treatment outcomes in perinatally-hiv- infected children ... … · treatment outcomes in...
Post on 01-May-2020
5 Views
Preview:
TRANSCRIPT
Treatment outcomes in perinatally-HIV-infected children and adolescents after
10+ years on antiretroviral therapy
Kim Anderson, Rudzani Muloiwa, Mary-Ann Davies
Maskew et al. AIDS 2016
Number of children on ART
The approaching wave of HIV+ adolescents
Johnson et al. PIDJ 2012
Cohort study results after ≥10 years on ART?
Not comparable locally.Local studies…? Nothing >3 years on ARTOur study: median follow-up 12 years
Study Country NMedian follow-up
time (years) Viral suppression CD4>500Dollfus et al. (2010) France 210 15 56% 59%
De Mulder et al. (2012)
Spain 243 15 61% 66%Van Dyke et al. (2011) USA 451 11 68%Collins et al. (2017) UK/Ireland 131 11 74% 38%
Who was included in this study?• Perinatally-infected children
• Age at ART initiation < 12
• Initiation at GSH between 2002 and 2005
• Attended GSH paediatric/adolescent ID clinic (G26) for a minimum of 10 years since ART initiation
= 127 patients
Study design: retrospective cohort (folder review)
Who was excluded?
349 children started ART (2002 – 2005):
• 150 transferred out (43%)• 33 lost to follow-up (9%)• 29 died (8%)• 10 missing records (3%)
127 remained at the clinic ≥10 years (36%)
Study objectivesPrimary
• Virologic outcomes (viral loads)
• Immunologic outcomes (CD4s)
Secondary
• Growth outcomes (heights & weights)
• ART history (drugs)
• Clinical outcomes: opportunistic infections & hospital admissions
• Drug resistance
Definitions• Viral suppression: VL <400• Viral failure: 2 consecutive VLs >1000, after at least 24 weeks since
ART start
Cohort characteristics at ART start, at 10 years since ART start and at last visit
Characteristic At ART start At 10 years At last visit
Female (%; n/N) 51% 65/127
Median (IQR) age (years) 2.6 1.3 - 4.9 15.1 13 - 17.7
Median (IQR) CD4 count (cells/µl) 502 275 - 813 768 589 - 987 686 545 - 859
Mean (95% CI) CD4 percent 13.7 13.6 - 13.9 29.6 27.7 - 31.4 29.3 27.6 - 31
Severe immune suppression* (%; n/N) 63% 76/121 3% 3/107 4% 5/127
CD4 count > 500 cells/µl (%; n/N) N/A 86% 92/107 79% 100/127
Growth stunted (HAZ <-2) 73% 82/113 33% 37/113 31% 40/127
PI-based regimen (%; n/N) 36% 46/127 66% 84/127 69% 87/127
HIV-RNA < 400 copies/ml (%; n/N) N/A 74% 81/109 80% 101/127
*WHO classification
Starting regimens
• NNRTI-based in 64%, PI-based in 36%
• Most common regimens:
AZT + 3TC + NVP (61%)
d4T + 3TC + LPV/rtv (21%)
d4T + 3TC + rtv (8%)
AZT + 3TC + LPV/rtv (6%)
• Drug switches made in 64 patients (50% of cohort) due to lipodystrophy, at median age of 11 (d4T, AZT, DDI)
10% of cohort had documented drug resistance• 13/16 patients tested had drug resistance
• 20% (26/127) of the cohort were transferred out and subsequently transferred back again, predominantly for adolescent support
Transfers
Regimens at last visit
• 50% on 1st-line (n=63; 49% on NNRTIs & 51% on PIs)• 43% on 2nd-line• 1.5% on salvage regimen (4 drugs)• 1.5% on 3TC monotherapy• 4% on no ART
Last visit outcomesStratified by those on 1st vs 2nd line ART
• Proportion virally suppressed
86% vs 77% (p=0.183)
• Proportion with CD4 count >500
92% vs 71% (p=0.003)
worse immunologic outcomes on 2nd line ART
Stratified by those on NNRTI vs PI• Proportion virally suppressed
89% vs 78% (p=0.169)• Proportion with CD4 count >500
94% vs 77% (p=0.003)worse immunologic outcomes on PI
• 10 year probability of VF : 57%
• Children on NNRTI-based
regimens had a higher 10-year
probability of VF (66 %)
compared to those on a PI-
based regimen (43%)
(logrank test, p=0.04)
• 10 year probability of switching
to 2nd-line ART was 45.7%
(95% CI 37.5 -54.8)
• Median time on ART to VF: 5.2
years
Kaplan Meier probability of viral failure (first episode) by initial ART regimen
Factors associated with first episode of VFCovariate Adjusted HR 95% CIGender male 1
female 0.44 0.23 - 0.85Type of regimen NNRTI-based 1
PI-based 0.62 0.20 - 1.98Age (years) 1.05 0.89 - 1.24Programme year 2002 1
2003 0.87 0.41 - 1.842004 0.94 0.19 - 4.792005 0.24 0.05 - 1.18
CD4 category at baseline not severely suppressed 1
severe immune suppression 1.42 0.63 - 3.23Baseline VL > 1 million 1.45 0.62 - 3.37Drug formulations tablets only 1
use of suspensions 3.48 1.13 - 10.75
Viral failure in adolescence
35% probability of experiencing VF between the age of 10 and 18
Hospital admissions
Year since ART start
Number of children with hospital admissions
% of children with
admissions Most common reasons
0 - 1 53 42%LRTI (51%) GE (8%) LRTI & GE (8%) Septicaemia (8%)
1 - 5 43 34%LRTI (40%) PTB (16%) GE (9%) Septicaemia (6%)
5 - 10 24 19% LRTI (45%) Measles (19%) GE (7%)
10 - 14 14 11% LRTI (40%) PTB (20%)
TB burden
• 58/127 (46%) of the children in total were ever on TB treatment since ART start • 51/127 (40%) had TB > 4 weeks since ART start• 33/127 (26%) documented with chronic lung disease
56% of TB cases notvirally suppressed
Time of TB diagnosissince ART start
Numberof TB
episodes
Number not virally
suppressed% not virally suppressed
On TB treatment at ART start or < 4 weeks of ART start 15 N/A
≥ 4 weeks and ≤ 24 weeks 4 N/A
> 24 weeks and ≤ 1 year 5 2 40%
> 1 year and ≤ 5 years 24 14 58%
> 5 years ≤ 10 years 14 9 64%
> 10 years <14 years 9 4 44%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
1 2 3 4 5 6 7 8 9 10 11 12 13
Year since ART initiation
Percentage of patients virally suppressed at each year since
ART initiation
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
0 1 2 3 4 5 6 7 8 9 10 11 12
Year since ART initiation
Percentage of patients with optimal immunologic status at each year since ART initiation
80% “goal”
Conclusions
• After median follow-up of 12 years on ART:
80% virally suppressed
79% optimal immune status
• Long-term virologic and immunologic outcomes were good
overall in children remaining in care for ≥10 years
• Worsening trend in adolescence (virologic and immunologic)
• Transitioning to adult care
contact: kim.anderson@uct.ac.za
Acknowledgements:
• Dr Paul Roux, Kidzpositive and One to One Children’s Fund for initiating ART provision at GSH.
• The children and caregivers attending G26 clinic.
• The dedication of the staff at G26 to their patients.
• The financial assistance of the National Research Foundation (NRF) towards this research is hereby acknowledged. Opinions expressed and conclusions arrived at, are those of the authors and are not necessarily to be attributed to the NRF.
127 start ART 96
Suppressed
75 Viral failure
30 Viral failure
8 Viral failure
1Viral failure
6 Suppressed
68 Suppressed
26 Suppressed
1 Suppressed
38 stay suppressed
18 stay suppressed
5 stay suppressed
31 44
7 stay VF*
52 stay suppressed
4 stay VF
2 stay VF
*2 never suppressed (since ART start)
91 instances of defaulting, which occurred in 40 patients (31% of cohort)
Median age 4
Median age 10
Median age 13
Age 15
top related