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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.
30-31 January 2019, Bucharest
• nothing
Wikipedia
PREVENTION PROGRAMS FOR HIV
30-31 January 2019, Bucharest
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
30-31 January 2019, Bucharest
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
30-31 January 2019, Bucharest
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
30-31 January 2019, Bucharest
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
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