731
Delayed Clearance of Latently Infected CD4+ T Cells in HIV-1-infected Infants Initiating HAART Younger than 6 Months of Age
Deborah Persaud*1, C Ziemniak1, K Ferguson1, J Chen2, S Gange3, B Heckman4, P Palumbo5, E Gould Chadwick6, and Pediatric AIDS Clinical Trials Group (PACTG) P1030 Team.
1Johns Hopkins Univ Sch of Med, Baltimore, MD, US; 2Harvard Sch of Publ Hlth, Boston, MA, US; 3Johns Hopkins Univ Bloomberg Sch of Publ Hlth, Baltimore, MD, US; 4Frontier Sci & Tech Res Fndn, Amherst, NY, US; 5Univ of Med and Dentistry of New Jersey, Newark, US; and 6Feinberg Sch of Med, Northwestern Univ, Chicago, IL, US
Background: The stable persistence of replication-competent HIV-1 in
resting CD4 cells of patients on HAART renders the infection incurable. Adults treated with HAART have an
initial phase of rapid decay of unstable latent forms of HIV-1 in CD4 T cells,
followed within weeks by stable levels of viral persistence that are maintained
for years. Similar dynamics have not
been established for infants undergoing HAART.
Methods: We (the Pediatric AIDS Clinical Trial Group,
PACTG, P1030) examined (at 24, 48, and 96 weeks of HAART), the decay of
replication-competent HIV-1 in resting CD4+ T cells from 21 U.S.
infants enrolled in a multi-center, phase I/II trial of lopinavir/ritonavir
(LPV/r). A standard limiting dilution co-culture assay of purified resting CD4+
T cells was used to assess the frequencies of replication-competent HIV-1
(median blood sample = 2.9 mL), and analyses of decay
using linear random effects models.
Results:
Blood volume limitations precluded assessing latently infected cell
frequencies before HAART. Among 21 infants initiating HAART (median age of 9.6
weeks), 17 had cultures performed at a median of 22 weeks on study treatment,
an overlapping 19 at a median of 44 weeks, and 12 infants reaching a median of
87 weeks of study treatment. Standard plasma viral load was undetectable in 9
of 17, in 15 of 19, and in 11 of 12 at the first, second, and third time-points,
respectively. The frequency of latently
infected cells at 6 months was quite variable (range <0.22 to 81.7
infectious units per million; median of 1.6). Variability was reduced with
further treatment, and decay to a median of 0.5 IUPM (range 0.1 to 3.2) was
observed at 96 weeks of study treatment. However, the change in latently
infected cells over time was not statistically different from 0 for the entire
group (p = 0.78) or for those with
undetectable HIV RNA (p = 0.11) at
week 24.
  Conclusions: Perinatally
infected infants beginning HAART during the first 6 months of life maintain
relatively high levels of latently infected resting CD4+ T cells
with replication-competent HIV-1 in the first year of life. The observed rates
of recovery of replication-competent virus are higher than reported for adults
at a similar stage in treatment during primary infection, but does not preclude
control of virus replication with standard HAART regimens. These findings may
have implications for the long-term outcome of therapy and for consideration
for treatment discontinuation in early-treated infants.
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