HIV Type 1 DNA Development during Long-Term Supervised Therapy Interruption

Abstract

We studied the pattern of HIV-1 DNA development and the association to other HIV-related factors during long-term supervised therapy interruption (LT-STI). Fifteen patients were treated with long-time protease inhibitor-based antiretroviral therapy (PI-ART). They had HIV-1 RNA at + cell counts of 875 (SD 415) × 10⁶/liter. A real-time polymerase chain reaction, amplifying fragments of the HIV-1 pol gene and the human albumin gene simultaneously, was used to quantify HIV-1 DNA molecules in CD4⁺ cells. The quantity of HIV-1 DNA in CD4⁺ cells increased during LT-STI in all 15 patients, with an average doubling time of 2 months. Tentatively, three patterns were observed: rapid initial increase with subsequent stabilizing levels, rapid continuous increase, and slow increase. The HIV-1 DNA slope was positively related to the HIV-1 RNA maximum and steady state level and the baseline HIV-1 DNA value. It was inversely related to the decrease in CD4⁺ cells both before the start of PI-ART and during the LT-STI. To conclude, HIV-1 DNA persists in infected CD4⁺ cells despite long-term effective PI-ART and will increase after therapy interruption. The most important clinical predictor of long-term STI failure was the rapid CD4⁺ cell decline before PI-ART. In patients with a steep pre-PI-ART slope it may be prudent to continue treatment and not initiate therapy interruption.