ABSTRACT
Homosexual men with symptomatic primary HIV-1 infection displayed a pronounced lymphopaenia with significantly depressed numbers of CD3+, CD4+ and CD8+ cells and B cells during the first week of illness. Subsequently, the CD8+ cell counts rose in parallel with numbers of CD3+ cells, atypical lymphocytes and activated (CD38+ and HLA-Dr+) cells to attain maximal levels about a month following onset of illness. In contrast CD4+ and B cell numbers remained low for an extended period of time. Early signs of a host response included a transient appearance of interferon-alpha in the blood and raised levels of neopterin and beta 2-microglobulin (beta 2-M). Neither CD4+/CD8+ cell ratio nor beta 2-M resumed completely normal values during a follow-up period of 2 years. These findings shed some light on pathogenetic events during early HIV-1 infection and suggest that the infection, following the acute symptomatic stage, usually enters a stage of chronic active rather than latent infection.
Subject(s)
HIV Infections/immunology , T-Lymphocytes/immunology , Adult , B-Lymphocytes/immunology , Biopterins/analogs & derivatives , Biopterins/blood , HIV-1 , Homosexuality , Humans , Immunoglobulin A/analysis , Immunoglobulin G/analysis , Immunoglobulin M/analysis , Interferon Type I/blood , Leukocyte Count , Lymphocyte Activation , Male , Neopterin , T-Lymphocyte Subsets , beta 2-Microglobulin/analysisABSTRACT
The levels of antibodies to HIV-1 and the occurrence of HIV-1 were determined in the cerebrospinal fluid (CSF) and the blood of 60 people in various stages of HIV-1 infection. Intrathecal synthesis of anti-HIV-1 immunoglobulin (Ig) G was detectable at a low frequency in individuals with normal immunological parameters, and in the majority of patients with various degrees of immunodeficiency. The intrathecal production of antibodies to HIV-1 was strongly associated with the recovery of the virus from CSF. A relationship between high anti-HIV-1 IgG levels and occurrence of HIV-1 was also found in blood. Patients without overt neurological symptoms exhibited intrathecal synthesis of anti-HIV-1 IgG as often as those with such symptoms. These findings suggest that intrathecal synthesis of antibodies to HIV-1 is related to a persistent HIV-1 antigenic stimulation in the central nervous system (CNS). HIV-1 often seems to elicit a humoral immune response in the CNS, without concomitant overt neurological symptoms.
Subject(s)
Acquired Immunodeficiency Syndrome/cerebrospinal fluid , Cerebrospinal Fluid/microbiology , HIV Antibodies/cerebrospinal fluid , HIV-1/immunology , Immunoglobulin G/cerebrospinal fluid , Acquired Immunodeficiency Syndrome/immunology , Acquired Immunodeficiency Syndrome/microbiology , Adult , Female , HIV Antibodies/biosynthesis , HIV-1/isolation & purification , Humans , Immunoglobulin G/biosynthesis , MaleABSTRACT
Neopterin and beta 2-microglobulin (beta 2-M) concentrations in cerebrospinal fluid (CSF) and blood were measured in 56 individuals in various stages of HIV-1 infection. Elevated levels of neopterin as well as beta 2-M were found in the CSF of three patients with primary HIV-1 infection and also in subjects in the early stages of chronic HIV-1 infection, with the highest levels in HIV-1 isolation-positive people. There was a clear correlation between the concentrations of the two substances and the levels seemed to increase in parallel with progress of infection. A similar pattern was found in blood. Higher concentrations of neopterin and beta 2-M in CSF than in blood were found in patients with advanced dementia in particular. These findings indicate that the cellular immune system in the central nervous system (CNS) may be activated during the early stages of HIV-1 infection without concomitant overt neurological symptoms. The pathological processes in CNS and blood seem to develop in parallel rather than being restricted to one compartment.
Subject(s)
Acquired Immunodeficiency Syndrome/cerebrospinal fluid , Biopterins/analogs & derivatives , HIV-1 , beta 2-Microglobulin/cerebrospinal fluid , Acquired Immunodeficiency Syndrome/blood , Acquired Immunodeficiency Syndrome/complications , Adult , Aged , Biopterins/blood , Biopterins/cerebrospinal fluid , Dementia/blood , Dementia/cerebrospinal fluid , Dementia/etiology , Female , Humans , Male , Middle Aged , Neopterin , beta 2-Microglobulin/analysisABSTRACT
Human immunodeficiency virus (HIV) could be isolated from the cerebrospinal fluid (CSF) of the majority (62%) of 72 patients in various stages of HIV infection. This high rate of successful virus isolation was achieved only when the time from lumbar puncture to initiation of the cell cultures was short, i.e. not exceeding 5 h. The HIV isolation rates were equally high in patients with persistent generalized lymphadenopathy (PGL), AIDS-related complex (ARC) and AIDS. Although the HIV recovery rate was low in patients with normal immunological parameters it was not correlated with the degree of severity of the immunodeficiency in the other patients. Furthermore, the recovery rates were not significantly correlated to the duration of the infection. HIV was recovered as often from patients with neurological symptoms as from patients without such symptoms. These findings suggest that in the majority of patients there is central nervous system (CNS) involvement early in the course of HIV infection and that HIV replication in the CNS may occur in the absence of a pronounced systemic cellular immunodeficiency and frequently without causing overt neurological symptoms.
