ABSTRACT:
We analyzed HIV-1 proviral DNA changes in HIV-1 infected patients receiving highly active antiretroviral therapy (HAART) plus recombinant interleukin-2 (rIL-2). Eight patients, with CD4 counts <250 cells/mm3 and plasma HIV-1 RNA levels < 200 copies/mL for more than 24 weeks received subcutaneous (s.c.) rIL-2 (3 MIU twice daily for 5 days and then 3 MIU once a day for every 4 weeks for five additional cycles). Patients maintained stable HAART during at least 6 months before entry into the study. Total and integrated DNA was measured at baseline and at the end of the study. HIV-1 DNA quantification was performed by a quantitative nested PCR on genomic PBMC. Plasma HIV-1 RNA was amintained below 200 copies/ mL (RT-PCR, Roche) throughout the study. Mean CD4 cell counts increased significantly in the IL-2 group at week 24 compared with the mean baseline values (134±47 cells/mm3; P<0.05). At baseline, the mean total DNA and integrated DNA was 3178 copies and 168 copies per 106 PBMCs, respectively. A significant decrease in total DNA was observed after the last cycle of rIL-2 (-2112 copies per 106 PBMCs). However, only a slight drop in integrated HIV-1 proviral DNA was detected (-29 copies per 106 PBMCs). Although the total amount of HIV-1 DNA decrease significantly, the integrated HIV-1 DNA present in total PBMCs did not decay after six doses s.c. rIL-2 in advanced HIV-1 patients. This finding may suggest that: (I) low doses of rIL-2 are not sufficient to reduce the pool of latently infected CD4 cells and higher doses and/ or more cycles of rIL-2 may be needed; and (ii) rIL-2 could favor the integration of unintegrated HIV-1 genome, thus explaining th non-reduction of integrated HIV-1 DNA.
