DR. I. KATJITAE

Specialist:

Internal Medicine, MOHSS

UNAIDS. Ending AIDS. Progress towards the 90-90-90 targets, 2017

Global ART Role-out

UNAIDS. Ending AIDS. Progress towards the 90-90-90 targets, 2017

Global AIDS Deaths

Life expectancy in years SSA

DA

LYs

pe

r 1

00

,00

0

1990 2015 1995 2000 2005 2010

Year

GBD 2015 Report

The disability-adjusted life year (DALY),

a measure of overall disease burden

UNAIDS. Ending AIDS. Progress towards the 90-90-90 targets, 2017

Global New HIV Infections

UNAIDS 2014

Treatment Target 90-90-90

UNAIDS data as of July 2017

ART Coverage

G. Friedland, CROI 2016

"From the outset, the epidemic was diverse,

and involved populations that were vulnerable, that were

marginalized, and somehow the virus had

this unique and diabolic way of finding

them"

12

G. Friedland, CROI 2016 13

Entry or

residence

restriction in

certain

countries for

HIV-positive

persons

Same-sex

relationship

criminalizatio

n

Criminalization of

some aspects of

sex work

Detention

centres for

intravenous

drug users

13

Gender

inequity

High pill burden for patients with co-Morbidities

15

2006 2012 2014 2014 2015

GENVOYA (elvitegravir + cobicistat +

emtricitabine + tenofovir

alafenamide)

Take with food

Att: drug-drug interactions

ODEFSEY (emtricitabine +

rilpivirine + tenofovir

alafenamide)

Take with food

Not appropriate for

baseline HIV RNA

above 100’000 copies

2016

EVIPLERA/COMPLERA (rilpivirine + emtricitabine

+ tenofovir)

Take with food

Not appropriate for

baseline HIV RNA above

100,000 copies

Stringent Regulatory Approval of two generic

suppliers for DTG/3(F)TC/TDF expected:

• Generic names: Atenef,

Atreslawin, Atroiza,

Citenvir, Heftenam,

Odimune, Tribuss,

Trivenz, Truno, Trustiva,

Viraday

*

Q1 2018

Not appropriate for HBV co-

infection

Att: drug-drug interactions

ATRIPLA EVI(COM)PLERA STRIBILD TRIUMEQ GENVOYA ODEFSEY

TDF/FTC/EFV TDF/FTC/RPV TDF/FTC/EVG/cob DTG/ABC/3TC EVG/cob/FTC/TAF TAF/FTC/RPV

Take with food Not with HBV Take with food Take with food co-infection

VL < 100'000 Attn: drug-drug Must be HLA Attn: drug-drug VL < 100'000

interactions B*5701 neg. interactions

For adults and adolescents, and children older than five years, advanced HIV disease is defined as CD4 cell count <200cells/mm3 or WHO stage 3 or 4 event. Includes both ART naïve individuals and those who interrupt treatment and return to care

All children younger than five years old with HIV are considered as having advanced HIV disease.

Ford et al, Lancet HIV 2016

A package of interventions including

screening, treatment and/or prophylaxis for

major opportunistic infections, rapid ART

initiation* and intensified adherence support

interventions should be offered to everyone

presenting with advanced HIV disease.

Strong recommendation, moderate-quality

evidence * linked recommendation

Namibia is one of the 30 high disease burden countries

In 2015:

◦ Estimated number of new cases: 12,000 (489/100,000)

Number of notified cases: 9,154 (CNR 436/100,000

population)

◦ Showing gradual decline since 2004

◦ Estimate case detection rate: 80%

◦ 40% were HIV positive

Sources: MoHSS NTLP Annual report2015

Y200

7

Y200

8

Y200

9

Y201

0

Y201

1

Y201

2

Y201

3

Y201

4

Y201

5

Y201

6

MDR TB (Excl XDR) 116 201 275 214 192 206 174 137 190 184

PDR-TB 7 47 80 63 46 41 19 14 17 17

Other RR 0 0 0 0 0 0 103 206 127 177

XDR 3 20 17 8 2 4 6 6 3 9

Total 126 268 327 285 240 251 302 363 337 387

0

50

100

150

200

250

300

350

400

450N

um

ber

of

case

s

National Tuberculosis and Leprosy

Programme

22

Lumbar Puncture

- India Ink/CrAg (CSF, lab)

- Acid Fast Bacilli (AFB)/

Gene expert (urine/CSF)/TB culture

- P. pneumoniae / N. meningitides POC

Implementation of ACTA

Bedside / POC tests

A phase III, randomised, controlled trial for the treatment of HIV-

associated cryptococcal meningitis: oral fluconazole plus

flucytosine or one week amphotericin B-based therapy vs two

weeks amphotericin B-based therapy

Percentage of

pregnant women

living with HIV

receiving most

effective

antiretroviral

medicines for

PMTCT

https://data.unicef.org/topic/hivai

ds/emtct/#

Percentage of pregnant women living with HIV receiving most effective antiretroviral medicines for PMTCT

New HIV infections among children (0-14y)

https://data.unicef.org/topic/hivaids/emtct/#

Global Plan 2011-2015

BACKGROUND

TB leading cause of maternal –infant mortality/morbidity in high HIV burden settings

Most TB in HIV+ pregnant women, despite universal ART

In SA 30% of all pregnant women HIV-infected

Symptoms identify those to be investigated with Xpert but: ◦ Pregnancy may mask TB symptoms

◦ All women are tested for HIV, syphilis, etc

Neil A Martinson

METHODS

• Cluster randomised trial 16 clinics

• 8 Universal: sputum from all

• 8 Symptom (SoC): If symptom/s presentsputum

• Public Sector lab: Xpert only; then Xpert + MGIT cult.

• 2 sites: high and medium burden

Baseline Characteristics by

Arm.

Universa

l

941

Symptom

1,100

Age 30.2 yrs 29.5 yrs

Gest 24.6 wks 24.4 wks

TB Sx 17.3% 22.1%

Prior

TB

9.8% 7.8%

On

ART

99.5% 98.6%

CD4

count

426

cells/mm3

451

cells/mm3

Hb 11.4 g/dl 10.8 g/dl

Yield of TB by Arm, by Visit and by Site

Study

Arm n/N

MTb

Yield (95%CI)

Baseline Matlosan

a

Vhembe

Univers

al

34/9

41

3.6%

(1.2-6.0)

26/34 4.5% 2.2%

Sympto

m

4/11

00

0.36%

(0.0-1.1)

4/4 0% 1.1%

Xpert MTB/RIF v MGIT Culture: Universal

MGIT Mycobacterial Culture

Positive Negative

Xpert

Result

Pos 5

(1.0%)

2

(0.4%) 7 (1.4%)

Neg 21

(4.1%) 479

(94.5%) 500

(98.6%)

Total 26

(5.1%) 481

(94.9%) 507

0.5 0.3

3.7

2.2

0 0.1

4.6

1

0

1

2

3

4

5

Ev

ents

per

10

0

S

U

CONCLUSION

• Universal: 10 fold detection of TB v Symptom based

• Xpert detects one third the rate of TB compared to MGIT – ?low bacillary load

• Halved infant and maternal deaths (not statistically significant)

Recommendations

• Improve on culture/Xpert

• Universal testing in other populations?

• Better understanding of those who would benefit from TB treatment

Katlego Mothlaoleng1, Ebrahim Variava1,4,

Grace Barnes2, Pattamakil Abraham1,

Limakatso Lebina1, Silvia Cohn2, Larry

Moulton5, Nicole Austin-Salazar2,

Richard E. Chaisson2

Funding: Departments of Health in the Limpopo and North West

Provinces. RO1 HD064354-05S1; AIDOAA-A1400060. The opinions

herein are not necessarily those of the funders.

p=0.134

p=0.879

p=0.424

Access Global

Affordability

Safety and

tolerability Convenience Efficacy

Table credit (adapted) clinicaloptions.com, with permission

Universal

prescription

in key

populations

Patient-specific Regimen-specific

Baseline HIV-1 RNA Long-term tolerability and safety

Chronic HBV or HCV coinfection Simplicity

Renal function Food intake requirements

Desire to become pregnant ART interactions with co-medication and

lifestyle drugs

Illicit drug use ART genetic barrier to resistance

HLA-B*5701 status Cost/Affordability

Age, Comorbidities

Previous ART exposure

Advanced HIV disease –

Acute Infection

2

Clinical criteria: Pregnant women,

Children/Adolescents/Aging, presence of

co-morbidities (TB/HCV/HBV), drug drug

interactions

HIV disease characteristics: Acute

infection, Late presenters, on efficient

chronic ART

Biological values: baseline VL;

Genetic barrier, presence of HLA-B*5701?

Epidemiological context:

Anticipated resistance, anticipated

adherence?

Convenient: one pill a day, minimal monitoring

Possibility of treatment harmonization (pregnant women, children,

HIV-TB co-infected individuals, HIV hepatitis B co-infected individuals)

TDF

+

3TC (or FTC)

+

EFV600 mg

1

2

Alternative

combinations

TDF + XTC + DTG

TDF + XTC* + EFV400 mg

* XTC= 3TC or FTC

2

ARV 2017 2018 2019 2020

Q3-Q4 Q1-Q2 Q3-Q4 Q1-Q2 Q3-Q4 Q1-Q2 Q3-Q4

DTG RADIO

DAWNING

ADVANZ-4 DOLPHIN 1

NAMSAL

DOLPHIN 2

D2EFT INSPIRING

VESTED

ODYSSEY

ADVANCE

PANNA

ING200336

EFV400

SSAT 062

SSAT 063

NAMSAL

Pregnant women Children TB Adults

Vitoria et al, JIAS 2016, Cohn J et al, AIDS 2015 33 *IAS 2017, Lamorde M et al, abstract # TUPDB0203 LB,

Zash R et al, #MOAX0202 LB (Botswana), Vannappagari et al, MOPEB0283 (APR)

YES, with some remaining uncertainties

Marco Vitoria courtesy, adapted from Vitoria et al, Curr Opin HIV/AIDS, 12: 369-76 2017

*

*

IMPAACT 1093

Vitoria et al, JIAS 2016, Cohn J et al, AIDS 2015 34

Study Drugs Intervention Major outcomes N Study

countries

Expected

completion

NAMSAL

(ANRS 12313)

NCT02777229

DTG

EFV400

Safety/efficacy of DTG vs EFV400

TDF/3TC + DTG vs

TDF/3TC + EFV400

VL at 24

and 48 weeks

606 Cameroon Q3 2018

ADVANCE

(WRHI 060)

NCT03122262

DTG

TAF

EFV600

Safety/efficacy of DTG and TAF

TDF+ FTC+ DTG vs

TAF + FTC + DTG vs

TDF + FTC + EFV600

1050 South Africa Q4 2019

DAWNING

(ViiV)

NCT02227238

DTG

LPV/r

Safety/efficacy of DTG vs LPV/r in

PLHIV failing first-line ART

2NRTI + DTG vs

2NRTI + LPVr

VL at 96 weeks 612

78% vs. 69% <50 c/mL at

week 24

Premature

interruption

ODYSSEY

(Penta)

NCT02259127

DTG

2NRTI + DTG vs SoC in children/

young adults (6-18 yrs) with HIV

starting first-line or switching to 2nd

ART

VL at 24 and 48

700 Multi countries Q3 2018

IAS 2017, Dawning study, Aboud et al, abstract # TUAB0105 LB

2

From Lazarus J et al, BMC Medicine 2016; 14: 94-98

“Penicillin cures, but wine makes people happy” Alexander Fleming

PEDIATRIC OPTIONS

Simple attractive regimens

Independence-childhood to adolescence

Bone development may be compromised

Adherence: Peer pressure

Co-Morbidities in children e.g.

Tuberculosis, dyslipidaemia, Renal failure

UNAIDS 2014

70% [51-84%]

44% [32-53%]

UNAIDS. Ending AIDS. Progress towards the 90-90-90 targets, 2017

UNAIDS 2014

70% [51-84%]

44% [32-53%]

UNAIDS. Ending AIDS. Progress towards the 90-90-90 targets, 2017