Updates on HIV/AIDS Management

Programme

Dr. Ismael Katjitae

Specialist Physician
Ministry of Health and Social Services
Namibia

16 August 2019
PRESENTATION OUTLINE
 Epidemiology of HIV/AIDs Global and National
 Global and National Treatment Targets
 Evolution of treatment Paradigm in Namibia
 Current Treatment in Namibia
 Future ART Treatment options in Namibia
 The missing 10-10-10
 Current ARV of Optimisation Global and Namibia
 New treatment options on the horizon; comparison of their
Strength and Weaknesses
 HIV/AIDS Pandemic in 2018 – Global
Perspective
M illio n s o f Pe o p le
36.9 Million

40

35

30 21.7
Million
25 17.5 Million
20

15
1.8 Million
10

0
2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017
New infections PLHIV
Receiving ART Virally suppressed

Source: UNAIDS, 2018

Gaps in achieving the UNAids 90 – 90 –
90 target

Source: UNAIDS 2018

Progress varies Globally

Treatment access
LOWER
Men vs women

MSM
Sex workers
PWUD
Adolescents
Vs. adult populations

Source: UNAIDS 2018

HIV/AIDS Pandemic – Namibia Perspective
 Population: 2,324,388
Rural population: 52%
 Population growth rate:
1.9%
 Total Fertility Rate: 3.6
 Density: 2.8 ppl/km2
 HIV incidence: 0.80%
 HIV prevalence: 14.0%

Sources: Namibia Demographic and Health

Survey
2013, 2016 National HIV Sentinel Survey and
UNAIDS 2015 Country Data
 NAMPHIA Objectives
Primary Objectives
In a nationally representative sample of the population, ages 15-64 years, to
estimate:
• National HIV incidence
• National and regional prevalence of viral load suppression (HIV RNA <1000 c/mL)

Secondary Objectives (among others)

• National and subnational HIV prevalence in adults
• Uptake of HIV testing and antiretroviral treatment (ART)
• National pediatric HIV prevalence (0-14 years)
 Viral Load Suppression (VLS)
100 92.5
84.0 87.4 86.3
VLS Prevalence among PLHIV (%)
76.5 78.8
80 71.2
65.4
60.7
60
50.5
Male
40
Female
20

0
15-24 25-34 35-44 45-54 55-64
Age (years)
VLS by Region
Progress towards 90-90-90 Target in Namibia
(adjusted for detectable ARVs)

Femal Male Total

Evolution of the Namibia HIV/Aids
Response programme
 Alternative
First-line Second-line
Year Eligible Adults first- line Summary of Changes
regimens regimens
regimens

Guidelines 2003-2014
NVP /D4T/3TC
LPV-r/AZT/3TC
NVP/AZT/3TC
LPV-r/D4T/3TC
NVP/AZT/DDI
LPV-r/D4T/DDI
Namibia Adult ART
 WHO stages I–II: CD4 cell NVP/D4T/DDI
200   IDV-r/DDI/AZT
count<200 cells/μL  
3 IDV-r/3TC/D4T LPV-r/DDI/AZT
 WHO stages IV: all patients EFV/D4T/3TC
IDV-r/3TC/AZT
EFV/AZT/3TC
IDV-r/AZT/DDI
EFV/AZT/DDI
 
EFV/D4T/DDI
 Number of alternate 1st line regimens
streamlined and greatly reduced
 WHO stages I–II: CD4 cell count o Protease inhibitor 1st line regimens phased
TDF+AZT+3TC+LP
<200 cells/μL for all and <250 out
EFV/D4T/3TC V/r
200 cells/ μL for pregnant women  WHO stage III became eligible
NVP /AZT/3TC EFV/AZT/3TC AZT+3TC+ddI
7  WHO stages III–IV: all patients  All TB/HIV co-infected recommended for early
NVP/D4T/3TC +LPV/r
 All TB/HIV co-infected initiation preferably within 8 weeks of starting
ABC+ DDI+ LPV/r *
  TB treatment
 Preferred first line changed from D4T based to
AZT based NRTI regimen
 D4T –based regimens phased out
EFV/TDF/3TC  ABC available for limited use in specific
 WHO stages I–II: CD4 cell count NVP/TDF/3TC conditions
<350 cells/μL for all EFV/AZT/3TC  Preferred 1st line regimen changed from AZT-
201
 WHO stages III–IV: All patients NVP /TDF/3TC NVP/AZT/3TC AZT/3TC/TDF/LPV-r based to TDF-based NRTI regimen
0  All TB/HIV co-infected EFV/3TC/ABCCC C  HIV/Hepatitis B co-infected with active disease
 HIV/Hepatitis B co-infected NVP/3TC/ABC recommended for treatment
EFV/3TC/DDI C C  CD4 threshold changed from 200 to 350 cells/
μL
 Test and Treat approach expanded to more
people (Pregnant and Breastfeeding women,
 WHO stages I–II: CD4 cell count
HIV-positive persons in Sero-discordant sexual
<500 cells/μL for all EFV/TDF/3TC
relationships, HIV/TB co-infected, HIV/Hep B co-
 All patients WHO stages III–IV: NVP/TDF/3TC
infected)
 All TB/HIV co-infected NVP/TDF/FTC
 Single dose EFV/FTC/TDF introduced as
201  All HIV/Hepatitis B co-infected EFV/AZT/3TC AZT/3TC/TDF/LPV-r
preferred first line regimen for all adults
4 All Pregnant and Breastfeeding EFV/FTC/TDF NVP/AZT/3TC AZT/3TC/TDF/ATV-r
 ATV-r introduced as alternative PI in second
 All HIV-Positive persons in Sero- NVP/3TC/ABC
line
Discordant Sexual relationships EFV/3TC/ABC
 Routine Viral Load monitoring at 12 months
 HIV-positive concordant couples  
and thereafter once every 12 months
intending to conceive a child
 Routine CD4 phased out for most patients on
Adoption of the “TREAT ALL" recommendation among adults
and adolescents living with HIV, October 2016
TEMPRANO Trial
 Study Site
 Côte d'Ivoire(Ivory Coast)
 Trial design
 Unblinded, multicenter, individual-
randomized controlled 2-by-2 factorial trial.
 HIV positive with CD4 count < 800
cells/mm3
 participants randomized to one of four
groups
 Deferred ART
 Deferred ART plus IPT
 Early ART
 Early ART plus IPT
Temprano Trial outcomes
Temprano Trial outcomes
The START Trial  Multicontinental randomized trial
 215 sites in 35 countries
 Study participants
 HIV positive > 18 years
 Not yet initiated on ART with no history of
AIDS
 CD4+ counts >500 cells/mm3
 Pregnant and breast feeding women not
eligible
 Randomized to
 Immediate ART or
 Deferred initiation until the CD4+ count
declined to 350 cells/mm3
Start Trial Outcomes
Start Trial Outcomes
 CURRENT ART OPTIMIZATION - ART
initiation simplified

 Test and start

 Same day initiation

 Fixed dose combinations

 Same day initiation improves

range of ART outcomes

WHO, 2015; Mateo-Urdiales,

2019
New drugs
new formulations

Past Present …and Future

Source: Charlotte Watts, Department for International Development

Recommended First Line ART Regimens
Preferred 1st line Alternative 1st
1st line ART Regimens line Regimens

Adults (including
AZT + 3TC + EFV
adolescents ≥ 10 years
old and weigh at least 35 AZT + 3TC + NVP
TDF + FTC (or 3TC) +
kg), pregnant and TDF + FTC (or
EFV
breastfeeding women, 3TC) + NVP
(once daily FDC)
adults with TB disease
ABC + 3TC + EFV
and adults with HBV
(or NVP)
co-infection
Laboratory Monitoring
Phase of HIV/Aids Tests Frequency
management
At initial clinic CD4 Once
visit HBsAg Once; if positive, repeat
after 6 months. If HBsAg is
reactive, then the lab will
  automatically do ALT
CrAg1 Once if CD4<200
Hb Once
CrCl Once
Urine Once
dipstick2
 CD4 Testing
 CD4 levels are important markers of immune function
 Recommended at baseline to determine degree of
immune suppression.
 Viral Load (VL) Testing is a more sensitive and an
earlier indicator of treatment failure therefore:
 Routine VL monitoring rather than CD4 count for
treatment monitoring is recommended.
The Missing 10-10-10: How to address
factors/problems among those left behind in the
90-90-90 targets to end the HIV/Aids epidemic
The Old Paradigm: Pre-HAART

Biology
(inflammation/ulceration)

Behavior
(condomless sex, ↑ partners)
STI HIV
Epidemiology
(populations at greater risk)

Immune
suppression
The New Paradigm: After U=U and PrEP

Biology
(inflammation/ulceration)
X PrEP
Behavior
(condomless sex,
STI ↑partners) HIV
U=U & PrEP
Epidemiology
(populations at X U=U

x
greater risk)
Immune
suppression
 Prevalence of STIs in sub-Saharan Africa: Individual
patient data meta-analysis of 18 HIV prevalence
studies
15 – 24 years old 25 – 49 years old
100 100
South Africa community South Africa
Southern Afr/Eastern Afr 83.3
80 community 80 SA/EA community 77.8
70

60 56.3
60
46.8
39.3
40 40

20 15.1 12.7 20 8.65.810

10.3 8.2 7 6.7
2.7 4.6 4.5
7.96.7
1.2 2.50.95.2 1 0.92.8
1.7 0.41.1
0 0

BV was high among 25–49 year-olds range: 33–44%

Torrone EA, Morrison CS, Chen PL, Kwok C, Francis SC, et al. PLoS Med. February
2018.
HIV is highly co-prevalent among patients
presenting with STI syndromes in South Africa,
2014-2016
There was a significant association between HIV seropositivity and all
STI syndromes (p<0.001).

STI N= HIV co- Per cent HIV

syndrome infected positive

Genital Ulcer 363 208 57.3%

Disease
Vaginal 742 350 47.2%
Discharge
Male urethral 784 211 26.6%
discharge

Source: Ranmini Kularatne, Centre for HIV & STIs, NICD. Aetiological Surveillance of Sexually Transmitted Infection Syndromes at Sentinel Sites:
Germs-SA 2014-2016. The Communicable Diseases Surveillance Bulletin, Volume 15. Issue 3 – November 2017.
http://www.nicd.ac.za/index.php/publications/communicable-diseases-surveillance-bulletin/
Rectal gonorrhea and syphilis are
predictive of future HIV infection

Katz et al. Sex Trans Dis. 43(4):249-254, 2016.

Also Bernstein et al from SF and Pathela et al from NYC
 Testing for STIs in Last 12 months
among MSM – an eCDC/Hornet Survey
n=8613 n=690

30.77%
Of those Of those
currently currently onPrEP
Men taking
not on PrEP test PrEP
more often for
STIs
69.23%

Noori T. et al EACS 2017

 Current optimization profiles of new ARV drugs
comparative analysis
Optimization criteria DTG EFV400 TAF DRV/r 400/50

Virologic potency
Efficacy and
Lower toxicity
safety
High genetic barrier to resistance
Available as generic FDC
Simplification
Low pill burden/pill size (*)

Use in pregnant women

Use in childbearing age women
Harmonization Use in children
Use in HIV-associated TB
Few drug interactions
Cost Low price

yes no ongoing studies

* DRVr 400/100 OD has been studied.
 Safety and Efficacy of DTG and EFV600 in 1st line ART
Quality of
(summary 2019
Major outcomesWHO Sys Review
DTG vs &
EFVNMA
600 )
evidence
Treatment discontinuation (any or due
DTG better high
outcomes
AEs)
Viral suppression (4-96 weeks), viral
DTG probably high to
Efficacy

suppression at delivery (PW),

transmission (PW) better moderate
DTG probably high to
CD4 recovery (24-144 weeks)
better moderate
Mortality comparable low
Neuropsychiatric AEs (any grade),
DTG probably moderate to
Tolerability,

depression
resistance

better low
outcomes
safety &

(grade 3 or 4), dizziness (any grade)

Sleep disorders (any grade) comparable very low
EFV probably
Body weight gain moderate
better
EFV may be
NTD low
better
Reference: Steve Kanters, For WHO ARV GDG, 5-7 June 2019
 Safety and Efficacy of EFV400 and EFV600 in 1st line
ART (PICO 3) (summary 2019 WHO Sys Review & NMA)
EFV400 vs quality of
major outcomes EFV600
evidence
outcomes

high to
EFV400 better
Efficacy

Treatment discontinuation (due AEs)

moderate
Viral suppression (48-96 weeks), VL
comparable moderate
suppression if baseline > 100,000 (48 weeks)
CD4 recovery (24-96 weeks) comparable moderate
comparable low
Tolerability,

Mortality
resistance
outcomes
safety &

Neuropsychiatric AEs (any grade), depression

low to very
(grade 3 or 4), dizziness (any grade), sleep comparable
disorders (any grade) low
Body weight gain comparable low
Treatment related adverse events EFV400 better moderate
HIVDR (overall, NRTI or anchor drug) comparable very low
Reference: Steve Kanters, For WHO ARV GDG, 5-7 June 2019
Safety and Efficacy of DTG and PIs (LPVr) in 2nd line
ART (summary 2019 WHO Sys Review & NMA)
quality of
major outcomes DTG vs LPVr
evidence
outcomes

Viral suppression (4-96 weeks) DTG better high

Efficacy

Viral suppression baseline VL > 100,000

comparable moderate
(48 weeks)
CD4 recovery (24-48 weeks) comparable moderate
Mortality comparable low
Neuropsychiatric AEs (any grade) comparable low
Tolerability,

resistance
outcomes
safety &

Treatment related SAE comparable low

DTG probably
Treatment emergent AE, related AEs high
better
Treatment discontinuation (any or due DTG probably
high
AEs) better
HIVDR ( overall)
Reference: Steve Kanters, For WHO ARV GDG, 5-7 June 2019
comparable very low
 TAF becoming an
option for NRTI backbone
Improved durability and sequencing (more favourable
resistance profile)
Reduction in adverse impact on bone and renal health
 Bone accretion throughout
childhood with peak in puberty
 Multiple factors impacting bone
health including nutrition, HIV and
HIV treatment
Children co-infected with HBV
(~8-10% among children with HIV
in SSA) are not receiving
treatment for Hep B.
Adult formulations of TAF can be
used in children over 25 kg
 NNRTIS vs INSTIs as First-line ART:
Possible Role of NNRTIs Today
Possible role for NNRTIs Challenges with NNRTI use
 Low barrier to resistance at VF with EFV, RPV [1,
 Adverse events of INSTIs 2]

 In women desiring pregnancy  Neuropsychiatric AEs with EFV[1]

 Higher rates of VF in RPV patients with HIV-1
 If patient experience weight gain RNA > 100,000 copies/mL and CD4+ cell
with INSTIs counts < 200 cells/mm³[3]
 RPV must be taken with a meal[2]
 Fixed-dose combination with DOR includes TDF
not TAF
 Lipid increases with EFV[1]
 Drug–drug interactions with EFV,
1. EFV PI. 2. RPV PI. 3 Cohen. AIDS. 2014;28:989. RPV[1, 2]
Slide credit: clinicaloptions.com
 Is There Still a Role for TDF in Today’s First-
line Regimens?
Supporting TDF
 Longer experience with greater number
of patients with TDF vs TAF
 Coformulations with many regimens
 Lipid decreases of uncertain clinical
significance seen with use of TDF
regimens
 Possible weight gain signal on TAF [1]
 Recommended NRTI in pregnancy
 Available as generic NRTI combination
with 3TC
1. Gomez. Infection. 2019;47:95. 2. DHHS Perinatal Guideline. December 2018.
3. Sax. Lancet. 2015;385:2606. 4. Arribas. JAIDS. 2017;75:211. 5. DHHS ART Guidelines. October 2018.
Supporting TAF
 At Wk 144, TAF superior to TDF[3,4]
 TAF had less impact than TDF on
bone mineral density (comparable
to ABC)[3]
 Less impact on markers of renal
tubular dysfunction
 Low dose allows small tablet
[2]
(co)formulations
Slide credit: clinicaloptions.com
2019 WHO 1ST LINE ART RECOMMENDATIONS
2019 WHO 2nd Line ART RECOMMENDATIONS
 DOLUTEGRAVIR AND NTDs
 NEURAL TUBE DEFECTS
Tsepamo: Conclusions
In current analysis, NTD prevalence among women who received DTG at conception lower
than initially signaled, but still slightly higher than other exposure groups [1]
 Data as of March 2019: 0.3% DTG vs 0.1% non-DTG ART; estimated difference: 0.20% to 0.27%

Investigators suggest clinical and policy recommendations should consider the small but
significant increased risk of NTD with DTG in context of other factors, including considerable
benefits of DTG, lack of comparable data for other ARVs, unknown risk factors of ART
exposure in utero
Based on current findings and additional surveillance reports, [2,3] WHO released updated
recommendations reconfirming use of DTG-based ART as preferred first-line and second-line
therapy[4]
 Committee emphasized need for continued monitoring of NTD prevalence and patient
counseling/shared decision-making
 DTG and WEIGHT GAIN
ADVANCE: Mean Change in Weight to Wk 96 by Sex
 Significantly greater weight increase* with DTG vs EFV, with TAF vs TDF;
plateauing in weight gain after Wk 48 observed in men but not in women
14 14
Women
12 DTG + FTC/TAF 12

Mean Weight Change (kg)

Mean Weight Change (kg)

10 DTG + FTC/TDF 10
Men EFV + FTC/TDF
+10 kg

P < .001
8 8

P < .001
6 6
+5 kg +5 kg

NS P < .01
4 4

P < .05
+4 kg

P < .01
+3 kg
2 2
+1 kg
0 0

0 4 12 24 36 48 60 72 84 96 0 4 12 24 36 48 60 72 84 96
Wk Wk
n = 430 418 402 387 376 374 366 292 232 140 n = 549 531 514 488 474 459 441 359 276 175
Hill. IAS 2019. Abstr MOAX0102LB. Reproduced with permission. *Wilcoxon rank-sum comparison at Wk 96. Slide credit: clinicaloptions.com
 New Options for Highly Treatment–Experienced Patients
With Virologic Failure - The Future
Reducing Dose Frequency and Number of Drugs
Agent MoA Phase Innovation
Elsulfavirine[1] NNRTI I Long acting
GS-6207[2] Capsid inhibitor I Long acting, fewer than 3 drugs
MK-8591[3] NRTTI II Long acting, fewer than 3 drugs
Leronlimab (PRO 140)[4] Anti-CCR5 mAb IIb/III Long acting, fewer than 3 drugs
CAB + RPV[5,6] INSTI + NRTI III Long acting, fewer than 3 drugs
FDA approved (initial therapy),
DTG/3TC[7,8] INSTI/NRTI Fewer than 3 drugs
III (maintenance)
DTG/RPV[9] INSTI/NRTI FDA approved (maintenance) Fewer than 3 drugs
Anti-CD4 post- FDA approved
Ibalizumab [10]
attachment Long acting
(multidrug resistant HIV-1)
HIV-1 inhibitor

1. NCT03730311. 2. Sager. CROI 2019. Abstr 141. 3. Grobler. CROI 2019. Abstr 0481. 4. Dhody. CROI 2019. Abstr 486.
5. Swindells. CROI 2019. Abstr 139. 6. Orkin. CROI 2019. Abstr 140LB. 7. Orkin. Glasgow 2018. Abstr P021.
8. DTG/3TC PI. 9. Llibre. Lancet. 2018;391:839. 10. Emu. NEJM. 2018; 379:645. Slide credit: clinicaloptions.com
 Summary
 Success of Namibian national ART programme due to government commitment and international
support
 Namibia has achieved many milestones relevant to our context and the international community
 Adopting the “Treat All” Policy allowed us to go beyond the 90 90 90 targets and
 To address the illusive 10 10 10 further scaling up of treatment and
 Next challenge for our programme is to address the illusive missing 10 10 10 gap which continue to
fuel the HIV/aids pandemic
 Important for HIV/Aids care providers to create patient friendly service delivery mechanisms through
ART simplification and harmonization
 Caution should be practiced that ART preventions such as PReP does not cause paradoxical effect
and nullify the gains achieved through a new pandemic of STIS
 New, potent but user friendly regiments are becoming readily available and for inclusion into HAART
 New salvage options for ART drug resistant patients are on the horizon which means all is not lost
 Let us all continue the good work to support the national programme
 Namibia’s classification as a middle income country in 2014 during the current economic hardships
poses a threat to the sustainability of the HIV/Aids pandemic control and could reverse all the gains.
The End!
Questions or Comments!!!