Drug resistance from preferred antiretroviral regimens for HIV infection in South Africa: A modeling study

被引:3
作者
Abbas, Ume L. [1 ,2 ,3 ,4 ]
Glaubius, Robert L. [3 ,4 ,6 ]
Ding, Yajun [1 ,2 ,7 ]
Hood, Gregory [5 ]
机构
[1] Baylor Coll Med, Sect Infect Dis, Dept Med, Houston, TX 77030 USA
[2] Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA
[3] Cleveland Clin, Dept Quantitat Hlth Sci, Cleveland, OH 44106 USA
[4] Cleveland Clin, Dept Infect Dis, Cleveland, OH 44106 USA
[5] Carnegie Mellon Univ, Pittsburgh Supercomp Ctr, Pittsburgh, PA 15213 USA
[6] Avenir Hlth, Glastonbury, CT USA
[7] PROS Holdings Inc, Houston, TX USA
关键词
DISCRETE-EVENT SIMULATION; SUB-SAHARAN AFRICA; FOLLOW-UP; PREEXPOSURE PROPHYLAXIS; STOCHASTIC SIMULATION; VIROLOGICAL OUTCOMES; THERAPY PROGRAM; NATIONAL-SURVEY; PERSISTENCE; PREVENTION;
D O I
10.1371/journal.pone.0218649
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Background Tenofovir-containing regimens comprise the preferred first-line antiretroviral therapy (ART) in many countries including South Africa, where utilization of second-line regimens is limited. Considerable HIV drug resistance has occurred among persons failing tenofovir-containing first-line ART. We evaluated drug resistance at the population level using mathematical modeling. Setting Heterosexual HIV epidemic in KwaZulu-Natal, South Africa. Methods We constructed a stochastic individual-based model and simulated scenarios of ART implementation, either CD4-based (threshold < 500 cells/mL) or Fast-track (81% coverage by 2020), with consideration of major drug-associated mutations (M184V, K65R and non-nucleoside reverse transcriptase inhibitor (NNRTI)). Using base case and uncertainty analyses, we assessed (majority) drug resistance levels. Results By 2030, the median total resistance (proportion of HIV-infected persons with drug resistance) is predicted to reach 31.4% (interquartile range (IQR): 16.5%-50.2%) with CD4-based ART, decreasing to 14.5% (IQR: 7.7%-25.8%) with Fast-track implementation. In both scenarios, we find comparably high prevalence (similar to 80%) of acquired NNRTI-associated, M184V and K65R mutations. Over 48% of individuals with acquired resistance harbor dual, 44% triple and 7% just single drug mutations. Drug-resistant HIV is predicted to comprise 40% (IQR: 27%-50%) of incident infections, while 70% of prevalent transmitted resistance is NNRTI-associated. At 2018, the projected total resistance is 15% (IQR: 7.5%-25%), with 18% (IQR: 13%-24%) of incident infections from transmitted drug-resistant HIV. Conclusions WHO-recommended preferred first-line ART could lead to substantial drug resistance. Effective surveillance of HIV drug resistance and utilization of second-line as well as alternative first-line regimens is crucial.
引用
收藏
页数:17
相关论文
共 92 条
[61]   Averted HIV infections due to expanded antiretroviral treatment eligibility offsets risk of transmitted drug resistance: a modeling study [J].
Nichols, Brooke E. ;
Sigaloff, Kim C. E. ;
Kityo, Cissy ;
Mandaliya, Kishor ;
Hamers, Raph L. ;
Bertagnolio, Silvia ;
Jordan, Michael R. ;
Boucher, Charles A. B. ;
de Wit, Tobias F. Rinke ;
van de Vijver, David A. M. C. .
AIDS, 2014, 28 (01) :73-83
[62]  
Organization WH, 2017, GUID PUBL HLTH RESP
[63]   Selection and persistence of non-nucleoside reverse transcriptase inhibitor-resistant HIV-1 in patients starting and stopping non-nucleoside therapy [J].
Palmer, S ;
Boltz, V ;
Maldarelli, F ;
Kearney, M ;
Halvas, EK ;
Rock, D ;
Falloon, J ;
Davey, RT ;
Dewar, RL ;
Metcalf, JA ;
Mellors, JW ;
Coffin, JM .
AIDS, 2006, 20 (05) :701-710
[64]   Differences in Reversion of Resistance Mutations to Wild-Type under Structured Treatment Interruption and Related Increase in Replication Capacity [J].
Paquet, Agnes C. ;
Baxter, John ;
Weidler, Jodi ;
Lie, Yolanda ;
Lawrence, Jody ;
Kim, Rose ;
Bates, Michael ;
Coakley, Eoin ;
Chappey, Colombe .
PLOS ONE, 2011, 6 (01)
[65]   Resistance to Antiretroviral Drugs in Newly Diagnosed, Young Treatment-Naive HIV-Positive Pregnant Women in the Province of KwaZulu-Natal, South Africa [J].
Parboosing, R. ;
Naidoo, A. ;
Gordon, M. ;
Taylor, M. ;
Vella, V. .
JOURNAL OF MEDICAL VIROLOGY, 2011, 83 (09) :1508-1513
[66]   Prevalence of HIV-1 Drug Resistance among Women Screening for HIV Prevention Trials in KwaZulu-Natal, South Africa (MTN-009) [J].
Parikh, Urvi M. ;
Kiepiela, Photini ;
Ganesh, Shayhana ;
Gomez, Kailazarid ;
Horn, Stephanie ;
Eskay, Krista ;
Kelly, Cliff ;
Mensch, Barbara ;
Gorbach, Pamina ;
Soto-Torres, Lydia ;
Ramjee, Gita ;
Mellors, John W. .
PLOS ONE, 2013, 8 (04)
[67]   Nucleoside reverse-transcriptase inhibitor cross-resistance and outcomes from second-line antiretroviral therapy in the public health approach: an observational analysis within the randomised, open-label, EARNEST trial [J].
Paton, Nicholas I. ;
Kityo, Cissy ;
Thompson, Jennifer ;
Nankya, Immaculate ;
Bagenda, Leonard ;
Hoppe, Anne ;
Hakim, James ;
Kambugu, Andrew ;
van Oosterhout, Joep J. ;
Kiconco, Mary ;
Bertagnolio, Silvia ;
Easterbrook, Philippa J. ;
Mugyenyi, Peter ;
Walker, A. Sarah .
LANCET HIV, 2017, 4 (08) :E341-E348
[68]   Risks and benefits of dolutegravir-based antiretroviral drug regimens in sub-Saharan Africa: a modelling study [J].
Phillips, Andrew N. ;
Venter, Francois ;
Havlir, Diane ;
Pozniak, Anton ;
Kuritzkes, Daniel ;
Wensing, Annemarie ;
Lundgren, Jens D. ;
De Luca, Andrea ;
Pillay, Deenan ;
Mellors, John ;
Cambiano, Valentina ;
Bansi-Matharu, Loveleen ;
Nakagawa, Fumiyo ;
Kalua, Thokozani ;
Jahn, Andreas ;
Apollo, Tsitsi ;
Mugurungi, Owen ;
Clayden, Polly ;
Gupta, Ravindra K. ;
Barnabas, Ruanne ;
Revill, Paul ;
Cohn, Jennifer ;
Bertagnolio, Silvia ;
Calmy, Alexandra .
LANCET HIV, 2019, 6 (02) :E116-E127
[69]   Cost-effectiveness of public-health policy options in the presence of pretreatment NNRTI drug resistance in sub-Saharan Africa: a modelling study [J].
Phillips, Andrew N. ;
Cambiano, Valentina ;
Nakagawa, Fumiyo ;
Revill, Paul ;
Jordan, Michael R. ;
Hallett, Timothy B. ;
Doherty, Meg ;
De Luca, Andrea ;
Lundgren, Jens D. ;
Mhangara, Mutsa ;
Apollo, Tsitsi ;
Mellors, John ;
Nichols, Brooke ;
Parikh, Urvi ;
Pillay, Deenan ;
de Wit, Tobias Rinke ;
Sigaloff, Kim ;
Havlir, Diane ;
Kuritzkes, Daniel R. ;
Pozniak, Anton ;
van de Vijver, David ;
Vitoria, Marco ;
Wainberg, Mark A. ;
Raizes, Elliot ;
Bertagnolio, Silvia .
LANCET HIV, 2018, 5 (03) :E146-E154
[70]   Impact of HIV Drug Resistance on HIV/AIDS-Associated Mortality, New Infections, and Antiretroviral Therapy Program Costs in Sub-Saharan Africa [J].
Phillips, Andrew N. ;
Stover, John ;
Cambiano, Valentina ;
Nakagawa, Fumiyo ;
Jordan, Michael R. ;
Pillay, Deenan ;
Doherty, Meg ;
Revill, Paul ;
Bertagnolio, Silvia .
JOURNAL OF INFECTIOUS DISEASES, 2017, 215 (09) :1362-1365