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 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A useful clinical framework for decision making in antiretroviral treatment is to consider treatment options and goals at 4 decision points: initial therapy, early treatment failure, late treatment failure with high CD4+ cell count, and late treatment failure with low CD4+ cell count. Basic principles appropriate to these decision points are discussed. For initial treatment, the goal is to suppress viral replication for as long as possible. In early failure, the aim is to achieve resuppression of viral replication. For late treatment failure in patients with high CD4+ cell counts with limited treatment options, a reasonable approach is to be cautious in making treatment changes, since sustained incomplete suppression is not associated with immunologic collapse. In patients with late treatment failure and lower CD4+ cell counts, a reasonable strategy is to maintain some form of antiretroviral therapy until new drug classes become available. These basic approaches are reviewed in this article, with findings reported at the recent 10th Conference on Retroviruses and Opportunistic Infections discussed in light of this strategic framework. This article summarizes a presentation given by Diane V. Havlir, MD, at the March 2003 International AIDS Society-USA course in Los Angeles.
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PMID:Strategic approaches to antiretroviral treatment. 1287 33

Human immunodeficiency virus (HIV) associated nephropathy (HIVAN) is the most common disease delineated in biopsy series of patients with HIV infection and renal disease. Although the renal histologic lesions in patients with HIV infection present a spectrum of findings, several groups have emphasized characteristic clinical and pathologic features of HIVAN. Consensus has since been reached that HIVAN has a distinctive pathology, consistent with focal segmental glomerulosclerosis, but involving all subunits of the kidney. Several studies have linked the pathogenesis of focal glomerulosclerosis to abnormalities of the glomerular epithelial cell. Recent advances in molecular histologic studies and treatment link the pathogenesis of HIVAN to factors associated with the viral lifecycle. Cytopathic effects of HIV gene products, apoptosis mediated by HIV infection, the elaboration of chemokines and cytokines as a result of viral or host protein synthesis in patients with genetic susceptibility to nephropathy, and the subversion of the host metabolic and synthetic machinery by the virus might be sufficient to create a rapidly progressive disease. If HIV infects and has cytopathic effects on glomerular epithelial cells, and dysfunction of these cells is intimately related to the pathogenesis and progression of renal disease, a reasonable pathogenic mechanism for the development of HIVAN may be inferred. The similarities of HIVAN and the collapsing variant of focal segmental glomerulosclerosis pose the intriguing possibility that the latter is a viral illness as well. The disease is marked by glomerular sclerosis with varying degrees of collapse, tubular epithelial cell degeneration, simplification, microcystic dilatation, interstitial fibrosis and immune cell infiltration. At the level of electron microscopy, tubular reticular inclusions in renal endothelial cells are a typical, but not pathognomonic feature of HIVAN.
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PMID:HIV-associated nephropathy: virologic issues related to renal sclerosis. 1295 44

HIV-1 encodes for one of the human glutathione peroxidases. As a consequence, as it is replicated, its genetic needs cause it to deprive HIV-1 seropositive individuals not only of glutathione peroxidase, but also of the four basic components of this selenoenzyme, namely selenium, cysteine, glutamine, and tryptophan. Eventually this depletion process causes severe deficiencies of all these substances. These, in turn, are responsible for the major symptoms of AIDS which include immune system collapse, greater susceptibility to cancer and myocardial infarction, muscle wasting, depression, diarrhea, psychosis and dementia. As the immune system fails, associated pathogenic cofactors become responsible for a variety of their own unique symptoms. Any treatment for HIV/AIDS must, therefore, include normalization of body levels of glutathione, glutathione peroxidase, selenium, cysteine, glutamine, and tryptophan. Although various clinical trials have improved the health of AIDS patients by correcting one or more of these nutritional deficiencies, they have not, until the present, been addressed together. Physicians involved in a selenium and amino-acid field trial in Botswana, however, are reporting that this nutritional protocol reverses AIDS in 99% of patients receiving it, usually within three weeks.
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PMID:How HIV-1 causes AIDS: implications for prevention and treatment. 1505 Jan 5

Lactic acidosis (LA), a rare but life-threatening adverse effect associated with antiretroviral therapy, has been reported with an increasing frequency since the mid-1990s. From June 1994 to June 2002, a total of six patients, four males and two females with a median age of 43 years (range, 30 to 74 years), had been diagnosed with LA. The estimated incidence of LA was 5.1 per 1000 patient-years (PYs) on highly active antiretroviral therapy (HAART) (95% confidence interval [95% CI], 4.5-5.5 per 1000 PYs) and 4.4 per 1000 PY on nucleoside analogues (NAs) (95% CI, 3.9-4.7 per 1000 PYs). Their median body mass index at diagnosis of LA was 17.6 kg/m(2) (range 16.3 to 22.6 kg/m(2)). The median CD4+ lymphocyte count at the initial diagnosis of HIV infection and at the onset of LA was 38 cells/ micro L (range, 4 to 103 cells/ micro L) and 108 cells/ micro L (range, 79 to 224 cells/ micro L), respectively. The most common symptoms were nausea, vomiting, and dyspnoea. All of the patients had findings suggestive of NA-related mitochondrial toxicity, such as myositis, pancreatitis, fatty hepatitis, peripheral neuropathy or lipodystrophy. The prescribed NA related to LA were stavudine in six patients, lamivudine, five, and didanosine, one. Despite treatment, all patients died of persistent circulatory collapse following LA. The median duration from diagnosis to death was eight days (range, 4-17 days). Our report highlights that clinicians caring for patients with AIDS should be alerted to the potentially fatal LA associated with antiretroviral therapy when patients present with low body mass index, lipodystrophy, unexplained abdominal symptoms, dyspnoea, or elevated aminotransferases.
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PMID:Fatal lactic acidosis associated with highly active antiretroviral therapy in patients with advanced human immunodeficiency virus infection in Taiwan. 1507 19

Cutaneous manifestations of miliary tuberculosis are rare. We report two patients with previously unknown advanced human immunodeficiency virus (HIV) infection, who presented with respiratory collapse and an erythematous papulopustular skin eruption. Skin biopsies demonstrated focal dermal microabscess in one patient, and a subcorneal vesicle with an underlying dermal microabscess in the other. Despite the lack of granulomatous inflammation, acid-fast bacilli (AFB) and Fite stains demonstrated numerous acid-fast bacilli, and Mycobacterium tuberculosis was subsequently isolated in either skin and/or sputum cultures. Pulmonary involvement was present in both cases, but was sufficiently diffuse and atypical so as not to be specific for tuberculosis upon initial clinical and radiographic examination. Our two cases illustrate the importance of careful skin examination in patients with HIV infection, since cutaneous dissemination can be an easily overlooked sign of miliary tuberculosis.
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PMID:Cutaneous miliary tuberculosis in two patients with HIV infection. 1509 43

Idiopathic collapsing glomerulopathy is a clinically and pathologically distinct variant of focal segmental glomerulosclerosis characterized clinically by a male and Afro-Caribbean racial predominance, proteinuria (often nephrotic range), and rapid progression to end-stage renal failure. Pathologically, the typical changes are global glomerular collapse leading to obliteration of glomerular capillary lumina, hypertrophy and hyperplasia of podocytes, and severe tubulointerstitial changes. A secondary form with almost identical pathologic features is described in association with human immunodeficiency virus infection. We describe a female patient who presented with multisystemic manifestations, including high spiking fever, arthralgias, lymphadenopathy, striking hyperferritinemia, and impaired renal function with proteinuria. Renal biopsy showed classic collapsing glomerulopathy. A diagnosis of adult Still's disease was made on the basis of Yamaguchi's criteria. The patient was treated with steroids, resulting in remission of the rheumatological condition closely paralleled by remission of proteinuria and renal function, thereby strongly suggesting a causative link between adult Still's disease and collapsing glomerulopathy in this patient. We propose that collapsing glomerulopathy ought to be considered in adult Still's disease with unexplained renal insufficiency or proteinuria.
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PMID:Collapsing glomerulopathy in adult still's disease. 1511 92

The recent success of the fusion inhibitor T-20 (enfuvirtide) in clinical studies has ushered in a new chapter in the development of anti-HIV-1 therapeutics. T-20 is the first FDA-approved drug that targets the viral transmembrane protein gp41. This protein, along with gp120, promotes viral entry through a coordinated cascade of conformational transitions that lead to the fusion of the HIV-1 and target cell membranes. The interaction of gp120 with CD4 and a chemokine receptor stimulates gp41 to extend and bridge the space between the virus and cell. Subsequently, gp41 collapses into a trimer-of-hairpins structure that brings the viral and cellular membranes into close proximity necessary for fusion. Enfuvirtide targets the gp41 amino-terminal region exposed in the transient extended state, blocking the ultimate collapse into the trimer-of hairpins and inhibiting membrane fusion. The vulnerability of this transient extended state has stimulated the development of new agents, ranging from small molecules to large proteins, that bind to gp41 and inhibit its structural transformations. The discovery and characterization of these inhibitors have not only led to new antiviral strategies, but have also shed light on the accessibility of gp41 epitopes that might play a role in HIV-1 vaccine development.
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PMID:HIV-1 gp41 as a target for viral entry inhibition. 1518 May 42

Within-patient HIV populations evolve rapidly because of a high mutation rate, short generation time, and strong positive selection pressures. Previous studies have identified "consistent patterns" of viral sequence evolution. Just before HIV infection progresses to AIDS, evolution seems to slow markedly, and the genetic diversity of the viral population drops. This evolutionary slowdown could be caused either by a reduction in the average viral replication rate or because selection pressures weaken with the collapse of the immune system. The former hypothesis (which we denote "cellular exhaustion") predicts a simultaneous reduction in both synonymous and nonsynonymous evolution, whereas the latter hypothesis (denoted "immune relaxation") predicts that only nonsynonymous evolution will slow. In this paper, we present a set of statistical procedures for distinguishing between these alternative hypotheses using DNA sequences sampled over the course of infection. The first component is a new method for estimating evolutionary rates that takes advantage of the temporal information in longitudinal DNA sequence samples. Second, we develop a set of probability models for the analysis of evolutionary rates in HIV populations in vivo. Application of these models to both synonymous and nonsynonymous evolution affords a comparison of the cellular-exhaustion and immune-relaxation hypotheses. We apply the procedures to longitudinal data sets in which sequences of the env gene were sampled over the entire course of infection. Our analyses (1) statistically confirm that an evolutionary slowdown occurs late in infection, (2) strongly support the immune-relaxation hypothesis, and (3) indicate that the cessation of nonsynonymous evolution is associated with disease progression.
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PMID:A statistical characterization of consistent patterns of human immunodeficiency virus evolution within infected patients. 1550 26

This review compares the neuropathology of highly active antiretroviral therapy (HAART)-treated HIV+ individuals with the reported central nervous system (CNS) findings from the pre-HAART era. HAART has had considerable success in combating HIV-related immune collapse and has prevented many of the former end-stage complications of AIDS. However, with increased survival times the prevalence of minor HIV-associated cognitive impairment appears to be rising among treated patients and this may be a particular risk for older individuals. HIV encephalitis (HIVE) is still prevalent in treated patients although attenuated forms of HIVE and CNS opportunistic disorders are also observed. Some subjects show very significant CNS lymphocytic infiltrates in the context of HAART-induced immune reconstitution. HIV-associated cognitive impairment correlates best with the increased presence of activated, though not necessarily infected, microglia and CNS macrophages. This suggests that indirect mechanisms of neuronal injury and loss occur in HIV/AIDS as a basis for dementia since neurones are not themselves productively infected. Research to elucidate the mechanisms of neuronal injury in HIV/AIDS may contribute to the understanding of CNS function not only in HAART-treated subjects but also in other neurodegenerative disorders.
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PMID:An update on the neuropathology of HIV in the HAART era. 1556 45

The purpose of this prospective study conducted from March to December 2000 in the Internal Medicine Department of the Sanou Souro University Hospital in Bobo-Dioulasso, Burkina Faso was to evaluate the epidemiological, clinical, biological and prognostic features of severe malaria in adult patients according to their HIV status. During the study period HIV testing was performed in 37 of the 72 adults with confirmed severe malaria. Findings were positive in 12 cases and negative in 25. The mean age of the 12 seropositive patients with severe malaria was 32.4 +/- 2.8 years and most (50%) had used self-prescribed antimalarial treatment. The most common reasons for seeking medical care were fever, headache and deterioration of general health. The main manifestations of severe malaria were coma (n=4), generalized seizure (n=4) and circulatory collapse (n=4). Six patients (50%) presented two severe manifestations. Mean parasitemia at the time of admission was 4066 parasites/microl for seropositive subjects versus 8563 parasites/microl for seronegative subjects. Outcome of malaria included 4 deaths and 8 recoveries in the seropositive group versus 2 deaths and 23 recoveries in the seronegative group. Comparison with the group of 25 seronegative patients presenting severe malaria demonstrated no significant difference in mean age (p=0.96), self-prescribed antimalarial treatment (p=0.50), parasitemia upon admission (p=0.28), or mortality (p=0.07). However co-infected patients were found to have a higher incidence of anemia (P=0.01) and never presented certain manifestations of severe malaria. Further studies of co-infection by HIV infection and malaria (especially severe malaria) is needed given the high human and economic impact of these two diseases in sub-Saharan Africa.
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PMID:[Severe malaria and HIV in adult patients in Bobo-Dioulasso, Burkina Faso]. 1561 84


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