Abstract
It has become clear that the acquired immunodeficiency syndrome follows continuous replication of the human immunodeficiency virus (HIV) and a decrease in immune capability, most obviously a decline in the number of CD4 lymphocytes. An understanding of key elements in the infectious life cycle of HIV has led to the development of potent antiretroviral drugs selectively targeting unique reverse transcriptase and protease enzymes of the virus. Completed clinical trials have shown that antiretroviral therapy for HIV infection, begun early, reduces viral replication and reverses the decline in CD4 lymphocyte numbers. Recent studies of combination therapies have shown that decreases in plasma HIV viremia to low levels and sustained increases in CD4 cell numbers are associated with longer survival. Potent combination regimens including protease inhibitors and non-nucleoside reverse transcriptase inhibitors suppress detectable viral replication and have demonstrated clinical benefits in patients with advanced disease. Progress in antiretroviral therapy and methods to monitor responses to treatment are providing new hope in the treatment of HIV infection.
Full text
PDF






Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Cao Y., Qin L., Zhang L., Safrit J., Ho D. D. Virologic and immunologic characterization of long-term survivors of human immunodeficiency virus type 1 infection. N Engl J Med. 1995 Jan 26;332(4):201–208. doi: 10.1056/NEJM199501263320401. [DOI] [PubMed] [Google Scholar]
- Carpenter C. C., Fischl M. A., Hammer S. M., Hirsch M. S., Jacobsen D. M., Katzenstein D. A., Montaner J. S., Richman D. D., Sáag M. S., Schooley R. T. Antiretroviral therapy for HIV infection in 1996. Recommendations of an international panel. International AIDS Society-USA. JAMA. 1996 Jul 10;276(2):146–154. [PubMed] [Google Scholar]
- Coffin J. M. HIV population dynamics in vivo: implications for genetic variation, pathogenesis, and therapy. Science. 1995 Jan 27;267(5197):483–489. doi: 10.1126/science.7824947. [DOI] [PubMed] [Google Scholar]
- Connor E. M., Sperling R. S., Gelber R., Kiselev P., Scott G., O'Sullivan M. J., VanDyke R., Bey M., Shearer W., Jacobson R. L. Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zidovudine treatment. Pediatric AIDS Clinical Trials Group Protocol 076 Study Group. N Engl J Med. 1994 Nov 3;331(18):1173–1180. doi: 10.1056/NEJM199411033311801. [DOI] [PubMed] [Google Scholar]
- Darby S. C., Ewart D. W., Giangrande P. L., Spooner R. J., Rizza C. R. Importance of age at infection with HIV-1 for survival and development of AIDS in UK haemophilia population. UK Haemophilia Centre Directors' Organisation. Lancet. 1996 Jun 8;347(9015):1573–1579. doi: 10.1016/s0140-6736(96)91073-9. [DOI] [PubMed] [Google Scholar]
- Deeks S. G., Smith M., Holodniy M., Kahn J. O. HIV-1 protease inhibitors. A review for clinicians. JAMA. 1997 Jan 8;277(2):145–153. [PubMed] [Google Scholar]
- Eron J. J., Benoit S. L., Jemsek J., MacArthur R. D., Santana J., Quinn J. B., Kuritzkes D. R., Fallon M. A., Rubin M. Treatment with lamivudine, zidovudine, or both in HIV-positive patients with 200 to 500 CD4+ cells per cubic millimeter. North American HIV Working Party. N Engl J Med. 1995 Dec 21;333(25):1662–1669. doi: 10.1056/NEJM199512213332502. [DOI] [PubMed] [Google Scholar]
- Hammer S. M., Katzenstein D. A., Hughes M. D., Gundacker H., Schooley R. T., Haubrich R. H., Henry W. K., Lederman M. M., Phair J. P., Niu M. A trial comparing nucleoside monotherapy with combination therapy in HIV-infected adults with CD4 cell counts from 200 to 500 per cubic millimeter. AIDS Clinical Trials Group Study 175 Study Team. N Engl J Med. 1996 Oct 10;335(15):1081–1090. doi: 10.1056/NEJM199610103351501. [DOI] [PubMed] [Google Scholar]
- Havlir D. V., Richman D. D. Viral dynamics of HIV: implications for drug development and therapeutic strategies. Ann Intern Med. 1996 Jun 1;124(11):984–994. doi: 10.7326/0003-4819-124-11-199606010-00006. [DOI] [PubMed] [Google Scholar]
- Henrard D. R., Phillips J. F., Muenz L. R., Blattner W. A., Wiesner D., Eyster M. E., Goedert J. J. Natural history of HIV-1 cell-free viremia. JAMA. 1995 Aug 16;274(7):554–558. [PubMed] [Google Scholar]
- Ho D. D., Neumann A. U., Perelson A. S., Chen W., Leonard J. M., Markowitz M. Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection. Nature. 1995 Jan 12;373(6510):123–126. doi: 10.1038/373123a0. [DOI] [PubMed] [Google Scholar]
- Holodniy M., Katzenstein D. A., Israelski D. M., Merigan T. C. Reduction in plasma human immunodeficiency virus ribonucleic acid after dideoxynucleoside therapy as determined by the polymerase chain reaction. J Clin Invest. 1991 Nov;88(5):1755–1759. doi: 10.1172/JCI115494. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Holodniy M., Katzenstein D., Mole L., Winters M., Merigan T. Human immunodeficiency virus reverse transcriptase codon 215 mutations diminish virologic response to didanosine-zidovudine therapy in subjects with non-syncytium-inducing phenotype. J Infect Dis. 1996 Oct;174(4):854–857. doi: 10.1093/infdis/174.4.854. [DOI] [PubMed] [Google Scholar]
- Jurriaans S., Van Gemen B., Weverling G. J., Van Strijp D., Nara P., Coutinho R., Koot M., Schuitemaker H., Goudsmit J. The natural history of HIV-1 infection: virus load and virus phenotype independent determinants of clinical course? Virology. 1994 Oct;204(1):223–233. doi: 10.1006/viro.1994.1526. [DOI] [PubMed] [Google Scholar]
- Katzenstein D. A., Hammer S. M., Hughes M. D., Gundacker H., Jackson J. B., Fiscus S., Rasheed S., Elbeik T., Reichman R., Japour A. The relation of virologic and immunologic markers to clinical outcomes after nucleoside therapy in HIV-infected adults with 200 to 500 CD4 cells per cubic millimeter. AIDS Clinical Trials Group Study 175 Virology Study Team. N Engl J Med. 1996 Oct 10;335(15):1091–1098. doi: 10.1056/NEJM199610103351502. [DOI] [PubMed] [Google Scholar]
- Katzenstein D. A. Viral phenotype and genotype as markers in clinical trials. J Acquir Immune Defic Syndr Hum Retrovirol. 1995;10 (Suppl 2):S25–S34. [PubMed] [Google Scholar]
- Katzenstein T. L., Pedersen C., Nielsen C., Lundgren J. D., Jakobsen P. H., Gerstoft J. Longitudinal serum HIV RNA quantification: correlation to viral phenotype at seroconversion and clinical outcome. AIDS. 1996 Feb;10(2):167–173. doi: 10.1097/00002030-199602000-00006. [DOI] [PubMed] [Google Scholar]
- Mellors J. W., Kingsley L. A., Rinaldo C. R., Jr, Todd J. A., Hoo B. S., Kokka R. P., Gupta P. Quantitation of HIV-1 RNA in plasma predicts outcome after seroconversion. Ann Intern Med. 1995 Apr 15;122(8):573–579. doi: 10.7326/0003-4819-122-8-199504150-00003. [DOI] [PubMed] [Google Scholar]
- Mientjes G. H., van Ameijden E. J., Weigel H. M., van den Hoek J. A., Coutinho R. A. Clinical symptoms associated with seroconversion for HIV-1 among misusers of intravenous drugs: comparison with homosexual seroconverters and infected and non-infected intravenous drug misusers. BMJ. 1993 Feb 6;306(6874):371–373. doi: 10.1136/bmj.306.6874.371. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Murray H. W., Godbold J. H., Jurica K. B., Roberts R. B. Progression to AIDS in patients with lymphadenopathy or AIDS-related complex: reappraisal of risk and predictive factors. Am J Med. 1989 May;86(5):533–538. doi: 10.1016/0002-9343(89)90380-x. [DOI] [PubMed] [Google Scholar]
- O'Brien T. R., Blattner W. A., Waters D., Eyster E., Hilgartner M. W., Cohen A. R., Luban N., Hatzakis A., Aledort L. M., Rosenberg P. S. Serum HIV-1 RNA levels and time to development of AIDS in the Multicenter Hemophilia Cohort Study. JAMA. 1996 Jul 10;276(2):105–110. [PubMed] [Google Scholar]
- Pantaleo G., Menzo S., Vaccarezza M., Graziosi C., Cohen O. J., Demarest J. F., Montefiori D., Orenstein J. M., Fox C., Schrager L. K. Studies in subjects with long-term nonprogressive human immunodeficiency virus infection. N Engl J Med. 1995 Jan 26;332(4):209–216. doi: 10.1056/NEJM199501263320402. [DOI] [PubMed] [Google Scholar]
- Pedersen C., Lindhardt B. O., Jensen B. L., Lauritzen E., Gerstoft J., Dickmeiss E., Gaub J., Scheibel E., Karlsmark T. Clinical course of primary HIV infection: consequences for subsequent course of infection. BMJ. 1989 Jul 15;299(6692):154–157. doi: 10.1136/bmj.299.6692.154. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Perelson A. S., Neumann A. U., Markowitz M., Leonard J. M., Ho D. D. HIV-1 dynamics in vivo: virion clearance rate, infected cell life-span, and viral generation time. Science. 1996 Mar 15;271(5255):1582–1586. doi: 10.1126/science.271.5255.1582. [DOI] [PubMed] [Google Scholar]
- Royce R. A., Luckmann R. S., Fusaro R. E., Winkelstein W., Jr The natural history of HIV-1 infection: staging classifications of disease. AIDS. 1991 Apr;5(4):355–364. doi: 10.1097/00002030-199104000-00001. [DOI] [PubMed] [Google Scholar]
- Saag M. S., Holodniy M., Kuritzkes D. R., O'Brien W. A., Coombs R., Poscher M. E., Jacobsen D. M., Shaw G. M., Richman D. D., Volberding P. A. HIV viral load markers in clinical practice. Nat Med. 1996 Jun;2(6):625–629. doi: 10.1038/nm0696-625. [DOI] [PubMed] [Google Scholar]
- Schacker T., Collier A. C., Hughes J., Shea T., Corey L. Clinical and epidemiologic features of primary HIV infection. Ann Intern Med. 1996 Aug 15;125(4):257–264. doi: 10.7326/0003-4819-125-4-199608150-00001. [DOI] [PubMed] [Google Scholar]
- Schnittman S. M., Greenhouse J. J., Lane H. C., Pierce P. F., Fauci A. S. Frequent detection of HIV-1-specific mRNAs in infected individuals suggests ongoing active viral expression in all stages of disease. AIDS Res Hum Retroviruses. 1991 Apr;7(4):361–367. doi: 10.1089/aid.1991.7.361. [DOI] [PubMed] [Google Scholar]
- Schooley R. T., Ramirez-Ronda C., Lange J. M., Cooper D. A., Lavelle J., Lefkowitz L., Moore M., Larder B. A., St Clair M., Mulder J. W. Virologic and immunologic benefits of initial combination therapy with zidovudine and zalcitabine or didanosine compared with zidovudine monotherapy. Wellcome Resistance Study Collaborative Group. J Infect Dis. 1996 Jun;173(6):1354–1366. doi: 10.1093/infdis/173.6.1354. [DOI] [PubMed] [Google Scholar]
- Schuurman R., Nijhuis M., van Leeuwen R., Schipper P., de Jong D., Collis P., Danner S. A., Mulder J., Loveday C., Christopherson C. Rapid changes in human immunodeficiency virus type 1 RNA load and appearance of drug-resistant virus populations in persons treated with lamivudine (3TC). J Infect Dis. 1995 Jun;171(6):1411–1419. doi: 10.1093/infdis/171.6.1411. [DOI] [PubMed] [Google Scholar]
- Shafer R. W., Kozal M. J., Winters M. A., Iversen A. K., Katzenstein D. A., Ragni M. V., Meyer W. A., 3rd, Gupta P., Rasheed S., Coombs R. Combination therapy with zidovudine and didanosine selects for drug-resistant human immunodeficiency virus type 1 strains with unique patterns of pol gene mutations. J Infect Dis. 1994 Apr;169(4):722–729. doi: 10.1093/infdis/169.4.722. [DOI] [PubMed] [Google Scholar]
- Wei X., Ghosh S. K., Taylor M. E., Johnson V. A., Emini E. A., Deutsch P., Lifson J. D., Bonhoeffer S., Nowak M. A., Hahn B. H. Viral dynamics in human immunodeficiency virus type 1 infection. Nature. 1995 Jan 12;373(6510):117–122. doi: 10.1038/373117a0. [DOI] [PubMed] [Google Scholar]
