1 7 th croi, san francisco, 2010 . hotel ac, barcelona – february 26 th 2010

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

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

Dr. José M. MiróInfectious Diseases Service - ICMiD

Hospital Clinic - IDIBAPS University of Barcelona

Barcelona (Spain)

Dr. José M. MiróInfectious Diseases Service - ICMiD

Hospital Clinic - IDIBAPS University of Barcelona

Barcelona (Spain)

Summary: Opportunistic Infections HCV/HBV Co-Infections & Tumors

Summary: Opportunistic Infections HCV/HBV Co-Infections & Tumors

E-mail address: [email protected] address: [email protected]

When to start cART Tuberculosis 2009 Influenza A(H1N1) Other opportunistic infections & IRIS HCV & HBV co-infections Tumors


OIs, Hepatitis Coinfections & Tumors


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 Study day

EnrollmentEnrollment

Opportunistic infections* Treatment

Starts

Opportunistic infections* Treatment

Starts

Immediate Arm

Start ART

Immediate Arm

Start ART

Deferred ArmStart ART

Deferred ArmStart ART

RecommendedStart window

RecommendedStart window

48wks48

wks

48wks48

wks

-14-14 00 22 2828 4242 8484 224224

Study schemaStudy schema

12 days vs. 45 days

*TB excluded !!!*TB excluded !!!

Results Through 48 WeeksResults Through 48 Weeks

• No difference in primary endpoint of virologic suppression• No difference in IRIS (10 immediate, 13 deferred) or need for ART changes

Prob

abili

ty o

f sur

vivi

ng

with

out

deat

h/ne

w A

IDS

defin

ing

even

t

Prob

abili

ty o

f sur

vivi

ng

with

out

deat

h/ne

w A

IDS

defin

ing

even

t

Immediate ARTDeferred ARTImmediate ARTDeferred ART

000.00.0

0.20.2

1.001.00

44 88 1212 1616 2020 2424 2828 3232 3636 4040 4444 4848

0.10.1

0.90.9

0.80.8

0.70.7

0.60.6

0.50.5

0.40.4

0.30.3

116116

9494

HR=0.5399%CI (0.25,1.09)P=0.023

HR=0.5399%CI (0.25,1.09)P=0.023

Early cART less new AIDS events or death

MonthsMonths





Characteristics Total Immediate DeferredCD4 (cells/mm3) 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 ART N (%) 259 (92) 131 (93) 128 (91)

PCP N (%) 177 (63) 88 (62) 89 (63)

BI N (%) 34 (12) 17 (12) 17 (12)

Other OI N (%) 71 (25) 36 (26) 35 (25)

Crypto / Histo N (%) 45 (16) 20 (14) 25 (18)

Toxoplasmosis N (%) 13 (5) 9 (6) 4 (3)

CMV N (%) 6 (2) 4 (3) 2 (1)

MAC N (%) 6 (2) 3 (2) 3 (2)

Multiple OI/BI w/in 30 days 33% 32% 33%*TB excluded !!!*TB excluded !!!





• Retrospective multicohort studyRetrospective 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 studyRetrospective 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 AnalysisMussini C et al. AIDS 2008, 22:2461–2469


• P. jiroveciiP. jirovecii pneumonia (PCP) pneumonia (PCP)• TuberculosisTuberculosis• Esophageal candidiasisEsophageal candidiasis• CNS toxoplasmosisCNS toxoplasmosis• CMV diseaseCMV disease• Kaposi’s sarcomaKaposi’s sarcoma• NHLNHL• Other Opportunistic InfectionsOther Opportunistic Infections

• P. jiroveciiP. jirovecii pneumonia (PCP) pneumonia (PCP)• TuberculosisTuberculosis• Esophageal candidiasisEsophageal candidiasis• CNS toxoplasmosisCNS toxoplasmosis• CMV diseaseCMV disease• Kaposi’s sarcomaKaposi’s sarcoma• NHLNHL• Other Opportunistic InfectionsOther Opportunistic Infections

268 (35%)268 (35%)168 (22%)168 (22%)94 (12%)94 (12%)65 (9%)65 (9%)51 (7%)51 (7%)65 (9%)65 (9%)28 (4%)28 (4%)

115 (15%)115 (15%)

268 (35%)268 (35%)168 (22%)168 (22%)94 (12%)94 (12%)65 (9%)65 (9%)51 (7%)51 (7%)65 (9%)65 (9%)28 (4%)28 (4%)

115 (15%)115 (15%)



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)

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, 529Miro JM, 529

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).

All patients Immediate Deferred p-value

N (% of total) 429 (100.0) 202 (47.1) 227 (52.9)

Male sex 333 (77.8) 154 (76.6) 179 (78.9) 0.66

Risk group IDU 43 (10.0) 18 (8.9) 25 (11.0) Homosexual 102 (23.8) 49 (24.3) 53 (23.4) Heterosexual 147 (34.3) 71 (35.2) 76 (33.5) Other 137 (31.9) 64 (31.7) 73 (32.2) 0.90

Age (years) Median (IQR) 39 (33, 47) 40 (33, 49) 39 (33, 47) 0.20

CD4 count (cells/mm3) Median (IQR) 36 (13, 104) 36 (12, 112) 34 (14, 98) 0.67

HIV RNA (log10 copies/ml)

Median (IQR) 5.3 (4.6, 5.7) 5.2 (4.3, 5.7) 5.4 (4.8, 5.8) 0.04

Country Italy 175 (40.8) 92 (45.5) 83 (36.6) Spain 92 (21.5) 42 (20.8) 50 (22.0) UK 114 (26.6) 55 (27.2) 59 (26.0) Canada 48 (11.2) 13 (6.4) 35 (15.4) 0.02

Type of AIDS event TB 93 (21.7) 39 (19.3) 54 (23.8) 0.31

PCP 178 (41.5) 82 (40.6) 96 (42.3) 0.80 KS 43 (10.0) 28 (13.9) 15 (6.6) 0.02 Lymphoma 10 (2.3) 3 (1.5) 7 (3.1) 0.35 Other 160 (37.3) 78 (38.6) 82 (36.1) 0.67

Type of ART NNRTI-based 117 (28.2) 50 (24.8) 67 (31.5) PI-based 261 (62.9) 136 (67.3) 125 (58.7) Other 37 (8.9) 16 (7.9) 21 (9.9) 0.19

Total follow-up (years) Median (IQR) 2.1 (0.8, 4.0) 2.4 (0.9, 4.0) 2.0 (0.7, 4.1) 0.07


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.


Factors associated with clinical progression (new AIDS event or death)

Model 1: No adjustment Model 2: Fully adjusted model Model 3: Parsimonious model

RH 95% CI p-value RH 95% CI p-value RH 95% CI p-value

Deferred vs. immediate treatment 2.00 (1.37, 2.92) 0.0003 1.89 (1.27, 2.82) 0.002 1.85 (1.25, 2.73) 0.002

AIDS-defining event TB - - - 1.01 (0.64, 1.59) 0.96 - - - PCP - - - 1.26 (0.75, 2.12) 0.38 - - - KS - - - 1.95 (1.07, 3.58) 0.03 - - - Lymphoma - - - 2.15 (0.75, 6.22) 0.16 2.51 (1.01, 6.21) 0.05

Female - - - 1.16 (0.72, 1.86) 0.55 - - -

Risk group Heterosexual - - - 1 - - - - - Homosexual - - - 0.69 (0.34, 1.40) 0.31 - - - IDU - - - 0.66 (0.38, 1.14) 0.14 - - - Other - - - 0.91 (0.56, 1.46) 0.68 - - -

Age (per 5 years older) - - - 1.09 (0.99, 1.19) 0.07 1.10 (1.01, 1.20) 0.02

CD4 count (per 50 cells/mm3 higher) - - - 0.95 (0.87, 1.04) 0.27 - - -

Viral load (per log10 higher) - - - 1.26 (1.04, 1.52) 0.02 1.30 (1.08, 1.56) 0.006


ConclusionsConclusions

• 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.


A5221/STRIDE A5221/STRIDE CAMELIA CAMELIA SAPITSAPIT

ENDPTENDPT

SITESSITES

No No

ARMSARMS

800/800800/800

Africa, Asia, SA, NAAfrica, Asia, SA, NA

429/429429/429660/660660/660

CambodiaCambodia South AfricaSouth Africa

Imm vs. 8-24Imm vs. 8-24Imm vs. 8Imm vs. 8Imm vs. 8-12Imm vs. 8-12

Death, AIDSDeath, AIDS DeathDeath DeathDeath

When to Start cART during TB treatment When to Start cART during TB treatment

Paper # 102Effectiveness of Isoniazid Preventive Therapy in Reducing Mortality in Patients on ARTCraig Innes et al. South Africa.

Paper # 102Effectiveness of Isoniazid Preventive Therapy in Reducing Mortality in Patients on ARTCraig Innes et al. South Africa.

Paper # 103Efficacy of a 6-month vs a 36-month Regimen for Prevention of Tuberculosis in HIV-infected Persons in India: A Randomized Clinical TrialSoumya Swaminathan et al. India.

Paper # 103Efficacy of a 6-month vs a 36-month Regimen for Prevention of Tuberculosis in HIV-infected Persons in India: A Randomized Clinical TrialSoumya Swaminathan et al. India.

Paper # 104LBRandomized, Placebo-controlled Trial of 6 vs 36 Months Isoniazid TB Preventive Therapy for HIV-infected Adults in BotswanaTaraz Samandari et al. Botswana.

Paper # 104LBRandomized, Placebo-controlled Trial of 6 vs 36 Months Isoniazid TB Preventive Therapy for HIV-infected Adults in BotswanaTaraz Samandari et al. Botswana.

Isoniazid Preventive Therapy (IPT) in HIV-infected Patients

YES

Better 6 mo.

Better 36 mo.

Samandari T. 104LB. Samandari T. 104LB.

IPT in HIV-infected Patients in Botswana: 6 vs. 36 months

Comparing a new IP-10 based test with the QuantiFERON In Tube test for diagnosing pulmonary

tuberculosis in an HIV-endemic population

Aabye MG, 770Aabye MG, 770IP-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.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.

Effect of HIV Infection on 2-Month Treatment Outcome of Therapy for Pulmonary Tuberculosis

Disease in Two Clinical Trials

Bliven E, 782Bliven E, 782

0

20

40

60

80

100

120

S1

8

S2

0

S2

2

S2

4

S2

6

S2

8

S3

0

S3

2

S3

4

S3

6

S3

8

S4

0

S4

2

S4

4

S4

6

S4

8

S5

0

HIV+ A(H1N1)+

NoHIV+ A(H1N1)+

Number of HIV- & HIV+ patients positive for influenza A (H1N1) per calendar week in Barcelona (Spain)

Number of HIV- & HIV+ patients positive for influenza A (H1N1) per calendar week in Barcelona (Spain)

Martinez E, 802LBMartinez E, 802LB

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)


Absolute CD4 (cells/mm3) at influenza A (H1N1) diagnosis

0

5

10

15

20

25

30

Absolute CD4 at influenza A (H1N1) diagnosis

<50

50-100

101-150

151-200

201-500

501-1000

>1000

<200/mm3: 9%


HIV+ (n=56) HIV- (n=168) P valueDemographics

Men (n, %) 44 (79) 74 (44) 0.0001 Age (years) (mean, SD) 44 ± 8 39 ± 15 0.0153 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) 0.0001Specific 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/m2) (n, %) 0 (0) 3 (2)

Ischemic CV disease (n, %) 0 (0) 2 (1)

Demographic characteristics and comorbities Demographic characteristics and comorbities


HIV+ (n=56) HIV- (n=168) P value

Dysthermia (n, %) 56 (100) 159 (95) 0.1691Cough (n, %) 48 (86) 145 (86) 0.9111Arthromyalgias (n, %) 44 (79) 128 (76) 0.7148Tiredness (n, %) 38 (68) 128 (76) 0.2176Headache (n, %) 22 (39) 78 (46) 0.3518Sore throat (n, %) 21 (38) 46 (27) 0.1521GI symptoms (n, %) 21 (38) 31 (19) 0.0035

Rinorrhea (n, %) 18 (32) 57 (34) 0.8063Expectoration (n, %) 23 (41) 57 (34) 0.3330Dyspnea (n, %) 10 (18) 36 (21) 0.5667

Clinical symptomsClinical symptoms


Influenza A (H1N1) at presentationInfluenza A (H1N1) at presentation

HIV+ (n=56) HIV- (n=168) P value

Days from onset (mean, SD) 2.8 ± 1.6 3.2 ± 2.0 0.1359

Axillar temperature (ºC) (mean, SD) 37.9 ± 0.9 37.7 ± 1.0 0.1685

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 (219 0.0362


Concommitant bacteria detected

HIV+ (n=56) HIV- (n=168) P

value

• Concommitant bacteria * (n, %) 4 (7) 13 (8) 0.8842

– S. pneumoniae 3 9

– S. aureus 0 4

– Capnocytophaga spp 1 0

* Detected from blood cultures and/or urine antigens and/or valid respiratory samples


Prognosis

HIV+ (n=56) HIV- (n=168) P Value

Days at hospital (mean, SD) 1.1 ± 2.3 2.0 ± 3.4 0.0812

>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


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 (mm3) 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 (mm3) 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)


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.


METHODSOngoing 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: AS03A-adjuvanted H1N1v vaccine 3.75µg HA n=154Group B: Non-adjuvanted H1N1v vaccine 15µg HA n=152

Randomization

D42 D182 D364D0 D21Follow-upSamples

D91

Vaccination (IM)

Immunogenicity of one dose of influenza A H1N1v 2009 vaccine formulated with and without AS03A-adjuvant in HIV+ adults

Preliminary Report of the ANRS 151 Randomized HIFLUVAC TrialOdile 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, 804LBLaunay O, 804LB

http://www.anrs.fr/index.php/anrs

Pre and post-vaccination seroprotection rates and GMTs

Seroprotection rate % (95% CI)

AS03A-adjuvanted H1N1v vaccine 3.75 µg HA (Group A)

Non-adjuvanted H1N1v vaccine15 μg HA (Group B)

B w/o HAART

n=33

A HAARTn=115

A w/o HAART

n=35

B HAARTn=115

010203040506070

8090

100

0

50

100

150

200

250

300

A Totaln=150

B Totaln=148

D0 D21 D0 D21 D0 D21 D0 D21 D0 D21 D0 D21

GM

T (95% C

I)

Regulatoryrequirements

CONCLUSIONA single dose of H1N1v vaccine was well tolerated and induces high immune response in this population.Higher immunogenicity (seroprotection rate and GMT) was obtained with the AS03A-adjuvanted H1N1v vaccine.

CONCLUSIONA single dose of H1N1v vaccine was well tolerated and induces high immune response in this population.Higher immunogenicity (seroprotection rate and GMT) was obtained with the AS03A-adjuvanted H1N1v 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, 804LBLaunay O, 804LB


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?

Incid

en

ce p

rim

ary

PC

P

per

10

00 P

YF

U (

95

% C

I)

0.1

1

10

100

1000

Off On Off On Off On Off On Off On Off On Off On Off On* Off On

Events

Median CD4!

Median VL!

5

68

2.6

76

51

5.1

30

163

4.9

5

70

2.6

2

152

3.2

8

150

4.9

11

530

2.6

8

489

3.4

44

415

4.6

5

320

2.6

0*

300

3.2

101-200cells/µL > 200 cells/µL

Low Middle High

*No events; incidence and lower bound of 95% CI=0.0; !During follow-up in strata; VL in log10copies/ml

Current VL

<100cells/µL

Low Middle High Low Middle High

Current CD4

Current use of PcP prophylaxis

5

70

3.4

6

64

3.2

4

300

4.7

4

168

3.4

7

156

2.6

2

170

2.6

31

46

5.1

Furrer H, 789Furrer H, 789

Prophylaxis PYFU PcP events Incidence per

1000 PYFU (95% CI)

On 3355 7 2.1( 0.8–4.3)

Off 1613 2 1.2 (0.2–4.5)

<400 <400 <400

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, 814Crum-Cianflone N, 814

A Randomized Clinical Trial Comparing Revaccination with Pneumococcal Polysaccharide Vaccine (PPV) to Pneumococcal

Conjugate Vaccine (PCV) among HIV-Infected Adults

Crum-Cianflone N, 814Crum-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.

CMV-specific T Cell Responses are Higher in HIV-infected Patients

Naeger et al, submitted

Decreasing Asymptomatic CMV Replication with Valganciclovir Decreases Immune Activationin HIV+ Patients with CD4<350 despite cART

Hunt et al, CROI, 2010, P#380

Valganciclovir Reduces CD8+ T Cell Activation among HIV-infected Patients with Suboptimal CD4+ T cell Recovery

During Antiretroviral Therapy

Hunt P, 380Hunt P, 380

September 2009

SNPs that are inherited together are compiled into "haplotypes"

Single nucleotide polymorphisms (SNPs) are identified in DNA from multiple individuals

"Tag" SNPs are identifiedand genotyped

Genome-wide association studies

www.hapmap.org

~500,000 “tag SNPs” characterise ~10,000,000 SNPs

>90% of common human genetic variants

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

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

Response to HCV therapy Natural HCV clearance

Correlation of genetic variation in IL28Bwith HCV recovery rates in diverse ethnicities

Thomas DL et al. Nature. 2009;461:798-801.Thomas DL et al. Nature. 2009;461:798-801.Ge D, et al. Nature 2009;461:399-401. 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 ratesDifferent frequencies in IL28B variants explain ethnical differences in HCV recovery rates

Consistent effect of genetic variation in IL28Bon spontaneous HCV clearance

Rauch A, et al. Gastroenterology 2010; Jan 7. Thomas et al. Nature. 2009;461:798-801. Rauch A, et al. Gastroenterology 2010; Jan 7. Thomas et al. Nature. 2009;461:798-801.

Carriage of IL28B risk alleles predicts chronic HCV infectionCarriage of IL28B risk alleles predicts chronic HCV infection

HCV monoinfection

HIV/HCV coinfection

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. 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 failureCarriage 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

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, 165LBRallón NI, 165LB

IL28B SNP is associated with spontaneous HCV clearance in HIV patients

rs12979860 & SVR

p<0.0001

p=0.001

p=0.684

p=0.08775%

38%

65%

30%

86%81%

67%

25%

SV

R

All HCV-1 HCV-3 HCV-4

CC

CT/TT


Predictors of SVR in HIV/HCV Co-infection


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)


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


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. 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.

Launay O, 623Launay 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 24 At weeks 0, 4, 8 and 24 At weeks 0, 4, 8 and 24


Launay O, 623Launay 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.


Rodriguez C, 170LBRodriguez 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.

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.

Trends in Cumulative Incidence of Cancer among HIV-infected Patients in North America

Trends in Cumulative Incidence of Cancer among HIV-infected Patients in North America

Silverberg MJ, 758Silverberg MJ, 758

Ortiz M, 1019Ortiz 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*p<0.05

Ortiz M, 1019Ortiz 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.

Wilkin T, 1015Wilkin 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. 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.

J. Del AmoP. Domingo

D.B. GoldsteinP. HuntD. Havlir

O. Launay

J. Del AmoP. Domingo

D.B. GoldsteinP. HuntD. Havlir

O. Launay

AcknowledgementsAcknowledgements

http://www.retroconference.org/2010http://www.retroconference.org/2010

C. ManzardoE. MartínezA. RauchI. Sereti

A. TelentiV.Soriano

C. ManzardoE. MartínezA. RauchI. Sereti

A. TelentiV.Soriano

1 7 th croi, san francisco, 2010 . hotel ac, barcelona – february 26 th 2010

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