Evaluation of residual viral replication by proviral DNA level and T cell turnover for optimization of HAART.

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Using a highly sensitive assay to detect proviral DNA(pDNA) and the turnover of T lymphocytes, we are attempting to optimize HAART to minimize residual viruses in patients with undetectable plasma viremia. The pDNA levels in PBMCs from HIV-1 positive patients were measured in the LTR region using a novel hypersensitive nested PCR. Quantitative real-time PCR fluorogenic assay was performed to detect pDNA after conventional first PCR. We also investigated CD4^+ and CD8^+ T cell turnover by measuring the nuclear antigen Ki-67 with four-color flow cytometry analysis. We measured the HIV pDNA level in PBMCs of 340 samples from viremic or aviremic patients. Among the patients with undetectable plasma viremia by HAART, the CD4^+ T cell count and CD4/8 ratio were significantly higher in patients with undetectable pDNA than in patients with detectable pDNA(p<0.01). We also followed a patient who has an option to choose treatment optimization based on results of pDNA and T-cell turnover. Significant decline of the pDNA level was observed when the regimen of HAART was optimized to a more potent combination. Both normalization of accelerated turnover of CD4^+ subset and decline of pDNA were observed after 30 months from the addition of efavirenz(EFV). Our study suggests that the measurement of both pDNA and T-cell turnover is suitable for evaluating the residual replication of HIV-1 in patients. Long-term successful treatment is achievable by providing these results with an informed choice of a potent combination of antiretrovirals.