Skip to main content
SpringerLink
Log in

Drugs Resistance and Treatment Failure in HIV and/or AIDS

  • Chapter
  • First Online:
Biochemistry of Drug Resistance

  • 1005 Accesses

Abstract

Human immunodeficiency virus (HIV) is an epidemic that has compelled the clinical sciences to profusely develop and modify this rapidly evolving pathogen. AIDS is fatal and incurable disease which severely affects immune system. The treatment for AIDS is a blend of two or more drugs known as antiretroviral drugs (ARV) and the therapy is cumulatively called Highly Active Anti-Retroviral Therapy (HAART). Although ARV drugs are successful and treatment is adapted with known efficacy, the major impediment resulting in treatment failure is drug resistance in HIV infected patients. Specific mutations in HIV genome result in the development of drug resistance against recommended therapy. These DNA mutations predict drug resistance against stated drug however there are number of factors contributing to the development of drug resistance. The main HIV targeted regions include developing countries due to deprived resources, poor clinical follow up and disease control management. Phenotype testing in link to computational modulation can be helpful in selecting the best treatment regimens however subsequent viral mutations and range of drug combinations can result in multifaceted scenario. Competing HIV along with evolving drug resistance challenges the efficiency of treatment and provokes more clinical trials towards threshold of failure.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  • Amangaldiyeva, A., Davlidova, S., & Baiserkin, B. (2019). Implementation of antiretroviral therapy (ART) in former Soviet Union countries. AIDS Resistant Therapy, 16, 35–43.

    Article  Google Scholar 

  • Armenia, D., Di Carlo, D., Flandre, P., Bouba, Y., Borghi, V., Forbici, F., Bertoli, A., Gori, C., Fabeni, L., Gennari, W., Pinnetti, C., Mondi, A., Cicalini, S., Gagliardini, R., Vergori, A., Bellagamba, R., Malagnino, V., Montella, F., Colafigli, M. … Santoro, M. M. (2020). HIV MDR is still a relevant issue despite its dramatic drop over the years. Journal of Antimicrobial Chemotherapy, 75, 1301–1310.

    Google Scholar 

  • Babiker, A., Castro Nee Green, H., & Compagnucci, A. (2011). First-line antiretroviral therapy with a protease inhibitor versus non-nucleoside reverse transcriptase inhibitor and switch at higher versus low viral load in HIV-infected children: An open-label, randomised phase 2/3 trial. Lancet Infectious Disease, 11, 273–283.

    Google Scholar 

  • Boender, T.S., Hamers, R. L., Ondoa, P., Wellington, M., Chimbetete, C., Siwale, M., Maksimos, E. E. F. L., Balinda, S. N., Kityo, C. N., Adeyemo, T. A., Akanmu, A. S., Mandaliya, K., Botes, M. E., Stevens, W., Rinke De Wit, T. F., & Sigaloff, K. C. E. (2016). Protease inhibitor resistance in the first 3 years of second-line antiretroviral therapy for HIV-1 in Sub-Saharan Africa. The Journal of Infectious Diseases, 214, 873–883.

    Google Scholar 

  • Boffito, M., Waters, L., Cahn, P., Paredes, R., Koteff, J., Wyk, J. V., Vincent, T., Demarest, J., Adkison, K., & Quercia, R. (2020). Perspectives on the barrier to resistance for Dolutegravir + Lamivudine, a two-drug antiretroviral therapy for HIV-1 infection. AIDS Research and Human Retroviruses, 36, 13–18.

    Article  CAS  Google Scholar 

  • Clutter, D. S., Jordan, M. R., Bertagnolio, S., & Shafer, R. W. (2016). HIV-1 drug resistance and resistance testing infection. Genetics and Evolution, 46, 292–307.

    Article  CAS  Google Scholar 

  • Davy-Mendez, T., Eron, J. J., Brunet, L., Zakharova, O., Dennis, A. M., & Napravnik, S. (2018). New antiretroviral agent use affects prevalence of HIV drug resistance in clinical care populations. AIDS, 32, 2593–2603.

    Article  CAS  Google Scholar 

  • Dimi, S., Zucman, D., Chassany, O., Lalanne, C., Prazuck, T., Mortier, E., Majerholc, C., Aubin-Auger, I., Verger, P., & Duracinsky, M. (2019). Patients’ high acceptability of a future therapeutic HIV vaccine in France: a French paradox? BMC Infectious Disease, 19, 401.

    Google Scholar 

  • Endalamaw, A., Mekonnen, M., Geremew, D., Fikadu, A., Yehualashet, F. A., Tesera, H., & Habtewold, T. D. (2020). HIV/AIDS treatment failure and associated factors in Ethiopia: Meta-analysis. BMC Public Health, 20, 82.

    Google Scholar 

  • Günthard, H. F., Calvez, V., Paredes, R., Pillay, D., Shafer, R. W., Wensing, A. M., Jacobsen, D. M., & Richman, D. D. (2019). Human immunodeficiency virus drug resistance: 2018 recommendations of the international antiviral society-USA panel. Clinical Infectious Disease, 68, 177–187.

    Article  Google Scholar 

  • Hamers, R. L., Rinke De Wit, T. F., & Holmes, C. B. (2018). HIV drug resistance in low-income and middle-income countries. Lancet HIV, 5, e588–e596.

    Google Scholar 

  • Hare, S., Vos, A. M., Clayton, R. F., Thuring, J. W., Cummings, M. D., & Cherepanov, P. (2010). Molecular mechanisms of retroviral integrase inhibition and the evolution of viral resistance. Proceedings of the National Academy of Sciences of the United States of America, 107, 20057–20062.

    Article  CAS  Google Scholar 

  • Himmel, D. M., & Arnold, E. (2020). Non-nucleoside reverse transcriptase inhibitors join forces with integrase inhibitors to combat HIV. Pharmaceuticals, 13, 122.

    Article  CAS  Google Scholar 

  • Hoesley, C. J., Chen, B. A., Anderson, P. L., Dezzutti, C. S., Strizki, J., Sprinkle, C., Heard, F., Bauermeister, J., Hall, W., Jacobson, C., Berthiaume, J., Mayo, A., Gundacker, H., Richardson-Harman, N., & Piper, J. (2019). Phase 1 safety and pharmacokinetics study of MK-2048/Vicriviroc (MK-4176)/MK-2048A intravaginal rings. Clinical Infectious Disease, 68, 1136–1143.

    Article  CAS  Google Scholar 

  • Hull, M. W., & Montaner, J. S. (2013). HIV treatment as prevention: The key to an AIDS-free generation. Journal of Food and Drug Analysis, 21, S95–S101.

    Article  Google Scholar 

  • Jade, G., Marie-Laure, C., & Constance, D. (2008). HIV-1 resistance to first- and second-generation non-nucleoside reverse transcriptase inhibitors. AIDS Reviews, 11, 165–173.

    Google Scholar 

  • Kevadiya, B. D., Woldstad, C., Ottemann, B. M., Dash, P., Sajja, B. R., Lamberty, B., Morsey, B., Kocher, T., Dutta, R., Bade, A. N., Liu, Y., Callen, S. E., Fox, H. S., Byrareddy, S. N., McMillan, J. M., Bronich, T. K., Edagwa, B. J., Boska, M. D., & Gendelman, H. E. (2018). Multimodal theranostic nanoformulations permit magnetic resonance bioimaging of antiretroviral drug particle tissue-cell biodistribution. Theranostics, 8, 256–276.

    Article  CAS  Google Scholar 

  • Kumar, R., Qureshi, H., Deshpande, S., & Bhattacharya, J. (2018). Broadly neutralizing antibodies in HIV-1 treatment and prevention. Therapeutic Advance in Vaccines and Immunotherapy, 6, 61–68.

    Article  CAS  Google Scholar 

  • Levi, J., Raymond, A., Pozniak, A., Vernazza, P., Kohler, P., & Hill, A. (2016). Can the UNAIDS 90–90-90 target be achieved? A systematic analysis of national HIV treatment cascades. BMJ Global Health, 1, e000010.

    Article  Google Scholar 

  • Llibre, J. M., Schapiro, J. M., & Clotet, B. (2010). Clinical implications of genotypic resistance to the newer antiretroviral drugs in HIV-1-infected patients with virological failure. Clinical Infectious Disease, 50, 872–881.

    Article  CAS  Google Scholar 

  • Margolis, A. M., Heverling, H., Pham, P. A., & Stolbach, A. (2014). A review of the toxicity of HIV medications. Journal of Medical Toxicology, 10, 26–39.

    Google Scholar 

  • Melikian, G. L., Rhee, S. Y., Taylor, J., Fessel, W. J., Kaufman, D., Towner, W., Troia-Cancio, P. V., Zolopa, A., Robbins, G. K., Kagan, R., Israelski, D., & Shafer, R. W. (2012). Standardized comparison of the relative impacts of HIV-1 reverse transcriptase (RT) mutations onnucleoside RT inhibitor susceptibility. Antimicrobial Agents Chemotherapy, 56, 2305–2313.

    Article  CAS  Google Scholar 

  • Melikian, G. L., Rhee, S. Y., Varghese, V., Porter, D., White, K., Taylor, J., Towner, W., Troia, P., Burack, J., Dejesus, E., Robbins, G. K., Razzeca, K., Kagan, R., Liu, T. F., Fessel, W. J., Israelski, D., & Shafer, R. W. (2014). Non-nucleoside reverse transcriptase inhibitor(NNRTI) cross-resistance: Implications for preclinical evaluation of novel NNRTIs and clinical genotypic resistance testing. Journal of Antimicrobial Chemotherapy, 69, 12–20.

    Article  CAS  Google Scholar 

  • Mitragotri, S., Burke, P. A., & Langer, R. (2014). Overcoming the challenges in administering biopharmaceuticals: Formulation and delivery strategies. Nature Reviews of Drug Discovery, 13, 655–672.

    Article  CAS  Google Scholar 

  • Paredes, R., Lalama, C. M., Ribaudo, H., Schackman, B. R., Shikuma, C., Giguel, F., Meyer, W. A., 3RD, Johnson, V. A., Fiscus, S. A., D’aquila, R. T., Gulick, R. M., & Kuritzkes, D. R. (2010). Pre-existing minority drug-resistant HIV-1 variants, adherence, and risk of antiretroviral treatment failure. The Journal of Infectious Diseases, 201, 662–671.

    Google Scholar 

  • Quinn, T. C. (2008). HIV epidemiology and the effects of antiviral therapy on long-term consequences. AIDS, 22, S7–S12.

    Google Scholar 

  • Rhee, S. Y., Jordan, M. R., Raizes, E., Chua, A., Parkin, N., Kantor, R., Van Zyl, G. U., Mukui, I., Hosseinipour, M. C., Frenkel, L. M., Ndembi, N., Hamers, R. L., Rinke De Wit, T. F., Wallis, C. L., Gupta, R. K., Fokam, J., Zeh, C., Schapiro, J. M., Carmona, S. … Shafer, R. W. (2015). HIV-1 drug resistance mutations: potential applications for point-of-care genotypic resistance testing. PloS One, 10, e0145772.

    Google Scholar 

  • Rusconi, S., Marcotullio, S., & Cingolani, A. (2017). Long-acting agents for HIV infection: Biological aspects, role in treatment and prevention, and patient’s perspective. NewMicrobiology, 40, 75–79.

    CAS  Google Scholar 

  • Sidibé, M., Loures, L., & Samb, B. (2016). The UNAIDS 90–90–90 target: A clear choice for ending AIDS and for sustainable health and development. Journal of International AIDS Society, 19, 21133.

    Article  Google Scholar 

  • Sillman, B., Bade, A. N., Dash, P. K., Bhargavan, B., Kocher, T., Mathews, S., Su, H., Kanmogne, G., Poluektova, L., Gorantla, S., Mcmillan, J., Gautam, N., Alnouti, Y., Benson, E., & Gendelman, H. (2018). Creation of a long-acting nanoformulated dolutegravir. Natural Communication, 9, 443.

    Google Scholar 

  • Su, Y., Chong, H., Qiu, Z., Xiong, S., & He, Y. (2015). Mechanism of HIV-1 resistance to short-peptide fusion inhibitors targeting the Gp41 pocket. Journal of Virology, 89, 5801–5811.

    Google Scholar 

  • Thigpen, M. C., Kebaabetswe, P. M., Paxton, L. A., Smith, D. K., Rose, C. E., Segolodi, T. M., Henderson, F. L., Pathak, S. R., Soud, F. A., Chillag, K. L., Mutanhaurwa, R., Chirwa, L. I., Kasonde, M., Abebe, D., Buliva, E., Gvetadze, R. J., Johnson, S., Sukalac, T., Thomas, V. T. … Group, T. D. F. S. (2012). Antiretroviral preexposure prophylaxis for heterosexual HIV transmission in Botswana. The New England Journal of Medicine, 367, 423–434.

    Google Scholar 

  • Trivedi, J., Mahajan, D., Jaffe, R. J., Acharya, A., Mitra, D., & Byraredy, S. N. (2020). Recent advances in the development of integrase inhibitors for HIV treatment. Current HIV/AIDS Reports, 17, 63–75.

    Article  Google Scholar 

  • Van Wesenbeeck, L., Rondelez, E., Feyaerts, M., Verheyen, A., Van der Borght, K., Smits, V, Cleybergh, C., De Wolf, H., Van baelen, K., & Stuyver, L. J. (2011). Cross-resistance profile determination of two second-generation HIV-1 integrase inhibitors using a panel of recombinant viruses derived from raltegravir-treated clinical isolates. Antimicrobial Agents and Chemotherapy, 55, 321–325.

    Google Scholar 

  • Vieillard, V., Combadière, B., Tubiana, R., Launay, O., Pialoux, G., Cotte, L., Girard, P. M., Simon, A., Dudoit, Y., Reynes, J., Rockstroh, J., Garcia, F., Gatell, J., Devidas, A., Yazdanpanah, Y., Weiss, L., Fätkenheuer, G., Autran, B., Joyeux, D. … Katlama, C. (2019). HIV therapeutic vaccine enhances non-exhausted CD4+ T cells in a randomised phase 2 trial. npj Vaccines, 4, 1–25.

    Google Scholar 

  • Walter, J., & Kredo, T. (2017). Boosted protease inhibitor (PI) monotherapy for treating HIV/AIDS. The Cochrane Database of Systematic Reviews, 8, CD008171.

    Google Scholar 

  • Wensing, A. M. J., Fun, A., & Nijhuis, M. (2017). HIV protease inhibitor resistance. In M. Gotte, A. Berghuis, G., Matlashewski, M. Wainberg, & D. Sheppard (Eds.), Handbook of antimicrobial resistance. https://doi.org/10.1007/978-1-4939-0694-9_28

  • Whitfield, T., Torkington, A., & van Halsema, C. (2016). Profile of cabotegravir and its potential in the treatment and prevention of HIV-1 infection: Evidence to date. HIV AIDS, 8, 157–164.

    CAS  Google Scholar 

  • Yubin, L., Liu, Y., Cao, W., Sun, M., & Li, T. (2020). Broadly neutralizing antibodies for HIV-1: efficacies, challenges and opportunities. Emerging Microbes & Infections, 9, 194–206.

    Google Scholar 

  • Zhou, T., Su, H., Dash, P., Lin, Z., Dyavar Shetty, B. L., Kocher, T., Szlachetka, A., Lamberty, B., Fox, H. S., Poluektova, L., Gorantla, S., Mcmillan, J., Gautam, N., Mosley, R. L., Alnouti, Y., Edagwa, B., & Gendelman, H. E. (2018). Creation of a nanoformulated cabotegravir prodrug with improved antiretroviral profiles. Biomaterials, 151, 53–65.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Chemistry, The Women University Multan, Multan, Pakistan

    Fahmida Jabeen & Adeela Saeed

  2. Institute of Chemical Sciences, Bahauddin Zakariya University, Multan, 60800, Pakistan

    Muhammad Salman Sajid, Saadat Majeed, Muhammad Naeem Ashiq & Muhammad Najam-ul-Haq

  3. Department of Biochemistry, Bahauddin Zakariya University, Multan, 60800, Pakistan

    Batool Fatima

  4. International Centre for Chemical and Biological Sciences, HEJ Research Institute of Chemistry, University of Karachi, Karachi, 75270, Pakistan

    Dilshad Hussain

Authors
  1. Fahmida Jabeen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Muhammad Salman Sajid
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Adeela Saeed
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Batool Fatima
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Dilshad Hussain
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Saadat Majeed
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Muhammad Naeem Ashiq
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Muhammad Najam-ul-Haq
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Basic Sciences, University of Veterinary and Animal Sciences, Narowal, Pakistan

    Sarfraz Ahmed

  2. Department of Infectious Diseases, The Affiliated Hospital of Southwest Medical University, Luzhou, China

    Suvash Chandra Ojha

  3. Department of Chemistry, Bahauddin Zakariya University, Multan, Pakistan

    Muhammad Najam-ul-Haq

  4. Department of Pathobiology, University of Veterinary and Animal Sciences, Narowal, Pakistan

    Muhammad Younus

  5. Department of Chemistry, COMSATS University Islamabad, Islamabad, Pakistan

    Muhammad Zaffar Hashmi

Rights and permissions

Reprints and permissions

Copyright information

© 2021 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Jabeen, F. et al. (2021). Drugs Resistance and Treatment Failure in HIV and/or AIDS. In: Ahmed, S., Chandra Ojha, S., Najam-ul-Haq, M., Younus, M., Hashmi, M.Z. (eds) Biochemistry of Drug Resistance. Springer, Cham. https://doi.org/10.1007/978-3-030-76320-6_14

Download citation

Publish with us

Policies and ethics

Search

Navigation