Low Prevalence of Transmitted Drug Resistance in Patients Newly Diagnosed with HIV-1 Infection in Sweden 2003–2010

Abstract

Transmitted drug resistance (TDR) is a clinical and epidemiological problem because it may contribute to failure of antiretroviral treatment. The prevalence of TDR varies geographically, and its prevalence in Sweden during the last decade has not been reported. Plasma samples from 1,463 patients newly diagnosed with HIV-1 infection between 2003 and 2010, representing 44% of all patients diagnosed in Sweden during this period, were analyzed using the WHO 2009 list of mutations for surveillance of TDR. Maximum likelihood phylogenetic analyses were used to determine genetic subtype and to investigate the relatedness of the sequences. Eighty-two patients showed evidence of TDR, representing a prevalence of 5.6% (95% CI: 4.5%–6.9%) without any significant time trends or differences between patients infected in Sweden or abroad. Multivariable logistic regression showed that TDR was positively associated with men who have sex with men (MSM) and subtype B infection and negatively associated with CD4 cell counts. Among patients with TDR, 54 (68%) had single resistance mutations, whereas five patients had multi-drug resistant HIV-1. Phylogenetic analyses identified nine significantly supported clusters involving 29 of the patients with TDR, including 23 of 42 (55%) of the patients with TDR acquired in Sweden. One cluster contained 18 viruses with a M41L resistance mutation, which had spread among MSM in Stockholm over a period of at least 16 years (1994–2010). Another cluster, which contained the five multidrug resistant viruses, also involved MSM from Stockholm. The prevalence of TDR in Sweden 2003–2010 was lower than in many other European countries. TDR was concentrated among MSM, where clustering of TDR strains was observed, which highlights the need for continued and improved measures for targeted interventions.

Transmitted drug resistance to rilpivirine in newly diagnosed antiretroviral naive adults

“…As most of the studies characterizing transmitted drug resistance across Europe and the USA have not looked for some of these rilpivirine-resistance-associated mutations (RAMs) (e.g. mutations at codons 138, 221 and 227) [2][3][4][5], little information on the prevalence of transmitted rilpivirine RAMs is available [6][7][8]. We have previously reported transmitted drug resistance over different periods in Spain [9][10][11], but none of these reports evaluated rilpivirine transmitted drug resistance.…”

Prevalence of Transmitted HIV-1 Drug Resistance Remains Low in Guangxi, China, Eight Years after Scale-Up of Highly-Active Antiretroviral Therapy

“…HIV originated from multiple zoonotic transmissions of simian immunodeficiency virus (SIV) from non-human primates to humans in West and Central Africa around 100 years ago. It is characterized by its enormous genetic variability, which results from the high mutation and recombination rates of the reverse transcriptase enzyme that lacks a proofreading mechanism, together with high rates of virus replication [2] and this leads to the accumulation of mutations that confer resistance to antiretroviral (ARV) drugs, during suboptimal ARV therapy (ART) [3]. …”

Infection with the frequently transmitted HIV-1 M41L variant has no influence on selection of tenofovir resistance

“…However, this particular variant is often encountered in clinical practice in several countries. 25,34 Moreover, none of the three genetically distinct M41L-containing HIV-1 variants in our extensive in vitro experiments selected for any TAMs. Combined, these observations suggest that our results are broadly applicable.…”