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17 th CROI, San Francisco, 2010. Hotel AC, Barcelona – February 26 th 2010 17 th CROI, San Francisco, 2010. Hotel AC, Barcelona – February 26 th 2010 Dr.

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Presentation on theme: "17 th CROI, San Francisco, 2010. Hotel AC, Barcelona – February 26 th 2010 17 th CROI, San Francisco, 2010. Hotel AC, Barcelona – February 26 th 2010 Dr."— Presentation transcript:

1 17 th CROI, San Francisco, 2010. Hotel AC, Barcelona – February 26 th 2010 17 th CROI, San Francisco, 2010. Hotel AC, Barcelona – February 26 th 2010 Dr. José M. Miró Infectious Diseases Service - ICMiD Hospital Clinic - IDIBAPS University of Barcelona Barcelona (Spain) Dr. José M. Miró Infectious Diseases Service - ICMiD Hospital Clinic - IDIBAPS University of Barcelona Barcelona (Spain) Summary: Opportunistic Infections HCV/HBV Co-Infections & Tumors E-mail address: jmmiro@ub.edu

2  When to start cART  Tuberculosis  2009 Influenza A(H1N1)  Other opportunistic infections & IRIS  HCV & HBV co-infections  Tumors  When to start cART  Tuberculosis  2009 Influenza A(H1N1)  Other opportunistic infections & IRIS  HCV & HBV co-infections  Tumors OIs, Hepatitis Coinfections & Tumors

3 Immediate vs. Deferred cART in the Setting of Acute AIDS-Related OIs (ACTG A5164) Zolopa AR, et al. PLoS ONE. 2009;4(5):e5575. Study day Enrollment Opportunistic infections* Treatment Starts Opportunistic infections* Treatment Starts Immediate Arm Start ART Immediate Arm Start ART Deferred Arm Start ART Deferred Arm Start ART Recommended Start window Recommended Start window 48 wks 48 wks 48 wks 48 wks -14 0 0 2 2 28 42 84 224 Study schema 12 days vs. 45 days *TB excluded !!!

4 Results Through 48 Weeks No difference in primary endpoint of virologic suppression No difference in IRIS (10 immediate, 13 deferred) or need for ART changes Probability of surviving withoutdeath/new AIDS defining event Immediate ART Deferred ART Immediate ART Deferred ART 0 0 0.0 0.2 1.00 4 4 8 8 12 16 20 24 28 32 36 40 44 48 0.1 0.9 0.8 0.7 0.6 0.5 0.4 0.3 116 94 HR=0.53 99%CI (0.25,1.09) P=0.023 Early cART  less new AIDS events or death Months Immediate vs. Deferred cART in the Setting of Acute AIDS-Related OIs (ACTG A5164) Zolopa AR, et al. PLoS ONE. 2009;4(5):e5575.

5 CharacteristicsTotalImmediateDeferred CD4 (cells/mm 3 )Median (IQR)29 (10-55)31 (12-54)28 (10-56) HIV RNA (log10)Median (IQR) 5.07 (4.71-5.63) 5.07 (4.74-5.59) 5.08 (4.64-5.64) No Prior ARTN (%)259 (92)131 (93)128 (91) PCPN (%)177 (63) 88 (62)89 (63) BIN (%)34 (12) 17 (12) Other OIN (%)71 (25)36 (26)35 (25) Crypto / HistoN (%)45 (16)20 (14)25 (18) ToxoplasmosisN (%)13 (5)9 (6)4 (3) CMVN (%)6 (2)4 (3)2 (1) MACN (%)6 (2)3 (2) Multiple OI/BIw/in 30 days33%32%33% *TB excluded !!! Immediate vs. Deferred cART in the Setting of Acute AIDS-Related OIs (ACTG A5164) Zolopa AR, et al. PLoS ONE. 2009;4(5):e5575.

6 Retrospective multicohort study Retrospective multicohort study Hospital cohorts: Italy (6), Spain (1), UK (1) and Canada (1). Study population: Study population: All patients with an AIDS diagnosis between 30 days before and 14 days after HIV diagnosis, recruited between 1997 and 2004. Patients included in the study: 760 Retrospective multicohort study Retrospective multicohort study Hospital cohorts: Italy (6), Spain (1), UK (1) and Canada (1). Study population: Study population: All patients with an AIDS diagnosis between 30 days before and 14 days after HIV diagnosis, recruited between 1997 and 2004. Patients included in the study: 760 Patients Presenting With AIDS in the HAART Era: A Collaborative Cohort Analysis Mussini C et al. AIDS 2008, 22 : 2461–2469

7 P. jirovecii pneumonia (PCP) P. jirovecii pneumonia (PCP) Tuberculosis Tuberculosis Esophageal candidiasis Esophageal candidiasis CNS toxoplasmosis CNS toxoplasmosis CMV disease CMV disease Kaposi’s sarcoma Kaposi’s sarcoma NHL NHL Other Opportunistic Infections Other Opportunistic Infections P. jirovecii pneumonia (PCP) P. jirovecii pneumonia (PCP) Tuberculosis Tuberculosis Esophageal candidiasis Esophageal candidiasis CNS toxoplasmosis CNS toxoplasmosis CMV disease CMV disease Kaposi’s sarcoma Kaposi’s sarcoma NHL NHL Other Opportunistic Infections Other Opportunistic Infections 268 (35%) 168 (22%) 94 (12%) 65 (9%) 51 (7%) 65 (9%) 28 (4%) 115 (15%) 268 (35%) 168 (22%) 94 (12%) 65 (9%) 51 (7%) 65 (9%) 28 (4%) 115 (15%) Patients Presenting With AIDS in the HAART Era: A Collaborative Cohort Analysis Mussini C et al. AIDS 2008, 22 : 2461–2469

8 Survival outcomes and effect of early vs. deferred cART among HIV-1-infected patients diagnosed at the time of an AIDS-defining event in Europe and Canada: a collaborative cohort analysis (1997-2004) The objectives os this study were: 1) to analyze the clinical progression (new AIDS event or death) among persons diagnosed with HIV at the time of an AIDS- defining event (TB, PCP, other OI, KS or lymphoma); and, 2) to assess the impact on outcome of timing of cART initiation in these individuals. The objectives os this study were: 1) to analyze the clinical progression (new AIDS event or death) among persons diagnosed with HIV at the time of an AIDS- defining event (TB, PCP, other OI, KS or lymphoma); and, 2) to assess the impact on outcome of timing of cART initiation in these individuals. Miro JM, 529

9 Characteristics of patients in study, overall and stratified by immediate/deferred treatment Overall, the characteristics of patients receiving immediate and deferred treatment were broadly similar with the exception of some differences by country and age. Those treated immediately were slightly older. cART regimens were similar in both groups. Patients with KS were more likely to be treated immediately (P= 0.02). Overall, the characteristics of patients receiving immediate and deferred treatment were broadly similar with the exception of some differences by country and age. Those treated immediately were slightly older. cART regimens were similar in both groups. Patients with KS were more likely to be treated immediately (P= 0.02). Miro JM, 529

10 Kaplan Meier plot showing the cumulative proportion of patients with clinical progression (new AIDS event or death), according to the type of AIDS-defining diagnosis disease. Miro JM, 529

11 Factors associated with clinical progression (new AIDS event or death) Miro JM, 529

12 Conclusions Older patients and those with a higher VL (>100K) or lymphoma at HIV diagnosis had a worse outcome. Patients who “deferred” cART had almost twice the risk of clinical progression than those who initiated cART immediately Whilst the results of this study confirm the findings from ACTG 5164, the small number of patients with KS or lymphoma in our study, and the potential for confounding, means that it remains important to conduct RCTs to validate our findings. Older patients and those with a higher VL (>100K) or lymphoma at HIV diagnosis had a worse outcome. Patients who “deferred” cART had almost twice the risk of clinical progression than those who initiated cART immediately Whilst the results of this study confirm the findings from ACTG 5164, the small number of patients with KS or lymphoma in our study, and the potential for confounding, means that it remains important to conduct RCTs to validate our findings. Miro JM, 529

13 A5221/STRIDE CAMELIA SAPIT ENDPT SITES No ARMS 800/800 Africa, Asia, SA, NA 429/429 660/660 Cambodia South Africa Imm vs. 8-24 Imm vs. 8 Imm vs. 8-12 Death, AIDS Death When to Start cART during TB treatment

14  When to start cART  Tuberculosis  2009 Influenza A(H1N1)  Other opportunistic infections & IRIS  HCV & HBV co-infections  Tumors  When to start cART  Tuberculosis  2009 Influenza A(H1N1)  Other opportunistic infections & IRIS  HCV & HBV co-infections  Tumors OIs, Hepatitis Coinfections & Tumors

15 Paper # 102 Effectiveness of Isoniazid Preventive Therapy in Reducing Mortality in Patients on ART Craig Innes et al. South Africa. Paper # 102 Effectiveness of Isoniazid Preventive Therapy in Reducing Mortality in Patients on ART Craig Innes et al. South Africa. Paper # 103 Efficacy of a 6-month vs a 36-month Regimen for Prevention of Tuberculosis in HIV-infected Persons in India: A Randomized Clinical Trial Soumya Swaminathan et al. India. Paper # 104LB Randomized, Placebo-controlled Trial of 6 vs 36 Months Isoniazid TB Preventive Therapy for HIV-infected Adults in Botswana Taraz Samandari et al. Botswana. Isoniazid Preventive Therapy (IPT) in HIV-infected Patients YES Better 6 mo. Better 36 mo.

16 Samandari T. 104LB. IPT in HIV-infected Patients in Botswana: 6 vs. 36 months

17 Samandari T. 104LB. IPT in HIV-infected Patients in Botswana: 6 vs. 36 months

18 Samandari T. 104LB. IPT in HIV-infected Patients in Botswana: 6 vs. 36 months

19 Samandari T. 104LB. IPT in HIV-infected Patients in Botswana: 6 vs. 36 months

20 Samandari T. 104LB. IPT in HIV-infected Patients in Botswana: 6 vs. 36 months

21 Samandari T. 104LB. IPT in HIV-infected Patients in Botswana: 6 vs. 36 months

22 Samandari T. 104LB. IPT in HIV-infected Patients in Botswana: 6 vs. 36 months

23 Comparing a new IP-10 based test with the QuantiFERON In Tube test for diagnosing pulmonary tuberculosis in an HIV-endemic population Aabye MG, 770 IP-10 (monocyte derived chemokine) is induced upon Mtb. specific antigen stimulation of whole blood with from patients with active TB infection but not from uninfected patients.

24 Effect of HIV Infection on 2-Month Treatment Outcome of Therapy for Pulmonary Tuberculosis Disease in Two Clinical Trials Bliven E, 782

25 Effect of HIV Infection on 2-Month Treatment Outcome of Therapy for Pulmonary Tuberculosis Disease in Two Clinical Trials Bliven E, 782

26  When to start cART  Tuberculosis  2009 Influenza A(H1N1)  Other opportunistic infections & IRIS  HCV & HBV co-infections  Tumors  When to start cART  Tuberculosis  2009 Influenza A(H1N1)  Other opportunistic infections & IRIS  HCV & HBV co-infections  Tumors OIs, Hepatitis Coinfections & Tumors

27 Number of HIV- & HIV+ patients positive for influenza A (H1N1) per calendar week in Barcelona (Spain) Martinez E, 802LB

28 HIV+ (n=56) Characteristics Route of transmission (n, %) –MSM: 26 (46) –IDU:18 (32) –Heterosexual:12 (21) Years from HIV-1 diagnosis (median, IQR)14 (5 – 19) Nadir CD4 (absolute) (median, IQR)222 (134 – 379) Nadir CD4 (%) (median, IQR)18 (14 – 22) Log HIV-1 RNA zenit (median, IQR)5.2 (4.7 – 5.5) Prior/current C events (n, %)16 (29) Hepatitis C (n, %)21 (38) At influenza A (H1N1) diagnosis: CD4 (absolute) (median, IQR)583 (370 - 715) CD4 (%) (median, IQR)26 (23 – 33) CD4 (absolute) (median, IQR)995 (828 – 1485) CD4 (%) (median, IQR)50 (41 – 60) Log HIV-1 RNA (median, IQR)1.7 (1.7 – 1.7) Patients with log HIV-1 RNA >50 copies/mL(n, log HIV-1 RNA)3 (2.7, 3.5, and 4.3) Martinez E, 802LB

29 Absolute CD4 (cells/mm 3 ) at influenza A (H1N1) diagnosis <200/mm 3: 9% Martinez E, 802LB

30 HIV+ (n=56)HIV- (n=168) P value Demographics Men (n, %)44 (79)74 (44)0.0001 Age (years) (mean, SD)44 ± 839 ± 150.0153 Active smoker (n, %)30 (54)21 (13)0.0001 Travel / contacts (n, %)4 (7%)40 (24)0.0066 Co-morbidities (n, %)8 (14)103 (61)0.0001 Specific co-morbidities COPD /asthma (n, %)3 (5)44 (26) Neoplasia (n, %) (solid/hemathologic) 2 (4) (0/2) 12 (7) (4/8) Pregnancy (n, %)0 (0)18 (11) Drug-induced immunesupression (n, %)1 (2)12 (7) Diabetes mellitus (n, %)1 (2)7 (4) Cirrhosis (n, %)1 (2)2 (1) Toxic abuse (drugs / alcohol) (n, %)0 (0)2 (1) Chronic kidney disease (n, %)0 (0)1 (1) Obesity (BMI >30 kg/m 2 ) (n, %)0 (0)3 (2) Ischemic CV disease (n, %)0 (0)2 (1) Demographic characteristics and comorbities Martinez E, 802LB

31 HIV+ (n=56)HIV- (n=168)P value Dysthermia (n, %)56 (100)159 (95)0.1691 Cough (n, %)48 (86)145 (86)0.9111 Arthromyalgias (n, %)44 (79)128 (76)0.7148 Tiredness (n, %)38 (68)128 (76)0.2176 Headache (n, %)22 (39)78 (46)0.3518 Sore throat (n, %)21 (38)46 (27)0.1521 GI symptoms (n, %)21 (38)31 (19)0.0035 Rinorrhea (n, %)18 (32)57 (34)0.8063 Expectoration (n, %)23 (41)57 (34)0.3330 Dyspnea (n, %)10 (18)36 (21)0.5667 Clinical symptoms Martinez E, 802LB

32 Influenza A (H1N1) at presentation HIV+ (n=56)HIV- (n=168)P value Days from onset (mean, SD)2.8 ± 1.63.2 ± 2.00.1359 Axillar temperature (ºC) (mean, SD) 37.9 ± 0.937.7 ± 1.00.1685 Delayed influenza A (H1N1) diagnosis (n, %) 4 (7)21 (13)0.2702 Pneumonia (n, %)5 (9)42 (25)0.0105 Respiratory failure (n, %)5 (9)36 (2190.0362 Martinez E, 802LB

33 Concommitant bacteria detected HIV+ (n=56) HIV- (n=168)P value Concommitant bacteria * (n, %)4 (7)13 (8)0.8842 – S. pneumoniae 39 – S. aureus 04 – Capnocytophaga spp 10 * Detected from blood cultures and/or urine antigens and/or valid respiratory samples Martinez E, 802LB

34 Prognosis HIV+ (n=56)HIV- (n=168)P Value Days at hospital (mean, SD)1.1 ± 2.32.0 ± 3.40.0812 >1 day at hospital (n, %)15 (27)70 (42)<0.05 Complications after admission (n, %)7 (13)18 (11)0.7132 Anti-influenza therapy (oseltamivir) (n, %) 53 (95)119 (71)0.0003 Antibiotic therapy (n, %)29 (52)82 (49)0.6997 Clinical recovery <1 week (n, %)43 (77)94 (56)0.0056 Evolution to death (n, %)0 (0)3 (2)0.7372 Martinez E, 802LB

35 CD4 and CD8 changes from influenza A (H1N1) diagnosis until 4-6 weeks later Influenza A (H1N1) diagnosis (n=56) 4-6 weeks post- diagnosis (n=51) Change CD4 cells (mm 3 ) Median (IQR) 583 (370 – 715) 466 (275 – 702) -15 (-44, 39) CD4 cells (%) Median (IQR) 26.3 (22.7 – 33.4) 26.5 (21.5 – 33.2) -0.4 (-0.8, 2.3) CD8 cells (mm 3 ) Median (IQR) 995 (828 – 1485) 917 (631 – 1250) -14 (-122, 77) CD8 cells (%) Median (IQR) 49.7 (40.6 – 59.59 48.5 (42.8 – 56.5) 0.7 (-2.8, 1.5) Log HIV-1 RNA (copies/mL) Median (IQR) 1.7 (1.7 – 1.7) 1.7 (1.7 – 1.7) 0 (0, 0) Martinez E, 802LB

36 Conclusions HIV infection did not make 2009 influenza A (H1N1) more severe. 2009 Influenza A (H1N1) did not have a major impact on HIV infection control. Martinez E, 802LB

37 METHODS Ongoing randomized (1:1) patient-blinded trial, HIV-1-infected adult patients, - either receiving HAART (HIV viral load <50 copies/mL ) - or not receiving HAART (without indication for treatment) Group A: AS03 A -adjuvanted H1N1 v vaccine 3.75µg HA n=154 Group B: Non-adjuvanted H1N1 v vaccine 15µg HA n=152 Randomization D42 D182D364 D0D21 Follow-up Samples D91 Vaccination (IM) Immunogenicity of one dose of influenza A H1N1 v 2009 vaccine formulated with and without AS03 A -adjuvant in HIV+ adults Preliminary Report of the ANRS 151 Randomized HIFLUVAC Trial Odile LAUNAY et al, ANRS, Paris, France Stratification according to HAART vs no HAART at baseline STUDY POPULATION: 306 patients : 237 on HAART, 69 untreated Median age : 47 years (IQR, 40-54); 19% were female; Median CD4: 536 cells/μL (IQR, 413–715) ; 556 (treated patients), 517 (untreated) STUDY POPULATION: 306 patients : 237 on HAART, 69 untreated Median age : 47 years (IQR, 40-54); 19% were female; Median CD4: 536 cells/μL (IQR, 413–715) ; 556 (treated patients), 517 (untreated) Launay O, 804LB

38 Pre and post-vaccination seroprotection rates and GMTs CONCLUSION A single dose of H1N1 v vaccine was well tolerated and induces high immune response in this population. Higher immunogenicity (seroprotection rate and GMT) was obtained with the AS03 A -adjuvanted H1N1 v vaccine. CONCLUSION A single dose of H1N1 v vaccine was well tolerated and induces high immune response in this population. Higher immunogenicity (seroprotection rate and GMT) was obtained with the AS03 A -adjuvanted H1N1 v vaccine. No short-term impact of vaccination on CD4 count or HIV viral load Multivariate analysis: HCV/HBV co-infection and non-adjuvanted vaccine were negatively associated to seroprotection No short-term impact of vaccination on CD4 count or HIV viral load Multivariate analysis: HCV/HBV co-infection and non-adjuvanted vaccine were negatively associated to seroprotection Launay O, 804LB

39  When to start cART  Tuberculosis  2009 Influenza A(H1N1)  Other opportunistic infections & IRIS  HCV & HBV co-infections  Tumors  When to start cART  Tuberculosis  2009 Influenza A(H1N1)  Other opportunistic infections & IRIS  HCV & HBV co-infections  Tumors OIs, Hepatitis Coinfections & Tumors

40 May Pneumocystis Prophylaxis Be Safely Discontinued in Virologically Suppressed Patients With CD4 Counts Below 200 cells/μL? May Pneumocystis Prophylaxis Be Safely Discontinued in Virologically Suppressed Patients With CD4 Counts Below 200 cells/μL? Furrer H, 789 <400

41 Study Population HIV-infected adults previously vaccinated with PPV 3-8 years earlier were randomized 2:1 to be revaccinated with PCV (Prevnar) or PPV (Pneumovax). A group of HIV-uninfected subjects (n=25) with no prior history of pneumococcal vaccination received a single injection of PCV. Study Population HIV-infected adults previously vaccinated with PPV 3-8 years earlier were randomized 2:1 to be revaccinated with PCV (Prevnar) or PPV (Pneumovax). A group of HIV-uninfected subjects (n=25) with no prior history of pneumococcal vaccination received a single injection of PCV. Endpoints The primary study endpoint was defined a priori as the proportion of subjects in the HIV infected PCV and PPV arms with positive antibody response to at least two of the four serotypes at day 60. - A positive response was defined as a 2-fold or greater rise in IgG level with a post-vaccination level value >1000 ng/mL Endpoints The primary study endpoint was defined a priori as the proportion of subjects in the HIV infected PCV and PPV arms with positive antibody response to at least two of the four serotypes at day 60. - A positive response was defined as a 2-fold or greater rise in IgG level with a post-vaccination level value >1000 ng/mL Objective  We evaluated the immunogenicity of revaccination of PCV compared with PPV in a RCT among HIV-infected adults to guide recommendations on revaccination of HIV-infected adults previously vaccinated with PPV. Objective  We evaluated the immunogenicity of revaccination of PCV compared with PPV in a RCT among HIV-infected adults to guide recommendations on revaccination of HIV-infected adults previously vaccinated with PPV. A Randomized Clinical Trial Comparing Revaccination with Pneumococcal Polysaccharide Vaccine (PPV) to Pneumococcal Conjugate Vaccine (PCV) among HIV-Infected Adults Crum-Cianflone N, 814

42 A Randomized Clinical Trial Comparing Revaccination with Pneumococcal Polysaccharide Vaccine (PPV) to Pneumococcal Conjugate Vaccine (PCV) among HIV-Infected Adults Crum-Cianflone N, 814 1) Although revaccination with PCV was initially more immunogenic than PPV among HIVinfected adults, all such differences waned by day 180. 2) HIV-infected adults, despite ↑ CD4 counts and use of cART, had significantly lower immune responses to vaccination than HIV-uninfected group. 1) Although revaccination with PCV was initially more immunogenic than PPV among HIVinfected adults, all such differences waned by day 180. 2) HIV-infected adults, despite ↑ CD4 counts and use of cART, had significantly lower immune responses to vaccination than HIV-uninfected group.

43 CMV-specific T Cell Responses are Higher in HIV-infected Patients Naeger et al, submitted Decreasing Asymptomatic CMV Replication with Valganciclovir Decreases Immune Activation in HIV+ Patients with CD4<350 despite cART Hunt et al, CROI, 2010, P#380

44 Valganciclovir Reduces CD8+ T Cell Activation among HIV- infected Patients with Suboptimal CD4+ T cell Recovery During Antiretroviral Therapy Hunt P, 380

45  When to start cART  Tuberculosis  2009 Influenza A(H1N1)  Other opportunistic infections & IRIS  HCV & HBV co-infections  Tumors  When to start cART  Tuberculosis  2009 Influenza A(H1N1)  Other opportunistic infections & IRIS  HCV & HBV co-infections  Tumors OIs, Hepatitis Coinfections & Tumors

46 September 2009

47 SNPs that are inherited together are compiled into "haplotypes" Single nucleotide polymorphisms (SNPs) are identified in DNA from multiple individuals "Tag" SNPs are identified and genotyped Genome-wide association studies www.hapmap.org ~500,000 “tag SNPs” characterise ~10,000,000 SNPs >90% of common human genetic variants

48 Genetic variation in IL28B strongly predicts spontaneous HCV clearance and response to anti- HCV therapy with Peg-INF and RBV. IL28B encodes interferon-, an antiviral cytokine Interferon- is a promising anti-HCV drug Genetic variation in IL28B strongly predicts spontaneous HCV clearance and response to anti- HCV therapy with Peg-INF and RBV. IL28B encodes interferon-, an antiviral cytokine Interferon- is a promising anti-HCV drug The Interleukin 28B (IL28B) Gene and HCV Recovery

49 rs12979860 (SNP near IL28B) on chromosome 19 is strongly associated with SVR

50 Response to HCV therapy Natural HCV clearance Correlation of genetic variation in IL28B with HCV recovery rates in diverse ethnicities Thomas DL et al. Nature. 2009;461:798-801. Ge D, et al. Nature 2009;461:399-401. rs12979860 C allele frequency (SNP near IL28B ) SVR (%) Different frequencies in IL28B variants explain ethnical differences in HCV recovery rates

51 Consistent effect of genetic variation in IL28B on spontaneous HCV clearance Rauch A, et al. Gastroenterology 2010 ; Jan 7. Thomas et al. Nature. 2009;461:798-801. Carriage of IL28B risk alleles predicts chronic HCV infection HCV monoinfection HIV/HCV coinfection

52 Consistent effect of genetic variation in IL28B on response to anti-HCV therapy with Peg-INF & RBV Ge D, et al. Nature 2009;461:399-401. Tanaka Y, et al. Nat Genet 2009;41:1105-9. Suppiah V, et al. Nat Genet 2009;41:1100-4. Rauch A, et al. Gastroenterology 2010 ; Jan 7. Odds ratio of treatment failure by rs8099917 carriage Carriage of the rs8099917 risk allele predicts treatment failure HIV/HCV coinfection (CROI 2010)  # 163 di Iulio et al  # 164 Nattermann et al  # 165 Rallon et al  # 656 Pineda et al

53 OBJECTIVES To evaluate the role of the IL28B rs12979860 SNP in HIV/HCV co-infection –Response to pegIFN alpha plus RBV (SVR) –Spontaneous HCV clearance To assess the role of the IL28B rs12979860 SNP in HCV genotypes other than HCV-1 To evaluate the role of the IL28B rs12979860 SNP in HIV/HCV co-infection –Response to pegIFN alpha plus RBV (SVR) –Spontaneous HCV clearance To assess the role of the IL28B rs12979860 SNP in HCV genotypes other than HCV-1 Rallón NI, 165LB

54 IL28B SNP is associated with spontaneous HCV clearance in HIV patients

55 rs12979860 & SVR p<0.0001 p=0.001 p=0.684 p=0.087 75 % 38 % 65 % 30 % 86 % 81 % 67 % 25 % SVR AllHCV-1HCV-3HCV-4 CC CT/TT Rallón NI, 165LB

56 Predictors of SVR in HIV/HCV Co- infection Rallón NI, 165LB

57 SVR rates according to the number of protective factors Low serum HCV-RNA HCV genotype 3 Lack of advanced liver fibrosis (Metavir F0-F2) rs12979860 CC genotype (IL28B) Rallón NI, 165LB

58 CONCLUSIONS A SNP at the IL28B gene in HIV/HCV coinfected patients is associated with: Spontaneous HCV clearance (GT1/GT4) Sustained virological response (GT1/GT4) IL28B genotyping should be part of the treatment decision algorithm in this difficult-to-treat population A SNP at the IL28B gene in HIV/HCV coinfected patients is associated with: Spontaneous HCV clearance (GT1/GT4) Sustained virological response (GT1/GT4) IL28B genotyping should be part of the treatment decision algorithm in this difficult-to-treat population Rallón NI, 165LB

59 Phase 1b trials: Comparable efficacy to IFN-α Synergistic effect with IFN-α Less side effects - Tissue specific receptor expression Phase 1b trials: Comparable efficacy to IFN-α Synergistic effect with IFN-α Less side effects - Tissue specific receptor expression Interferon- : A promising HCV drug Marcello T, et al. Gastroenterology 2006;131:1887-1898. Dodds MG, et al. EASL 2009. Lawitz E, et al. AASLD 2009. Shiffman M, et al. EASL 2009. Sommereyns et al. PLoS Pathog. 2008 14;4:e1000017.

60 Launay O, 623 RCT Comparing the Efficacy and Safety of Four Intramuscular Double Doses and Four Intradermal Low Doses with Three Intramuscular Standard Doses of Hepatitis B vaccine in HIV infected persons: Results of the ANRS HB03 VIHVAC-B Trial. Subjects with anti-HBs > 10 mIU/ml at weeks 28 were defined as responders (main endpoint). Subjects with anti-HBs > 100 mIU/ml at week 28 were defined as high responders. At weeks 0, 4 and 24At weeks 0, 4, 8 and 24

61 Launay O, 623 RCT Comparing the Efficacy and Safety of Four Intramuscular Double Doses and Four Intradermal Low Doses with Three Intramuscular Standard Doses of Hepatitis B vaccine in HIV infected persons: Results of the ANRS HB03 VIHVAC-B Trial.

62 Rodriguez C, 170LB Ultra-deep Sequencing Analysis Demonstrates Pre- existence of HBV Resistance Substitutions at Baseline in Patients Who Subsequently Develop Clinical Resistance Conclusions: Ultra-deep sequencing is a new powerful tool to study HBV resistance to NUC. This technique allowed us to demonstrate that resistant HBV variants pre-exist to treatment administration and are selected in the presence of the NUC according to complex viral population dynamics. HBV variants isolated from 119 serial serum samples taken over 25 to 56 months from 7 patients who developed adefovir resistance on monotherapy were ultra-deep sequenced (Titanium kit on a 454 Genome Sequencer FLX; Roche Diagnostics Corporation). Analysis was carried out using ActivePerl 5.10.0.

63  When to start cART  Tuberculosis  2009 Influenza A(H1N1)  Other opportunistic infections & IRIS  HCV & HBV co-infections  Tumors  When to start cART  Tuberculosis  2009 Influenza A(H1N1)  Other opportunistic infections & IRIS  HCV & HBV co-infections  Tumors OIs, Hepatitis Coinfections & Tumors

64 Trends in Cumulative Incidence of Cancer among HIV-infected Patients in North America Silverberg MJ, 758

65 Ortiz M, 1019 High-Risk HPV (HR-HPV) prevalence by HIV-1 Status in Spanish Men Who Have Sex with Men (MSM) in an Out Patient STD Clinic in Madrid (Spain) *p<0.05

66 Ortiz M, 1019 High-Risk HPV (HR-HPV) prevalence by HIV-1 Status in Spanish Men Who Have Sex with Men (MSM) in a prospective cohort of HIV-positive MSM belonging to CoRIS Prevalence of HR-HPV infection is higher in anus than in cervix in women. A high prevalence of anal intraepithelial lesions is observed in HIV positive men. Prevalence of HR-HPV infection is higher in anus than in cervix in women. A high prevalence of anal intraepithelial lesions is observed in HIV positive men.

67 Wilkin T, 1015 Safety and Immunogenicity of the Quadrivalent HPV Vaccine (qHPV) in HIV-Infected Men: Primary Results of AIDS Malignancy Consortium Trial 052 Conclusions: The qHPV vaccine is generally safe, well tolerated, and highly immunogenic in HIV- infected men. Background: HIV-infected men are at an increased risk of anal cancer. Human papillomavirus (HPV) vaccination may prevent anal cancer caused by vaccine types. However, the safety and immunogenicity of the quadrivalent vaccine in HIV-infected men are unknown. Methods: Single-arm, open label study of the qHPV (types 6, 11, 16, 18) recombinant vaccine in HIV- infected adult men.

68 J. Del Amo P. Domingo D.B. Goldstein P. Hunt D. Havlir O. Launay J. Del Amo P. Domingo D.B. Goldstein P. Hunt D. Havlir O. Launay Acknowledgements http://www.retroconference.org/2010 C. Manzardo E. Martínez A. Rauch I. Sereti A. Telenti V.Soriano C. Manzardo E. Martínez A. Rauch I. Sereti A. Telenti V.Soriano


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