HIV-1 transmitted drug resistance surveillance: shifting trends in study design and prevalence estimates

Soo-Yon Rhee, Seble G Kassaye, Geoffrey Barrow, Jagadish Chandrabose Sundaramurthi, Michael R Jordan, Robert W Shafer, Soo-Yon Rhee, Seble G Kassaye, Geoffrey Barrow, Jagadish Chandrabose Sundaramurthi, Michael R Jordan, Robert W Shafer

Abstract

Introduction: HIV-1 transmitted drug resistance (TDR) prevalence increased during the initial years of the antiretroviral therapy (ART) global scale-up. Few studies have examined recent trends in TDR prevalence using published genetic sequences and described the characteristics of ART-naïve persons from whom these published sequences have been obtained.

Methods: We identified 125 studies published between 2014 and 2019 for which HIV-1 reverse transcriptase (RT) with or without protease from ≥50 ART-naïve adult persons were submitted to the GenBank sequence database. The population characteristics and TDR prevalence were compared to those in 122 studies published in the preceding five years between 2009 and 2013. TDR prevalence was analysed using median study-level and person-level data.

Results and discussion: The 2009 to 2013 and 2014 to 2019 studies reported sequence data from 32,866 and 41,724 ART-naïve persons respectively. Studies from the low- and middle-income country (LMIC) regions in sub-Saharan Africa, South/Southeast Asia and Latin America/Caribbean accounted for approximately two-thirds of the studies during each period. Between the two periods, the proportion of studies from sub-Saharan Africa and from South/Southeast Asia countries other than China decreased from 43% to 32% and the proportion of studies performed at sentinel sites for recent HIV-1 infection decreased from 33% to 22%. Between 2014 and 2019, median study-level TDR prevalence was 4.1% in South/Southeast Asia, 6.0% in sub-Saharan Africa, 9.1% in Latin America/Caribbean, 8.5% in Europe and 14.2% in North America. In the person-level analysis, there was an increase in overall, NNRTI and two-class NRTI/NNRTI resistance in sub-Saharan Africa; an increase in NNRTI resistance in Latin America/Caribbean, and an increase in overall, NNRTI and PI resistance in North America.

Conclusions: Overall, NNRTI and dual NRTI/NNRTI-associated TDR prevalence was significantly higher in sub-Saharan Africa studies published between 2014 and 2019 compared with those published between 2009 and 2013. The decreasing proportion of studies from the hardest hit LMIC regions and the shift away from sentinel sites for recent infection suggests that global TDR surveillance efforts and publication of findings require renewed emphasis.

Keywords: HIV-1; antiretroviral therapy; drug resistance; protease; reverse transcriptase; surveillance.

© 2020 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.

Figures

Figure 1
Figure 1
Flow chart showing the derivation of study sets meeting meta‐analysis inclusion criteria.
Figure 2
Figure 2
Distribution of sample collection years for studies published between 2009 and 2013 and between 2014 and 2019.
Figure 3
Figure 3
TDR prevalence estimates in studies containing ≥50 ART‐naïve persons published 2009 to 2013 and 2014 to 2019 for those regions with ≥5 studies.

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