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Non-nucleoside reverse transcriptase inhibitor-based combination antiretroviral therapy is associated with lower cell-associated HIV RNA and DNA levels compared to protease inhibitor-based therapy. | LitMetric

AI Article Synopsis

  • Two cross-sectional studies investigated whether antiretroviral therapy (ART) regimens using non-nucleoside reverse transcriptase inhibitors (NNRTIs) or protease inhibitors (PIs) have different effects on HIV replication suppression.
  • The study measured levels of cell-associated (CA) HIV RNA and DNA in participants treated with triple ART regimens and found that NNRTI-based treatments resulted in significantly lower levels of these markers compared to PI-based treatments.
  • The results suggest that NNRTIs may be more effective in reducing CA HIV RNA, indicating a potentially stronger suppression of HIV replication within long-lived reservoir cells.

Article Abstract

Background: It remains unclear whether combination antiretroviral therapy (ART) regimens differ in their ability to fully suppress human immunodeficiency virus (HIV) replication. Here, we report the results of two cross-sectional studies that compared levels of cell-associated (CA) HIV markers between individuals receiving suppressive ART containing either a non-nucleoside reverse transcriptase inhibitor (NNRTI) or a protease inhibitor (PI).

Methods: CA HIV unspliced RNA and total HIV DNA were quantified in two cohorts (n = 100, n = 124) of individuals treated with triple ART regimens consisting of two nucleoside reverse transcriptase inhibitors (NRTIs) plus either an NNRTI or a PI. To compare CA HIV RNA and DNA levels between the regimens, we built multivariable models adjusting for age, gender, current and nadir CD4 count, plasma viral load zenith, duration of virological suppression, NRTI backbone composition, low-level plasma HIV RNA detectability, and electronically measured adherence to ART.

Results: In both cohorts, levels of CA HIV RNA and DNA strongly correlated (rho = 0.70 and rho = 0.54) and both markers were lower in NNRTI-treated than in PI-treated individuals. In the multivariable analysis, CA RNA in both cohorts remained significantly reduced in NNRTI-treated individuals (p = 0.02 in both cohorts), with a similar but weaker association between the ART regimen and total HIV DNA (p = 0.048 and p = 0.10). No differences in CA HIV RNA or DNA levels were observed between individual NNRTIs or individual PIs, but CA HIV RNA was lower in individuals treated with either nevirapine or efavirenz, compared to PI-treated individuals.

Conclusions: All current classes of antiretroviral drugs only prevent infection of new cells but do not inhibit HIV RNA transcription in long-lived reservoir cells. Therefore, these differences in CA HIV RNA and DNA levels by treatment regimen suggest that NNRTIs are more potent in suppressing HIV residual replication than PIs, which may result in a smaller viral reservoir size.

Funding: This work was supported by ZonMw (09120011910035) and FP7 Health (305522).

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8460250PMC
http://dx.doi.org/10.7554/eLife.68174DOI Listing

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