The demise of multidrug-resistant HIV-1: the national time trend in Portugal

Abstract

ObjectivesDespite a decreasing mortality and morbidity in treated HIV-1 patients, highly active antiretroviral treatment (HAART) can still fail due to the development of drug resistance. Especially, multidrug-resistant viruses pose a threat to efficient therapy. We studied the changing prevalence of multidrug resistance (MDR) over time in a cohort of HIV-1-infected patients in Portugal.Patients and methodsWe used data of 8065 HIV-1-infected patients followed from July 2001 up to April 2012 in 22 hospitals located in Portugal. MDR at a specific date of sampling was defined as no more than one fully active drug (excluding integrase and entry inhibitors) at that time authorized by the Portuguese National Authority of Medicines and Health Products (INFARMED), as interpreted with the Rega algorithm version 8.0.2. A generalized linear mixed model was used to study the time trend of the prevalence of MDR.ResultsWe observed a statistically significant decrease in the prevalence of MDR over the last decade, from 6.9% (95% CI: 5.7–8.4) in 2001–03, 6.0% (95% CI: 4.9–7.2) in 2003–05, 3.7% (95% CI: 2.8–4.8) in 2005–07 and 1.6% (95% CI: 1.1–2.2) in 2007–09 down to 0.6% (95% CI: 0.3–0.9) in 2009–12 [OR = 0.80 (95% CI: 0.75–0.86); P < 0.001]. In July 2011 the last new case of MDR was seen.ConclusionsThe prevalence of multidrug-resistant HIV-1 is decreasing over time in Portugal, reflecting the increasing efficiency of HAART and the availability of new drugs. Therefore, in designing a new drug, safety and practical aspects, e.g. less toxicity and ease of use, may need more attention than focusing mainly on efficacy against resistant strains.

Profile of the HIV Epidemic in Cape Verde: Molecular Epidemiology and Drug Resistance Mutations among HIV-1 and HIV-2 Infected Patients from Distinct Islands of the Archipelago

“…The frequency in Cape Verde is lower than that observed in Senegal [59], but higher than West Africa countries [60] and Portugal [61]. M184V (69.7%) and K103N (30.3%) were the major NRTI and NNRTI mutations, respectively, in Cape Verde, identical to those described in others countries [59], [62].…”

Recent trends in HIV-1 drug resistance

“…Clinical experience and recent observational studies indicate that the incidence and prevalence of HIV-1 drug resistance is actually declining [25**,26*,27*,28*,29*]. A comprehensive study of essentially all infected individuals in Sweden found a dramatic decrease in the prevalence of resistance between 2003 and 2007 with slower decreases thereafter [25**].…”

“…Selection of the NRTI resistance mutation K65R has also been declining despite the widespread use of tenofovir, which selects this mutation [28*]. The prevalence of multidrug resistance has been declining in Portugal in the time between 2001 and 2013 [29*]. Overall, these studies suggest that improvements in ART, including convenient single pill regimens consisting of three relatively non-toxic drugs, have improved adherence and allowed the full potential of ART to become apparent.…”

VIRULIGN: fast codon-correct alignment and annotation of viral genomes

“…• Identification of HIV-1 drug resistance mutations and the pathways emerging under drug selective pressure, as well as modeling the different factors leading to treatment failure and trends over time [14,24,27,26,4,5].…”

“…• VIRULIGN was recently integrated into the RegaDB data management and analysis platform for the clinical follow-up of HIV-1 patients [27,11].…”