0.2 SSA, p=0.2 CD4 CD4 cART cART start, p=0.3 start, p=0.3 Age 10 y Age 10 y increase increase , p=0.3 , p=0.3 Female sex Female sex , p=0.4 , p=0.4 Log HIV RNA at HIV RNA cART cART start, p<0.0001 start, p<0.0001 Per log 10 10 HCV HCV infection infection , p=0.02 , p=0.02 AIDS at AIDS at cART cART start, p=0.005 start, p=0.005 cART cART start start after after 1999, p<0.001 1999, p<0.001 .8 .8 .9 .9 1 1 1.1 1.1 1.2 1.2 1.4 1.4 1.6 1.6 1.8 1.8 Adjusted Adjusted HR HR Time to viral suppression(VL <50c/ml)

  9. Viral failure (RNA 2x >400 c/ml) Log-rank p=0.13 1.00 0.75 0.50 0.25 0.00 0 12 24 36 48 analysis time (months) Number at risk NWE 3109 2586 2078 1714 1371 SSA 598 495 380 274 196 NW Europe SS Africa Cox Regression Time to Cox Regression Time to viral failure viral failure (RNA 2x >400) SSA, p=0.07 SSA, p=0.7 CD4 CD4 cART cART start, p<0.001 start, p<0.001 Age 10y Age 10y increase increase , p=0.002 , p=0.002 Female sex Female sex , p=0.5 , p=0.5 Log10 HIV RNA Log10 HIV RNA cART cART start, p=0.07 start, p=0.07 HCV HCV infection infection , p=0.2 , p=0.2 AIDS at AIDS at cART cART start, p=0.06 start, p=0.06 cART cART start start after after 1999, p<0.001 1999, p<0.001 NNRTI NNRTI or boosted or boosted PI, p=0.01 PI, p=0.01 .6 .6 .7 .7 .8 .8 .9 .9 1 1 1.1 1.1 1.2 1.2 1.4 1.4 1.8 1.8 Adjusted Adjusted HR HR Time to viral failure(2x VL >400c/mL)Intent to stay on treatment

  10. Viral failure on cART Log-rank: p=0.001 1.00 0.75 0.50 0.25 0.00 0 12 24 36 48 analysis time (months) Number at risk NWE 3142 2250 1720 1352 1056 SSA 671 433 298 207 143 NW Europe SS Africa Cox Regression Cox Regression Viral failure Viral failure on on cART cART SSA, p<0.001 SSA, p<0.001 CD4 CD4 cART cART start, p<0.001 start, p<0.001 Age 10y Age 10y increase increase , p=0.01 , p=0.01 Female sex Female sex , p=0.02 , p=02 Log10 HIV RNA Log10 HIV RNA cART cART start, p=0.6 start, p=0.6 HCV HCV infection infection , p=0.4 , p=0.4 AIDS at AIDS at cART cART start, p=0.01 start, p=0.01 cART cART start start after after 1999, p<0.001 1999, p<0.001 Boosted Boosted PI PI or or NNRTI, p<0.001 NNRTI, p<0.001 .4 .4 .6 .6 .8 .8 .9 .9 1 1 1.2 1.2 1.4 1.4 1.8 1.8 2.4 2.4 Adjusted Adjusted HR HR Time to viral failure(2x VL >400c/mL)only on cART analysis

  11. Kaplan-Meier survival estimates Log-rank: p<0.001 1.00 0.75 0.50 0.25 NWE 0.00 SSA 0 1 2 3 4 5 6 7 8 9 10 analysis time (years) Number at risk NWE 3109 2746 2433 2176 1912 1654 1411 1227 976 705 378 SSA 598 529 455 382 310 256 193 137 89 57 17 SSA = NW Europe SSA = SS Africa Survival F - up (yrs) Deaths Mortality /100 py (95% CI) 17136.2 267 1.6 (1.4 - 1.8) 2715.9 15 0.5 (0.3 - 0.9) Cox Regression Mortality SSA, p=0.3 SSA, p=0.3 CD4 CD4 cART cART start, p=0.001 start, p=0.001 Age 10y Age 10y increase increase , p<0.001 , p<0.001 Female sex Female sex , p=0.3 , p=0.3 Log10 HIV RNA Log10 HIV RNA cART cART start, p=0.8 start, p=0.8 HCV HCV infection infection , p<0.001 , p<0.001 HBsAg HBsAg positive, p=0.003 positive, p=0.003 AIDS at AIDS at cART cART start, p=0.03 start, p=0.03 cART cART start start after after 1999, p=0.4 1999, p=0.4 NNRTI NNRTI or boosted or boosted PI, p=0.004 PI, p=0.004 .4 .4 .6 .6 .8 .8 .9 .9 1 1 1.2 1.2 1.6 1.6 2 2 2.4 2.4 3.2 3.2 4.2 4.2 Adjusted Adjusted HR HR

  12. Viral suppression CD4 recovery Survival Time to HIV RNA < 50 Log rank p=0.16 1.00 0.75 0.50 0.25 0.00 0 6 12 18 24 30 36 analysis time (months) Number at risk NWE 3109 1258 586 414 324 267 231 SSA 598 201 115 84 72 57 48 NW Europe SS Africa Viral failure Conclusions • Little evidence for inferior outcome to cART in SSA migrants HOWEVER • Higher loss to follow-up • Concern about longer-term stability of viral response

  13. Thank you for your attention twice twice The members of the Swiss HIV Cohort Study are M. Battegay, E. Bernasconi, J. Böni, HC Bucher, Ph. Bürgisser, A. Calmy, S. Cattacin, M. Cavassini, R. Dubs, M. Egger, L. Elzi, M. Fischer, M. Flepp, A. Fontana, P. Francioli (President of the SHCS), H. Furrer (Chairman of the Clinical and Laboratory Committee), C. Fux, M. Gorgievski, H. Günthard (Chairman of the Scientific Board), H. Hirsch, B. Hirschel, I. Hösli, Ch. Kahlert, L. Kaiser, U. Karrer, C. Kind, Th. Klimkait, B. Ledergerber, G. Martinetti, B. Martinez, N. Müller, D. Nadal, M. Opravil, F. Paccaud, G. Pantaleo, A. Rauch, S. Regenass, M. Rickenbach (Head of Data Center), C. Rudin (Chairman of the Mother & Child Substudy), P. Schmid, D. Schultze, J. Schüpbach, R. Speck, P. Taffé, A. Telenti, A. Trkola, P. Vernazza, R. Weber, S. Yerly.

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