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

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.

Keywords:

• Antiretroviral therapy
• Adherence
• Viral load monitoring
• Resource-limited settings
• Virologic suppression
• Virologic failure

Acknowledgments

The authors thank the study participants and site and ACTG staff who conducted the study. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Boehringer Ingelheim, Bristol-Myers Squibb, GlaxoSmithKline and Gilead Sciences provided study drugs and Gilead Sciences provided funding to purchase a study drug that was not otherwise available. Representatives of these companies participated as study team members, but did not participate in data collection or analysis, or in the preparation of this manuscript or the decision to publish. Dr Campbell reports having received money from Gilead for participation on an advisory board. Dr La Rosa reports being an employee of Merck Sharp and Dohme Peru. Dr Flanigan reports having stock ownership in Abbot, Bristol-Myers Squibb, Gilead Sciences and Glaxo SmithKline. The other authors do not have any potential conflicts of interest to declare. This work was presented in part at the Conference on Retroviruses and Opportunistic Infections: Abstract number 539, 3–6 March 2014, Boston, MA, USA.