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