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AIDS. 2016 Mar 13;30(5):713-21. doi: 10.1097/QAD.0000000000000974.

HIV-1 transcriptional activity during frequent longitudinal sampling in aviremic patients on antiretroviral therapy.

Author information

1
aDepartment of Infectious Diseases, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99- 8200 Aarhus N, Denmark bAarhus Institute for Advanced Studies, Nordre Ringgade 1, 8000 Aarhus C, Denmark cInstitute of Clinical Medicine, Palle Juul-Jensens Boulevard 82, 8200 Aarhus N. Denmark. *Steffen Leth, Rasmus Nymann and Sofie Jørgensen contributed equally to this article.

Abstract

BACKGROUND:

HIV-1 transcription during suppressive antiretroviral therapy (ART) is not well understood. This is problematic as latency-reactivating agent-based HIV-1 eradication trials utilize changes in viral transcription as an efficacy biomarker.

METHODS:

We conducted an observational cohort study enrolling aviremic, HIV-1-infected adults on long-term ART. Cell-associated unspliced (CA-US) HIV-1 RNA and total HIV-1 DNA were quantified in unfractionated CD4 T cells monthly for a total of six consecutive visits. Random-effects models were used to determine the following: (i) proportion of variation attributable to intra-individual versus inter-individual changes; (ii) range estimate for random samples from any participant or cohort-matched individual (95% prediction interval); and (iii) range estimate for random samples from the same person (95% variation intervals expressed as fold change).

RESULTS:

Among our cohort of 26 HIV-1 patients, 10.4% of variation in CA-US HIV-1 RNA was attributable to intra-individual fluctuations. Similarly, intra-individual changes also accounted for minor proportions of the variation in total HIV-1 DNA (5.1%) and RNA/DNA (28.3%). The 95% prediction interval (per 10 CD4 T cells) for CA-US HIV-1 RNA and HIV-1 DNA were each approximately 2 log10. Finally, model-derived 95% variation intervals indicate that spontaneous changes above 2.11-fold in CA-US HIV-1 RNA would occur in less than 5% of repeated measurements in an individual on long-term ART.

CONCLUSION:

The individual CA-US HIV-1 RNA levels are remarkably stable during ART. Importantly, the observed variations were less than the reported changes for latency-reactivating agent trials. These data will serve as a foundation for planning and interpreting future eradication trials.

PMID:
26595541
DOI:
10.1097/QAD.0000000000000974
[Indexed for MEDLINE]

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