Outcomes in ART treatment programmes with and without access to routine viral load monitoring Olivia...
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Outcomes in ART treatment programmes with and without
access to routine viral load monitoring
Olivia Keiser on behalf of IeDEA Southern Africa
2
• Debate on place of routine viral load monitoring in scale-up programmes
• South Africa: routine VL monitoring part of national programme
Malawi and Zambia: no routine viral load monitoring
Background
3
Site Country Routine VL Patients
Lighthouse Malawi CIDRZ Zambia
no 9,60471,333
GugulethuKhayelitsha South Tygerberg Africa Thembalethu
yes2,6587,2301,3617,457
• Treatment naïve patients > 15 years, NNRTI-based ART regimen.
Selection of patients/ programmes
All sites participate in IeDEA Southern Africasee: www.iedea-sa.org
Mortality0.
000.
050.
10
0 1 2 3
Years since HAART start
No viral load monitoring(Malawi and Zambia)
Routine viral load monitoring(South Africa)
Cum
ulat
ive
mor
talit
y
5
1) Differences in patient characteristics ?
6
Patient characteristics at start of ART
Non VL sites
VL sites
Age 35 (30-42) 34 (30-41)
CD4 count
132 (66-203)
93 (39-159)
7
Sites with and without (reference) VL monitoring
Hazard ratio(95% CI)
P value
Crude 0.81 (0.76-0.87) <0.001
Adjusted * 0.74 (0.69-0.80) < 0.001
Competing risk regression with loss to follow-up and start of second-line therapy as competing events
*Adjusted for age, sex, CD4 cell count and clinical stage of disease
8
2) Differences in loss to follow-up ?
9
Adjusted* Hazard Ratio (95% CI)
P value
Mortality 0.74 (0.69-0.80) < 0.001
Loss to follow-up
0.70 (0.65-0.75) < 0.001
Competing risk regression
*Adjusted for age, sex, CD4 cell count and clinical stage of disease
• Sites with < 15% loss to follow-up 2 years after ART start
Sites with and without (reference) VL monitoring
10
3) Differences in background mortality?
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Expected non-HIV-related death rate per 100 pyrs
SettingObserved
rate/100 pyrs
Assuming identical non-HIV-related mortality*
VL sites 2.12 (1.93-2.34) 2.12 (1.93-2.34)
Non VL sites 3.10 (2.99-3.20) 2.92 (2.82-3.02)
Rate ratio 0.68 (0.62-0.76) 0.73 (0.65-0.81)
* Based on South African rates
12
4) Delayed/missed detection of treatment failure and
switching in non-VL sites?
Six months after ART start
Treatment failure - virologic (viral load sites) - immunologic (non viral load sites)
Switch
DeathLoss to follow-up
Multistate model
Putter et al., Stat Medicine 2007
From 6 months after ART start
0 200 400 600 800 0 200 400 600 800
Non VL sites VL sites
Loss to follow-upSecond-line therapyDeathCD4 criteria for switching
Remaining on first-line ART
Time (days) Time (days)
1
0.75
0.5
0.25
Prop
ortio
n of
pa
tient
s
0
From failureNon VL sites VL sites
8000 200 400 600 8000 200 400 600
Loss to follow-upSecond-line therapyDeathCD4 criteria for switching
Time (days) Time (days)
1
0.75
0.5
0.25
Prop
ortio
n of
pa
tient
s
0
From switchNon VL sites VL sites
0 200 400 600 8000 200 400 600 800Time (days) Time (days)
Loss to follow-upSecond-line therapyDeath
1
0.75
0.5
0.25
Prop
ortio
n of
pa
tient
s
0
From switchNon VL sites VL sites
(linkage with death registry)
0 200 400 600 800Time (days) Time (days)
Loss to follow-upSecond-line therapyDeath
0 200 400 600 800
1
0.75
0.5
0.25
Prop
ortio
n of
pa
tient
s
0
18
Conclusions Mortality rate higher in sites without routine viral load monitoring
Difference probably not explained by differences in- Patient characteristics- Loss to follow-up- Background mortalityAlternative explanations:- Delayed/missed switching- Diagnostic and treatment capacities (for OIs), other differences in patient management
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Diagnostic capacities Non VL sites
VL sites
Site LH CI TL TB GU KHTuberculosis
Culture MTb/other M.
Cryptococcus Culture Ag test
Amphotericin treatment
Not generally available or off siteyes no
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Limitations - Few sites and countries included
- Mortality in patients lost to follow-up unknown in many sites
- Linkage with death registry only possible for patients with South African ID number available
- Estimates of HIV-free mortality might be inaccurateThis is an observational study - Ideally one would need a randomized
trial
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Acknowledgement University of Bern: Matthias Egger, Thomas Gsponer, Janne Estill, Gilles Wandeler, Franziska Schöni-Affolter, Martin Brinkhof, Fritz Käser, Claire Graber
Data center Cape Town: Andrew Boulle, Morna Cornell, Leigh Johnson, Nicola Maxwell
Site investigators: Benjamin Chi, Matt Fox, Mhairi Maskew, Catherine Orrell, Hans Prozesky, Ralf Weigel, Andrew Westfall