• Journal article

Phenotypic and genotypic analyses to guide selection of reverse transcriptase inhibitors in second-line HIV therapy following extended virological failure in Uganda

R. L. Goodall, D. T. Dunn, T. Pattery, A. van Cauwenberge, P. Nkurunziza, P. Awio, N. Ndembi, P. Munderi, C. Kityo, C. F. Gilks, P. Kaleebu, D. Pillay, P. Kaleebu, D. Pillay, P. Awio, M. Chirara, D. Dunn, D. M. Gibb, C. Gilks, R. Goodall, A. Kapaata, M. Katuramur, F. Lyagoba, R. Magala, B. Magambo, K. Mataruka, A.L. McCormick, L. Mugarura, T. Musunga, M. Nabankkema, J. Nkalubo, P. Nkurunziza, C. Parry, V. Robertson, M. Spyer, D. Yirrell, H. Grosskurth, P. Munderi, G. Kabuye, D. Nsibambi, R. Kasirye, E. Zalwango, M. Nakazibwe, B. Kikaire, G. Nassuna, R. Massa, K. Fadhiru, M. Namyalo, A. Zalwango, L. Generous and P. Khauka 2014. Phenotypic and genotypic analyses to guide selection of reverse transcriptase inhibitors in second-line HIV therapy following extended virological failure in Uganda. Journal of Antimicrobial Chemotherapy. 69 (7), pp. 1938-1944. https://doi.org/10.1093/jac/dku052

TitlePhenotypic and genotypic analyses to guide selection of reverse transcriptase inhibitors in second-line HIV therapy following extended virological failure in Uganda
TypeJournal article
AuthorsR. L. Goodall, D. T. Dunn, T. Pattery, A. van Cauwenberge, P. Nkurunziza, P. Awio, N. Ndembi, P. Munderi, C. Kityo, C. F. Gilks, P. Kaleebu, D. Pillay, P. Kaleebu, D. Pillay, P. Awio, M. Chirara, D. Dunn, D. M. Gibb, C. Gilks, R. Goodall, A. Kapaata, M. Katuramur, F. Lyagoba, R. Magala, B. Magambo, K. Mataruka, A.L. McCormick, L. Mugarura, T. Musunga, M. Nabankkema, J. Nkalubo, P. Nkurunziza, C. Parry, V. Robertson, M. Spyer, D. Yirrell, H. Grosskurth, P. Munderi, G. Kabuye, D. Nsibambi, R. Kasirye, E. Zalwango, M. Nakazibwe, B. Kikaire, G. Nassuna, R. Massa, K. Fadhiru, M. Namyalo, A. Zalwango, L. Generous and P. Khauka
Abstract

Objectives
We investigated phenotypic and genotypic resistance after 2 years of first-line therapy with two HIV treatment regimens in the absence of virological monitoring.

Methods
NORA [Nevirapine OR Abacavir study, a sub-study of the Development of AntiRetroviral Therapy in Africa (DART) trial] randomized 600 symptomatic HIV-infected Ugandan adults (CD4 cell count <200 cells/mm3) to receive zidovudine/lamivudine plus abacavir (cABC arm) or nevirapine (cNVP arm). All virological tests were performed retrospectively, including resistance tests on week 96 plasma samples with HIV RNA levels ≥1000 copies/mL. Phenotypic resistance was expressed as fold-change in IC50 (FC) relative to wild-type virus.

Results
HIV-1 RNA viral load ≥1000 copies/mL at week 96 was seen in 58/204 (28.4%) cABC participants and 21/159 (13.2%) cNVP participants. Resistance results were available in 35 cABC and 17 cNVP participants; 31 (89%) cABC and 16 (94%) cNVP isolates had a week 96 FC below the biological cut-off for tenofovir (2.2). In the cNVP arm, 16/17 participants had resistance mutations synonymous with high-level resistance to nevirapine and efavirenz; FC values for etravirine were above the biological cut-off in 9 (53%) isolates. In multivariate regression models, K65R, Y115F and the presence of thymidine analogue-associated mutations were associated with increased susceptibility to etravirine in the cABC arm.

Conclusions
Our data support the use of tenofovir following failure of a first-line zidovudine-containing regimen and shed further light on non-nucleoside reverse transcriptase inhibitor hypersusceptibility.

JournalJournal of Antimicrobial Chemotherapy
Journal citation69 (7), pp. 1938-1944
ISSN0305-7453
1460-2091
Year2014
PublisherOxford University Press
Publisher's version
License
CC BY 3.0
File Access Level
Open (open metadata and files)
Digital Object Identifier (DOI)https://doi.org/10.1093/jac/dku052
Web address (URL)http://dx.doi.org/10.1093/jac/dku052
Publication dates
Published01 Jul 2014

Related outputs

Dual production of polyhydroxyalkanoates and antibacterial/antiviral gold nanoparticles
McCormick, A.L., Basnett, P., Vecchiato, V., Wright, E., Noble, B., Marcello, E. and Paxinou, A. 2023. Dual production of polyhydroxyalkanoates and antibacterial/antiviral gold nanoparticles. Frontiers in Nanotechnology. 5 1243056. https://doi.org/10.3389/fnano.2023.1243056

Author Correction: A HML6 endogenous retrovirus on chromosome 3 is upregulated in amyotrophic lateral sclerosis motor cortex
Jones, A.R., Iacoangeli, A., Adey, B.N., Bowles, H., Shatunov, A., Troakes, C., Garson, J.A., McCormick, A.L. and Al‑Chalabi, A. 2022. Author Correction: A HML6 endogenous retrovirus on chromosome 3 is upregulated in amyotrophic lateral sclerosis motor cortex. Scientific Reports. 12 14171. https://doi.org/10.1038/s41598-022-18488-y

A HML6 endogenous retrovirus on chromosome 3 is upregulated in amyotrophic lateral sclerosis motor cortex.
Jones, A.R., Iacoangeli, A., Adey, B.N., Bowles, H., Shatunov, A, Troakes, C., Garson, J.A., McCormick, A.L. and Al‑Chalabi, A. 2021. A HML6 endogenous retrovirus on chromosome 3 is upregulated in amyotrophic lateral sclerosis motor cortex. Scientific Reports. 11 14283. https://doi.org/10.1038/s41598-021-93742-3

Elevated microRNA expression could be diagnostic biomarker for PDAC
Mortoglou, M., Arisan, D., Ferreira, T., McCormick, A.L. and Uysal Onganer, P. 2020. Elevated microRNA expression could be diagnostic biomarker for PDAC. Pancreatology. 20 (8) e19. https://doi.org/10.1016/j.pan.2020.10.015

Response to the Letter from Garcia-Montojo and colleagues concerning our paper entitled, Quantitative analysis of human endogenous retrovirus-K transcripts in postmortem premotor cortex fails to confirm elevated expression of HERV-K RNA in amyotrophic lateral sclerosis.
Garson, J.A., Usher, L., Al-Chalabi, A., Huggett, J., Day, E. and McCormick, A.L. 2019. Response to the Letter from Garcia-Montojo and colleagues concerning our paper entitled, Quantitative analysis of human endogenous retrovirus-K transcripts in postmortem premotor cortex fails to confirm elevated expression of HERV-K RNA in amyotrophic lateral sclerosis. Acta Neuropathologica Communications. 7 102. https://doi.org/10.1186/s40478-019-0756-9

Quantitative analysis of Human Endogenous Retrovirus-K transcripts in postmortem premotor cortex fails to confirm elevated expression of HERV-K RNA in amyotrophic lateral sclerosis
Garson, J.A., Usher, L., Al-Chalabi, A., Huggett, J., Day, E.F. and McCormick, A.L. 2019. Quantitative analysis of Human Endogenous Retrovirus-K transcripts in postmortem premotor cortex fails to confirm elevated expression of HERV-K RNA in amyotrophic lateral sclerosis. Acta Neuropathologica Communications. 7 45. https://doi.org/10.1186/s40478-019-0698-2

Correction: Evidence for Reduced Drug Susceptibility without Emergence of Major Protease Mutations following Protease Inhibitor Monotherapy Failure in the SARA Trial.
Sutherland, K.A., Parry, C.M., McCormick, A.L., Kapaata, A., Lyagoba, F., Kaleebu, P., Gilks, C.F., Goodall, R., Spyer, M., Kityo, C., Pillay, D., Gupta, R.K. and DART Virology Group 2016. Correction: Evidence for Reduced Drug Susceptibility without Emergence of Major Protease Mutations following Protease Inhibitor Monotherapy Failure in the SARA Trial. PLoS ONE. 11 (6) e0157094. https://doi.org/10.1371/journal.pone.0157094

Gag-Protease Sequence Evolution Following Protease Inhibitor Monotherapy Treatment Failure in HIV-1 Viruses Circulating in East Africa.
Sutherland, K.A., Goodall, R.L., McCormick, A.L., Kapaata, A., Lyagoba, F., Kaleebu, P., Thiltgen, G., Gilks, C.F., Spyer, M., Kityo, C., Pillay, D., Dunn, D. and Gupta, R.K. 2015. Gag-Protease Sequence Evolution Following Protease Inhibitor Monotherapy Treatment Failure in HIV-1 Viruses Circulating in East Africa. AIDS Research and Human Retroviruses. 31 (10), pp. 1032-1037. https://doi.org/10.1089/aid.2015.0138

Evidence for Reduced Drug Susceptibility without Emergence of Major Protease Mutations following Protease Inhibitor Monotherapy Failure in the SARA Trial
Sutherland, K.A., Parry, C.M., McCormick, A.L., Kapaata, A., Lyagoba, F., Kaleebu, P., Gilks, C.F., Goodall, R., Spyer, M., Kityo, C., Pillay, D., Gupta, R.K. and DART Virology Group 2015. Evidence for Reduced Drug Susceptibility without Emergence of Major Protease Mutations following Protease Inhibitor Monotherapy Failure in the SARA Trial. PLoS ONE. 10 (9) e0137834. https://doi.org/10.1371/journal.pone.0137834

IL28B genotype predicts response to chronic hepatitis C triple therapy with telaprevir or boceprevir in treatment naïve and treatment-experienced patients other than prior partial- and null-responders
Calisti, G., Tavares, A., Macartney, M.J., McCormick, A.L., Labbett, W., Jacobs, M., Dusheiko, G., Rosenberg, W.M. and Haque, T. 2015. IL28B genotype predicts response to chronic hepatitis C triple therapy with telaprevir or boceprevir in treatment naïve and treatment-experienced patients other than prior partial- and null-responders. SpringerPlus. 4 (1). https://doi.org/10.1186/s40064-015-1137-x

Evaluation of sequencing of HCV core/E1, NS5A and NS5B as a genotype predictive tool in comparison with commercial assays targeting 5′UTR
McCormick, A.L., Macartney, M.J., Abdi-Abshir, I., Labbett, W., Smith, C., Irish, D., Webster, D.P. and Haque, T. 2015. Evaluation of sequencing of HCV core/E1, NS5A and NS5B as a genotype predictive tool in comparison with commercial assays targeting 5′UTR. Journal of Clinical Virology. 66 (May), pp. 56-59. https://doi.org/10.1016/j.jcv.2015.03.006

Ultra-deep sequencing provides insights into the virology of hepatitis C super-infections in a case of three sequential infections with different genotypes
Chung, E., Ferns, R.B., He, M., Rigatti, R., Grant, P., McCormick, A.L., Bhagani, S., Webster, D.P., Nastouli, E. and Waters, L.J. 2015. Ultra-deep sequencing provides insights into the virology of hepatitis C super-infections in a case of three sequential infections with different genotypes. Journal of Clinical Virology. 70 (Sept), pp. 63-66. https://doi.org/10.1016/j.jcv.2015.06.105

The utility of genotypic tropism testing in clinical practice
Wyatt, H., Herman, O., Macartney, M.J., Conibear, T., Garcia-Diaz, A., Booth, C., McCormick, A.L., Smith, C., Johnson, M., Irish, D. and Webster, D. 2015. The utility of genotypic tropism testing in clinical practice. International Journal of STD and AIDS. 26 (8), pp. 593-594. https://doi.org/10.1177/0956462414546917

Feasibility of testing and detection of HIV-1 drug resistance in proviral DNA
Booth, C., McCormick, A.L., Garcia-Diaz, A., Macartney, M., Youle, M., Johnson, M. and Webster, D. 2014. Feasibility of testing and detection of HIV-1 drug resistance in proviral DNA. BMC Infectious Diseases. 14 (Supplement 4) O25. https://doi.org/10.1186/1471-2334-14-s4-o25

Analysis of transmitted HIV-1 drug resistance using 454 ultra-deep-sequencing and the DeepChek(®)-HIV system.
Garcia-Diaz, A., McCormick, A.L., Booth, C., Gonzalez, D., Sayada, C., Haque, T., Johnson, M. and Webster, D. 2014. Analysis of transmitted HIV-1 drug resistance using 454 ultra-deep-sequencing and the DeepChek(®)-HIV system. Journal of the International AIDS Society. 17 (Suppl 3) 19752. https://doi.org/10.7448/ias.17.4.19752

Telaprevir or boceprevir based therapy for chronic hepatitis C infection: Development of resistance-associated variants in treatment failure
Macartney, M.J., Irish, D., Bridge, S.H., Garcia-Diaz, A., Booth, C., McCormick, A.L., Labbett, W., Smith, C., Velazquez, C., Tanwar, S., Trembling, P., Jacobs, M., Dusheiko, G., Rosenberg, W.M. and Haque, T. 2014. Telaprevir or boceprevir based therapy for chronic hepatitis C infection: Development of resistance-associated variants in treatment failure. Antiviral Research. 105, pp. 112-7. https://doi.org/10.1016/j.antiviral.2014.02.019

Prevalence of baseline polymorphisms for potential resistance to NS5A inhibitors in drug-naive individuals infected with hepatitis C genotypes 1–4
McCormick, A.L., Wang, L., Garcia-Diaz, A., Macartney, M.J., Webster, D.P. and Haque, T. 2014. Prevalence of baseline polymorphisms for potential resistance to NS5A inhibitors in drug-naive individuals infected with hepatitis C genotypes 1–4 . Antiviral Therapy. 20 (1), pp. 81-85. https://doi.org/10.3851/IMP2763

The utility of different bioinformatics algorithms for genotypic HIV-1 tropism testing in a large clinical cohort with multiple subtypes
Bartlett, A., Macartney, M.J., Conibear, T., Feyertag, F., Smith, C., Johnson, M., Hyams, C., Garcia-Diaz, A., McCormick, A.L., Booth, C., Robertson, D. and Webster, D.P. 2014. The utility of different bioinformatics algorithms for genotypic HIV-1 tropism testing in a large clinical cohort with multiple subtypes. AIDS. 28 (11), pp. 1611-7. https://doi.org/10.1097/QAD.0000000000000288

Baseline drug-resistance mutations are detectable in HCV genes NS3 and NS5A but not NS5B in acute and chronic HIV-coinfected patients
McCormick, A.L., Moynihan, L., Macartney, M.J., Garcia-Diaz, A., Smith, C., Johnson, M., Rodger, A.J., Bhagani, S., Haque, T. and Webster, D. 2014. Baseline drug-resistance mutations are detectable in HCV genes NS3 and NS5A but not NS5B in acute and chronic HIV-coinfected patients. Antiviral Therapy. 20 (3), p. 2015. https://doi.org/10.3851/IMP2871

Evaluation of the Roche prototype 454 HIV-1 ultradeep sequencingdrug resistance assay in a routine diagnostic laboratory
Garcia-Diaz, A., Guerrero-Ramos, A., McCormick, A.L., Macartney, M.J., Conibear, T., Johnson, M., Haque, T. and Webster, D.P. 2013. Evaluation of the Roche prototype 454 HIV-1 ultradeep sequencingdrug resistance assay in a routine diagnostic laboratory. Journal of Clinical Virology. 58 (2), pp. 468-473. https://doi.org/10.1016/j.jcv.2013.07.009

Impact of the N348I Mutation in HIV-1 Reverse Transcriptase on Nonnucleoside Reverse Transcriptase Inhibitor Resistance in Non-Subtype B HIV-1
McCormick, A.L., Parry, C.M., Crombe, A., Goodall, R.L., Gupta, R.K., Kaleebu, P., Kityo, C., Chirara, M., Towers, G.J. and Pillay, D. 2011. Impact of the N348I Mutation in HIV-1 Reverse Transcriptase on Nonnucleoside Reverse Transcriptase Inhibitor Resistance in Non-Subtype B HIV-1. Antimicrobial Agents and Chemotherapy. 55 (4), pp. 1806-1809. https://doi.org/10.1128/AAC.01197-10

Full length HIV-1 Gag determines protease inhibitor susceptibility within in vitro assays
Gupta, R.K., Kohli, A., McCormick, A.L., Towers, G.J., Pillay, D. and Parry, C.M. 2010. Full length HIV-1 Gag determines protease inhibitor susceptibility within in vitro assays. AIDS. 24 (11), p. 1651–1655. https://doi.org/10.1097/QAD.0b013e3283398216

Lack of Minority K65RResistant Viral Populations Detected After Repeated Treatment Interruptions of Tenofovir/Zidovudine and Lamivudine in a Resource-Limited Setting
McCormick, A.L., Goodall, R.L., Joyce, A., Ndembi, N., Chirara, M., Katunduk, P., Walker, A.S., Yirrell, D.L., Gilks, C.F. and Pillay, D. 2010. Lack of Minority K65RResistant Viral Populations Detected After Repeated Treatment Interruptions of Tenofovir/Zidovudine and Lamivudine in a Resource-Limited Setting. Journal of Acquired Immune Deficiency Syndromes. 54 (2), pp. 215-216. https://doi.org/10.1097/QAI.0b013e3181cc1058

Viral Rebound and Emergence of Drug Resistance in the Absence of Viral Load Testing: A Randomized Comparison between Zidovudine-Lamivudine plus Nevirapine and Zidovudine-Lamivudine plus Abacavir
Ndembi, N., Goodall, R.L., Dunn, D.T., McCormick, A.L., Burke, A., Lyagoba, F., Munderi, P., Katundu, P., Kityo, C., Robertson, V., Yirrell, D.L., Walker, A.S., Gibb, D.M., Gilks, C.F., Kaleebu, P. and Pillay, D. 2010. Viral Rebound and Emergence of Drug Resistance in the Absence of Viral Load Testing: A Randomized Comparison between Zidovudine-Lamivudine plus Nevirapine and Zidovudine-Lamivudine plus Abacavir. The Journal of Infectious Diseases. 201 (1), pp. 106-113. https://doi.org/10.1086/648590

Quantification of reverse transcriptase in ALS and elimination of a novel retroviral candidate
McCormick, A.L., Brown, R.H., Cudkowicz, M.E., Al-Chalabi, A. and Garson, J.A. 2008. Quantification of reverse transcriptase in ALS and elimination of a novel retroviral candidate. Neurology. 70 (4), pp. 278-283. https://doi.org/10.1212/01.wnl.0000297552.13219.b4

An interferon gamma-gp120 fusion delivered as a DNA vaccine induces enhanced priming
Nimal, S., McCormick, A.L., Thomas, M.S. and Heath, A.W. 2005. An interferon gamma-gp120 fusion delivered as a DNA vaccine induces enhanced priming. Vaccine. 23 (10), pp. 3984-3990. https://doi.org/10.1016/j.vaccine.2005.01.160

CD40 antibody as an adjuvant induces enhanced T cell responses
Carlring, J., Barr, T.A., McCormick, A.L. and Heath, A.W. 2004. CD40 antibody as an adjuvant induces enhanced T cell responses. Vaccine. 22 (25-26), p. 3323–3328. https://doi.org/10.1016/j.vaccine.2004.02.043

A potent adjuvant effect of CD40 antibody attached to antigen
Barr, T.A., McCormick, A.L., Carlring, J. and Heath, A.W. 2003. A potent adjuvant effect of CD40 antibody attached to antigen. Immunology. 109 (1), pp. 87-92. https://doi.org/10.1046/j.1365-2567.2003.01634.x

Immunization with an Interferon-g–gp120 Fusion Protein Induces Enhanced Immune Responses to Human Immunodeficiency Virus gp120
McCormick, A.L., Thomas, M.S. and Heath, A.W. 2001. Immunization with an Interferon-g–gp120 Fusion Protein Induces Enhanced Immune Responses to Human Immunodeficiency Virus gp120. The Journal of Infectious Diseases. 184 (11), pp. 1423-1430. https://doi.org/10.1086/324371

Gag Determinants of Fitness and Drug Susceptibility in Protease Inhibitor-Resistant Human Immunodeficiency Virus Type 1
Parry, C.M., Kohli, A., Boinett, C.J., Towers, G.J., McCormick, A.L. and Pillay, D. 1999. Gag Determinants of Fitness and Drug Susceptibility in Protease Inhibitor-Resistant Human Immunodeficiency Virus Type 1. Journal of Virology. 83 (18), pp. 9094-9101. https://doi.org/10.1128/JVI.02356-08

Cell Surface Expression of CD154 Inhibits Alloantibody Responses: A Mechanism for the Prevention of Autoimmune Responses against Activated T Cells?
McCormick, A.L., Santos-Argumedo, L., Thomas, M.S. and Heath, A.W. 1999. Cell Surface Expression of CD154 Inhibits Alloantibody Responses: A Mechanism for the Prevention of Autoimmune Responses against Activated T Cells? Cellular Immunology. 195 (2), pp. 157-161. https://doi.org/10.1006/cimm.1999.1528

Enhancement of immunogenicity of recombinant antigens by production of a cytokine-antigen fusion protein for vaccination
McCormick, A.L., Thomas, M.S. and Heath, A.W. 1997. Enhancement of immunogenicity of recombinant antigens by production of a cytokine-antigen fusion protein for vaccination. Biochemical Society Transactions. 25, p. 297S. https://doi.org/10.1042/bst025297s

Permalink - https://westminsterresearch.westminster.ac.uk/item/w56yw/phenotypic-and-genotypic-analyses-to-guide-selection-of-reverse-transcriptase-inhibitors-in-second-line-hiv-therapy-following-extended-virological-failure-in-uganda


Share this

Tweet
Email

Usage statistics

42 total views
18 total downloads
These values cover views and downloads from WestminsterResearch and are for the period from September 2nd 2018, when this repository was created.