HIV-1 dynamics in vivo: implications for therapy (original) (raw)
Lander, E. S. et al. Initial sequencing and analysis of the human genome. Nature409, 860–921 (2001). ArticleCASPubMed Google Scholar
Cowan, S. et al. Cellular inhibitors with Fv1-like activity restrict human and simian immunodeficiency virus tropism. Proc. Natl Acad. Sci. USA99, 11914–11919 (2002). ArticleCASPubMedPubMed Central Google Scholar
Bieniasz, P. D. Restriction factors: a defense against retroviral infection. Trends Microbiol.11, 286–291 (2003). ArticleCASPubMed Google Scholar
Sheehy, A. M., Gaddis, N. C., Choi, J. D. & Malim, M. H. Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein. Nature418, 646–650 (2002). ArticleCASPubMed Google Scholar
Mangeat, B. et al. Broad antiretroviral defence by human APOBEC3G through lethal editing of nascent reverse transcripts. Nature28, 99–103 (2003). ArticleCAS Google Scholar
Towers, G. J. et al. Cyclophilin A modulates the sensitivity of HIV-1 to host restriction factors. Nature Med.9, 1138–1143 (2003). ArticleCASPubMed Google Scholar
Mariani, R. et al. Species-specific exclusion of APOBEC3G from HIV-1 virions by Vif. Cell114, 21–31 (2003). ArticleCASPubMed Google Scholar
Harris, R. S. et al. DNA deamination mediates innate immunity to retroviral infection. Cell113, 803–809 (2003). ArticleCASPubMed Google Scholar
Freed, E. O. & Martin, M. A. in Fields Virology (eds Knipe, D. M. & Howley, P. M.) 1971–2042 (Lippincott Williams & Wilkins, Philadelphia, 2001). Google Scholar
Gao, F. et al. Origin of HIV-1 in the chimpanzee Pan troglodytes troglodytes. Nature397, 436–441 (1999). ArticleCASPubMed Google Scholar
Corbet, S. et al. env sequences of simian immunodeficiency viruses from chimpanzees in Cameroon are strongly related to those of human immunodeficiency virus group N from the same geographic area. J. Virol.74, 529–354 (2000). ArticleCASPubMedPubMed Central Google Scholar
Korber, B. et al. Timing the ancestor of the HIV-1 pandemic strains. Science288, 1789–1796 (2000). ArticleCASPubMed Google Scholar
Barre-Sinoussi, F. et al. Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science220, 868–871 (1983). ArticleCASPubMed Google Scholar
Barre-Sinoussi, F. The early years of HIV research: integrating clinical and basic research. Nature Med.9, 844–846 (2003). ArticleCASPubMed Google Scholar
Korber, B. et al. Evolutionary and immunological implications of contemporary HIV-1 variation. Br. Med. Bull.58, 19–42 (2001). ArticleCASPubMed Google Scholar
Daar, E. S., Moudgil, T., Meyer, R. D. & Ho, D. D. Transient high levels of viremia in patients with primary human immunodeficiency virus type 1 infection. N. Engl. J. Med.324, 961–964 (1991). ArticleCASPubMed Google Scholar
Koup, R. A. et al. Temporal association of cellular immune responses with the initial control of viremia in primary human immunodeficiency virus type 1 syndrome. J. Virol.68, 4650–4655 (1994). CASPubMedPubMed Central Google Scholar
Schacker, T. et al. Productive infection of T cells in lymphoid tissues during primary and early human immunodeficiency virus infection. J. Infect. Dis.183, 555–562 (2001). ArticleCASPubMed Google Scholar
Zhang, Z. et al. Sexual transmission and propagation of SIV and HIV in resting and activated CD4+ T cells. Science286, 1353–1357 (1999). ArticleCASPubMed Google Scholar
Pope, M. & Haase, A. T. Transmission, acute HIV-1 infection and the quest for strategies to prevent infection. Nature Med.9, 847–852 (2003). ArticleCASPubMed Google Scholar
Connick, E. et al. Relationship between human immunodeficiency virus type 1 (HIV-1)-specific memory cytotoxic T lymphocytes and virus load after recent HIV-1 seroconversion. J. Infect. Dis.184, 1465–1469 (2001). ArticleCASPubMed Google Scholar
Mellors, J. W. et al. Plasma viral load and CD4+ lymphocytes as prognostic markers of HIV-1 infection. Ann. Intern. Med.126, 946–954 (1997). ArticleCASPubMed Google Scholar
Mellors, J. W. et al. Prognosis in HIV-1 infection predicted by the quantity of virus in plasma. Science272, 1167–1170 (1996). ArticleCASPubMed Google Scholar
Moonis, M., Lee, B., Bailer, R. T., Luo, Q. & Montaner, L. J. CCR5 and CXCR4 expression correlated with X4 and R5 HIV-1 infection yet not sustained replication in Th1 and Th2 cells. AIDS15, 1941–1949 (2001). ArticleCASPubMed Google Scholar
Meng, G. et al. Lamina propria lymphocytes, not macrophages, express CCR5 and CXCR4 and are the likely target cell for human immunodeficiency virus type 1 in the intestinal mucosa. J. Infect. Dis.182, 785–791 (2000). ArticleCASPubMed Google Scholar
Zamarchi, R. et al. Expression and functional activity of CXCR-4 and CCR-5 chemokine receptors in human thymocytes. Clin. Exp. Immunol.127, 321–330 (2002). ArticleCASPubMedPubMed Central Google Scholar
Valentin, A., Trivedi, H., Lu, W., Kostrikis, L. G. & Pavlakis, G. N. CXCR4 mediates entry and productive infection of syncytia-inducing (X4) HIV-1 strains in primary macrophages. Virology269, 294–304 (2000). ArticleCASPubMed Google Scholar
Lee, B., Sharron, M., Montaner, L. J., Weissman, D. & Doms, R. W. Quantification of CD4, CCR5, and CXCR4 levels on lymphocyte subsets, dendritic cells, and differentially conditioned monocyte-derived macrophages. Proc. Natl Acad. Sci. USA96, 5215–5220 (1999). ArticleCASPubMedPubMed Central Google Scholar
Zhu, T. HIV-1 in peripheral blood monocytes: an underrated viral source. J. Antimicrob. Chemother.50, 309–311 (2002). ArticleCASPubMed Google Scholar
Stevenson, M. HIV-1 pathogenesis. Nature Med.9, 853–860 (2003). This review provides an excellent summary of the present understanding of HIV-1 pathogenesis. ArticleCASPubMed Google Scholar
Yarchoan, R. et al. Administration of 3′-azido-3′-deoxythymidine, an inhibitor of HTLV-III/LAV replication, to patients with AIDS or AIDS-related complex. Lancet1, 575–580 (1986). ArticleCASPubMed Google Scholar
Fischl, M. A. et al. The efficacy of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. A double-blind, placebo-controlled trial. N. Engl. J. Med.317, 185–191 (1987). ArticleCASPubMed Google Scholar
Edlin, B. R. et al. In-vitro resistance to zidovudine and α-interferon in HIV-1 isolates from patients: correlations with treatment duration and response. Ann. Intern. Med.117, 457–460 (1992). ArticleCASPubMed Google Scholar
Montaner, J. S. et al. Clinical correlates of in vitro HIV-1 resistance ot zidovudine. Results of the Multicentre Canadian AZT Trial. AIDS7, 189–196 (1993). ArticleCASPubMed Google Scholar
Gulick, R. M. et al. Treatment with indinavir, zidovudine, and lamivudine in adults with human immunodeficiency virus infection and prior antiretroviral therapy. N. Engl. J. Med.337, 734–739 (1997). ArticleCASPubMed Google Scholar
Hammer, S. M. et al. A controlled trial of two nucleoside analogues plus indinavir in persons with human immunodeficiency virus infection and CD4 cell counts of 200 per cubic millimeter or less. AIDS Clinical Trials Group 320 Study Team. N. Engl. J. Med.337, 725–733 (1997). ArticleCASPubMed Google Scholar
Dybul, M., Fauci, A. S., Bartlett, J. G., Kaplan, J. E. & Pau, A. K. Guidelines for using antiretroviral agents among HIV-infected adults and adolescents. Ann. Intern. Med.137, 381–433 (2002). ArticlePubMed Google Scholar
Lalezari, J. P. et al. Enfuvirtide, an HIV-1 fusion inhibitor, for drug-resistant HIV infection in North and South America. N. Engl. J. Med.348, 2175–2185 (2003). ArticleCASPubMed Google Scholar
Lazzarin, A. et al. Efficacy of enfuvirtide in patients infected with drug-resistant HIV-1 in Europe and Australia. N. Engl. J. Med.348, 2186–2195 (2003). ArticleCASPubMed Google Scholar
Murphy, E. L. et al. Highly active antiretroviral therapy decreases mortality and morbidity in patients with advanced HIV disease. Ann. Intern. Med.135, 17–26 (2001). ArticleCASPubMed Google Scholar
Palella, F. J. Jr et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV outpatient study investigators. N. Engl. J. Med.338, 853–860 (1998). ArticlePubMed Google Scholar
Mocroft, A. et al. Decline in the AIDS and death rates in the EuroSIDA study: an observational study. Lancet362, 22–29 (2003). ArticleCASPubMed Google Scholar
Chun, T. W. et al. Quantification of latent tissue reservoirs and total body viral load in HIV-1 infection. Nature387, 183–188 (1997). ArticleCASPubMed Google Scholar
Hance, A. J. et al. Changes in human immunodeficiency virus type 1 populations after treatment interruption in patients failing antiretroviral therapy. J. Virol.75, 6410–6417 (2001). ArticleCASPubMedPubMed Central Google Scholar
Ho, D. D. & Zhang, L. HIV-1 rebound after anti-retroviral therapy. Nature Med.6, 736–737 (2000). ArticleCASPubMed Google Scholar
Zhang, L. et al. Quantifying residual HIV-1 replication in patients receiving combination antiretroviral therapy. N. Engl. J. Med.340, 1605–1613 (1999). ArticleCASPubMed Google Scholar
Coombs, R. W. et al. Plasma viremia in human immunodeficiency virus infection. N. Engl. J. Med.321, 1626–1631 (1989). ArticleCASPubMed Google Scholar
Ho, D. D., Moudgil, T. & Alam, M. Quantitation of human immunodeficiency virus type 1 in the blood of infected persons. N. Engl. J. Med.321, 1621–1625 (1989). ArticleCASPubMed Google Scholar
Piatak, M. Jr et al. High levels of HIV-1 in plasma during all stages of infection determined by competitive PCR. Science259, 1749–1754 (1993). ArticleCASPubMed Google Scholar
Gupta, P. et al. Quantitation of human immunodeficiency virus type 1 DNA and RNA by a novel internally controlled PCR assay. J. Clin. Microbiol.33, 1670–1673 (1995). CASPubMedPubMed Central Google Scholar
Pantaleo, G. et al. Evolutionary pattern of human immunodeficiency virus (HIV) replication and distribution in lymph nodes following primary infection: implications for antiviral therapy. Nature Med.4, 341–345 (1998). ArticleCASPubMed Google Scholar
Pantaleo, G. et al. HIV infection is active and progressive in lymphoid tissue during the clinically latent stage of disease. Nature362, 355–358 (1993). ArticleCASPubMed Google Scholar
Graziosi, C. et al. Kinetics of human immunodeficiency virus type 1 (HIV-1) DNA and RNA synthesis during primary HIV-1 infection. Proc. Natl Acad. Sci. USA90, 6405–6409 (1993). ArticleCASPubMedPubMed Central Google Scholar
Simmonds, P. et al. Human immunodeficiency virus-infected individuals contain provirus in small numbers of peripheral mononuclear cells and at low copy numbers. J. Virol.64, 864–872 (1990). CASPubMedPubMed Central Google Scholar
Ho, D. D. et al. Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection. Nature373, 123–126 (1995). ArticleCASPubMed Google Scholar
Wei, X. et al. Viral dynamics in human immunodeficiency virus type 1 infection. Nature373, 117–122 (1995). References 57 and 58 show for the first time the rapid turnover of infected cells using potent antiretroviral drugs to disturb the steady state. ArticleCASPubMed Google Scholar
Wodarz, D. & Nowak, M. A. Mathematical models of HIV pathogenesis and treatment. Bioessays24, 1178–1187 (2002). ArticlePubMed Google Scholar
Perelson, A. S. Modelling viral and immune system dynamics. Nature Rev. Immunol.2, 28–36 (2002). References 59 and 60 provide in-depth reviews on mathematical models used to analyse viral dynamicsin vivo. ArticleCAS 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. Science271, 1582–1586 (1996). Refined estimates for the half-life of productively infected T lymphocytes and clearance rate of plasma virions. ArticleCASPubMed Google Scholar
Perelson, A. S. et al. Decay characteristics of HIV-1-infected compartments during combination therapy. Nature387, 188–191 (1997). Description of the second phase of plasma HIV-1 RNA decay. ArticleCASPubMed Google Scholar
Perelson, A. S., Essunger, P. & Ho, D. D. Dynamics of HIV-1 and CD4+ lymphocytes in vivo. AIDS11, S17–S24 (1997). PubMed Google Scholar
Hlavacek, W. S., Stilianakis, N. I., Notermans, D. W., Danner, S. A. & Perelson, A. S. Influence of follicular dendritic cells on decay of HIV during antiretroviral therapy. Proc. Natl Acad. Sci. USA97, 10966–10971 (2000). ArticleCASPubMedPubMed Central Google Scholar
Louie, M. et al. Determining the relative efficacy of highly active antiretroviral therapy. J. Infect. Dis.187, 896–900 (2003). ArticleCASPubMed Google Scholar
Markowitz, M. et al. A novel antiviral intervention results in more accurate assessment of human immunodeficiency virus type 1 replication dynamics and T-cell decay in vivo. J. Virol.77, 5037–5038 (2003). Refined estimates for the half-life of productively infected T lymphocytes using potent combination therapy. ArticleCASPubMedPubMed Central Google Scholar
Bonhoeffer, S., May, R. M., Shaw, G. M. & Nowak, M. A. Virus dynamics and drug therapy. Proc. Natl Acad. Sci. USA94, 6971–6976 (1997). ArticleCASPubMedPubMed Central Google Scholar
Louie, M. et al. Determining the antiviral activity of tenofovir disoproxil fumarate in treatment-naive chronically HIV-1-infected individuals. AIDS17, 1151–1156 (2003). ArticleCASPubMed Google Scholar
Zhang, L. et al. Rapid clearance of simian immunodeficiency virus particles from plasma of rhesus macaques. J. Virol.73, 855–860 (1999). CASPubMedPubMed Central Google Scholar
Nowak, M. A. et al. Viral dynamics of primary viremia and antiretroviral therapy in simian immunodeficiency virus infection. J. Virol.71, 7518–7525 (1997). CASPubMedPubMed Central Google Scholar
Schultz, I. & Neva, F. A. Relationship between blood clearance and viruria after intravenous injection of mice and rats with bacteriophage and polioviruses. J. Immunol.94, 833–841 (1965). CASPubMed Google Scholar
Brunner, K. T., Hures D., McCluskey R. T. & Benacerraf, B. Blood clearance of P32-labeled vesicular stomatitis and New castle disease viruses by the reticuloendothelial system in mice. J. Immunol.85, 99–105 (1960). CASPubMed Google Scholar
Ramratnam, B. et al. Rapid production and clearance of HIV-1 and hepatitis C virus assessed by large volume plasma apheresis. Lancet354, 1782–1785 (1999). Direct assessment of HIV-1 and hepatitis C virion clearance ratesin vivo. ArticleCASPubMed Google Scholar
Bagnarelli, P. et al. Dynamic features of human immunodeficiency virus type 1 (HIV-1) viremia: kinetics of cell-free HIV-1 RNA after therapeutic plasma exchange. J. Infect. Dis.176, 801–804 (1997). ArticleCASPubMed Google Scholar
McCune, J. M. The dynamics of CD4+ T-cell depletion in HIV disease. Nature410, 974–979 (2001). ArticleCASPubMed Google Scholar
Mohri, H. et al. Increased turnover of T lymphocytes in HIV-1 infection and its reduction by antiretroviral therapy. J. Exp. Med.194, 1277–1287 (2001). ArticleCASPubMedPubMed Central Google Scholar
Ribeiro, R. M., Mohri, H., Ho, D. D. & Perelson, A. S. In vivo dynamics of T cell activation, proliferation, and death in HIV-1 infection: why are CD4+ but not CD8+ T cells depleted? Proc. Natl Acad. Sci. USA99, 15572–15577 (2002). ArticleCASPubMedPubMed Central Google Scholar
Kovacs, J. A. et al. Identification of dynamically distinct subpopulations of T lymphocytes that are differentially affected by HIV. J. Exp. Med.194, 1731–1741 (2001). ArticleCASPubMedPubMed Central Google Scholar
Silvestri, G. & Feinberg, M. B. Turnover of lymphocytes and conceptual paradigms in HIV infection. J. Clin. Invest.112, 821–824 (2003). ArticleCASPubMedPubMed Central Google Scholar
Douek, D. C. et al. HIV preferentially infects HIV-specific CD4+ T cells. Nature417, 95–98 (2002). ArticleCASPubMed Google Scholar
Badley, A. D., Pilon, A. A., Landay, A. & Lynch, D. H. Mechanisms of HIV-associated lymphocyte apoptosis. Blood96, 2951–2964 (2000). CASPubMed Google Scholar
Douek, D. C., Picker, L. J. & Koup, R. A. T cell dynamics in HIV-1 infection. Annu. Rev. Immunol.21, 265–304 (2003). Review summarizing the current knowledge on T cell dynamics. ArticleCASPubMed Google Scholar
Hazenberg, M. D. et al. Persistent immune activation in HIV-1 infection is associated with progression to AIDS. AIDS17, 1881–1888 (2003). ArticlePubMed Google Scholar
Hazenberg, M. D., Hamann, D., Schuitemaker, H. & Miedema, F. T-cell depletion in HIV-1 infection: how CD4+ T cells go out of stock. Nature Immunol.1, 285–289 (2000). ArticleCAS Google Scholar
Sousa, A. E., Carneiro, J., Meier-Schellersheim, M., Grossman, Z. & Victorino, R. M. CD4 T cell depletion is linked directly to immune activation in the pathogenesis of HIV-1 and HIV-2 but only indirectly to the viral load. J. Immunol.169, 3400–3406 (2002). ArticleCASPubMed Google Scholar
Zhang, L., Dailey, P. J., Gettie, A., Blanchard, J. & Ho, D. D. The liver is a major organ for clearing simian immunodeficiency virus in rhesus monkeys. J. Virol.76, 5271–5273 (2002). ArticleCASPubMedPubMed Central Google Scholar
van Furth, R. et al. The mononuclear phagocyte system: a new classification of macrophages, monocytes, and their precursor cells. Bull. World Health Organ.46, 845–852 (1972). CASPubMedPubMed Central Google Scholar
Kimberly, R. P. & Ralph, P. Endocytosis by the mononuclear phagocyte system and autoimmune disease. Am. J. Med.74, 481–493 (1983). ArticleCASPubMed Google Scholar
Hume, D. A. et al. The mononuclear phagocyte system revisited. J. Leukoc. Biol.72, 621–627 (2002). CASPubMed Google Scholar
Burton, G. F., Keele, B. F., Estes, J. D., Thacker, T. C. & Gartner, S. Follicular dendritic cell contributions to HIV pathogenesis. Semin. Immunol.14, 275–284 (2002). ArticleCASPubMed Google Scholar
Estes, J. D. et al. Follicular dendritic cell-mediated up-regulation of CXCR4 expression on CD4 T cells and HIV pathogenesis. J. Immunol.169, 2313–2322 (2002). ArticleCASPubMed Google Scholar
Hlavacek, W. S., Stilianakis, N. I. & Perelson, A. S. Influence of follicular dendritic cells on HIV dynamics. Philos. Trans R. Soc. Lond. B Biol. Sci.355, 1051–1058 (2000). ArticleCASPubMedPubMed Central Google Scholar
Igarashi, T. et al. Human immunodeficiency virus type 1 neutralizing antibodies accelerate clearance of cell-free virions from blood plasma. Nature Med.5, 211–216 (1999). ArticleCASPubMed Google Scholar
Veazey, R. S. et al. Gastrointestinal tract as a major site of CD4+ T cell depletion and viral replication in SIV infection. Science280, 427–431 (1998). ArticleCASPubMed Google Scholar
Poles, M. A., Elliott, J., Taing, P., Anton, P. A. & Chen, I. S. A preponderance of CCR5+ CXCR4+ mononuclear cells enhances gastrointestinal mucosal susceptibility to human immunodeficiency virus type 1 infection. J. Virol.75, 8390–8399 (2001). ArticleCASPubMedPubMed Central Google Scholar
Malaspina, A. et al. Human immunodeficiency virus type 1 bound to B cells: relationship to virus replicating in CD4+ T cells and circulating in plasma. J. Virol.76, 8855–8863 (2002). ArticleCASPubMedPubMed Central Google Scholar
Moir, S. et al. B cells of HIV-1-infected patients bind virions through CD21-complement interactions and transmit infectious virus to activated T cells. J. Exp. Med.192, 637–646 (2000). ArticleCASPubMedPubMed Central Google Scholar
Finzi, D. et al. Identification of a reservoir for HIV-1 in patients on highly active antiretroviral therapy. Science278, 1295–1300 (1997). First report on the persistence of latently infected memory T lymphocytes despite suppressive HAART. ArticleCASPubMed Google Scholar
Blankson, J. N., Persaud, D. & Siliciano, R. F. The challenge of viral reservoirs in HIV-1 infection. Annu. Rev. Med.53, 557–593 (2002). Review summarizing the current knowledge on HIV-1 persistence. ArticleCASPubMed Google Scholar
Nabel, G. & Baltimore, D. An inducible transcription factor activates expression of human immunodeficiency virus in T cells. Nature326, 711–713 (1987). ArticleCASPubMed Google Scholar
Kao, S. Y., Calman, A. F., Luciw, P. A. & Peterlin, B. M. Anti-termination of transcription within the long terminal repeat of HIV-1 by tat gene product. Nature330, 489–493 (1987). ArticleCASPubMed Google Scholar
Swingler, S. et al. HIV-1 Nef intersects the macrophage CD40L signalling pathway to promote resting-cell infection. Nature424, 213–219 (2003). ArticleCASPubMed Google Scholar
Gunthard, H. F. et al. Evolution of envelope sequences of human immunodeficiency virus type 1 in cellular reservoirs in the setting of potent antiviral therapy. J. Virol.73, 9404–9412 (1999). CASPubMedPubMed Central Google Scholar
Furtado, M. R. et al. Persistence of HIV-1 transcription in peripheral-blood mononuclear cells in patients receiving potent antiretroviral therapy. N. Engl. J. Med.340, 1614–1622 (1999). ArticleCASPubMed Google Scholar
Lewin, S. R. et al. Use of real-time PCR and molecular beacons to detect virus replication in human immunodeficiency virus type 1-infected individuals on prolonged effective antiretroviral therapy. J. Virol.73, 6099–6103 (1999). CASPubMedPubMed Central Google Scholar
Dornadula, G. et al. Residual HIV-1 RNA in blood plasma of patients taking suppressive highly active antiretroviral therapy. JAMA282, 1627–1632 (1999). ArticleCASPubMed Google Scholar
Havlir, D. V. et al. Prevalence and predictive value of intermittent viremia with combination HIV therapy. JAMA286, 171–179 (2001). ArticleCASPubMed Google Scholar
Percus, J. K. et al. The distribution of viral blips observed in HIV-1 infected patients treated with combination antiretroviral therapy. Bull. Math. Biol.65, 263–277 (2003). ArticlePubMed Google Scholar
Cohen Stuart, J. W. et al. Transient relapses ('blips') of plasma HIV RNA levels during HAART are associated with drug resistance. J. Acquir. Immune Defic. Syndr.28, 105–113 (2001). ArticleCASPubMed Google Scholar
Zhang, H. et al. Human immunodeficiency virus type 1 in the semen of men receiving highly active antiretroviral therapy. N. Engl. J. Med.339, 1803–1809 (1998). ArticleCASPubMed Google Scholar
Ramratnam, B. et al. The decay of the latent reservoir of replication-competent HIV-1 is inversely correlated with the extent of residual viral replication during prolonged anti-retroviral therapy. Nature Med.6, 82–85 (2000). ArticleCASPubMed Google Scholar
Siliciano, J. D. et al. Long-term follow-up studies confirm the stability of the latent reservoir for HIV-1 in resting CD4+ T cells. Nature Med.9, 727–728 (2003). ArticleCASPubMed Google Scholar
Finzi, D. et al. Latent infection of CD4+ T cells provides a mechanism for lifelong persistence of HIV-1, even in patients on effective combination therapy. Nature Med.5, 512–517 (1999). ArticleCASPubMed Google Scholar
Ramratnan, B. et al. Intensification of antiretroviral therapy accelerates the decay of the HIV-1 latent reservoir and decreases, but does not eliminate, ongoing virus replication. J. Acquir. Immune Defic.Syndr. (in the press).
Strain, M. C. et al. Heterogeneous clearance rates of long-lived lymphocytes infected with HIV: intrinsic stability predicts lifelong persistence. Proc. Natl Acad. Sci. USA100, 4819–4824 (2003). ArticleCASPubMedPubMed Central Google Scholar
Kulkosky, J. et al. Intensification and stimulation therapy for human immunodeficiency virus type 1 reservoirs in infected persons receiving virally suppressive highly active antiretroviral therapy. J. Infect. Dis.186, 1403–1411 (2002). ArticleCASPubMed Google Scholar
From the Centers for Disease Control and Prevention. 1993 revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. JAMA269, 729–730 (1993).