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
Algunos descubrimientos recientes han permitido un mejor conocimiento de la fisiopatología de la enfermedad debida al HIV, lo que ha producido un cambio de las teorías hasta ahora aceptadas acerca de la replicación viral. De acuerdo con un modelo matemático recientemente desarrollado, la replicación viral alcanza proporciones astronómicas, lo que acompañado a numerosos errores que ocurren durante la transcripción del ARN permite la aparición de nuevas cuasi-especies. Las cepas mutantes son responsables en parte del fracaso de la monoterapia, hecho que es superado por la administración de tratamiento combinado que disminuye la replicación viral. Estos nuevos agentes terapéuticos han logrado aumentar el número de linfocitos TCD4(+) y reducir los niveles de la carga viral. Recientes publicaciones muestran que un pequeño grupo de pacientes presentaron infecciones oportunistas con un recuento de CD4 alto a pesar de estar recibiendo Terapéutica Antiviral Altamente Efectiva (HAART sus siglas en inglés). Por otro lado, algunos enfermos resolvieron sus patologías oportunistas a pesar de no recibir tratamiento específico contra las mismas, excepto HAART. Estos conceptos, y también otros referidos a la dinámica viral y la restauración inmune, son analizados en la presente revisión (AU)
Subject(s)
Humans , HIV Infections/drug therapy , HIV Infections/immunology , HIV Infections/virology , Viral Load , Virus Replication/immunology , CD4-Positive T-Lymphocytes/virology , Mutation , Mutagenesis , Virion/immunology , AIDS-Related Opportunistic Infections/immunologyABSTRACT
Algunos descubrimientos recientes han permitido un mejor conocimiento de la fisiopatología de la enfermedad debida al HIV, lo que ha producido un cambio de las teorías hasta ahora aceptadas acerca de la replicación viral. De acuerdo con un modelo matemático recientemente desarrollado, la replicación viral alcanza proporciones astronómicas, lo que acompañado a numerosos errores que ocurren durante la transcripción del ARN permite la aparición de nuevas cuasi-especies. Las cepas mutantes son responsables en parte del fracaso de la monoterapia, hecho que es superado por la administración de tratamiento combinado que disminuye la replicación viral. Estos nuevos agentes terapéuticos han logrado aumentar el número de linfocitos TCD4(+) y reducir los niveles de la carga viral. Recientes publicaciones muestran que un pequeño grupo de pacientes presentaron infecciones oportunistas con un recuento de CD4 alto a pesar de estar recibiendo Terapéutica Antiviral Altamente Efectiva (HAART sus siglas en inglés). Por otro lado, algunos enfermos resolvieron sus patologías oportunistas a pesar de no recibir tratamiento específico contra las mismas, excepto HAART. Estos conceptos, y también otros referidos a la dinámica viral y la restauración inmune, son analizados en la presente revisión
Subject(s)
Humans , AIDS-Related Opportunistic Infections/immunology , CD4-Positive T-Lymphocytes/virology , HIV Infections/drug therapy , HIV Infections/immunology , HIV Infections/virology , Mutagenesis , Mutation , Virus Replication/immunology , Viral Load , Virion/immunologySubject(s)
Ampicillin/therapeutic use , Drug Resistance, Multiple , Enterococcus faecium/drug effects , Gram-Positive Bacterial Infections/drug therapy , Streptomycin/therapeutic use , Surgical Wound Infection/drug therapy , Dose-Response Relationship, Drug , Drug Resistance, Microbial , Drug Therapy, Combination , Humans , Male , Middle AgedABSTRACT
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.
Subject(s)
Acquired Immunodeficiency Syndrome/drug therapy , Antiviral Agents/therapeutic use , HIV Infections/drug therapy , Viral Load/methods , Drug CombinationsSubject(s)
HIV Infections/immunology , Hepatitis B Antibodies/blood , Hepatitis B Core Antigens/immunology , Adult , Carrier State/immunology , Cross Reactions , Epidemiologic Factors , Female , HIV Infections/complications , HIV Infections/epidemiology , Hepatitis B/complications , Hepatitis B/epidemiology , Hepatitis B/immunology , Humans , Male , Massachusetts/epidemiologySubject(s)
HIV Infections/virology , HIV-1/genetics , Hepatitis B Vaccines/immunology , RNA, Viral/blood , HumansABSTRACT
A questionnaire survey for which there were 538 respondents from American clinical microbiology laboratories was used to assess the need for prolonged incubation of Septi-Chek blood culture bottles for the recovery of HACEK bacilli, Brucella species, Francisella tularensis, and nutritionally deficient streptococci from blood. Among a total of 219 reported isolates of these bacteria, in only 6 cases (2.7%) was incubation longer than 7 days required. Only 2 of 136 patients (1.5%) were noted to be bacteremic exclusively following incubation of Septi-Chek blood culture bottles for periods of greater than 7 days. It appeared from the results of this study, that incubation of Septi-Chek blood culture bottles for 7 days is usually sufficient in patients suspected of having bacteremia due to fastidious bacteria.
