1. Hospital de Pediatría “Prof. Dr. Juan P. Garrahan”.
Dynamics of HIV-1 DNA in Children Over Long-term Sustained Viral Suppression: Impact of the Time of Infection at Viral Control on Reservoir Size
M. Moragas, M. Distefano, D. Mecikovsky, S. Arazi Caillaud, R. Bologna, P. Aulicino, A. Mangano.
Hospital de Pediatría “Prof. Dr. Juan P. Garrahan”.

2. Conflict of Interest
No conflicts of interest to declare.

3. Aims
To determine the decay of viral reservoirs throughout sustained virological suppression in perinatally infected children.
How the time to achieve effective ART response affects the persistence of HIV-1.

4. Design and Methodology
A retrospective study including 37 HIV-1 perinatally infected children born between
At least sustained viral suppression during 4 years.
Total HIV-DNA was quantified by semi-nested real time PCR, and analyzed longitudinally by linear mixed-effect model.
2-LTR circles were detected by hemi-nested real time PCR and followed over VS by logistic regression.

5. Infant Characteristics
Value
Subjects, No. 37
Sex, No. (%), Female
19 (51.4)
ACTG 076 prophylaxis regimen, No. (%)
None
24 (64.9)
Partial
5 (13.5)
Complete
Unknown
3 (8.1)
Age at ART initiation, median (IQR), yrs
2.4 ( )
First ART regimen, No. (%)
2 NRTIs + NNRTI
16 (43.2)
2 NRTs + PI
21 (56.8)
Age at VS, median (IQR), yrs
5.3 ( )
ART regimen at VS, No. (%)
23 (62.2)
14 (37.8)
pVL at pre-VS, median (IQR), log10 copies/mL
5.89 ( )

6. Total HIV-DNA and 2-LTRs have a strong decay during the first two years of VS
 Variable
Values in PBMCs
No. of children 37
Intercept
Estimated (95% CI)
2.44 (2.17 to 2.70)
First slope (0-2 yrs)
Estimated ( 95% CI)
-0.26 (-0.43 to -0.09)
P-value
.0028
Second slope (2-4 yrs)
-0.06 (-0.15 to 0.55)
.2578
Level of CA-HIV-DNA (log10 cpm)
At 0 yrs of VS, mean (95% PI)
2.55 (2.18 to 2.93)
At 2 yrs of VS, mean (95% PI)
2.03 (1.79 to 2.27)
At 4 yrs of VS, mean (95% PI)
1.98 (1.66 to 2.30)
Piecewise linear mixed-effect model.
2-LTRs circles
- At VS: 82.9% (29/35)
- At 2 yrs. of VS: 37.5% (9/24)
At 4 yrs. of VS: 28.1% (9/32)
Significant decay (P=.0009)
2-LTRs = CA-HIV-DNA
2.48 (IQR: 1.68 to 3.01) vs.
1.89 (IQR: 0.78 to 2.39) log10 cpm (P<.005).

7. Decay of total HIV-DNA according to the age at VS
 Variable
Time of Infection at VS
≤1.5 yrs
>1.5-4 yrs
>4 yrs
P-value
No. of children 4 6 27 NA
Intercept
Estimated (95% CI)
2.44 (2.18 to 2.70)
2.44 (2.18 to2.70)
First slope (0-2 yrs)
Estimated ( 95% CI)
-0.51 (-0.94 to -0.07)
-0.35 (-0.83 to 0.14)
-0.21 (-0.39 to -0.02)
.1645
.0235
.1583
.0287
Second slope (2-4 yrs)
(-1.50 to 1.50)
-0.11 (-1.64 to 1.44)
-0.07 (-0.63 to 0.49)
.7346
.3477
.6495
.4798
Level of CA-HIV-DNA (log10 cpm)
At 0 yrs of VS, mean (95% PI)
2.73 (2.01 to 3.45)
2.58 (1.86 to 3.30)
2.52 (2.13 to 2.90)
.5941
At 2 yrs of VS, mean (95% PI)
1.72 (1.24 to 2.20)
1.89 (1.40 to 2.37)
2.11 (1.85 to 2.37)
.1614
At 4 yrs of VS, mean (95% PI)
1.56 (0.75 to 2.37)
1.83 (0.94 to 2.73)
2.08(1.73 to 2.43)
.1942

8. Discussion
These data highlight the difficulty to eliminate the circulating reservoirs from peripheral blood, reinforcing the clinical benefit of very early effective therapy in perinatally infected children.
Peripheral blood HIV-1 reservoir size decayed markedly during the first two years of VS.
Children with VS before 18 months tended to have a higher decay rate.
After two years of VS peripheral blood HIV-1 reservoirs decay very slowly and independently of the time to achieve VS.

9. Acknowledgement