Important note: Information in this article was accurate in 2000. The state of the art may have changed since the publication date.
Rapid communication: development of in vitro resistance to macrophage-tropic- and T-cell-line-adapted HIV-1 strains among HIV-positive volunteers treated with highly active antiretroviral therapy.
J Acquir Immune Defic Syndr. 2000 Jul 1;24(3):197-202. Unique Identifier : AIDSLINE MED/20429896 Castillo RC; Arango-Jaramillo S; John R; Turner BC; Zimmerman E; Schwartz DH; Department of Molecular Microbiology and Immunology, The Johns; Hopkins University, School of Hygiene and Public Health,; Baltimore, Maryland 21205, USA.
Abstract:
We have described a peripheral blood mononuclear cell (PBMC) culture system in which control of endogenous virus and resistance to exogenous HIV-1 correlates with low viremia among HIV-1-positive people. Nineteen patients remained consistently resistant or susceptible for more than 5 years of follow-up. On the fifth year, 5 consistently susceptible volunteers with high viral loads began receiving highly active anti-retroviral therapy (HAART). After >6 months on HAART, 5 of 5 became completely or predominantly resistant on four visits over the next 6 months. Among HIV-1-positive donors, we had never observed reversal of PBMC phenotype from consistently susceptible to consistently resistant. Resistance correlated with suppression of plasma viremia and rebound in CD4+ T-cell counts and percentages. When resistant PBMCs were challenged after CD8+ T-cell depletion, 38 of 41 and 40 of 59 cultures became susceptible to HIV-1MN and HIV-1BaL, respectively. After combined CD8+ T-cell depletion and antibody neutralization of beta-chemokines, 16 of 18 cultures became susceptible to HIV-1BaL. Overall, the finding that >90% of these cultures depleted of relevant antiviral effector arms could become infected indicates resistance was not due to residual antiretroviral drug metabolites in vitro. For 2 volunteers who discontinued therapy because of side effects, pretreatment viral load correlated with loss of in vitro resistance and viral rebound. In addition to resistance to laboratory strains of HIV-1, all patients developed resistance to at least one of two CCR5-tropic, clade B primary isolates: HIV-1P15 and HIV-1P27.
Keywords: JOURNAL ARTICLE Acquired Immunodeficiency Syndrome/DRUG THERAPY/IMMUNOLOGY/ VIROLOGY Anti-HIV Agents/*THERAPEUTIC USE Antibodies/PHARMACOLOGY Cell Line Chemokines/ANTAGONISTS & INHIB/IMMUNOLOGY Cohort Studies Comparative Study CD4 Lymphocyte Count CD8-Positive T-Lymphocytes/IMMUNOLOGY Drug Therapy, Combination Human HIV Core Protein p24/ANALYSIS HIV Infections/*DRUG THERAPY/IMMUNOLOGY/VIROLOGY HIV-1/*IMMUNOLOGY/ISOLATION & PURIF In Vitro Macrophages/*DRUG EFFECTS/VIROLOGY Substance Withdrawal Syndrome/IMMUNOLOGY Support, U.S. Gov't, P.H.S. Viral Load Viremia
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Important note: Information in this article was accurate in 2000. The state of the art may have changed since the publication date.
