La Pedrera, Barcelona March th13 2018 Summary I: TB ... · La Pedrera, Barcelona March th13 2018...

La Pedrera, Barcelona

March 13th 2018

Dr. José M. Miró Infectious Diseases Service

Hospital Clinic - IDIBAPS University of Barcelona

Barcelona (Spain)

Summary I:

TB, Opportunistic Infections, HCV/HBV

Co-Infections, HPV, STI & Tumors

E-mail address: jmmiro@ub.edu

Accepted, 1105 (51%)

- Oral, 114 (10%)

- Poster, 991 (90%) Hepatitis, 91 (8%)

Tuberculosis, 46 (4%)

Cryptococcal meningitis + OIs 51 (5%)

STI / HPV, 43 (4%)

Cancer, 68 (6%)

Abstracts - CROI 2018

TB/OIs, HCV/HBV, STI/HPV & Tumors

Tuberculosis

Cryptococcal meningitis

Other Infections

IRIS

HCV/HBV coinfection

HPV/STI

Cancer

JoAnne L. Flynn, CROI 2018

JoAnne L. Flynn, CROI 2018

RCT ONE MONTH OF RIFAPENTINE/ISONIAZID TO PREVENT

TB IN PEOPLE WITH HIV: BRIEF-TB/A5279 RCT (#37LB)

Rifapentine + Isoniazid, 1 month

=

Isoniazid, 9 months

ONE MONTH OF RIFAPENTINE/ISONIAZID TO PREVENT TB IN

PEOPLE WITH HIV: BRIEF-TB/A5279 RCT (#37LB)

ONE MONTH OF RIFAPENTINE/ISONIAZID TO PREVENT TB IN

PEOPLE WITH HIV: BRIEF-TB/A5279 RCT (#37LB)

First RCT to focus on IPT in

HIV-infected pregnant and

postpartum women at high

risk of developing TB

RCT OF SAFETY OF ISONIAZID PREVENTIVE

THERAPY DURING OR AFTER PREGNANCY (#142LB)

RCT OF SAFETY OF ISONIAZID PREVENTIVE

THERAPY DURING OR AFTER PREGNANCY (#142LB)

RCT OF SAFETY OF ISONIAZID PREVENTIVE

THERAPY DURING OR AFTER PREGNANCY (#142LB)

RCT OF SAFETY OF ISONIAZID PREVENTIVE

THERAPY DURING OR AFTER PREGNANCY (#142LB)

RCT OF SAFETY OF ISONIAZID PREVENTIVE

THERAPY DURING OR AFTER PREGNANCY (#142LB)

RCT OF SAFETY OF ISONIAZID PREVENTIVE

THERAPY DURING OR AFTER PREGNANCY (#142LB)

RCT OF SAFETY OF ISONIAZID PREVENTIVE

THERAPY DURING OR AFTER PREGNANCY (#142LB)

!

URINE-BASED SCREENING FOR TUBERCULOSIS:

A RCT IN HIV-POSITIVE INPATIENTS (#38LB)

URINE-BASED SCREENING FOR TUBERCULOSIS:

A RCT IN HIV-POSITIVE INPATIENTS (#38LB)

URINE-BASED SCREENING FOR TUBERCULOSIS:

A RCT IN HIV-POSITIVE INPATIENTS (#38LB)

STATIS RCT: SYSTEMATIC vs. TEST-GUIDED

TUBERCULOSIS TREATMENT (#29LB)

• The trial was conducted in Côte d'Ivoire, Uganda, Cambodia and Vietnam

(African and Asian countries).

• ART-naïve HIV-1 infected adults with CD4<100 cells/µl ready to start ART

were randomly assigned to either ART + extensive TB screening using

Xpert MTB/RIF and urine LAM (arm 1) or ART + systematic empirical

TB treatment (4HRZE/2HR) (arm 2).

• 1047 participants were included (arm 1: 525; arm 2: 522; 56% from Africa;

44% from South-East Asia).

• The W24 hazard ratio of events between arm 2 vs. arm 1 was 0.93 (95%

CI 0.61-1.42) for death or IBD, 0.92 (0.57-1.48) for death alone, 1.14

(0.54-2.40) for IBD alone and 2.70 (1.80-4.04) for grade 3-4 drug-related

toxicity.

→ Systematic TB treatment is not superior to extensive TB

screening in ART-naïve adults ready to start ART with CD4<100/µl.

SAFETY AND EFFICACY OF DOLUTEGRAVIR-BASED ART IN

TB/HIV COINFECTED ADULTS AT WEEK 24 (#33)

DTG-based ART =

EFV-based ART

TB Disease

RIF-based TB treatment

SAFETY AND EFFICACY OF DOLUTEGRAVIR-BASED ART IN

TB/HIV COINFECTED ADULTS AT WEEK 24 (#33)

SAFETY AND EFFICACY OF DOLUTEGRAVIR-BASED ART IN

TB/HIV COINFECTED ADULTS AT WEEK 24 (#33)

SAFETY AND EFFICACY OF DOLUTEGRAVIR-BASED ART IN

TB/HIV COINFECTED ADULTS AT WEEK 24 (#33)

Tuberculosis “Pearls”

#767 IMPROVED SENSITIVITY OF A NOVEL RECOMBINANT

PROTEIN SKIN TEST FOR THE DIAGNOSIS OF TB.

#772 C-REACTIVE PROTEIN (CRP) TO SCREEN FOR HIV-

ASSOCIATED TUBERCULOSIS IN SOUTH AFRICA.

#773 PLASMA INDOLEAMINE 2, 3-DIOXYGENASE (IDO)*, A

BIOMARKER FOR TUBERCULOSIS DISEASE IN HIV

INFECTION

* IDO is an immunoregulatory enzyme that breaks down tryptophan (Trp) to metabolites known as kynurenines (Kyns) and the ratio

of Kyn to Trp is very useful for TB diagnosis: PPV 89% & NPV 100%. Adu-Gyamfi CG ET AL. Clin Infect Dis. 2017; 65:1356-58.

TB/OIs, HCV/HBV, STI/HPV & Tumors

Tuberculosis

Cryptococcal meningitis

Other Infections

IRIS

HCV/HBV coinfection

HPV/STI

Cancer

RCT HIGHER HIGH DOSE FLUCONAZOLE FOR THE

TREATMENT OF CRYPTOCOCCAL MENINGITIS (#35)

RCT HIGHER DOSE FLUCONAZOLE FOR THE

TREATMENT OF CRYPTOCOCCAL MENINGITIS (#35)

RCT HIGHER DOSES FLUCONAZOLE FOR THE

TREATMENT OF CRYPTOCOCCAL MENINGITIS (#35)

1,600 mg oral FLU is the most effective

dose and safer than 2,000 mg,

although less effective than AMB !!!

ASTRO-CM RCT ADJUNCTIVE SERTRALINE IN HIV-

ASSOCIATED CRYPTOCOCCAL MENINGITIS (#36)

• Amphotericin B 7-14 days

plus fluconazole starting at

800 mg daily.

• Sertraline: 400 mg/day for 2

weeks, followed by 200

mg/day for 10 weeks.

ASTRO-CM RCT ADJUNCTIVE SERTRALINE IN HIV-

ASSOCIATED CRYPTOCOCCAL MENINGITIS (#36)

Sertraline did not reduce mortality

among patients with HIV-associated

cryptococcal meningitis

TB/OIs, HCV/HBV, STI/HPV & Tumors

Tuberculosis

Cryptococcal meningitis

Other Infections

IRIS

HCV/HBV coinfection

HPV/STI

Cancer

CMV VIREMIA AND DISEASE IN PATIENTS WITH ADVANCED

HIV INFECTION: A PROSPECTIVE STUDY (N=49) (#801)

Prevalence CMV viremia ↑

CMV EOD ↓ (only 1 case)

→ CMV Rx is not necessary

TB/OIs, HCV/HBV, STI/HPV & Tumors

Tuberculosis

Cryptococcal meningitis

Other Infections

IRIS

HCV/HBV coinfection

HPV/STI

Cancer

Integrase Inhibitor-based ART regimens

are a Risk Factor for IRIS in CROI 2017

Dutch cohort*

French cohort**

OR (95%CI)

3.25 (1.83 - 5.80)

1.99 (1.09 - 3.47)

*CROI 2017 # 731 (ATHENA) & **CROI 2017 # 732 (Dat’AIDS Study Group)

IMPACT OF RALTEGRAVIR INTENSIFICATION OF

FIRST-LINE ART ON IRIS IN THE REALITY TRIAL (#23)

IMPACT OF RALTEGRAVIR INTENSIFICATION OF

FIRST-LINE ART ON IRIS IN THE REALITY TRIAL (#23)

IMPACT OF RALTEGRAVIR INTENSIFICATION OF

FIRST-LINE ART ON IRIS IN THE REALITY TRIAL (#23)

IMPACT OF RALTEGRAVIR INTENSIFICATION OF

FIRST-LINE ART ON IRIS IN THE REALITY TRIAL (#23)

IMPACT OF RALTEGRAVIR INTENSIFICATION OF

FIRST-LINE ART ON IRIS IN THE REALITY TRIAL (#23)

RALTEGRAVIR intensification did

not increase IRIS incidence

TB-IRIS: INSPIRING Trial (#33)

DOLUTEGRAVIR ART did not

increase TB-IRIS incidence

IRIS: OPTIMAL Trial (#495)

INSTI based ART did not increase

IRIS incidence in OPTIMAL RCT

PCP-IRIS RISK FACTORS (#795)

IRIS occurred in 12 of 97 German patients (12.4%)

There were no significant differences regarding other parameters including death, initial

CD4 count or time between start of PCP therapy and ART.

KS-IRIS (#133)

KS-IRIS (#133)

KS-IRIS (#133)

TB/OIs, HCV/HBV, STI/HPV & Tumors

Tuberculosis

Cryptococcal meningitis

Other Infections

IRIS

HCV/HBV coinfection

HPV/STI

Cancer

TasP in Switzerland: The Swiss HCVree Trial (#81LB)

INTERNATIONAL vs. DOMESTIC

HCV TRANSMISSION IN MSM (#130)

Foreing-to-Swiss transmission was

estimated to range between 24% and 62%

LOW RATES OF SPONTANEOUS CLEARANCE

OF ACUTE HCV COINFECTION (#129)

8 WEEKS OF GRAZOPREVIR/ELBASVIR FOR ACUTE

HCV: A MULTICENTER RCT (DAHHS 2) (#128)

8 WEEKS OF GRAZOPREVIR/ELBASVIR FOR ACUTE

HCV: A MULTICENTER RCT (DAHHS 2) (#128)

94%-98%

SVR12

RETREATMENT OF HEPATITIS C INFECTION IN PATIENTS

WHO FAILED GLECAPREVIR/PIBRENTASVIR (#128)

RETREATMENT OF HEPATITIS C INFECTION IN PATIENTS

WHO FAILED GLECAPREVIR/PIBRENTASVIR (#128)

RETREATMENT OF HEPATITIS C INFECTION IN PATIENTS

WHO FAILED GLECAPREVIR/PIBRENTASVIR (#128)

HIGH INCIDENCE OF HCV REINFECTION IN

MSM IN THE GECCO COHORT (#128)

Out of 2,074 patients, 41(1.97%) were identified with an HCV reinfection.

Reinfection occurred within a median of 63 weeks (range16-180) after end-of-treatment response.

Hepatitis “Pearls”

#637 POTENTIAL FOR SERUM MICRO-RNAs TO PREDICT

FIBROSIS REGRESSION DURING HBV TREATMENT.

#639 CIRCULATING MICRO-RNAs IN HIV PATIENTS REVEAL

SPECIFIC SIGNATURES FOR LIVER DAMAGE

#640 MICRO-RNA PROFILE OF HCV SPONTANEOUS

CLEARANCE INDIVIDUALS SHOW PREVIOUS HCV

INFECTION

Hepatitis “Pearls”: “EXPANDING HOPE”

HIV D+/R+ Transplants (HOPE action)

• N = 24, KT 14, LT 10

• All patients survived with good graft function

HCV D+/R- Kidney transplantation (EXPANDER Trial)

• N=10 cases

• All cases received DAA: GZR/EBR±SOF

• SVR 100%, HCV Ab + 50% (SC)

• Safe 100% (No D/C) Christine Durand, CROI 2018

*Durand C et al. Ann Intern Med. 2018 Mar 6. doi: 10.7326/M17-2871.

TB/OIs, HCV/HBV, STI/HPV & Tumors

Tuberculosis

Cryptococcal meningitis

Other Infections

IRIS

HCV/HBV coinfection

HPV/STI

Cancer

2014 WHO Guidelines

69

Single visit screen-and-treat using cryotherapy.

Loop electrosurgical excision procedure (LEEP) is an alterative for women not eligible for cryotherapy.

Conditional recommendations for the optimal treatment to prevent cancer.

1. Santesso N, et al. International Journal of Gynecology and Obstetrics World Health Organization Guidelines for

treatment of cervical intraepithelial neoplasia 2 – 3 and screen-and-treat strategies to prevent cervical cancer the Guideline Support Group : Int J Gynecol Obstet 2016.

2014

ACTG 5282: HPV TEST & TREAT vs. CYTOLOGY-BASED

CERVICAL CANCER PREVENTION IN HIV+ WOMEN (#134)

ACTG 5282: HPV TEST & TREAT vs. CYTOLOGY-BASED

CERVICAL CANCER PREVENTION IN HIV+ WOMEN (#134)

ACTG 5282: HPV TEST & TREAT vs. CYTOLOGY-BASED

CERVICAL CANCER PREVENTION IN HIV+ WOMEN (#134)

ACTG 5282: HPV TEST & TREAT vs. CYTOLOGY-BASED

CERVICAL CANCER PREVENTION IN HIV+ WOMEN (#134)

HPV test-and-treat was not

associated with better outcomes

as compared to a single round of

cytology-based screening

INCIDENT HIV, HEPATITIS C AND OTHER STI IN

DAILY vs. EVENT-DRIVEN PrEP USERS (#1026)

PRIOR SYPHILIS PROTECTS AGAINST T. PALLIDUM

DISSEMINATION IN REPEAT INFECTION (#798)

SYPHILIS TREATMENT WITH DOXYCYCLINE IN

HIV-INFECTED PATIENTS (#796)

TB/OIs, HCV/HBV, STI/HPV & Tumors

Tuberculosis

Cryptococcal meningitis

Other Infections

IRIS

HCV/HBV coinfection

HPV/STI

Cancer

STATIN EXPOSURE IS ASSOCIATED WITH DECREASED

RISK OF CANCER (#132)

STATIN EXPOSURE IS ASSOCIATED WITH DECREASED

RISK OF CANCER (#132)

STATIN EXPOSURE IS ASSOCIATED WITH DECREASED

RISK OF CANCER (#132)

STATIN EXPOSURE IS ASSOCIATED WITH DECREASED

RISK OF CANCER (#132)

STATIN EXPOSURE IS ASSOCIATED WITH DECREASED

RISK OF CANCER (#132)

STATIN EXPOSURE IS ASSOCIATED WITH DECREASED

RISK OF CANCER (#132)

Statin exposure is associated

with lower risk of cancer

independent of HIV status.

Cancer “Pearls”

#651 STILL HIGH RISK OF VIRUS-RELATED CANCER

DESPITE 20 YEARS OF cART IN ICONA COHORT

#644 FAILURE RATE OF ULTRASOUND SURVEILLANCE

OF HEPATOCELLULAR CARCINOMA IN HIV+ PATIENTS

#669 PRESENTATION AND OUTCOME OF BIOPSY-

PROVEN HEPATOCELLULAR CARCINOMA BY HIV

STATUS

J. Baker C. Boesecke D.A. Braun R. Chaisson M. Colombo K. Dooley C. Durand

Acknowledgements

http://www.croiconference.org

J.L. Flynn A. Gupta S.P. Koenig J.M. Llibre N. Merchante J. Schillinger T. Sterling