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. 2019 Dec 6;16(1):39.
doi: 10.1186/s12981-019-0255-x.

Antiretroviral concentration measurements as an additional tool to manage virologic failure in resource limited settings: a case control study

Allan Buzibye  1 , Joseph Musaazi  2 , Amrei von Braun  3 , Sarah Nanzigu  4 , Christine Sekaggya-Wiltshire  2 , Andrew Kambugu  2 , Jan Fehr  5 , Mohammed Lamorde  2 , Ursula Gutteck  6 , Daniel Muller  6 , Stefanie Sowinski  7 , Steven J Reynolds  8   9 , Barbara Castelnuovo  2
Affiliations

Antiretroviral concentration measurements as an additional tool to manage virologic failure in resource limited settings: a case control study

Allan Buzibye et al. AIDS Res Ther. .

Abstract

Background: Several 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.

Methods: This 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.

Results: Sub-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.

Conclusions: These results support prior indication for therapeutic drug monitoring in cases of suspected virologic failure.

Keywords: HIV; Resource limited setting; Therapeutic drug monitoring; Uganda; Virologic failure.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
A box plot of drug concentration by drug type stratified by cases and controls. x = Marks the lower and upper cut-off of normal ranges
See this image and copyright information in PMC

References

    1. Murphy EL, Collier AC, Kalish LA, Assmann SF, Para MF, Flanigan TP, et al. Highly active antiretroviral therapy decreases mortality and morbidity in patients with advanced HIV disease. Ann Intern Med. 2001;135(1):17–26. doi: 10.7326/0003-4819-135-1-200107030-00005. - DOI - PubMed
    1. Miiro G, Todd J, Mpendo J, Watera C, Munderi P, Nakubulwa S, et al. Reduced morbidity and mortality in the first year after initiating highly active anti-retroviral therapy (HAART) among Ugandan adults. Trop Med Int Health. 2009;14(5):556–563. doi: 10.1111/j.1365-3156.2009.02259.x. - DOI - PubMed
    1. WHO Guidelines Approved by the Guidelines Review Committee. In: nd, editor. Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a Public health approach. Geneva: World Health Organization. Copyright (c) World Health Organization 2016.; 2016.
    1. Hamers RL, Schuurman R, Sigaloff KC, Wallis CL, Kityo C, Siwale M, et al. Effect of pretreatment HIV-1 drug resistance on immunological, virological, and drug-resistance outcomes of first-line antiretroviral treatment in sub-Saharan Africa: a multicentre cohort study. Lancet Infect Dis. 2012;12(4):307–317. doi: 10.1016/S1473-3099(11)70255-9. - DOI - PubMed
    1. Hassan AS, Nabwera HM, Mwaringa SM, Obonyo CA, Sanders EJ, Rinke de Wit TF, et al. HIV-1 virologic failure and acquired drug resistance among first-line antiretroviral experienced adults at a rural HIV clinic in coastal Kenya: a cross-sectional study. AIDS Res Ther. 2014;11(1):9. doi: 10.1186/1742-6405-11-9. - DOI - PMC - PubMed

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