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Reduced adherence to antiretroviral therapy is associated with residual low-level viremia

Authors Maggiolo F, Di Filippo E, Comi L, Callegaro A, Colombo GL, Di Matteo S, Valsecchi D, Rizzi M

Received 17 November 2016

Accepted for publication 23 February 2017

Published 26 May 2017 Volume 2017:8 Pages 91—97


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Dr David B. Price

Franco Maggiolo,1 Elisa Di Filippo,1 Laura Comi,1 Annapaola Callegaro,2 Giorgio L Colombo,3,4 Sergio Di Matteo,4 Daniela Valsecchi,5 Marco Rizzi1

1USC of Infectious Diseases, 2USC Microbiology and Virology, 3Department of Drug Sciences, University of Pavia, 4S.A.V.E. Studi – Health Economics & Outcomes Research, Milan, 5USC of Pharmacy, ASST Papa Giovanni XXIII, Bergamo, Italy

Abstract: The source and significance of residual low-level viremia (LLV) during combinational antiretroviral therapy (cART) remain a matter of controversy. It is unclear whether residual viremia depends on ongoing release of HIV from the latent reservoir or if viral replication contributes to LLV. We examined the relationship between adherence and LLV. Adherence was estimated by pharmacy refill and dichotomized as ≥95% or <95%. Plasma HIV-RNA was determined, with an ultrasensitive test having a limit of detection of 3 copies/mL at least 2 times over the follow-up period. Patients were grouped according to HIV-RNA over time as K<3: constantly <3 copies/mL; V<3: sometimes below or above the cutoff limit but always <50  copies/mL; K>3: constantly between 3 and 50 ­copies/mL; and V>50: a measure of >50 copies/mL minimum. Overall, 2789 patients were included. At each time point approximately 92% of the patients presented an HIV-RNA <50 copies/mL and two-thirds of those <3 copies/mL, 34.6% of patients had <3 copies/mL constantly, 32.7% sometimes below or above the cutoff limit but always <50 copies/mL, 9.5% constantly between 3 and 50 copies/mL, and 23.2% a measure of >50 copies/mL minimum. The mean adherence rate was 92.1% (95% confidence interval [CI] from 91.1% to 93.1%) in K<3 patients, similar in V<3 patients (91.9%), but lowered to 88.8% in K>3 patients and to 88.4% in V>50 patients (P<0.0001). Approximately 55% of patients in groups K<3 and V<3 showed an adherence rate ≥95%; this proportion lowered to ~51% in K>3 and to 48% in V>50. Moreover, 34% of patients with a steady adherence <95% were categorized as K>3, whereas 21.7% of those with a drug holiday (21.7%) were observed in the V>50 group (P=0.002). A steady viral suppression can occur despite moderate cART non-adherence, but reduced adherence is associated with low-level residual viremia, which could reflect new rounds of HIV replication. However, a detectable HIV-RNA could also be detected in patients with optimal cART adherence, indicating additional mechanisms favoring HIV persistence.

Keywords: adherence, drug-refill, LLV, low-level viremia, viral replication, residual viremia cART

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