A run-in period is needed in randomized controlled trials of directly observed antiretroviral therapy for HIV infection.
values ,37 but detectable (Target Detected) than in patients with undetectable viremia (Target Not Detected) (Fig. 1A, B) [total DNA = 3.5 (IQR, 2.7–3.8) log10/10 PBMC vs 2.6 (IQR, 2.0–3.1) log10/10 PBMC, P = 0.003; integrated DNA = 3.1 (IQR, 2.4–3.6) log10/10 PBMC vs 2.5 (IQR, 1.2–3.1) log10/10 PBMC, P = 0.01]. In addition, there was a positive correlation between residual viremia levels and total HIV DNA (r = 0.41; P = 0.004) and integrated HIV-1 DNA (r = 0.36; P = 0.02) (Fig. 1C, D). These findings further support the association between HIV-1 DNA levels and residual viremia observed in other studies. Indeed, Mexas et al reported a lack of correlation between total HIV-1 DNA and residual viremia. The discrepancy with our data is probably due to both the different number of samples and different analysis times. In our study, the association between levels of total HIV-1 DNA and residual viremia was analyzed after 144 and 196 weeks of RAL-based therapy. Considering that most patients showed undetectable viremia at 52 weeks of treatment, we can assume that integrated HIV-1 genomes represent the main component of total HIV-1 DNA in PBMCs after prolonged viral suppression as discussed above. Although the correlation between residual viremia and HIV DNA suggests that low-level replication may contribute to maintenance of the reservoir, the absence of genetic evolution in viral reservoirs does not support this possibility. In addition, HIV persistence is ensured by homeostatic proliferation of infected T cells, and ongoing viral replication is unlikely to be responsible for the stability of the viral reservoir. Despite these controversies and the small cohort analyzed in this study, our findings strongly support the hypothesis that most HIV-1 DNA is integrated in virologically controlled patients, and that residual viremia is linked to the size of the viral reservoir. Understanding this link is crucial to devise a new eradication strategy.