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Waning Incidence of Multidrug-Resistant HIV in Europe?
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5th European HIV Drug Resistance Workshop
Cascais, Portugal
March 29, 2007
Mark Mascolini
Two studies presented at the 5th European HIV Drug Resistance Workshop found that multidrug-resistant (MDR) virus may be on the wane, at least in some parts of the continent. A 22-hospital survey in Portugal charted significantly declining incidence (new detection) of MDR HIV from 2000-2001 to 2005-2006 [1]. And rates of resistance to the first three antiretrovirals fell precipitously from 1999 through 2005 in a single-center Italian cohort [2].
With colleagues in Portugal, Jurgen Vercauteren of Belgium's Rega Institute analyzed incidence of MDR virus across Portugal. Vercauteren argued that earlier reports of MDR prevalence (overall rate regardless of detection time) offer a limited view of how MDR virus rates may be evolving [1]. He defined MDR HIV as virus to which one or no antiretrovirals are susceptible according to the Rega algorithm; by class resistance he meant virus to which no drugs in a class are susceptible. Vercauteren eliminated enfuvirtide, tipranavir, and darunavir as susceptible drugs in this analysis because they were not available over the whole study period, June 2001 through June 2006.
The analysis involved 3039 viral samples from 2373 antiretroviral-experienced people divided into five July-to-June periods, 2001-2002, 2002-2003, 2003-2004, 2004-2005, and 2005-2006. Incidence of MDR virus dropped significantly from 5.7% in 2001-2002, to 5.2%, 3.8%, 3.4%, and 2.7% in the following periods (P = 0.004). Risk of MDR virus in these Portuguese patients dwindled 18% yearly over this half-decade (odds ratio [OR] 0.82, 95% confidence interval [CI] 0.72 to 0.94).
Class resistance to nonnucleosides climbed from 2001-2002 through 2003-2004 (from 35.6% to 47.6%), then fell significantly in the following two periods (to 43.5% and 41.9%) (P < 0.02). Class resistance to nucleosides and protease inhibitors dropped significantly over the entire study period--from 13.5% to 6.1% (P < 0.001) for nucleosides, and from 10.6% to 7.3% (P = 0.015) for protease inhibitors.
Multivariate analysis picked out three factors that independently affected risk of MDR virus. Each more recent year lowered the risk 20% (OR 0.80, 95% CI 0.69 to 0.93, P = 0.003), each year on treatment raised the risk 16% (OR 1.16, 95% CI 1.09 to 1.23, P < 0.001), and an unknown antiretroviral therapy start date upped the risk almost 8 times (OR 7.88, 95% CI 4.60 to 13.48, P < 0.001).
Vercauteren proposed that increasing antiretroviral efficacy explains the significant falloff in MDR and class-resistant virus. But workshop attendees counseled caution in drawing that conclusion, noting, for example, that a continuously rising death rate of people with the most resistant virus or increasing rates of resistance testing may also contribute to the findings. If Vercauteren's conclusion does prove true, one would expect similar trends in other countries with free antiretroviral access and a population similar to Portugal's.
Clinicians at Rome's Catholic University did not chart trends in MDR virus per se [2]. But their analysis of resistance mutation prevalence from 1999 through 2005 found that mutations conferring resistance to the first three antiretroviral classes fell significantly over that period (P < 0.001 for each class).
This study evaluated virus from people with at least 6 months of antiretroviral experience, a viral load above 1000 copies on two consecutive assays, and no drug holidays in the 3 months before genotyping. Mutation prevalence calculations involved 128 people in 1999, 50 in 2000, 95 in 2001, 102 in 2002, 59 in 2003, 68 in 2004, and 78 in 2005.
During these years prevalence of any resistance mutation faded from about 95% to 55%, while rates of nucleoside, nonnucleoside, and protease inhibitor mutations fell from about 90% to 45%, 30% to 10%, and 65% to 25%. The low rate of nonnucleoside mutations reflects a preference for protease inhibitor-based regimens at Catholic University during these years.
References
1. Vercauteren J, Theys K, Debruyne M, et al. The incidence of multidrug and class resistance in HIV-1 infected patients is decreasing over time (2001-2006). 5th European HIV Drug Resistance Workshop. March 28-30, 2007. Cascais, Portugal. Abstract 1.
2. Colafigli M, Di Giambenedetto S, Bracciale L,et al. Variables associated with the declining prevalence of HIV-1 drug resistance mutations in treatment experienced patients: a clinical cohort study. 5th European HIV Drug Resistance Workshop. March 28-30, 2007. Cascais, Portugal. Abstract 2.
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