The relationship between antiretroviral drug concentrations and persistent low-level viremia among HIV-infected women in the United States Öffentlichkeit

Abstract

Background: While most HIV-infected patients receiving combination antiretroviral therapy (cART) achieve plasma HIV RNA level (viral load, VL) below the assay limit of detection, some patients experience episodes of low-level viremia (LLV) with detectable VL <1000 copies/ml. Persistent LLV is associated with cART drug resistance and regimen failure; its cause remains unclear, but could be due to inadequate antiretroviral (ARV) concentrations. The levels of ARVs in hair were previously shown to predict virologic success. We estimated the prevalence of persistent LLV in a cohort of HIV-infected women receiving cART and evaluated the relationship between persistent LLV and hair ARV concentrations.

Methods: 1320 HIV-infected women enrolled in the Women's Interagency HIV Study who reported ARV use for at least 1 year and achieved plasma VL <1000 copies/mL were classified into one of four virologic outcome categories: 1) virologic failure (single VL ≥1000 copies/ml), 2) persistent LLV (≥2 consecutive detectable VL <1000 copies/ml), 3) intermittent LLV (<2 consecutive detectable VL <1000 copies/ml), or 4) sustained virologic suppression (undetectable VL for all visits). 797 women had at least one hair ARV concentration measurement during the follow-up period. We used multivariable logistic regression models to evaluate the relationship between hair ARV concentrations and persistent LLV.

Results: Sustained virologic suppression, intermittent LLV, persistent LLV and virologic failure occurred in 31%, 26%, 14% and 29% of participants, respectively. Participants with virologic failure reported lower adherence, started cART earlier, were more likely to receive protease-inhibitor-based cART, and were more likely to have hair ARV concentrations in the lowest quartile. Only receipt of protease-inhibitor-based cART was significantly associated with persistent LLV (compared with intermittent LLV or viral suppression). In a multivariable logistic regression model, hair ARV concentrations did not significantly differ between women with persistent LLV versus intermittent LLV/ viral suppression.

Conclusions: Virologic outcomes for this large cohort of HIV-infected women were suboptimal, with almost half of participants experiencing either persistent LLV or virologic failure. Hair ARV concentrations were not associated with persistent LLV, suggesting that ongoing viremia arises independently of ARV exposure. Future research is needed to elucidate the pathogenesis of persistent LLV to improve cART outcomes.

Table of Contents

INTRODUCTION. 1

BACKGROUND. 3

METHODS. 7

RESULTS. 15

DISCUSSION/CONCLUSIONS. 19

REFERENCES. 25

TABLES AND FIGURES. 32

Figure 1. 32

Table 1. 33

Figure 2. 34

Table 2. 35

Table 3. 36

Table 4. 37

Table 5. 38

Table 6. 39

Table 7. 40

Table 8. 41

About this Master's Thesis

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School	Laney Graduate School
Department	Clinical Research Curriculum Program
Degree	MS
Submission	Master's Thesis
Language	English
Research Field	Health Sciences, Pharmacology Health Sciences, Medicine and Surgery Health Sciences, Epidemiology
Stichwort	antiretroviral therapy low-level viremia HIV/AIDS
Committee Chair / Thesis Advisor	Ofotokun, Igho, Emory University
Committee Members	McGowan Jr., John E, Emory University Klein, Mitchel, Emory University

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