High Rates of Transmission of Drug-resistant HIV in Aruba Resulting in Reduced Susceptibility to the WHO Recommended First-line Regimen in Nearly Half of Newly Diagnosed HIV-infected Patients.
In Western countries emergence of human immunodeficiency virus (HIV) drug resistance has tremendously decreased, and transmission of drug resistance has merely stabilized in recent years. However, in many endemic settings with limited resources rates of emerging and transmitted drug resistance are not regularly assessed.



We performed a survey including all HIV-infected individuals who received resistance testing in 2010-2015 in Aruba, a highly endemic HIV area in the Caribbean. Transmitted HIV drug resistance was determined using World Health Organization (WHO) criteria. Transmission dynamics were investigated using phylogenetic analyses. In a subset, baseline samples were re-analyzed using next generation sequencing (NGS).



Baseline resistance testing was performed in 104 newly diagnosed untreated individuals (54% of all newly diagnosed individuals in 2010-2015): 86% were men, 39% were foreign-born, and 22% had AIDS at diagnosis. And 33% (95% CI: 24-42%) was infected with a drug-resistant HIV variant. The prevalence of resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) reached 45% (95% CI: 27-64%) in 2015, all based on the prevalence of mutation K103N. NGS did not demonstrate additional minority K103N-variants compared to routine resistance testing. K103N-harboring strains were introduced into the therapy-unexposed population via at least 6 independent transmissions epidemiologically linked to the surrounding countries. Virological failure of the WHO-recommended first-line NNRTI-based regimen was higher in the presence of K103N.



The prevalence of resistant HIV in Aruba has increased to alarming levels, compromising the WHO-recommended first-line regimen. As adequate surveillance as advocated by the WHO is limited, the Caribbean region could face an unidentified rise of NNRTI-resistant HIV.
Virology, Department of Medical Microbiology, University Medical Center Utrecht, The Netherlands.|Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg.
L Marije
LM
Hofstra
Department of Internal Medicine, Dr Horacio E. Oduber Hospital, Oranjestad, Aruba.
Elena
E
Sánchez Rivas
Virology, Department of Medical Microbiology, University Medical Center Utrecht, The Netherlands.
Monique
M
Nijhuis
Virology, Department of Medical Microbiology, University Medical Center Utrecht, The Netherlands.|Department of Internal Medicine and Infectious Diseases, University Medical Center Utrecht, The Netherlands.
Leonie E A
LEA
Bank
Africa Centre for Population Health, Myeki, South Africa.|School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban, Republic of South Africa.
Eduan
E
Wilkinson
Department of Internal Medicine, Dr Horacio E. Oduber Hospital, Oranjestad, Aruba.
Karina
K
Kelly
Department of Internal Medicine and Infectious Diseases, University Medical Center Utrecht, The Netherlands.
Tania
T
Mudrikova
Virology, Department of Medical Microbiology, University Medical Center Utrecht, The Netherlands.
Rob
R
Schuurman
Africa Centre for Population Health, Myeki, South Africa.|School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban, Republic of South Africa.
Tulio
T
de Oliveira
Department of Internal Medicine, Dr Horacio E. Oduber Hospital, Oranjestad, Aruba.
Jaclyn
J
de Kort
Virology, Department of Medical Microbiology, University Medical Center Utrecht, The Netherlands.
Annemarie M J
AMJ
Wensing
D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017691:Caribbean Region / Q000453:epidemiology; D024882:Drug Resistance, Viral; D005260:Female; D006678:HIV / Q000187:drug effects* / Q000302:isolation & purification; D015658:HIV Infections / Q000453:epidemiology* / Q000635:transmission / Q000821:virology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011795:Surveys and Questionnaires
D019380:Anti-HIV Agents
HIV-1; drug resistance; surveillance; transmission; therapy