ABSTRACT
Treatment of HIV-1-infected individuals with a combination of anti-retroviral agents results in sustained suppression of HIV-1 replication, as evidenced by a reduction in plasma viral RNA to levels below the limit of detection of available assays. However, even in patients whose plasma viral RNA levels have been suppressed to below detectable levels for up to 30 months, replication-competent virus can routinely be recovered from patient peripheral blood mononuclear cells and from semen. A reservoir of latently infected cells established early in infection may be involved in the maintenance of viral persistence despite highly active anti-retroviral therapy. However, whether virus replication persists in such patients is unknown. HIV-1 cDNA episomes are labile products of virus infection and indicative of recent infection events. Using episome-specific PCR, we demonstrate here ongoing virus replication in a large percentage of infected individuals on highly active anti-retroviral therapy, despite sustained undetectable levels of plasma viral RNA. The presence of a reservoir of 'covert' virus replication in patients on highly active anti-retroviral therapy has important implications for the clinical management of HIV-1-infected individuals and for the development of virus eradication strategies.
Subject(s)
Anti-HIV Agents/therapeutic use , HIV Infections/drug therapy , HIV Infections/virology , HIV Long Terminal Repeat , HIV-1/genetics , Base Sequence , CD4 Lymphocyte Count/drug effects , DNA Primers , Drug Therapy, Combination , HIV Infections/immunology , HIV-1/physiology , Humans , Lymphocytes/immunology , RNA, Viral/blood , Reference Values , Reverse Transcriptase Inhibitors/therapeutic use , Viral Load , Virus ReplicationABSTRACT
Highly active antiretroviral therapy (HAART) leads to a profound and sustained suppression of viral replication, along with a rise in CD4+ cells in most HIV-infected patients. However, reports are accumulating of growing numbers of patients suffering from opportunistic infections despite recovery of CD4+ cells and plummeting viral loads as part of a new syndrome called immune restoration disease. We describe this syndrome in two patients and review the current literature.
Subject(s)
AIDS-Related Opportunistic Infections/etiology , Acquired Immunodeficiency Syndrome/drug therapy , Antiretroviral Therapy, Highly Active/adverse effects , CD4 Lymphocyte Count , Acquired Immunodeficiency Syndrome/immunology , Acquired Immunodeficiency Syndrome/virology , Adult , Female , Humans , Male , Viral LoadABSTRACT
The discovery of two novel structures (CXCR4, CCR5) that act as HIV-1 coreceptors in target cells has allowed a better understanding of the virus-cell interaction. The recent discovery that chemokines interact with the same receptors as HIV-1 has shed light in the comprehension of the viral molecular biology and pathophysiology, setting the stage for new efforts aimed at blocking virus-cell interaction.
Subject(s)
HIV Infections/physiopathology , Receptors, Chemokine/physiology , HIV-1 , Receptors, CCR5/physiology , Receptors, CXCR4/physiologyABSTRACT
Recent findings have led to important changes in the understanding of HIV kinetics that allowed a novel therapeutic approach. This article reviews the most common methods used to gauge viral load and their use in medical decision making, the characteristics of the protease inhibitors just released in Argentina, and preliminary reports from several trials of combined treatment that have changed the standard of care. The viral load is a surrogate marker with predictive value independent of the CD4 cell count. Combined treatment is the election in case it is decided to initiate treatment.
