ABSTRACT Human immunodeficiency virus (HIV)-associated nephropathy (HIVAN) is one of the most important causes of progressive kidney failure in HIV-1-seropositive patients. Since the 1980s, much has been published regarding the epidemiology, pathogenesis, and treatment of HIVAN. Our knowledge of the clinical features, pathologic manifestations, course, and potential outcome of HIVAN has increased considerably. The use of highly active antiretroviral therapy has shown significant improvement in the outcome of human immunodeficiency virus infection and is found to be effective in preventing end-stage renal disease. The purpose of this review is to summarize the data about the clinical manifestations, pathogenesis and pathophysiologic mechanisms of HIVAN with particular attention on treatment including pharmaceutical and renal replacement options.
- SourceAvailable from: Enrique Morales
An Update on Glomerulopathies - Clinical and Treatment Aspects, 11/2011; , ISBN: 978-953-307-673-7
- "These structures are synthesized by the stimulation of alpha-interferon, as in the cases of patients with lupus nephritis. The histological differential diagnoses of focal segmental glomerulosclerosis are the collapsing nephropathy heroin abuse, caused by bisphosphonates, interferon or parvovirus (Klotman, 1999). Main manifestation of HIV-associated nephropathy is a nephrotic syndrome (Herman & Klotman, 1998). "
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- "The presence of plasma viral loads in these macaques indicates that virus may have persisted in populations of cells that probably either did not express A3G/F/DE/ C/B or expressed these proteins at very low levels. These results correlate with our previous studies that showed restricted expression of A3G in brain and kidney tissues (Hill et al., 2006; 2007), both of which are targets for HIV-1, SIV and SHIV (Gattone et al., 1998; Khan et al., 2006; Letendre et al., 2008; Raghavan et al., 1997; Stephens et al., 2000; Zink and Clements, 2002). Thus, a major question that emerged was, " Are the viruses produced from these cellular reservoirs infectious, replication competent viruses? "
ABSTRACT: The simian-human immunodeficiency virus (SHIV)/macaque model for human immunodeficiency virus type 1 has become a useful tool to assess the role of accessory genes in lentiviral pathogenesis. In this study, we introduced two amino acid changes in the highly conserved SLQYLA domain (to AAQYLA) of the SIV Vif protein. The resulting virus, SHIV(VifAAQYLA), was used to infect three macaques, which were followed for over six months. Plasma viral loads and circulating CD4(+) T cell levels were assessed during the course of infection. The three macaques inoculated with SHIV(VifAAQYLA) did not develop significant CD4(+) T cell loss over the course of their infection, had plasma viral RNA loads that were over 100-fold lower than macaques inoculated with parental SHIV(KU-1bMC33), and developed no histological lesions in lymphoid tissues. DNA and RT-PCR analysis revealed that only a select number of tissues were infected with this virus. Sequence analysis indicates that the site-directed changes were stable during the first three weeks after inoculation but thereafter the S147A amino acid substitution changed to a threonine in two of three macaques. The L148A substitution remained stable in the vif amplified from the PBMC of all three macaques. Sequence analysis of vif, vpu, env and nef genes revealed G-to-A mutations in the genes amplified from macaques inoculated with SHIV(VifAAQYLA), which were higher than in a macaque inoculated with parental SHIV(KU-1bMC33). We found that the majority (>85%) of the G-to-A mutations were in the context of 5'-TC (minus strand) and not 5'-CC, suggestive that one or more of the rhesus APOBEC3 proteins may be responsible for the observed mutational patterns. The data also suggest that rhesus APOBEC3G probably accounted for a minority of the mutations since its GG-to-AG mutational pattern was infrequently detected. Finally, macaques inoculated with SHIV(VifAAQYLA) developed immunoprecipitating antibody responses against the virus. The results from this study provide the first in vivo evidence of the importance of the SLQYLA domain in viral pathogenesis and show that targeted mutations in vif can lead to a persistent infection with G-to-A changes accumulating in the viral genome.Virology 12/2008; 383(2):362-72. DOI:10.1016/j.virol.2008.10.013 · 3.28 Impact Factor
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- "While clearly this type of treatment is intended only for patients who are likely to become extremely ill or die as the result of infection, it is also clear that these are the diseases whose solution is most highly sought after. Perhaps equally important is the fact that a significant population of HIVþ patients already receive dialysis treatments as a result of HIV-associated nephropathy (Winston and Klotman, 1998; Saha and Agarwal, 2001). "
ABSTRACT: We propose an artificial lymph node to improve immune function in fighting viral diseases. The device is based on hemodialysis using a cartridge containing a solid phase affinity resin. Virus capture is mediated by a collection of broad specificity antibodies covalently coupled to agarose. Viral proteins, which can directly damage uninfected cells, are also efficiently removed. Immobilized antisense DNA provides a mechanism to remove infectious viral nucleic acids. Theoretical calculations suggest that the device could effectively remove virus, toxic viral proteins and infectious viral nucleic acids from the blood thereby limiting disease by preventing reinfection of new cells. In the absence of newly infected cells, previously infected cells are cleared by the immune system. For a typical immobilized antibody, calculations predict a pseudo-first order rate of capture (t1/2 ∼ 10 min) with viral load reduction ∼ 660-fold at equilibrium. Theoretical calculations of a diffusion limited process predict t1/2 ∼ 2.8 h. Measured transport rates for latex particles in a prototype device are significantly faster than the theoretical diffusion limit suggesting that transport is primarily convective and sufficient to allow rapid virus clearance. Since the device is highly selective it can be used in conjunction with drug therapy and other treatments.Journal of Theoretical Medicine 01/2002; DOI:10.1080/1027366021000041395