The focus of this review is to examine the importance of quantifying total HIV DNA to target the HIV reservoir and the clinical implications and challenges involved in its future application in clinical practice. Despite intrinsic limitations, the quantification of total HIV DNA is currently the most widely used marker for exploring the HIV reservoir. As it allows estimating all forms of HIV DNA in the infected cells, total HIV DNA load is the biomarker of the HIV reservoir that provides most of the insights into HIV pathogenesis. The clinical role of total HIV-DNA in both untreated and treated patients is extensively supported by important lines of evidence. Thus, predictive models that include total HIV DNA load together with other variables could constitute a prognostic tool for use in clinical practice. To date, however, this marker has been primarily used in experimental evaluations. The main challenge is technical. Although the implementation of droplet digital PCR could improve analytical performance over real-time PCR, the lack of standardization has made cross-comparisons of the data difficult. An effort by investigators to compare protocols is needed. Furthermore, the main effort now should be to involve the biomedical industry in the development of certified assays for in vitro diagnostics use.
Keywords: HIV; HIV DNA; digital droplet PCR; real-time PCR; reservoirs; total HIV-1 DNA.