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Declining HIV Drug Resistance in Europe

A retrospective analysis involving 20,323 samples from ART-experienced patients revealed that, despite increasing overall drug exposure, the prevalence of resistance mutations decreased between 1997 and 2008.

One of the greatest concerns about ever-expanding access to antiretroviral therapy (ART) is an increase in drug resistance. To assess trends in — and determinants of — such resistance in Western Europe, researchers examined HIV genotype data on samples obtained from ART-experienced patients in the U.K., Italy, Portugal, Germany, Sweden, Spain, and Belgium between 1997 and 2008.

Records for 20,323 samples were included in the analysis. Overall, 16,278 samples (80%) showed at least one resistance mutation. Resistance to nucleoside reverse transcriptase inhibitors (NRTIs) was most common (67%), followed by nonnucleoside reverse transcriptase inhibitors (NNRTIs; 51%) and protease inhibitors (PIs; 33%). Resistance to one, two, and three of these drug classes was seen in 26%, 38%, and 16% of the samples, respectively. For NRTIs, the most common resistance mutations were M184V/I and thymidine analogue mutations; for NNRTIs, K103N, Y181C/I, and G190A; and for PIs, L90M, M46I/L, V82A/F/L/S/T, and I84V. The proportion of samples with at least one resistance mutation declined over time, from 81% in 1997 to 71% in 2008; NRTI and PI mutations showed notable decreases. The proportion of sampled patients who exhausted available drug options dropped dramatically, from 32% in 2000 to 1% in 2008.

During the sampling period, NRTI use decreased (from 98% of the patients in 1997 to 94% in 2008), NNRTI use increased (from 6% in 1997 to 41% in 2000, leveling off at 32% in 2008), unboosted PI use decreased (from 55% in 1997 to 7% in 2008), and boosted PI use increased (from 1% in 1997 to 48% in 2008).

In multivariable analysis, factors associated with detection of resistance included being a man who has sex with men, non-B subtype virus, history of suboptimal therapy, failure of higher-line regimens, and longer duration of ART exposure.

Comment: The declining HIV drug resistance over time in this European meta-cohort could reflect adherence, choice of regimens, and switching strategies that have counterbalanced any potential increases in resistance with greater drug exposure. The introduction of new antiretrovirals has almost eliminated the problem of exhausted drug options.

— Salim S. Abdool Karim, MD, PhD

Published in Journal Watch HIV/AIDS Clinical Care February 15, 2013

Citation(s):

De Luca A et al. Declining prevalence of HIV-1 drug resistance in antiretroviral treatment-exposed individuals in Western Europe. J Infect Dis 2013 Jan 11; [e-pub ahead of print.] (http://dx.doi.org/10.1093/infdis/jit017)

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