Predictors of late virologic failure after initial successful suppression of HIV replication on efavirenz-based antiretroviral therapy.

TitlePredictors of late virologic failure after initial successful suppression of HIV replication on efavirenz-based antiretroviral therapy.
Publication TypeJournal Article
Year of Publication2016
AuthorsSingini I, Campbell TB, Smeaton LM, Kumarasamy N, La Rosa A, Taejareonkul S, Safren SA, Flanigan TP, Hakim JG, Hughes MD
Corporate AuthorsACTG A5175/PEARLS Study Team.
JournalHIV Clin Trials
Pagination1-8
Date Published2016 Jul 29
ISSN1945-5771
Abstract

BACKGROUND: Practical issues, including cost, hinder implementing virologic monitoring of patients on antiretroviral therapy (ART) in resource-limited settings. We evaluated factors that might guide monitoring frequency and efforts to prevent treatment failure after initial virologic suppression.

METHODS: Participants were the 911 HIV-infected antiretroviral-naïve adults with CD4 count <300 cells/μL who started efavirenz-based ART in the international A5175/PEARLS trial and achieved HIV-1 RNA <1000 copies/mL at 24 weeks. Participant report of ART adherence was evaluated using a structured questionnaire in monthly interviews. Adherence and readily available clinical and laboratory measures were evaluated as predictors of late virologic failure (late VF: confirmed HIV-1 RNA ≥1000 copies/mL after 24 weeks).

RESULTS: During median follow-up of 3.5 years, 82/911 participants (9%) experienced late VF. Of 516 participants reporting missed doses during the first 24 weeks of ART, 55 (11%) experienced late VF, compared with 27 (7%) of 395 participants reporting no missed doses (hazard ratio: 1.73; 95% CI: 1.08, 2.73). This difference persisted in multivariable analysis, in which lower pre-ART hemoglobin and absence of Grade ≥3 laboratory results prior to week 24 were also associated with higher risk of late VF.

DISCUSSION: In this clinical trial, the late VF rate after successful suppression was very low. If achievable in routine clinical practice, virologic monitoring involving infrequent (e.g. annual) measurements might be considered; the implications of this for development of resistance need evaluating. Patients reporting missed doses early after ART initiation, despite achieving initial suppression, might require more frequent measurement and/or strategies for promoting adherence.

DOI10.1080/15284336.2016.1201300
Alternate JournalHIV Clin Trials
PubMed ID27472067
Grant ListUM1 AI069424 / AI / NIAID NIH HHS / United States
UM1 AI068634 / AI / NIAID NIH HHS / United States
UM1 AI069399 / AI / NIAID NIH HHS / United States
U01 AI068636 / AI / NIAID NIH HHS / United States
UM1 AI069463 / AI / NIAID NIH HHS / United States
UM1 AI106701 / AI / NIAID NIH HHS / United States
UM1 AI068636 / AI / NIAID NIH HHS / United States