what is new in prevention programmes for hiv, tb and ... · adult trial n=6859 event rates,...

What is new in prevention

programmes for HIV, TB and hepatitis

in Europe and worldwide?

Jürgen Kurt Rockstroh, EACS President,

Department of Medicine I, University Hospital

Bonn, Bonn, Germany

30-31 January 2019, Bucharest

• Honoraria for lectures and/or consultancies from

Abbott, AbbVie, Abivax, Gilead, Janssen, Merck, and

ViiV.

• Research grants from Dt. Leberstiftung, DZIF,

Hectorstiftung, NEAT ID.

Conflict of Interest: JKR

• Kevin M. De Cock, M.D., F.R.C.P. (UK), D.T.M. & H., is Director of the U.S. Centers for Disease Control and Prevention’s (CDC) country mission in Kenya.[1] He has previously served as the team lead for CDC response to Ebola in Liberia,[2] as Director of the CDC Center for Global Health, and as Director of the CDC Division of HIV/AIDS Prevention, Surveillance, and Epidemiology. Dr. De Cock additionally served as the Director of the World Health Organization (WHO) Department of HIV/AIDS from 2006-2009, overseeing all of WHO’s work related to HIV/AIDS focusing on initiatives to assist low- and middle-income countries in scaling up their treatment, prevention, care, and support programs.


• nothing

Wikipedia

PREVENTION PROGRAMS FOR HIV


1980’s 2030

Scheckter M, 2002

?

Early population-level successes (late 1980s)

Behavior change (Uganda)

100% Condom use (Thailand)

STI Treatment

Grosskurth, Lancet 2000, (likely to work mainly in HIV epidemics /sub-populations with high bacterial STIs)

Male & female condoms

Male circumcision

Auvert, PloS Med 2005; Bailey, Lancet 2007; Gray, Lancet 2007

Coates, Lancet 2000 Sweat, Lancet 2011 (effects mostly for persons who test HIV positive and couples)

HIV testing & counselling

Post-exposure prophylaxis

Cohen, NEJM, 2011; Donnell, Lancet 2010; Tanser, Science 2013

Treatment as prevention

Oral pre-exposure prophylaxis

Grant, NEJM 2010 (MSM) Baeten, NEJM 2012 (Couples) Paxton, NEJM 2012 (Heterosex.); Choopanya, Lancet 2013 (PWID)

Ongoing research

Vaccines

Vaginal ring

Antibodies

Long-acting Injectable ARVs

Carey, 1992 Weller, Cochrane DBS 2002

Hanenberg, Lancet 1994

Stoneburner, Science 2004

Harm reduction

Ljungberg, AIDS 1996 Des Jarlais, Lancet 1996 Hurley, Lancet 1997

Preventing transmission and acquisition of HIV: A timeline

1990’s 2000’s 2020’s

HIV Pandemic in 2018

1.8 Million

21.7 Million

17.5 Million

0

5

10

15

20

25

30

35

40

2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017

Mill

ion

s o

f Pe

op

le

New infections PLHIV Receiving ART Virally suppressed

36.9 Million

Source: UNAIDS, 2018

0 – 24%

decrease

1 – 24%

increase

25 – 49%

decrease

25 – 49%

increase

Data not

available

≥50% decrease

≥50% increase

Percent change in new HIV infections among adults (15 years and older), from

2010 to 2017

43% of countries with documented injecting drug use do not have harm reduction programmes or enabling policies for service delivery

Kilonzo N AIDS 2018

Impact of treatment and prevention interventions on

HIV incidence – Botswana: Design

• Pair-matched community-randomized trial in 30 communities

• Rapid scale-up of interventions in intervention communities, following enrollment of HIV incidence cohort in October 2013

– Intervention Group: • Community mobilization

• Home-based / mobile HIV testing campaigns, targeted testing

• Linkage to care support: scheduled clinic appointment, SMS reminder, active tracing if missed appointment

• Expanded antiretroviral treatment (ART):

– Expanded ART for residents with CD4 351-500, or with CD4 >500 + HIV-1 RNA ≥10,000

– Universal ART as of June 2016 (with treatment started at first clinic visit)

• Strengthened male circumcision (MC) services

– Standard of Care Group:

– ART for persons with CD4<350, WHO III/IV disease or pregnancy until June 2016, when transitioned to universal ART

• Primary Outcome: cumulative HIV incidence in Incidence Cohort

Makhema MJ, et al. AIDS 2018; Amsterdam, the Netherlands; July 23-27, 2018; Abst. WEAX0105LB.

IMPACT OF TREATMENT AND PREVENTION INTERVENTIONS ON HIV INCIDENCE –

BOTSWANA: RESULTS

Analysis Incidence Ratio

95% CI 2-sided p-value

Primary analysis (permutation test, pair-specific Cox PHM), unadjusted

0.69 0.09

Analysis to obtain 95% CI (standard pair-stratified Cox PHM), unadjusted

0.65 0.46-0.90 0.01

Primary analysis, adjusted* 0.62 0.04

Analysis to obtain 95% CI, adjusted* 0.70 0.50-0.99 0.04

Incidence Cohort Number Infections Annualized Incidence

Intervention (n=4,257) 57 0.59%

Control (n=4,290) 90 0.92%

* Covariates in adjusted analyses were: sex, age, education, marital status, concurrent sexual partners, and alcohol during last sex

Makhema MJ, et al. AIDS 2018; Amsterdam, the Netherlands; July 23-27, 2018; Abst. WEAX0105LB.

30-31 January 2019, Bucharest JAMA 2019

7.0 23.9

68.5

87

110

0

20

40

60

80

100

120 19,4

17,4

15,6

14,1 13,6

0

5

10

15

20

Rates of TDF/FTC for PrEP and HIV Diagnosis across units

3 5

12

26

35

7,51 7,48 7,57 7,75 7,94

0

2

4

6

8

10

0

10

20

30

40

HIV

Dia

gno

ses/

10

0,0

00

P

op

ula

tio

n

PrE

P U

se/1

00

0 P

op

ula

tio

n

2012 2013 2014 2015 2016

PrEP Use Rate HIV Diagnosis Rate

Rates in 10 States with Lowest PrEP Use Rates in 10 States with Highest PrEP Use

2012 2013 2014 2015 2016

Sullivan P, et al. AIDS 2018; Amsterdam, the Netherlands; July 23-27, 2018; Abst. LBPEC036.

Status of formal PrEP implementation in Europe December, 2018

Source: ECDC. Dublin Declaration monitoring 2018; validated unpublished data. Source: ECDC. Dublin Declaration monitoring 2018; validated unpublished data.

What issues are limiting or preventing the implementation of PrEP in your country?

0% 20% 40% 60% 80% 100%

Drug resistance

Adherence

Concerns about lower condom use

Increases in STIs

Feasibility

Cost of service delivery

Limited tehnical capacity

Cost of the drug

Percentage of countries (n=33)

High importance Medium Importance

Source: ECDC. Dublin Declaration monitoring 2018; validated unpublished data. Source: ECDC. Dublin Declaration monitoring 2018; validated unpublished data.

Cabotegravir Longacting as

PrEP efficacy studies

• HPTN 083

– 4500 international study in MSM/TGW (double blind, double dummy)

– Comparator arm: TDF/FTC

– Powered for non-inferiority

– Requires 187 infections

• HPTN 084

– 3200 women aged 18-45 in Sub-Saharan Africa (double blind, double dummy)

– Comparator arm: TDF/FTC

– Powered for non-inferiority and superiority depending on level of adherence in the oral TDF/FTC arm

– Requires approximately 100 infections

• China CAB LA Program

– 1000 MSM/TGW

– Open label comparison to elective TDF/FTC

– Powered for both non-inferiority and superiority

– Assumes infection rate of 5% in China and 1% or less in Australia

– Design protects against futility

Slide courtesy of Marty Markowitz

PREVENTION PROGRAMS FOR TB


TB the big challenge

• Europe’s TB burden is among the lowest in the world - # of new TB patients has been falling at an average

rate of 4.3% per year in the last decade.

• 290 000 new TB cases and 26 000 TB deaths were reported in the Region in 2017

• BUT #of new MDR-TB cases is the highest - 19% of new TB cases and 55% of previously treated TB cases are

MDR-TB

• Strongly associated with social determinants of health - imprisonment, migration and social marginalization.

• Countries in the eastern part of the Region are the most affected by the TB epidemic: 18 high-priority

countries for TB control bear 85% of the TB burden and 99% of the MDR-TB burden

• Between 2007–2017, the WHO European Region faced an unprecedented increase in HIV prevalence in

incident TB cases from 3% to 12% - higher than global average of 10%

• Despite universal treatment coverage for TB and RR/MDR-TB patients, the treatment success rate in the

Region is still below the 85% target


Probability of death in the Temprano Study IPT reduces risk of death by 37% - independent of ART

Badje et al., Lancet Global Health, 2017

• HIV+ adults and children with CD4 <100 starting ART

• ‘Enhanced prophylaxis’ (3 mos. IPT, fluconazole, azithro, albendazole, TMP-SMZ)

• Control: ART + TMP-SMZ

% Mortality

Hakim et al., N Engl J Med 2017;377:233-45

Enhanced prophylaxis plus ART in advanced

HIV-infection The REALITY STUDY

Poor Global Uptake of IPT for People with HIV

WHO. Global TB Report, 2017

4 months of rifampin to prevent TB in high-risk people 4v9 Trial – 4R vs 9H

Adult trial

N=6859

Event rates, confirmed and possible TB:

4R 0.1/100 PY

9H 0.12/100 PY

Rate difference 0.01, 95% CI -0.24, 0.21

Excellent safety with both regimens

Pediatric trial

N=829

Events, clinical TB:

4R No cases 0/100 PY

9H 2 cases 0.25/100 PY

Excellent safety with both regimens

Menzies et al; NEJM 2018;379:440-53;454-63.

Make Preventive Therapy Even Shorter?

BRIEF TB: A5279

Design: Multicenter, randomized, open-label, phase III clinical trial

Population: 3000 participants HIV-infected individuals ≥13 years old and no evidence of active TB 97% enrolled from high-burden countries

Treatments Daily rifapentine/isoniazid for 4 weeks (1HP)

Daily isoniazid for 36 weeks (9H)

S. Swindells, R. Ramanchandi, A. Gupta, et al., CROI 2018, 37-LB

BRIEF TB – Time to endpoint 1HP

9H

Swindells, et al., CROI 2018

Strategies for improving uptake

of TB preventive therapy

• Make testing for infection easier and more accurate

• Make screening of potential recipients easier

• Make preventive therapy easier/safer

• Link TPT to ART – universal treatment for all

• Motivate programs, clinicians, and patients to accept

preventive therapy

TB vaccine…???

PREVENTION PROGRAMS FOR HEPATITIS


Interventions 2030 targets

1. Service coverage

1. Three dose hepatitis B vaccine 90%

2. HBV PMTCT 90%

3. Blood and injection safety 100 % screened donations

90% reuse-prevention devices

4. Harm reduction 300 injection sets/PWID/yr

5. Treatment 90% diagnosed

80% eligible treated

2. Impact A. Incidence reduction 90%

B. Mortality reduction 65%

HEPATITIS STRATEGY, 2016: ELIMINATION BY 2030

PMTCT: Prevention of mother to child transmission PWID: Person who injects drugs

3-DOSE HEPATITIS B VACCINE: 84% COVERAGE HBV

30

20

10

0

40

50

60

70

80

90

100

1990 1995 2000 2005 2010 2015

Co

vera

ge (%

)

Year

African

American

Eastern Mediterranean

European

South East Asia

Western Pacific

Global

Source: WHO AND UNICEF

HBV

50

40

30

20

10

0

60

70

80

90

2000 2005 2010 2015

Co

vera

ge (

%)

Year

African

American

Western Pacific

Global

Source: WHO AND UNICEF

HEPATITIS B BIRTH DOSE: 39% COVERAGE

BLOOD AND INJECTION SAFETY

Proportion of unsafe injections by region: challenges remain, particularly in the Eastern Mediterranean region

Source: Pepin et al, 2013

HARM REDUCTION– NEEDLE SYRINGE DISTRIBUTION

0 0.5 1 1.5 2 2.5 3 3.5 4

EUR

WPR

AMR

EMR

SEAR

AFR

PWID population (Millions)

4.50 10 60 20 30 40 50

Number of syringe/ needle sets / PWID / year

11.8 million PWIDs* worldwide 27 needle and syringes/ PWID* / year

EUR: European Region, WPR: Western Pacific Region, AMR: American Region, EMR: Eastern Mediterranean Region, SEAR: South East Asia Region, AFR: African Region

*PWID: Person who injects drugs

Source: UNODC, UNAIDS, WHO

Marked reduction in the prevalence of HCV among PWID

during 2nd year of the Treatment as Prevention (TraP HepC)

programme in Iceland

• Nationwide treatment programme initiated Jan 2016, aiming for elimination of CHC infection as

a public health threat. Estimated 800–1000 HCV-infected individuals in Iceland

• Vogur Addiction Hospital, a key sentinel site where most PWID in Iceland seek treatment;

provides an opportunity to monitor trends in HCV prevalence among PWID

Runarsdottir V, et al. ILC 2018, #1705 (PS-095)

HCV PCR positive PWID at Vogur Hospital 2015–17

0

40

80

120

160

2015 2016 2017

Nu

mb

er o

f p

atie

nts

Start of TrapHepC • After 2 years of TrapHep C,

80–85% of all patients evaluated or initiated on DAA treatment

• HCV prevalence among PWID:

– 2015: 42.6% – among those admitted for addiction treatment prior to TraP HepC

– 2017: 11.6% – representing a 73% reduction (p<0.001)

• Conclusion:

– A major scale-up in HCV treatment all patient groups has been successfully initiated in Iceland

– This has already translated into a significant reduction in prevalence among PWID

– Key population, should be the focus of treatment scale-up to curtail spread of HCV

Successful treatment intervention among

HIV/HCV co-infected MSM in Switzerland:

HCVree study

• Systematic population-based screening identified 203 potential HCV spreaders

• 89% of identified HCV-infected MSM accepted DAA treatment

• SVR rate = 99.5%

Braun D. CROI 2018; Oral #0-06

31 16

147

12

050

100150200

Oct 2015–Jun 2016

Mar 2017–Nov 2017

Oct 2015–Jun 2016

Mar 2017–Nov 2017

Tota

l nu

mb

er

of

infe

ctio

ns

92.5% decrease in chronic infections

49% decrease in acute infections

Phase A Phase C Phase A Phase C

Successful treatment intervention among

HIV/HCV co-infected individuals in Spain:

GeSIDA study

• Comparison of HCV prevalence among HIV-infected individuals in Spain from 2002–2017

• In 2017, the reference population = 40,322, and sample size = 1690 patients

González J, et al Enferm Infecc Microbiol Clin 2005;23:340–8;

González J, et al. IV Congreso Nacional de GeSIDA 2012; Abstract #PO-41;

Berenguer J, et al. Open Forum Infect Dis 2016;3:ofw059;

Berenguer J, et al. Open Forum Infect Dis 2018;5:ofw258;

Berenguer J, González J, et al. Personal communication (2018)

*, ** P trend <0.001

HCV serology was known in 1675 patients.

61 50 38 35 34 [WERT] [WERT] 22 12 [WERT] 0

10

20

30

40

50

60

70

2002 2009 2015 2016 2017

% o

f p

atie

nts

Prevalence of HCV seropositivity and active HCV infection

HCV Ab+HCV RNA+

*

**

**

**

** *

*

*

* *

↓ 37%

↓ 35%

↓ 47%

↓ 32%

*

[WERT]

[WERT] 59 75 82

0

20

40

60

80

100

2002 2009 2015 2016 2017

% o

f p

atie

nts

HCV treatment uptake P<0.001

Big thank you to: Fiona Mulcahy Teymur Noori

Cristiana Oprea Anton Pozniak

what is new in prevention programmes for hiv, tb and ... · adult trial n=6859 event rates,...

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