AIDS research and human retroviruses
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AIDS Res. Hum. Retroviruses · Feb 2008
Cytokine genotype suggests a role for inflammation in nucleoside analog-associated sensory neuropathy (NRTI-SN) and predicts an individual's NRTI-SN risk.
Nucleoside analog-associated sensory neuropathy (NRTI-SN) attributed to stavudine, didanosine, or zalcitabine (the dNRTIs) and distal sensory polyneuropathy (DSP) attributed to HIV are clinically indistinguishable. As inflammatory cytokines are involved in DSP, we addressed a role for inflammation in NRTI-SN by determining the alleles of immune-related genes carried by patients with and without NRTI-SN. Demographic details associated with risk of various neuropathies were included in the analysis. ⋯ Of the demographic details considered, increasing height was associated with NRTI-SN risk. A model including cytokine genotype and height predicted NRTI-SN status (p < 0.0001, R(2) = 0.54). Late onset NRTI-SN patients clustered genetically with NRTI-SN-resistant patients, so these patients may be genetically "protected." In addition to patient height, cytokine genotype influenced NRTI-SN risk following dNRTI exposure, suggesting inflammation contributes to NRTI-SN.
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AIDS Res. Hum. Retroviruses · Jun 2007
Clinical TrialEvaluation of modified vaccinia virus Ankara as an alternative vaccine against smallpox in chronically HIV type 1-infected individuals undergoing HAART.
The fear of malevolent use of variola virus by terrorists has led to the implementation of a health care worker vaccination program and to the consideration of vaccination for the general public. However, due to concerns about side effects of the classical smallpox vaccine, especially for immunocompromised individuals, a safer vaccine is urgently needed. We characterized the immunogenicity of modified vaccinia virus Ankara (MVA), one of the more promising alternative smallpox vaccines, in a cohort of 10 chronically HIV-1-infected individuals undergoing highly active antiretroviral therapy (HAART). ⋯ The immune responses were maintained over 1 year. Similar vaccinia specific humoral immune responses were observed when our cohort of HIV-1-infected individuals was compared to smallpox-vaccinated healthy subjects. The observed immune responses suggest that the highly attenuated MVA could be used as a substitute vaccine against smallpox in chronically HIV-1-infected individuals undergoing HAART.
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AIDS Res. Hum. Retroviruses · Mar 2007
CD25+ regulatory T cells isolated from HIV-infected individuals suppress the cytolytic and nonlytic antiviral activity of HIV-specific CD8+ T cells in vitro.
HIV infection is characterized by CD4(+) T cell depletion and progressive immune dysfunction; particularly impacted are HIV-specific T cell responses. An important component of immune-mediated control of HIV replication, killing of infected cells, appears to be impaired, in part due to poor cytolytic activity of HIV-specific cytotoxic T cells (CTL). In vitro, several functions of HIV-specific T cells, such as cytokine production, can be enhanced by the depletion of the immunosuppressive CD25(+) FoxP3(+) CD4(+) regulatory (Treg) cell subset. ⋯ In addition, CD25(+) Treg cells suppress effector function (coexpression of TNF-alpha and IFN-gamma) of HIV-specific CD8(+) T cells that proliferate in response to HIV antigen. Finally, the secretion of HIV-inhibitory CC-chemokines by HIV-specific and nonspecific CD8(+) T cells is significantly reduced in the presence of CD25(+) Treg cells. These data suggest that CD25(+) Treg-mediated suppression of the antiviral activity of HIV-specific CD8(+) T cells could impact the ability of HIV-infected individuals to control HIV replication in vivo.
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AIDS Res. Hum. Retroviruses · Aug 2006
Pharmacokinetics of saquinavir hard-gel/ritonavir and atazanavir when combined once daily in HIV Type 1-infected individuals administered different atazanavir doses.
The pharmacokinetics and short-term safety of atazanavir 150 and 200 mg, when coadministered with saquinavir/ritonavir 1600/100 mg once daily, were evaluated. On day 1, atazanavir 150 mg once daily, was added to saquinavir/ritonavir regimens and sampling was performed to evaluate saquinavir, ritonavir, and atazanavir pharmacokinetics (day 11). Atazanavir was increased to 200 mg and pharmacokinetic assessment repeated (day 30). ⋯ While saquinavir enhancement was apparently independent of atazanavir dose, atazanavir 300 mg produced an increase in ritonavir Cmax, which is not observed with lower atazanavir doses. Atazanavir-related hyperbilirubinemia was dose dependent. However, higher saquinavir and atazanavir exposure may be required to suppress HIV-resistant strain replication.
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Lipodystrophy resulting from HIV disease or the antiretroviral therapy used to treat it is a common complication. We report on the treatment of cervical lipohypertrophy ("buffalo hump") with suction-assisted lipectomy in six patients.