AI Article Synopsis
- Modern antiretroviral therapy (ART) is believed to be effective even with some nonadherence, but it's unclear if HIV-1 replication is completely suppressed at adherence levels above 70%.
- A study examined HIV-1 RNA and DNA levels in 40 patients using electronic adherence tracking, categorizing them into optimal, improving, and poor adherence groups, all of which maintained adherence above 70% without any increases in plasma viral levels.
- Despite this, patients with poor adherence showed significant increases in cell-associated HIV RNA levels, indicating that modest nonadherence can lead to undetectable cycles of HIV-1 replication, as ART only prevents new cell infections but not the viral activity in already infected cells.
Article Abstract
Background: Modern antiretroviral therapy (ART) regimens are widely assumed to forgive modest nonadherence, because virological suppression in plasma is common at adherence levels of >70%. Yet, it is unknown whether human immunodeficiency virus type 1 (HIV-1) replication is completely suppressed at these levels of adherence.
Methods: We longitudinally quantified levels of cell-associated HIV-1 RNA and DNA in 40 patients (median duration of successful ART before study initiation, 46 months), whose 1-week adherence to therapy prior to the sampling moments was measured electronically.
Results: Patients were constantly 100% adherent (the optimal-adherence group), demonstrated improving adherence over time (the improving-adherence group), or neither of the above (the poor-adherence group). Adherence never decreased to <70% in any patient, and no rebound in plasma virological levels was observed. Nevertheless, poor adherence but not optimal or improving adherence caused a significant longitudinal increase in cell-associated HIV RNA levels (P = .006). Time-weighted changes and regression slopes of viral RNA load for the poor-adherence group were significantly higher than those for the optimal-adherence group (P < .01).
Conclusions: Because ART only blocks infection of new cells but not viral RNA transcription in cells infected before therapy initiation, the observed effects strongly suggest that modest nonadherence can cause new cycles of HIV-1 replication that are undetectable by commercial plasma viral load assays.
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| http://dx.doi.org/10.1093/infdis/jis502 | DOI Listing |
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