2 : Emergence of Human Immunodeficiency Virus Drug Resistance

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The global pandemic of human immunodeficiency virus (HIV) infection represents a prime example of an emerging infection. The HIV pandemic has wreaked the majority of its havoc in the developing world, whereas drug-resistant HIV has been a problem among the more privileged economies. It was learned that the use of protease inhibitors as monotherapy or when added to an ongoing regimen was substandard practice, and patients failed with resistant virus. This was followed by another discovery that analogous to tuberculous chemotherapy, prescribing an optimal regimen without the education and support system to encourage patient adherence is no accomplishment and may lead to multiple-drug resistance. One significant difference between tuberculosis and HIV is that the former can be cured. The levels are highest in primary infection, which may be the most infectious period. The genetic barrier to viral escape will have to be raised in using combinations that require multiple mutations and incompatable mutations. The pharmacologic aspects of chemotherapy needs improvement, as many of the protease inhibitors that have relatively short half-lives give trough levels that are really borderline or suboptimal. Drug levels in the various tissue compartments that may represent pharmacologic sanctuaries will have to be attained. It has been learned from multiply resistant tuberculosis that the natural history resembled untreated tuberculosis, especially in the immunosuppressed.

Citation: Richman D. 2000. Emergence of Human Immunodeficiency Virus Drug Resistance, p 17-21. In Scheld W, Craig W, Hughes J (ed), Emerging Infections 4. ASM Press, Washington, DC. doi: 10.1128/9781555816971.ch2
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1. Coates, E.0.,, G. M. Meade,, W. Steeken,, E. Wolinsky,, and G. L. Brinkman. 1953. The clinical significance of the emergence of drug-resistant organisms during therapy of chronic pulmonary tuberculosis with hydrazides of isonicotinic acid. N. Engl. J. Med. 248: 1081 1087.
1a.. Cohen, M. S.,, L F. Hoffman,, R. A. Royce,, P. Kazembe,, J. R. Dyer,, C. C. Daly,, D. Zimba,, P. L. Vernazza,, M. Maida,, S. A. Fiscus,, and J. J. Eron, Jr. 1997. Reduction of concentration of HIV-I in semen after treatment of urethritis: implications for prevention of sexual transmission of HIV-1. Lancet 349: 1868 1873.
2. Cohn, M. L.,, G. Middlebrook,, and W. F. Russell. 1959. Combined drug treatment of tuberculosis. I. Prevention of emergence of mutant populations of tubercle bacilli resistant to both streptomycin and isoniazid. J. Clin. Invest. 38: 1349 1355.
3. Erice. A.,, D. L. Mayers,, D. G. Strike,, K. J. Sannerud,, F. E. McCutchan,, K. Henry,, and H. H. Balfour Jr. 1993. Brief report: primary infection with zidovudine-resistant human immunodeficiency virus type 1. N. Engl. J. Med. 328: 1163 1166.
4. Finzi, D.,, M. Hermankova,, T. Pierson,, L. M. Carruth,, R. E. Chaisson,, T. C. Quinn,, R. Brookmeyer,, J. Gallant,, M. Markowitz,, D. D. Ho,, D. D. Richman,, and R. F. Siliciano. 1997. Identification of a reservoir for HIV-l in patients on highly active antiretroviral therapy. Science 278: 1295 1300.
5. Havlir, D. V.,, S. Eastman,, A. Gamst,, and D. D. Richman. 1996. Nevirapine-resistant human immunodeficiency virus: kinetics of replication and estimated prevalence in untreated patients. J. Virol. 70: 7894 7899.
6. Ho, D. D.,, T. Toyoshima,, H. Mo,, D. J. Kempf,, D. Norbeck,, C.-M. Chen,, N. E. Wideburg,, S. K. Burt,, J. W. Erickson,, and M. K. Singh. 1994. Characterization of human immunodeficiency virus type 1 variants with increased resistance to a C 2-symmetric protease inhibitor. J. Virol. 68: 2016 2020.
7. Larder, B.,, G. Darby,, and D. D. Richman. 1989. HIV with reduced sensitivity to zidovudine isolated during prolonged therapy. Science 243: 1731 1734.
8. Little, S. J.,, E. S. Daar,, R. T. D' Aquila,, P. H. Keiser,, E. Connick,, J. M. Whitcomb,, N. S. Hellmann,, C. J. Petropoulos,, J. A. Pitt,, E. S. Rosenberg,, R. A. Koup,, and D. D. Richman. 1999. The spectrum and frequency of reduced antiretroviral drug susceptibility with primary HIV infection in the United States. JAMA 282: 1142 1149.
9. Mansky, L. M.,, and H. M. Temin. 1995. Lower in vivo mutation rate of human immunodeficiency virus type 1 than that predicted from the fidelity of purified reverse transcriptase. J. Viral. 69: 5087 5094.
10. Martinez-Picado, J.,, A. Savara,, L. Sutton,, and R. D' Aquila. 1999. Replicative fitness of protease inhibitor resistant mutants of human immunodeficiency virus type 1. J. Virol. 73: 3744 3752.
11. Perclson, A. S.,, A. U. Nemnann,, M. Markowitz,, J. M. Leonard,, and D. D. Ho. 1996. HIV-l dynamics in vivo: virion clearance rate, infected cell lifetime, and viral generation time. Science 271: 1582 1586.
12. Pyle, M. M. 1947. Relative numbers of resistant tubercle bacilli in sputa of patients before and during treatment with streptomycin. Pmc. Staff Meetings Mayo Clinic 22: 465 473.
13. Richman, D. D.,, J. M. Grimes,, and S. W. Lagakos. 1990. Effect of stage of disease and drug dose on zidovudine susceptibilities of isolates of human immunodeficiency virus. J. AIDS 3: 743 746.
14. Wong,, J. K. M. Hezarch,, H. Günthard,, D. V. Havlir,, C. C. Ignacio,, C. A. Spina,, and D. D. Richman. 1997. Recovery of replication-competent HIV despite prolonged suppression of plasma viremia. Science 278: 1291 1294.
15. Wong, J. K.,, C. C. Ignacio,, F. Torriani,, D. Havlir,, N. J. S. Fitch,, and D. D. Richman. 1997. In vivo compartmentalization of HIV: evidence from the examination of pol sequences from autopsy tissues. J. Viral. 71: 2059 2071.
16. Zhang, H.,, G. Dornadula,, M. Beumont,, L. Livornese, Jr.,, B. Van Uitert,, K. Henning,, and R. J. Pomerantz. 1998. Human immunodeficiency virus type 1 in the semen of men receiving highly active antiretroviral therapy. N. Engl. J. Med. 339: 1803 1809.

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