Total HIV DNA: a global marker of HIV persistence

Abstract

Among the different markers of HIV persistence in infected cells, total HIV DNA is to date the most widely used. It allows an overall quantification of all viral forms of HIV DNA in infected cells, each playing a different role in HIV replication and pathophysiology. The real-time PCR technology is to date, a precise, sensitive and reproducible technology that allows the description of the distribution of HIV infected cells in blood and tissues. The objective of this review is to present some examples which show the interest to quantify total HIV DNA levels. This marker brought an undeniable and considerable contribution to reservoir studies. Many results, both in clinical and basic research, allowed to get a large overview of the distribution of infected cells in the body, at all stages of HIV disease and during therapy. Future clinical studies aiming at reducing HIV reservoirs will benefit from HIV DNA quantification in blood and tissues, in association with other markers of HIV reservoir activity.

Genetic diversity in the env V1-V2 region of proviral quasispecies from long-term controller MHC-typed cynomolgus macaques infected with SHIV SF162P4cy

“…Despite control of viremia, human HIV controllers present ongoing evolution and divergence of viral RNA sequences, although at a significantly lower rate than that observed for typical progressors [9]. In contrast, the DNA proviral population is highly homogenous, mostly composed of ancestral sequences, suggesting that in these individuals ongoing replication does not permit the significant reseeding of the latent reservoir [10]. However, given the ability of HIV and SIV to establish a stable latent viral reservoir in anatomic sites early in infection, viral replication might persist in tissues; this is the case where immune responses developed by controllers fail to eradicate HIV/SIV infections [11].…”

Measuring the Success of HIV-1 Cure Strategies

“…HIV-1 DNA quantification methods rely on amplification of short genomic regions and so cannot distinguish intact and defective provirus and therefore vastly overestimate the size of the LR (Figure 2; Eriksson et al, 2013). Despite this limitation, HIV-1 DNA quantification has been shown to predict viral rebound (Williams et al, 2014) and offers the potential to identify different DNA forms, such as integrated HIV-1 DNA, non-integrated HIV-1 DNA (2-LTR and 1-LTR circular forms) or both (total HIV-1 DNA) (Mexas et al, 2012;Rouzioux and Avettand-Fenoël, 2018). Several factors affect the specificity, accuracy and reproducibly of HIV-1 DNA assays and as there is no standard method, meaningful comparison between different studies is limited.…”

Antiretroviral Therapy Interruption (ATI) in HIV-1 Infected Patients Participating in Therapeutic Vaccine Trials: Surrogate Markers of Virological Response

“…Another uncertainty is that measuring methods are not well standardized even though several different tests have been developed. The quantitative viral outgrowth assay (QVOA), which measures infectious units per million (UIPM) in resting CD4+ T cells is considered the gold standard for measuring latent HIV reservoir [ 58 , 59 ]; other measurements obtained by PCR have been proposed as surrogate biomarkers such as total DNA, also called cell-associated DNA (CA-DNA) [ 60 ], proviral, or integrated DNA [ 61 , 62 ] and cell-associated RNA (CA-RNA) [ 63 ].…”