integration of hiv prevention and care treatment and support … 09 17 - dawood, h.pdf · 2020. 9....
TRANSCRIPT
CAPRISA hosts a MRC
HIV-TB Pathogenesis and Treatment Research Unit
CAPRISA hosts a DST-NRF Centre
of Excellence in HIV Prevention
CAPRISA is the UNAIDS
Collaborating Centre forHIV Research and Policy
Integration of HIV Prevention and Care, Treatment and support (TB/HIV co-infection)
SAHCS Continuing Medical Education : TB Course
17 September 2020
Halima Dawood (MBCHB)
Head of Clinical unit: Greys hospital
Honorary Senior Scientist :CAPRISA
Overview
• Global and Local HIV and TB epidemics
– Prevalence
– Incidence
– Mortality
• Current Strategies for Prevention and Control of TB and TB-associated mortality
• Current Strategies for Prevention of HIV
• Conclusion
Global HIV epidemic - 2017
36.9 million living with HIV, 1.8 million new infections, 1.0 million deathsSource: UNAIDS 2018
Middle East & North Africa
230 000[160 000 – 380 000]
Eastern and Southern Africa
19.6 million[17.8 million–21.1 million]
Eastern Europe & Central Asia
1.6 million [1.4 million – 1.7 million]
Asia and the Pacific
5.1 million[3.9 million – 7.2 million]
North America and Western and Central Europe
2.1 million [2.0 million – 2.3 million]
Latin America &Caribbean
1.8 million[1.4 million–2.1 million]
West & CentralAfrica
6.1 million[4.9 million–7.6 million]
Worsening of the HIV epidemic in young women in SA from 1990 to 2005
The HIV epidemic in South Africa has been characterisedby high prevalence rates in young women
High rates of HIV among key
populations: young women in
Africa
HIV in 15–24 year men and women(2008–2011)
Young women have up to 8 times more HIV than men
Source: Adapted from UNAIDS 2012
Zimbabwe
Young women: a key population for HIV prevention in South Africa (CAPRISA 055)
Age Group (years)HIV Prevalence
2004-2008 (N=1237) 2009-2011 (N=728)
12-16 10.6% 6.7%
17-18 21.3% 18.5%
19-20 33.0% 27.9%
21-22 44.3% 33.6%
23-24 51.0% 43.8%
Top 15 countries: People living with HIV
Rank Country% of people withHIV in the world
1 South Africa 18%
2 Nigeria 9%
3 India 6%
4 Kenya 5%
5 Mozambique 4%
6 Uganda 4%
7 Tanzania 4%
8 Zimbabwe 4%
9 USA 4%
10 Malawi 3%
11 Zambia 3%
12 China 2%
13 Ethiopia 2%
14 Russia 2%
15 Brazil 2%
Remaining countries
27%
73%
33%
South Africa
Nigeria
India
Kenya
Mozambique
Uganda
TanzaniaZimbabwe
USAMalawi
Zambia
China
Ethiopia
Russia
Brazil
Remaining countries
HIV Incidence and mortality in South Africa
~ 270 000 new
HIV infections in
2017
~150 000 new HIV
infections in
women 15 years
and older
Knowledge of HIV status, treatment coverage & viral load suppression globally in 2016
PLWH who know their status
PLWH on treatment
PLWH who are virally suppressed
Source: UNAIDS
Great progress on increasing HIV treatment but we are lagging in prevention
Source: Global AIDS Response Progress Report.
7,5
9,1
10,9
12,9
15
17,1
19,520,8
0
5
10
15
20
25
2010 2011 2012 2013 2014 2015 2016 2017
Peo
ple
on
An
tire
tro
vir
al th
era
py
(millio
ns)
Year
Number of people receiving antiretroviral therapy, by WHO region, 2010–2017
2015 target within the 2011 United National Political
Declaration on HIV and AIDS
5% reduction in new infections 2013 - 2016
Highest Priority: Reducing HIV in young girls HIV in rural South Africa (Grade 9/10)
Age Group (years)
HIV Prevalence (2010)% (95% Confidence Interval)
Male (n=1252)
≤15 1.0 (0.0 - 2.2)
16-17 1.1 (0.2 - 2.0)
18-19 1.5 (0 - 3.7)
≥20 1.8 (0 - 3.9)
Female (n= 1423)
2.6 (1.2 - 4.0)
6.1 (2.6 - 9.6)
13.6 (9.0 - 18.1)
24.7 (6.3 - 43.1)
Overall Prevalence:• HIV : 6.7% • HSV-2 : 10.7% • Pregnancy : 3.6%
HIV prevalence in the community – more people infected than uninfected!
6,011,6
18,1
32,8
40,1
47,8 47,8
58,7
70,266,1
3,66,2 8,3 8,1
11,3
21,7
33,3 34,940,1
50,2
0
10
20
30
40
50
60
70
80
15-16 17-18 19-20 21-22 23-24 25-26 27-28 29-30 31-32 33-34
HIV
Pre
vale
nce (
%)
Age group in years
Women Men
HIV prevalence in 2 year age bands in 2014/5 in rural KZN, n=9,812
Most men & women 25-40 years acquire
HIV from similarly aged partners (Mean
age difference = 1.1 years)
Men 25-40 years (N=79)
Knew HIV status: 21.5%
VL > 50,000 : 37.1%
Young women <25 years (N=43)
Knew HIV status: 23.3%62% of male partners are 25-40 years
Women 25-40 years (N=56)
Knew HIV status: 42.6%63% of male partners are 25-40 years
Most young women <25 years acquire HIV
from older men (Mean age difference =
8.7 years)
When young women reach >25 years they continue the cycle
39% of the men linked to a woman <
25 are simultaneously also linked to a
woman 25-40 years
Community HIV prevalence: 22.3% Community HIV prevalence: 59.8%
Community HIV prevalence: 40.3%
De Oliviera T, Kharsany A, et al. Lancet HIV 2016
90 phylogenetically linked clusters (man
& woman) from 1,589 viruses
Cycle of HIV transmission in rural KZNSchematic of sexual networks from clusters with heterosexual transmission
What are the HIV prevention options for women?
Existing HIV prevention strategies - ABCC:
• Pre-Exposure Prophylaxis
• Condoms (Male & Female)
• Circumcision
• Abstinence
• Behaviour (Be faithful)
Note: PMTCT, Screening transfusions, Harm reduction, Universal precautions, etc. have not been included –this is focused on reducing sexual transmission
Behavioural Intervention- Abstinence- Be Faithful
HIV Counselling and TestingCoates T, Lancet 2000
Male Condoms
Female Condoms
Treatment of STIs
Grosskurth H, Lancet 2000
Male circumcision
Auvert B, PloS Med 2005Gray R, Lancet 2007Bailey R, Lancet 2007
Treatment for prevention
Donnell D, Lancet 2010Cohen M, NEJM 2011
Microbicidesfor women
Abdool Karim Q, Science 2010
Grant R, NEJM 2010 (MSM)Baeten J , 2011 (Couples)Paxton L, 2011 (Heterosexuals)
Oral pre-exposure prophylaxis
Post Exposureprophylaxis (PEP)
Scheckter M, 2002
HIV
PREVENTION
ARV prophylaxis
New Hope in HIV Prevention
• Several studies: show that antiretroviral drugs prevent HIV infection
• Treatment for prevention
• Tenofovir gel: Promising new HIV prevention technology that can empower
women to protect themselves from HIV
• New discourse: 3 zeroes, AIDS-free generation, end in sight
Key challenges in PrEP & TasP:
1. Adherence: Healthy take medication everyday during risk life time course
2. Safety: Are ARVs safe in long-term?
3. Resistance: PrEP can cause ARV resistance and TasP lead to widespread resistance with poor adherence in well people?
4. Displacing condoms: Behavioural disinhibition / risk compensation…
5. Cost and Health service burden:Impact on health care systems:largepopulations on ARVs as PrEP or TasP
SA: Implementation success at country level
HIV testing campaign: 13 million HIV tests in 2010/11
Medical Male circumcision: 250,000 in 2011↑ 50-fold from 5190 circumcisions in 2008
Preventing mother-to-child transmission: Vertical transmission rate 2008 vs 2011 : 9.6% vs 2.7%
Scale up of ART provision South Africa has the largest ART programme in the world with 52% of those in need of ART receiving
treatment in South Africa in 2011
Tuberculosis detection Between March 2011 and July 2012, 472,734 specimens were tested using GeneXpert
6 year increase in Life Expectancy
The landmark HIV Prevention Trials Network
(HPTN) 052 trial in HIV-discordant couples
demonstrated unequivocally that treatment with
antiretroviral therapy (ART) substantially lowers
the probability of HIV transmission to the HIV-
uninfected partner. However, it has been
vigorously debated whether substantial
population-level reductions in the rate of new
HIV infections could be achieved in “real-world”
sub-Saharan African settings where stable,
cohabiting couples are often not the norm and
where considerable operational challenges exist
to the successful and sustainable delivery of
treatment and care
to large numbers of patients. We used data from
one of Africa’s largest population-based
prospective cohort studies (in rural KwaZulu-
Natal, South Africa) to follow up a total of 16,667
individuals who were HIV-uninfected at baseline,
observing individual HIV seroconversions over the
period 2004 to 2011. Holding other key HIV risk
factors constant, individual HIV acquisition risk
declined significantly with increasing ART
coverage in the surrounding local community.
For example, an HIV-uninfected individual living
in a community with high ART coverage (30 to
40% of all HIV-infected individuals
on ART) was 38% less likely to acquire HIV than
someone living in a community where ART
coverage was low (<10% of all HIV-infected
individuals on ART).
One of the most successful public health
interventions ever undertaken has been the
provision of combination antiretroviral therapy
(ART) to more than 6.2 million people in sub-
Saharan Africa (1). The ART scale-up has resulted
in substantial population-level reductions in HIV-
relatedmortality inmany populations (2, 3) and
overall is estimated to have saved a total of
more than nine million life-years (1). The results
of the landmark HIV Prevention Trials Network
(HPTN) 052 trial in HIV-discordant couples
demonstrated unequivocally that reducing the
infected partner’s viral load through ART
Measured population level
reduction in rate of new infections
Prospective cohort study : n=16 667
HIV uninfected between 2004-2011
HIV decline with increasing ART
coverage
ART coverage of 30-40% :38% less
likely to acquire HIV
Population cohort of over 101 000 in rural KZN
Changes in adult life expectancy between
2000-2011
Changes in life expectancy from 49,2 years to
60,5 years: 11.3 year gain
HIV has yet to be controlled!3 Key obstacles to an AIDS-free generation
• Dysfunctional health systems
– Implementation :failure to convert efficacious treatment and prevention interventions into effectiveness
– Scale up access to services
• HIV continues to grow in Key Populations
– Reducing HIV in young women is key
• Stigma & discrimination
– Major obstacle to testing
– Barrier to access prevention & care services
Failure to prevent HIV infection in young women
=
Failure to control HIV in southern Africa
22
Stigma: Major impediment to HIV prevention and treatment
SILENCE
IGNORANCE
FEARSTIGMA
DISCRIMINATION
HIV/AIDS
Vaginal gel applicator Vaginal ring Vaginal film
What is a microbicide?
A microbicide is a product that can be applied in the vagina
or rectum with the intention of preventing the transmission
of sexually transmitted infections including HIV
Evidence on the effectiveness of topical and oral PrEP in women and the challenge of adherence
Effectiveness of oral PrEP in men
Effectiveness (%)-130 -60 -40 -20 0 20 40 60 80 100
Ora
l P
rEP
Study Effect size (CI)
TDF2 – daily Truvada(Heterosexual men - Botswana)
82%* (-3; 99)
Partners PrEP – daily Truvada(Discordant couples – Kenya, Uganda)
84%* (54; 94)
Partners PrEP – daily oral Tenofovir(Discordant couples – Kenya, Uganda)
63%* (20; 83)
*point estimate for men only
iPrEx – daily Truvada(MSM - America’s, Thailand, South Africa)
44% (15; 63)
IPERGAY – on demand Truvada(MSM – France)
86% (39; 99)
PROUD – daily oral Truvada(MSM – United Kingdom)
86% (62; 96)
Association between drug detection and HIV incidence
in tenofovir gel studies
a - Marrazzo et al. NEJM 2015; b - Kashuba et al. JAIDS 2015; c - Rees et al. CROI 2015
Tenofovir is effective when used…
Clinical trials of intravaginal rings in women
27%reduction
31%reduction
Baeten et al., Nel et al., NEJM 2016
New WHO policy on PrEP to prevent the spread of HIV by sex
New WHO PrEPguidelines
“..the use of daily oral pre-
exposure prophylaxis is recommended as an additional prevention choice for people at substantial risk of HIV infection as part of combination prevention approaches..”
PrEP recommended as global standard for all at
high risk, including young womenDaily
Truvada
Implementation of PrEP globally
Source: AVAC: April 2018
Implementation of oral PrEP for HIV prevention in South Africa
Implementation of oral PrEP for HIV prevention
2016June 2016 –February 2018
4 511 initiationsat 28 sites
Uptake:
Sex worker sites: 3408/27 486 (12%)MSM sites: 1061/ 2 032 (52%)
University sites: 42/ 645 (7%)
November 2015
March 2018 – PrEP initiations in SA: 8,500-9,500
What’s in store for new prevention technologies…
2-3 monthlyinjectable
antiretrovirals
Passive Immunity Broadly neutralising
antibodies
CAP256-VRC26.25
Once-off HIV vaccines
Annual sub-dermal
implants
TAF implantCabotegravir & Rilpivirine
Key Lessons
• Preventing HIV infection is a complex challenge - No quick fix, no magic bullets, no one size fits all
– Diversity of epidemics & Key populations
– Programmes need to be evidence based viz prevent HIV infection
– Knowledge based advances need to be implemented
– Target high burden districts for intensified action
– Strong health information systems to implement, monitor and plan locally
• As with vertical transmission and treatment our hope for prevention lies in the power of technology and research but It is only a starting point
– The needs of infected and uninfected persons and communities need to be met
– Success of interventions require awareness, acceptability, accessibility and uptake – products need to be available and used to work
– Supportive social environments are key – the bio-behavioural nexus is critical
– Most impacted populations need to be engaged and take ownership - passive recipients vs pro-active drivers
– Address needs of young women (including adolescents)
Health Systems Strengthening
• Feasibility of TasP
• QI approach
• Comprehensive services
• Care cascade for services
• Introduce new services
• Meet increased demand
• Increase coverage of what works
• Linkage to community
• Staff training and capacity building
• Systems and infrastructure strengthening
Global TB Epidemic –TB Incidence (2018)
• 10 million new TB cases • 8.6 % in PLWASource: WHO Global TB Report 2019
HIV prevalence in new TB cases (2018)
~10% of 14 million new TB cases were in
people with HIV
~374 000 deaths were from HIV-
associated TB Source: WHO TB Report 2019
HIV & TB epidemics in South Africa
0
100
200
300
400
500
600
700
800
900
1000
0
5
10
15
20
25
30
35
1990 1992 1994 1996 1998 2000 2002 2004 2006 2008 2010 2012
HIV
pre
vale
nce (
%)
Year
TB
(I
ncid
en
ce p
er
100 0
00 p
op
ula
tio
n)
0
100
200
300
400
500
600
700
800
900
1000
0
5
10
15
20
25
30
35
1990 1992 1994 1996 1998 2000 2002 2004 2006 2008 2010 2012
HIV
pre
vale
nce (
%)
Source: Annual point estimates from the South African Department of Health; http://www.tbfacts.org/tb-statistics-south-africa/ and http://data.worldbank.org/indicator/SH.TBS.INCDNote: The lines are based on fitted mathematical models developed by E Gouws (HIV) and A Grobler (TB)
Blue Line = Antenatal HIV prevalenceRed Line = TB incidence
Background – Unit builds on past research that impacted HIV-TB treatment and mortality
37
56% lower
mortality with integrated
TB-HIV treatment
2009: All patients with both TB and HIV will get treatment with antiretrovirals if their CD4 count is 350 or less. TB and HIV will now be treated under one roof.
52% decrease in annual TB
deaths since SAPIT results –declining for many reasons
COVID-19:Co-morbidity and CFR
Projected acceleration of TB incidence decline to target levels
Optimize use of current & new tools emerging from pipeline, pursue UHC and
social protection
Introduce new tools: a vaccine, a new easier prophylaxis &
treatment regimen, a PoC test
Average -10%/yearby 2025
-5%/year
Current global trend: -1.5%/year
Average-17%/year
Evidence of IPT and ART
• Retrospective data from South Africa* and Brazil**
• South Africa: 2778 HIV-infected patients, 4287 person-years,
• 267 TB incident cases (IR 6.2/100 pyrs)
Without IPT or ART IR 7.1 (95% CI 6.2–8.2)
ART alone IR 4.6 (95% CI 3.4–6.2)
IPT alone IR 5.2 (95% CI 3.4–7.8)
ART and IPT IR 1.1 (95% CI 0.02–7.6)
• Compared to treatment-naive patients:
ART-only patients had a 64% decreased risk of TB (aHR 0.36; 95% CI 0.25–0.51)
Patients receiving ART after IPT had a 89% decreased risk of TB (aHR 0.11; 95% CI 0.02–0.78)
• Brazil**: 11 026 HIV-infected patients between 1 Sep 2003 and 1 Sep 2005
Compared to treatment-naive patients those on ART had a 76% reduced TB risk (aHR 0.24) after starting IPT
*Golub JE, AIDS 2009, 23:631–636
**Golub JE, AIDS 2007, 21:1441–1448
Risk of death or severe HIV-related illness was 35% and 39% lower with IPT than
with no IPT among patients with baseline CD4 ≥ 500 and < 500 cells/mm3
Evidence from Recent RCT’s
RCT 2056
patients
Ivory Coast
Early vs deferred
ART with and
without IPT
TB vaccines
Future biomedical technologies to Control TB
rBCG
Viral vector
Protein/adjuvant
Attenuated M.tb
Immunotherapeutic:
Mycobacterial – whole cell
or extract
TB Drug Development
Pipeline4 Repurposed Drugs
6 New Drugs3 New Classes
Reducing HIV in young women could change the course of the epidemic in
Africa & reverse current poor global progress in HIV prevention
Need multiple strategies – current daily Truvada® as PrEP is a start but
better options needed
Both behaviour and biology can impact on PrEP effectiveness
For future PrEP options for women, need diverse strategies, especially long-
acting products for > 6 months per application
Conclusion
Conclusion
• Now is NOT the time to slow down our HIV/AIDS and TB efforts
– Opportunity is now!
– Prioritise prevention
• Implement evidence base interventions :
– Health systems & information strengthening
– Efficacious prevention in key populations
– Provide ART : test and treat
– Maintain high ARV adherence
– Mind set :Risk is personalized and internalised: eliminates stigma and discrimination (HIV and non HIV related)
– Gender issues need to be urgently and actively addressed
Conclusion
• TB is the number one cause of death in SA:yet curable and preventable
• Need to strengthen approach to managing TB irrespective of site, except for TB bone/meningitis
• Enhanced diagnostic capacity for TB yet ongoing TB transmission
• TB Prevention: key strategy for reducing TB related morbidity and mortality
• Every opportunity to screen for TB and HIV
The world has made defeating AIDS a top priority…. But TB remains ignored. Today we are calling on the world to recognize that we can’t fight AIDS unless we do much more to fight TB as well.
- Nelson Mandela
Bangkok, July 15, 2004