Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This perspective is part of an ongoing series of articles that describe the drugs that were dropped from clinical development during the previous year. This paper focuses on those drugs that were discontinued in 2008. The drugs represent a diverse collection of compounds targeted at diseases including cancer, diabetes, infections, arthritis, HIV, restenosis, allergies, anaemia, osteoporosis, wound healing, and growth deficiency. No consistent theme is apparent that accounts for the diversity of discontinued drugs. Still, this diversity, coupled with the numbers of novel drugs that were approved in 2008 suggests a healthy ongoing drug development process.
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PMID:Discontinued biological drugs in 2008. 1991 30

The prognosis of HIV infection has been considerably improved by the introduction of antiretroviral drugs. However, the longer survival times are associated with the emergence of new complications including decreased bone mineral density (BMD) values and/or bone insufficiency fractures. A meta-analysis of studies published between 1966 and 2005 showed bone absorptiometry results indicating osteoporosis in 15% of HIV patients and osteopenia in 52%. Longitudinal studies found no evidence that antiretroviral drug therapy contributed to the occurrence of bone loss. Available data indicate uncoupling with increases in bone resorption markers and decreases in bone formation markers. In addition to conventional risk factors for osteoporotic fractures, factors in HIV-infected patients may include malnutrition (wasting syndrome), hypogonadism, disorders in calcium and phosphate metabolism, and HIV infection per se. In patients with established bone insufficiency, bisphosphonate therapy should be considered. Alendronate in combination with vitamin D and calcium supplementation has been found effective in improving BMD values.
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PMID:Bone loss in patients with HIV infection. 1994 22

PURPOSE OF REVIEW: Low bone-mineral density is a recently recognized metabolic complication of HIV infection and its treatment. While the clinical impact of low bone-mineral density remains uncertain, the prolongation of survival attributable to more effective antiretroviral therapy has contributed to an aging population of HIV-infected patients who may be prone to developing fragility fractures. RECENT FINDINGS: While most of the available data are on young men, recent publications have increased our understanding of the epidemiology of low bone-mineral density and bone loss in HIV-positive women. Most studies suggest that initiation of certain combinations of antiretroviral agents may be associated with moderate bone loss initially, but bone-mineral density usually stabilizes or improves with longer follow-up. Most studies suggest that, despite lower bone-mineral density, fragility fractures are relatively uncommon in HIV-positive patients, perhaps because of their relative youth. SUMMARY: The pathogenesis of low bone-mineral density in HIV-positive patients is complex and multifactorial, and its clinical impact remains unclear. Further research is needed to clarify the approach to optimal screening and treatment of osteoporosis in the setting of HIV infection.
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PMID:Low bone-mineral density in patients with HIV: pathogenesis and clinical significance. 2046 68

There is a high prevalence of osteoporosis in HIV-infected patients. Initially described in HIV-positive men, studies have also demonstrated a high prevalence of osteoporosis in HIV-infected women. It would appear that antiretroviral therapy (ART) plays an important role in the pathogenesis of osteoporosis in HIV-infected patients, although little is known about its importance in relation to osteoporosis and fractures in HIV-positive women. The aim of this systematic review was to evaluate the frequency of bone loss, bone mineral density (BMD) and fractures in HIV-positive women taking ART or protease inhibitors (PI). After screening 597 citations from the databases of PubMed, EMBASE and Lilacs, five studies were selected for the review. A difference was demonstrated of over 3% in the BMD at the femoral neck of HIV-positive women taking PI/ART. No difference was registered in the BMD at the lumbar spine between users and non-users of PI/ART. The lack of studies has made it impossible to reach any conclusion regarding the occurrence of fractures.
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PMID:Bone mineral density in HIV-infected women taking antiretroviral therapy: a systematic review. 2048 1

Bone mass loss with the subsequent development of osteopenia and osteoporosis is related to HIV infection and antiretroviral treatment, even though the mechanisms involved have not yet been elucidated. In this report analyzes the early effects of some specific protease inhibitors on OPG/RANKL yielding and cell survival in osteoblast-like HOBIT cell line. None of the compounds, tested at scalar concentrations (C1, C2, C3), affected cell survival except for tipranavir that elicited a reliable induction of apoptosis at the highest concentration (C3). Atazanavir, saquinavir and indinavir did not affect OPG/RANKL in the cell surnatant in our experimental conditions. By contrast, at optimal concentration (C2), fosamprenavir induced a significant increase in OPG associated with a RANKL decrease whereas tipranavir down-regulated both OPG and RANKL (at C2 and C3) and darunavir increased RANKL only at C3 concentration. Together these data (coupled with the analysis of OPG/RANKL ratio) indicate that at early times and at optimal concentrations the PIs did not impair the OPG/RANKL system with the exception of fosamprenavir that showed a relative positive OPG/RANKL ratio regulation. Instead, cell cultures treated by the highest concentrations of tipranavir or darunavir showed a change in cell survival or an increase in RANKL, with a negative effect on the OPG/RANKL balance.
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PMID:Analysis of the effects of specific protease inhibitors on OPG/RANKL regulation in an osteoblast-like cell line. 2051 72

Osteoporosis and bone fractures are increasingly recognized complications of HIV-1 infection. Although antiretroviral therapy itself has complex effects on bone turnover, it is now evident that the majority of HIV-infected individuals already exhibit reduced bone mineral density before therapy. The mechanisms responsible are likely multifactorial and have been difficult to delineate in humans. The HIV-1 transgenic rat recapitulates many key features of human AIDS. We now demonstrate that, like their human counterparts, HIV-1 transgenic rats undergo severe osteoclastic bone resorption, a consequence of an imbalance in the ratio of receptor activator of NF-kappaB ligand, the key osteoclastogenic cytokine, to that of its physiological decoy receptor osteoprotegerin. This imbalance stemmed from a switch in production of osteoprotegerin to that of receptor activator of NF-kappaB ligand by B cells, and was further compounded by a significantly elevated number of osteoclast precursors. With the advancing age of individuals living with HIV/AIDS, low bone mineral density associated with HIV infection is likely to collide with the pathophysiology of skeletal aging, leading to increased fracture risk. Understanding the mechanisms driving bone loss in HIV-infected individuals will be critical to developing effective therapeutic strategies.
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PMID:Alterations in the immuno-skeletal interface drive bone destruction in HIV-1 transgenic rats. 2064 42

Advances in management have resulted in a dramatic decline in mortality for individuals infected with human immunodeficiency virus (HIV). This decrease in mortality, initially the result of improved prophylaxis and treatment of opportunistic infections but later mediated by the use of highly-active antiretroviral therapy (HAART) has led to the need to consider long-term complications of the disease itself, or its treatment. Bone disease is increasingly recognised as a concern. The prevalence of reduced BMD and possibly also fracture incidence are increased in HIV-positive individuals compared with HIV-negative controls. There are many potential explanations for this - an increased prevalence of established osteoporosis risk factors in the HIV-positive population, a likely direct effect of HIV infection itself and a possible contributory role of ARV therapy. At present, the assessment of bone disease and fracture risk remains patchy, with little or no guidance on identifying those at increased risk of reduced BMD or fragility fracture. Preventative and therapeutic strategies with bone specific treatments need to be developed. Limited data suggest bisphosphonates may be beneficial in conjunction with vitamin D and calcium supplementation in the treatment of reduced BMD in HIV-infected patients but larger studies of longer duration are needed. The safety and cost-effectiveness of these and other treatments needs to be evaluated.
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PMID:HIV and bone disease. 2068 80

The prevalence of human immunodeficiency virus (HIV) in the over 50 age group is increasing as a consequence of younger adults ageing with HIV, in addition to new diagnoses in later life. We conducted searches in MEDLINE for English language studies published between January 1984 and January 2010 using search terms 'HIV', 'AIDS', 'HIV testing' and 'HIV complications' and selected articles relevant to adults aged 50 years and over. The prevalence, natural history and complications of HIV infection and treatment in older adults are reviewed. In 2007 the Centers for Disease Control and Prevention in the United States reported that 16.8% of new diagnoses of HIV that year were in individuals aged over 50 years. Older adults are vulnerable to late or missed diagnosis, and poorer treatment outcomes, due to the misconception that they are not at risk. A heightened awareness of HIV as a possible diagnosis in older adults is becoming increasingly important. As the HIV population ages, the emergence of disease and treatment complications such as cardiovascular disease, osteoporosis and dementia are evident. Management of older adults with HIV and multiple co-morbidities presents challenges to infectious diseases physicians and geriatricians alike. Inclusion of older adults in future HIV clinical trials will help design healthcare models to provide for this growing population.
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PMID:The ageing of HIV: implications for geriatric medicine. 2068 13

Bone mineral density (BMD) is an important factor linked to bone health. Little is known of the prevalence of low BMD and its associated risk factors in an urban underserved population. Between 2001 and 2004, we recruited 338 subjects who completed drug use and medical history questionnaires, underwent hormonal measurements, and underwent whole-body dual-energy X-ray absorptiometry (DXA) for evaluation of BMD and body composition. Of these, 132 subjects had site-specific DXA (lumbar spine and hip) performed. Osteoporosis was defined as a T-score of -2.5 or less for men 50 years of age and older and postmenopausal women and a Z-score of -2.0 or less in men younger than 50 years of age and premenopausal women at either the lumbar spine, total hip, or femoral neck, according to National Osteoporosis Foundation (NOF) guidelines. The cohort consisted of mostly African-American, middle-aged people with a high prevalence of illicit drug use, 50% HIV(+), and 39% hepatitis C(+). Osteoporosis was identified in 22% of subjects (24 men, 5 women), with the majority of cases (90%) attributable to osteoporosis at the lumbar spine. Osteoporosis was more common in men than in women. Lower whole-body BMD among women was associated with multiple risk factors, but only with lower lean mass among men. Osteoporosis was highly prevalent in men, mainly at the spine. The risk factors for bone loss in this population need to be further clarified. Screening men for osteoporosis starting at age 50 might be warranted in this population given the multiple risk factors and the unexpectedly high prevalence of low BMD.
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PMID:Prevalence of low bone mineral density in a low-income inner-city population. 2072 37

The use of antiretroviral therapy has significantly reduced the number of deaths due to HIV/AIDS. However, no current therapy can suppress the virus completely, and as the HIV-infected population continues to live longer new complications are emerging from the persistence of the virus and use of antiretroviral therapy. This review summarizes the clinical evidence linking HIV-associated osteoporosis to direct infection and antiretroviral therapy (ART) use. The purported molecular mechanisms involved in bone loss are also reviewed. Additionally, recommendations regarding the pharmacologic management of HIV/ART-related osteoporosis are given.
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PMID:HIV and bone loss. 2083 May 38


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