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
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