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Low Level of HIV Reservoir in Rectal Biopsies of Patients in "Remission" after HAART Interruption and HIV Controllers
Véronique Avettand-Fenoel*1,2, Véronique Avettand-Fenoel*1,2, T Prazuck3, L Hocqueloux3, R Kerdraon3, H Djarech3, C Rouzioux1,2, and C Rouzioux1,2
1Ctr Hosp Univ Necker, Paris, France; 2Univ Paris 5, Faculty of Med, Paris, France; and 3Ctr Hosp Univ Orleans, France
Background: Low levels of HIV replication and HIV DNA
have been reported in blood of some patients, particularly HIV controllers and
patients in “remission.” We addressed the issue of HIV reservoir size in
profound tissues like rectum in such patients, compared to others at different
stages.
Methods: Rectal biopsies were proposed to 14 patients,
including 4 patients in “remission,” ie, who
had initiated HAART during primary infection and presented sustained viral
control (HIV RNA <1.7 log copies/mL) and CD4>500 cells/mm3
more than 30 months after HAART interruption, 2 HIV controllers, 5 patients who
had initiated therapy during chronic infection and presented with HIV RNA
<1.7 log copies/mL and 3 untreated patients (median HIV RNA at 4.5 log
copies/mL). Total HIV DNA was quantified in peripheral blood mononuclear cells
(PBMC) and in rectal biopsies using a real time polymerase chain reaction
(RT-PCR) assay (LTR region—ANRS), with an average of 2 PCR
results in 4 rectal biopsies per patient was calculated. Median proportion of
CD4+ cells in biopsies was estimated by immuno-staining. Spearman
and Mann-Whitney tests were used.
Results: HIV-1 DNA was detectable in all the 56 rectal
biopsies. The median HIV DNA was 2.0, 2.0, 2.5, and 3.3 log copies/106 rectal
cells vs 1.9, 2.2, 3.5, and 3.7 log copies/106 PBMC for patients in
“remission,” HIV controllers, aviremic patients treated during chronic
infection, and untreated patients, respectively. We observed a good correlation
between HIV DNA in PBMC and in rectal biopsies (r = 0.898, p = 0.001 and r = 0.799, p = 0.004 with HIV DNA in rectum expressed in log copies/106
rectal cells or log copies/106 CD4+ rectal cells,
respectively). HIV DNA level in PBMC permitted us to distinguish 2 groups of
patients: 7 patients with HIV DNA
<2.7 log copies/106 PBMC (median:
2.2 log) including 4 patients in “remission,” 2 HIV controllers, 1
patient treated during chronic infection; and 7 patients with HIV DNA >2.7
log copies/106 PBMC (median: 3.5 log), including 4 patients on HAART
from chronic infection and 3 untreated patients. HIV DNA in rectal biopsies was
significantly lower for group A than group B (medians 1.9 vs 2.8 log copies/106
rectal cells, p = 0.002).
Conclusions: Patients in “remission” and HIV controllers
showed a very low HIV DNA level, not only in blood but also in some profound
anatomical reservoirs, such as rectum. HIV
DNA in blood reflects HIV DNA in rectal biopsies for patients at different
stages of HIV infection.
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