Acquired Immunodeficiency Syndrome: Rosenberg E

Thorner A, Rosenberg E. · Partners AIDS Research Center, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. · Drugs. · Pubmed #12825959 No free full text.

Abstract: The development and implementation of highly active antiretroviral therapy (HAART) for the treatment of the human immunodeficiency virus has revolutionised the care of patients with this disease. Despite the positive impact that antiretroviral therapy has had on the lives of individuals with HIV infection, the adverse effects, potential long-term toxicities, complexity of regimens, development of drug resistance and cost have made decisions about when to initiate HAART difficult. The benefits and risks of antiretroviral therapy vary considerably among patients at different stages of disease, mainly as a result of the irreversible destruction of the immune system that occurs as HIV infection progresses.In acute HIV infection, the primary aim of treatment is preservation and reconstitution of HIV-specific immune function. In symptomatic or late-stage disease, the goal is control of viral replication with resulting improvement in non-HIV-specific immunity, which leads to decreased morbidity and increased survival. The most controversial decision involves when to start therapy in persons with asymptomatic chronic HIV, where the benefits are less well established and may be outweighed by the drawbacks, depending on the individual patient. In all patients, the advantages and disadvantages must be considered carefully, and the readiness and ability of the individual to adhere to a complex multidrug regimen needs to be assessed before the initiation of therapy.

Chien PC, Chen D, Chen PD, Tuen M, Cohen S, Migueles SA, Connors M, Rosenberg E, Malhotra U, Gonzalez C, Hioe CE. · Department of Pathology, New York University School of Medicine, and Veterans Affairs New York Harbor Healthcare System, New York, New York 10010, USA. · J Infect Dis. · Pubmed #14976603 No free full text.

Abstract: BACKGROUND: Antibodies to the CD4-binding domain (CD4bd) of human immunodeficiency virus type 1 (HIV-1) glycoprotein 120 (gp120) inhibit gp120 antigen presentation to CD4 T cells. These findings imply that the presence of anti-CD4bd antibodies might contribute to the dearth of envelope-specific T helper responses observed in most HIV-1-positive patients. In the absence of these antibodies, however, anti-envelope T helper responses might be maintained. METHODS: We used ELISA to evaluate the levels of anti-CD4bd antibodies in rare HIV-1-positive patients who exhibit envelope-specific lymphoproliferation. Subsequently, we examined the contribution of anti-CD4bd antibodies to disease progression by comparing anti-CD4bd antibody levels in 3 cohorts of HIV-1-positive patients with distinct rates of disease progression. RESULTS: Although most HIV-1-positive individuals produce anti-CD4bd antibodies, 77% of patients with envelope-specific lymphoproliferation have undetectable anti-CD4bd antibody levels. Moreover, comparison of the 3 HIV-1-positive cohorts revealed that individuals with long-term nonprogression have significantly lower anti-CD4bd antibody titers than do those with rapid or slow progression. Unlike immunoglobulin G (IgG) from rapid progressors, IgG from nonprogressors had no suppressive effects on glycoprotein (gp) 120-specific T cell proliferation. CONCLUSIONS: Low anti-CD4bd antibody levels are associated with the absence of disease progression. A number of HIV-1-positive individuals without these antibodies also appear to sustain gp120-specific T helper responses needed to help control the infection.

Kiepiela P, Smith AN, Rosenberg E. · Nelson R Mandela School of Medicine, University of Kwazulu-Natal, HIV Pathogenesis Programme, DDMRI, 719 Umbilo Road, Congella, Durban, 4013 Natal, South Africa. · Best Pract Res Clin Obstet Gynaecol. · Pubmed #15778113 No free full text.

Abstract: Infection with HIV may develop to AIDS at different rates in different individuals, with a spectrum varying from rapid progression to long-term non-progression. The variable course of HIV-1 infection causes emotional trauma for the infected person and complicates the design and interpretation of therapeutic trials because of unrecognized differences in prognosis. Owing to the variable clinical expression of HIV infection, the use of non-clinical disease markers has become important to patient management. Thus, it is essential to have tests which can accurately assess the stage of infection in an individual, as well as predict its course and monitor its progression. These laboratory tests are valuable during the period of clinical latency and subsequently supplement various clinical parameters.