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The Alphabet Soup of HIV Reservoir Markers

  • HIV Pathogenesis and Treatment (AL Landay and N Utay, Section Editors)
  • Published:
Current HIV/AIDS Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Despite the success of antiretroviral therapy in suppressing HIV, life-long therapy is required to avoid HIV reactivation from long-lived viral reservoirs. Currently, there is intense interest in searching for therapeutic interventions that can purge the viral reservoir to achieve complete remission in HIV patients off antiretroviral therapy. The evaluation of such interventions relies on our ability to accurately and precisely measure the true size of the viral reservoir. In this review, we assess the most commonly used HIV reservoir assays, as a clear understanding of the strengths and weaknesses of each is vital for the accurate interpretation of results and for the development of improved assays.

Recent Findings

The quantification of intracellular or plasma HIV RNA or DNA levels remains the most commonly used tests for the characterization of the viral reservoir. While cost-effective and high-throughput, these assays are not able to differentiate between replication-competent or defective fractions or quantify the number of infected cells. Viral outgrowth assays provide a lower bound for the fraction of cells that can produce infectious virus, but these assays are laborious, expensive and substantially underestimate the potential reservoir of replication-competent provirus. Newer assays are now available that seek to overcome some of these problems, including full-length proviral sequencing, inducible HIV RNA assays, ultrasensitive p24 assays and murine adoptive transfer techniques.

Summary

The development and evaluation of strategies for HIV remission rely upon our ability to accurately and precisely quantify the size of the remaining viral reservoir. At this time, all current HIV reservoir assays have drawbacks such that combinations of assays are generally needed to gain a more comprehensive view of the viral reservoir. The development of novel, rapid, high-throughput assays that can sensitively quantify the levels of the replication-competent HIV reservoir is still needed.

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Papers of particular interest have been highlighted as: •• Of major importance

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  1. Brigham and Women’s Hospital, Harvard Medical School, 65 Landsdowne St, Rm 421, Cambridge, Boston, MA, 02139, USA

    Radwa R. Sharaf & Jonathan Z. Li

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JL has received research funding and consulted for Gilead and Merck. JL was funded in part by a grant from NIH/NIAID (125109).

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There were no human or animal experiments performed for the purpose of this review.

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Sharaf, R.R., Li, J.Z. The Alphabet Soup of HIV Reservoir Markers. Curr HIV/AIDS Rep 14, 72–81 (2017). https://doi.org/10.1007/s11904-017-0355-y

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