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Biomedical subjects

Shaffiq Essajee

Publications and source records attributed to Shaffiq Essajee.

4 recordsLinked to original sources

Human immunodeficiency virus (HIV) reverse transcriptase activity correlates with HIV RNA load: implications for resource-limited settings.

Measurement of human immunodeficiency virus type 1 (HIV-1) plasma RNA levels using Roche AMPLICOR version 1.5 (HIV RNA) is an integral part of monitoring HIV-infected patients in industrialized countries. These assays are currently unaffordable in resource-limited settings. We investigated a reverse transcriptase (RT) assay as a less expensive alternative for measuring viral burden that quantifies RT enzyme activity in clinical plasma samples. A comparison of RT and HIV RNA assays was performed on 29 paired plasma samples from patients living in the United States and 21 paired plasma samples from patients living in Cameroon. RT levels correlated significantly with plasma HIV RNA viral loads in plasma from U.S. patients (r = 0.898; P < 0.001) and Cameroonian patients, a majority of whom were infected with HIV-1 clade type CRF02_AG (r = 0.669; P < 0.01). Among 32 samples with HIV viral load of >2,000 copies/ml, 97% had detectable RT activity. One Cameroon sample had undetectable RNA viral load but detectable RT activity of 3 fg/ml. The RT assay is a simple and less expensive alternative to the HIV RNA assay. Field studies comparing these assays in resource-limited settings are warranted to assess the practicality and usefulness of this assay for monitoring HIV-infected patients on antiretroviral therapy.

Cohort Studies↗

Correlation between HIV-Specific CD8 cell production of interferon- gamma and plasma levels of HIV RNA in perinatally infected pediatric populations.

BACKGROUND: CD8 cell responses to human immunodeficiency virus (HIV) have been correlated with virus control in adults, and this study outcome has been controversial. Attempts to establish the same correlation in small numbers of children have also been made, with similar controversy resulting. METHODS: A total of 110 perinatally infected children were studied. Nine of the children (mean age, 1.9 years vs. 11.8 years for the remaining 101 children) received treatment with antiretrovirals within the first 3 months of life. CD4 cell and HIV RNA levels were measured. Production of interferon- gamma after exposure to recombinant vaccinia vectors was measured by enzyme-linked immunospot (ELISPOT) assay. RESULTS: Responses to Pol and Gag antigens exceeded those to Nef and Env antigens, with responses significantly approximated by a quadratic function for which peak responses occurred at plasma HIV RNA levels of 103-104 HIV RNA copies/mL. Children who are treated early in life with highly active antiretroviral therapy have fewer total responses of ELISPOT-forming cells to HIV antigens than do children who are treated later in life.

Adolescent↗

Poxvirus vaccines for cancer and HIV therapy.

The poxviridae have a long history of causing disease in society, and their biological effects in humans and other mammals have been extensively studied. In the 1980s, genetic engineering techniques were applied to vaccinia in order to create replicating recombinant vectors that could express inserted genes encoding influenza virus proteins. In animal models, these recombinant viruses were able to deliver their foreign antigens to the immune system and elicit a specific adaptive immune response. Since then, improvements in our understanding of immunobiology, as well as technical advances in bioengineering, have led to the creation and clinical testing of a large number of recombinant poxviruses as candidate vaccines. Poxviruses can infect a broad range of cells, replicate with high efficiency and elicit strong immune responses - factors that make them especially well-suited as vaccines for the prevention and treatment of human immunodeficiency virus (HIV) and cancer. Both of these diseases are characterised by chronic antigen expression in the setting of focal or global deficits in the immune system that hamper the generation of protective immunity. This review traces the history of poxviruses as pathogens and immunogens, examines some of the approaches that have been taken to design poxviral vaccines for HIV and cancer and summarises the results of existing clinical trials of these vectors. In addition, the review aims to identify some of the factors that may shape the development of future therapies based on recombinant poxviruses.

AIDS Vaccines↗

Immunoreconstitution in children receiving highly active antiretroviral therapy depends on the CD4 cell percentage at baseline.

The effect of highly active antiretroviral therapy (HAART) in 85 children infected with human immunodeficiency virus type 1 (HIV-1) was compared retrospectively among Centers for Disease Control and Prevention (CDC) immunologic groups 1-3. The duration of HAART did not vary significantly among the immunologic groups (median, 39.07 months). The CD4 cell percentage increased in 39.1%, 58.3%, and 90% of patients in CDC groups 1-3, respectively (P <.001). HAART resulted in the suppression of HIV-1 below detectable levels in 34.8%, 25%, and 32% of patients in the 3 CDC groups, respectively, and in a frequent switch from syncytium-inducing to nonsyncytium-inducing virus. Thymic excision circles increased in a subset of patients with increases in CD4 cell percentage independently of HIV RNA level. The results support the option of delaying HAART in early asymptomatic HIV-1 disease in children and the use of other markers of disease progression, in addition to virus load.

Acquired Immunodeficiency Syndrome↗