Patterns of Transmitted HIV Drug Resistance in Europe Vary by Risk Group

Background: In Europe, a continuous programme (SPREAD) has been in place for ten years to study transmission of drug resistant HIV. We analysed time trends of transmitted drug resistance mutations (TDRM) in relation to the risk behaviour reported.

Methods: HIV-1 patients newly diagnosed in 27 countries from 2002 through 2007 were included. Inclusion was representative for risk group and geographical distribution in the participating countries in Europe. Trends over time were calculated by logistic regression.

Results: From the 4317 patients included, the majority was men-having-sex-with-men -MSM (2084, 48%), followed by heterosexuals (1501, 35%) and injection drug users (IDU) (355, 8%). MSM were more often from Western Europe origin, infected with subtype B virus, and recently infected (<1 year) (p<0.001). The prevalence of TDRM was highest in MSM (prevalence of 11.1%), followed by heterosexuals (6.6%) and IDU (5.1%, p<0.001). TDRM was predominantly ascribed to nucleoside reverse transcriptase inhibitors (NRTI) with a prevalence of 6.6% in MSM, 3.3% in heterosexuals and 2.0% in IDU (p = 0.001). A significant increase in resistance to non- nucleoside reverse transcriptase inhibitors (NNRTIs) and a decrease in resistance to protease inhibitors was observed in MSM (p = 0.008 and p = 0.006, respectively), but not in heterosexual patients (p = 0.68 and p = 0.14, respectively).

Conclusions: MSM showed to have significantly higher TDRM prevalence compared to heterosexuals and IDU. The increasing NNRTI resistance in MSM is likely to negatively influence the therapy response of first-line therapy, as most include NNRTI drugs.

Citing Articles

Estimating the Current Routes of Transmission in HIV-1 F1 Subtype Infected Persons in Romania: Differences Between Self-Reporting and Phylogenetic Data.

Hohan R, Paraschiv S, Nicolae I, Otelea D Pathogens. 2024; 13(11).

PMID: 39599513 PMC: 11597275. DOI: 10.3390/pathogens13110960.

The Phenomenon of Antiretroviral Drug Resistance in the Context of Human Immunodeficiency Virus Treatment: Dynamic and Ever Evolving Subject Matter.

Apetroaei M, Velescu B, Nedea M, Dinu-Pirvu C, Draganescu D, Faca A Biomedicines. 2024; 12(4).

PMID: 38672269 PMC: 11048092. DOI: 10.3390/biomedicines12040915.

Disparity of HIV-1 Pretreatment Drug Resistance in Men Who Have Sex With Men and the Heterosexual Population in Guangxi, China.

Pang X, Liang S, Tang K, Huang J, He Q, Fang N Open Forum Infect Dis. 2023; 10(2):ofad016.

PMID: 36751650 PMC: 9898876. DOI: 10.1093/ofid/ofad016.

Phylogeographic Assessment Reveals Geographic Sources of HIV-1 Dissemination Among Men Who Have Sex With Men in Kenya.

Nduva G, Otieno F, Kimani J, McKinnon L, Cholette F, Sandstrom P Front Microbiol. 2022; 13:843330.

PMID: 35356525 PMC: 8959701. DOI: 10.3389/fmicb.2022.843330.

Transmitted HIV-1 is more virulent in heterosexual individuals than men-who-have-sex-with-men.

James A, Dixit N PLoS Pathog. 2022; 18(3):e1010319.

PMID: 35271687 PMC: 8912199. DOI: 10.1371/journal.ppat.1010319.

References

Bezemer D, van Sighem A, Lukashov V, van der Hoek L, Back N, Schuurman R . Transmission networks of HIV-1 among men having sex with men in the Netherlands. AIDS. 2009; 24(2):271-82. DOI: 10.1097/QAD.0b013e328333ddee. View

Hamers R, Wallis C, Kityo C, Siwale M, Mandaliya K, Conradie F . HIV-1 drug resistance in antiretroviral-naive individuals in sub-Saharan Africa after rollout of antiretroviral therapy: a multicentre observational study. Lancet Infect Dis. 2011; 11(10):750-9. DOI: 10.1016/S1473-3099(11)70149-9. View

Bollerup A, Donoghoe M, Lazarus J, Nielsen S, Matic S . Access to highly active antiretroviral therapy (HAART) in the WHO European Region 2003-2005. Scand J Public Health. 2008; 36(2):183-9. DOI: 10.1177/1403494807085191. View

Brenner B, Roger M, Routy J, Moisi D, Ntemgwa M, Matte C . High rates of forward transmission events after acute/early HIV-1 infection. J Infect Dis. 2007; 195(7):951-9. DOI: 10.1086/512088. View

Wheeler W, Ziebell R, Zabina H, Pieniazek D, Prejean J, Bodnar U . Prevalence of transmitted drug resistance associated mutations and HIV-1 subtypes in new HIV-1 diagnoses, U.S.-2006. AIDS. 2010; 24(8):1203-12. DOI: 10.1097/QAD.0b013e3283388742. View

Lima V, Gill V, Yip B, Hogg R, Montaner J, Harrigan P . Increased resilience to the development of drug resistance with modern boosted protease inhibitor-based highly active antiretroviral therapy. J Infect Dis. 2008; 198(1):51-8. DOI: 10.1086/588675. View

Donoghoe M, Bollerup A, Lazarus J, Nielsen S, Matic S . Access to highly active antiretroviral therapy (HAART) for injecting drug users in the WHO European Region 2002-2004. Int J Drug Policy. 2007; 18(4):271-80. DOI: 10.1016/j.drugpo.2007.02.010. View

Booth C, Garcia-Diaz A, Youle M, Johnson M, Phillips A, Geretti A . Prevalence and predictors of antiretroviral drug resistance in newly diagnosed HIV-1 infection. J Antimicrob Chemother. 2007; 59(3):517-24. DOI: 10.1093/jac/dkl501. View

Abecasis A, Wensing A, Paraskevis D, Vercauteren J, Theys K, van de Vijver D . HIV-1 subtype distribution and its demographic determinants in newly diagnosed patients in Europe suggest highly compartmentalized epidemics. Retrovirology. 2013; 10:7. PMC: 3564855. DOI: 10.1186/1742-4690-10-7. View

10.

Luber A . Genetic barriers to resistance and impact on clinical response. MedGenMed. 2005; 7(3):69. PMC: 1681671. View

11.

Schuurman R, Nijhuis M, van Leeuwen R, Schipper P, de Jong D, Collis P . Rapid changes in human immunodeficiency virus type 1 RNA load and appearance of drug-resistant virus populations in persons treated with lamivudine (3TC). J Infect Dis. 1995; 171(6):1411-9. DOI: 10.1093/infdis/171.6.1411. View

12.

Wood E, Montaner J, Yip B, Tyndall M, Schechter M, OShaughnessy M . Adherence and plasma HIV RNA responses to highly active antiretroviral therapy among HIV-1 infected injection drug users. CMAJ. 2003; 169(7):656-61. PMC: 202281. View

13.

Vercauteren J, Wensing A, van de Vijver D, Albert J, Balotta C, Hamouda O . Transmission of drug-resistant HIV-1 is stabilizing in Europe. J Infect Dis. 2009; 200(10):1503-8. DOI: 10.1086/644505. View

14.

Mills A, Nelson M, Jayaweera D, Ruxrungtham K, Cassetti I, Girard P . Once-daily darunavir/ritonavir vs. lopinavir/ritonavir in treatment-naive, HIV-1-infected patients: 96-week analysis. AIDS. 2009; 23(13):1679-88. DOI: 10.1097/QAD.0b013e32832d7350. View

15.

Morrison S, Banushi V, Sarnquist C, Gashi V, Osterberg L, Maldonado Y . Barriers to care and current medical and social needs of HIV-positive patients in Albania. Cent Eur J Public Health. 2011; 19(2):91-7. DOI: 10.21101/cejph.a3644. View

16.

van Asten L, Boufassa F, Schiffer V, Brettle R, Robertson J, Hernandez Aguado I . Limited effect of highly active antiretroviral therapy among HIV-positive injecting drug users on the population level. Eur J Public Health. 2004; 13(4):347-9. DOI: 10.1093/eurpub/13.4.347. View

17.

Jain V, Sucupira M, Bacchetti P, Hartogensis W, Diaz R, Kallas E . Differential persistence of transmitted HIV-1 drug resistance mutation classes. J Infect Dis. 2011; 203(8):1174-81. PMC: 3107558. DOI: 10.1093/infdis/jiq167. View

18.

Xiridou M, van Veen M, Coutinho R, Prins M . Can migrants from high-endemic countries cause new HIV outbreaks among heterosexuals in low-endemic countries?. AIDS. 2010; 24(13):2081-8. DOI: 10.1097/QAD.0b013e32833a6071. View

19.

Wittkop L, Gunthard H, de Wolf F, Dunn D, Cozzi-Lepri A, De Luca A . Effect of transmitted drug resistance on virological and immunological response to initial combination antiretroviral therapy for HIV (EuroCoord-CHAIN joint project): a European multicohort study. Lancet Infect Dis. 2011; 11(5):363-71. DOI: 10.1016/S1473-3099(11)70032-9. View

20.

Palella Jr F, Delaney K, Moorman A, Loveless M, Fuhrer J, Satten G . Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. N Engl J Med. 1998; 338(13):853-60. DOI: 10.1056/NEJM199803263381301. View