Treatment intensification followed by interleukin-7 reactivates HIV without reducing total HIV DNA: a randomized trial.

BACKGROUND: As a first step towards HIV cure, we assessed a strategy of antiretroviral therapy (ART) intensification followed by interleukin-7 (IL-7) used as an HIV-reactivating agent. METHODS: A multicentre, randomized clinical trial included patients on suppressive ART with CD4 cell counts at least 350/µl and HIV-DNA between 10 and 1000 copies/10 peripheral blood mononuclear cells (PBMCs). After an 8-week raltegravir and maraviroc intensification, patients were randomized to intensification alone or with 3 weekly IL-7 injections at weeks 8, 9 and 10. The primary endpoint was at least 0.5 log10 decrease in HIV-DNA in PBMC at W56. Secondary endpoints included ultrasensitive plasma viremia, immunologic changes and safety. RESULTS: Twenty-nine patients were enrolled with median baseline 558 CD4 cell counts/µl, 360 HIV-DNA copies/10 PBMCs and 12 years on ART. No patient in either arm achieved the primary endpoint. Addition of IL-7 induced a significant expansion of CD4 T cells, primarily central-memory cells (+5%, P = 0.001) at week 12, together with an increase in levels of HIV-DNA/10 PBMC (+0.28 log10 copies/P = 0.001), and the proportion of patients with detectable ultrasensitive plasma HIV-RNA increased compared with week 8 (P = 0.07). At weeks 56 and 80, total and memory CD4 cell counts and total HIV-DNA/ml of blood remained elevated. In contrast, HIV-DNA/million PBMC and plasma viremia returned to baseline levels whereas activated HLA-DRCD4 T cells significantly decreased. CONCLUSION: IL-7 administration and dual ART intensification induced, despite a mild HIV reactivation, an amplification of the HIV reservoir, as a result of central-memory CD4 T-cell expansion, thus limiting this IL-7 based strategy. CLINICAL TRIAL REGISTRATION: This trial was registered with ClinicalTrials.gov, number NCT01019551.

Direct quantification of cell-associated HIV DNA in isolated rectal and blood memory CD4 T cells revealed their similar and low infection levels in long-term treated HIV-infected patients.

To evaluate the contribution of CD4 T cells from blood and gut compartments to the HIV-1 reservoir, we directly quantified cell-associated HIV DNA in isolated rectal (R-) and peripheral blood (PB-) memory CD4 T cells from 11 successfully long-term treated patients. Proportion of activated (CD25(+); CD69(+); and HLA-DR(+)) and CCR5 expressing CD4 T cells were markedly higher in rectal tissue compared with blood. However, HIV-1 infection levels of R- and PB-memory CD4 T cells did not significantly differ (medians: 4000 and 2100 copies per million cells) after effective long-term viral control, suggesting that each of these 2 compartments does not contribute in a similar fashion to the total HIV reservoir.