Abstract
BackgroundSeveral studies demonstrate a correlation between sub-therapeutic concentrations of antiretroviral drugs and virologic failure. We examined the sensitivity, specificity and predictive values of sub-therapeutic drug levels in predicting viralogic failure.MethodsThis was a case control study with cases being samples of participants with virologic failure, and controls samples of participants with virologic suppression. We analyzed samples obtained from participants that had been on antiretroviral treatment (ART) for at least 6 months. Virologic failure was defined as HIV-RNA viral load ≥ 1000 copies/ml. Sub-therapeutic drug levels were defined according to published reference cutoffs. The diagnostic validity of drug levels for virologic failure was assessed using plasma viral loads as a gold standard.ResultsSub-therapeutic ART concentrations explained only 38.2% of virologic failure with a probability of experiencing virologic failure of 0.66 in a patient with low drug levels versus 0.25 for participants with measurements within or above the normal range. Approximately 90% of participants with ART concentrations above the lower clinical cut off did not have virologic failure.ConclusionsThese results support prior indication for therapeutic drug monitoring in cases of suspected virologic failure.
Highlights
Several studies demonstrate a correlation between sub-therapeutic concentrations of antiretroviral drugs and virologic failure
Virologic failure is defined according to the 2016 World Health Organization (WHO) guidelines as two consecutive human immunodeficiency virus (HIV)-ribonucleic acid (RNA) viral loads ≥ 1000 copies/ml [3]
Materials and methods This study was conducted at the Infectious Diseases Institute (IDI), Makerere University, an HIV centre of excellence located in Mulago teaching Hospital in Kampala with over 8000 HIV-positive individuals receiving care [15]
Summary
Several studies demonstrate a correlation between sub-therapeutic concentrations of antiretroviral drugs and virologic failure. Two factors that may contribute to virologic failure include pre-treatment resistance and acquired drug resistance [4, 5]. Acquired drug resistance normally results from sub-therapeutic drug exposure. Factors that may lead to sub-therapeutic exposure include single nucleotide polymorphisms [4, 5], drug–drug interactions, drug–herb interactions, non-adherence and mal-absorption [6,7,8,9]. Therapeutic drug monitoring (TDM) may detect suboptimal concentrations, and inform the clinicians on the need to address factors which may Buzibye et al AIDS Res Ther (2019) 16:39 lead to drug resistance and prevent unnecessary switching where treatment options are already limited
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