Quantitation of integrated proviral DNA in viral reservoirs

Integrated HIV DNA can give rise to infectious virus, and therefore may be a surrogate of reservoir size. How this form reflects the amount of replication competent virus in vivo remains to be established. This review highlights the technical hurdles involved in measuring integrated HIV DNA, progress toward overcoming these hurdles by repetitive sampling and recent important in-vivo findings monitoring this HIV DNA intermediate.

The dynamics of integration levels after antiretroviral therapy may provide clues to how reservoirs accumulate over time and why early intervention may be beneficial. Recent studies including a multilab collaboration showed that integrated HIV DNA correlate with several viral DNA intermediates including replication competent virus as measured by a quantitative coculture assay. Because this assay performs robustly over a large dynamic range and is reproducible, it may be useful for detecting small changes in reservoir size in trials that target reservoirs as suggested by a recent trial with interferon-α.

Integrated HIV DNA provides an important surrogate for reservoir size and may be useful in trials that target HIV reservoirs. By performing large replicates (repetitive sampling), it is possible to provide more robust estimates and to detect small changes that other assays may overlook. This in turn is critical for evaluating eradication therapies that may have modest but important effects.