Background: T-cell-mediated immunity can be induced during acute infection by structured treatment interruptions (STI-HAART). However, the hope of inducing protective immunity through auto-vaccination is tempered by the fact that early diagnosis of the infection is a rather rare occurrence, and immune control is not achieved by STI-HAART during chronic HIV infection. Our objective was to test the induction of immune control during STI-HAART by a novel topical DNA vaccination in late stage of AIDS.

Methods: 10 monkeys with late stage AIDS were randomized to compare HAART with STI-HAART (3 weeks on/3 weeks off).  After 6 cycles of STI-HAART, monkeys received DermaVir immunizations in combination with HAART during 4 additional STI-HAART cycles. DermaVir is a new composition of plasmid DNA mixed with polyethylenimine-mannose (PEIm). PEIm was chosen to transduce Langerhans cells (LC) in the epidermis (through the mannose component) and lyse the endosomes (through the PEI component) in order to avoid DNA degradation and optimize DNA expression. The DNA was designed to express a safe replication and integration defective SHIV. LC transduced by DermaVir were expected to present DNA-derived antigens to naïve T cells in the lymph node and consequently induce T-cell-mediated immune responses.

Results: Both HAART and STI-HAART controlled viral load and increased CD4 counts during the treatment, but not during treatment interruption cycles. All macaques on continuous HAART died within 7 months, whereas only 1 animal on STI-HAART died after 9 months. The 3 surviving animals on STI-HAART had consistent viral rebounds during the 6 consecutive treatment interruption cycles. Following the DermaVir immunizations, viral load gradually decreased during the following interruption cycles from a median of 4,292,260 to 12,000, 460, and <200 copies/mL, respectively. The rate of viral rebound, unchanged before the initiation of vaccine therapy, decreased sharply after vaccination from 0.26 to 0.09, 0.01, and 0 log/day. This trend was remarkably similar to that observed previously in the animals treated with STI-HAART early after infection. Viral control was associated with the induction of vigorous SIV-specific T-cell-mediated immune responses.

Conclusions: The results suggest that DermaVir immunization in combination with STI-HAART can induce immune control of virus replication during treatment interruption. These results were surprising and unexpected, because they were obtained during late stage AIDS, that is the most unfavorable condition to achieve immune control of virus replication.