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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A brief review is provided for several oral presentations on HIV drugs delivered at the 6th Conference on Retroviruses and Opportunistic Infections. Topics cover cross resistance with respect to potential new drugs, the new protease inhibitor ABT-378, Triangle Pharmaceuticals' drug FTC, and one study on the different classes of anti-HIV drugs now on the market. Viral load reduction data are highlighted for Zerit/Videx when combined with 3TC, Viramune, or Indinavir. Contact information is provided.
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PMID:The latest antiviral news. 1136 51

Despite the promise of highly active antiretroviral therapies (HAART) to potentially suppress HIV, the ability of the virus to hide in reservoirs makes HIV difficult to eradicate. The virus' ability to remain latent in cells, and continue to replicate, makes targeting and eliminating known reservoirs only a partial solution. Recognizing the continuing multiplication of viral cells may alter future treatment strategies. Following the theory of David Ho, MD, implementation of HAART produces a gradual decline in the levels of HIV. HAART protects new cells being produced, while older infected cells eventually die off. A more recent model concludes that HIV continues to infect new cells possibly because of non-uniform drug distribution to various tissues. The virus is produced in the lymphoid tissue in bursts, responding to the immune system. These "viral bursts" are diminished by HAART, which slowly decreases their size and number, and consequently decreases the number of new cells infected. The newer theory calls for less disturbance of latently infected cells, and greater use of drugs with the best pharmacokinetics, like ABT-378/r, efavirenz (Sustiva), Indinavir (Crixivan) and Ritonavir (Norvir).
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PMID:Why the fat lady hasn't sung: the limits of HAART. 1136 92

The FDA recently approved efavirenz (Sustiva, DMP 266), which is a powerful anti-HIV drug when used in combination therapy. Efavirenz is believed to be as potent as Indinavir in many cases. Testing positive for marijuana use is a possible side effect of using efavirenz, but this false positive can be verified with a test that uses gas chromatography.
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PMID:Efavirenz newly approved. 1136 1

Protease inhibitors used in the treatment of HIV infection have been causally associated with lipodystrophy and insulin resistance and were shown to alter adipocyte differentiation in cultured cells. We aimed to delineate the mechanism by which indinavir impaired adipocyte function. We report that indinavir altered neither the growth nor insulin sensitivity of 3T3-F442A preadipocytes, nor did it alter the initial step of their differentiation, i.e., clonal proliferation. However, adipose conversion was inhibited by indinavir (by 50-60%), as shown by 1) the decrease in the number of newly formed adipocytes; 2) the lower level of the adipogenic protein markers, sterol regulatory element-binding protein-1 (SREBP-1), peroxisome proliferator-activated receptor-gamma (PPAR-gamma), and the insulin receptor (IR); and 3) the lack of SREBP-1 and PPAR-gamma immunoreactivity in the nucleus of most indinavir-treated cells. Partial adipose conversion also correlated with an accumulation of SREBP-1 at the nuclear periphery and an alteration in its electrophoretic mobility. Defective expression and nuclear localization of PPAR-gamma probably resulted from the decreased level of nuclear SREBP-1. Indinavir also rendered 3T3-F442A adipocytes resistant to insulin for mitogen-activated protein kinase activation at a step distal to IR substrate-1 tyrosine phosphorylation. Hence, indinavir impairs differentiation at an early step of adipose conversion probably involving the process controlling SREBP-1 intranuclear localization.
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PMID:The HIV protease inhibitor indinavir impairs sterol regulatory element-binding protein-1 intranuclear localization, inhibits preadipocyte differentiation, and induces insulin resistance. 1137 39

Indinavir (IDV) is a potent and selective human immunodeficiency virus type 1 (HIV-1) protease inhibitor (PI) widely used in antiretroviral therapy for suppression of HIV, but its effects on the immune system are relatively unknown. Recently, it has been reported that PIs inhibit lymphocyte apoptosis. In the present study we have investigated the effects of ex vivo addition of IDV on lymphocyte activation and apoptosis in cells from HIV-infected children (n = 18) and from healthy uninfected individuals (controls, n = 5) as well as in Jurkat and PM1 T-cell lines. Pretreatment of control peripheral blood mononuclear cell (PBMC) cultures with IDV resulted in a dose-dependent inhibition of lymphoproliferative responses to different activation stimuli. Additionally, this treatment led to cell-cycle arrest in G0/G1 phase in anti-CD3 monoclonal antibody-stimulated PBMC cultures in controls and in 15 of 18 HIV-infected children. Spontaneous- or activation-induced apoptosis of PBMCs from HIV-infected or uninfected individuals or of Fas-induced apoptosis in Jurkat and PM1 T cell lines were not inhibited by IDV. Moreover, IDV did not inhibit activation of caspases-1, -3, -4, -5, -9, and -8 in lysates of Jurkat T cells undergoing Fas-induced apoptosis. The findings indicate that IDV interferes with cell-cycle progression in primary cells but does not directly affect apoptosis. It is concluded that IDV may prolong cell survival indirectly by inhibiting their entry into cell cycle. In individuals on PI therapy, PI-mediated effects could potentially modulate immunologic responses independently of antiviral activity against HIV.
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PMID:The HIV protease inhibitor Indinavir inhibits cell-cycle progression in vitro in lymphocytes of HIV-infected and uninfected individuals. 1143 7

Oropharyngeal candidiasis is one of the first and most commonly reported opportunistic infections of untreated AIDS patients. With the introduction of the new antiviral HAART therapy, including HIV protease inhibitors, this mucocutaneous infection is nowadays only rarely observed in treated patients. It was recently shown that HIV protease inhibitors have a direct attenuating effect on Candida albicans secreted aspartic proteinases (Saps), an investigation prompted by the fact that both Sap and HIV protease belong to the superfamily of aspartic proteinases and by the observation that mucocutaneous infections sometimes resolve even in the absence of an immunological improvement of the host. As these Saps are important fungal virulence factors and play a key role in adhesion to human epithelial cells we tried to assess the effect of the HIV protease inhibitors Ritonavir, Indinavir and Saquinavir on fungal adhesion to these cells. The effect on phagocytosis by polymorphonuclear leukocytes was also assessed. Ritonavir was found to be the most potent inhibitor of fungal adhesion. A dose-dependent inhibition of adhesion to epithelial cells was found already at 0.8 microM and was significant at 4 microM or higher, at 500 microM the inhibition was about 55%. Indinavir and Saquinavir inhibited significantly at 4 microM or 20 microM, respectively; at 500 microM the inhibition was 30% or 50%. In contrast, no protease inhibitor was able to modulate phagocytosis of Candida by polymorphonuclear leukocytes. In conclusion, inhibition of Saps by HIV protease inhibitors may directly help to ease the resolution of mucosal candidiasis. In future, derivatives of HIV protease inhibitors, being more specific for the fungal Saps, may form an alternative in the treatment of mucosal candidiasis insensitive to currently available antimycotics.
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PMID:HIV protease inhibitors attenuate adherence of Candida albicans to epithelial cells in vitro. 1147 84

The HIV protease inhibitor indinavir may cause nephrolithiasis and interstitial nephritis. The renal consequences of indinavir-associated nephrotoxicity are uncertain. We report a case of papillary necrosis in a patient treated with indinavir. An asymptomatic HIV-infected woman experienced right-sided renal colicky pain during treatment with indinavir. She passed a non-solid stone and continued indinavir treatment. Intravenous pyelogram performed 20 months later following an episode of left-sided colicky pain showed right-sided papillary necrosis. Indinavir-associated nephrolithiasis and chronic interstitial nephritis were the only possible causes identified in this patient. Physicians should be aware that indinavir nephrolithiasis may cause papillary necrosis.
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PMID:Papillary necrosis associated with the HIV protease inhibitor indinavir. 1154 87

This paper summarises some of the oral adverse effects of antiretroviral agents. Some are related to bone marrow suppression which may also predispose to mouth ulcers. Erythema multiforme and toxic epidermal necrolysis are especially well recognized in HIV disease, particularly as reactions to sulphonamides and to antiretroviral agents. Oral lichenoid reactions have been described in HIV disease often relating to zidovudine use. Didanosine has also produced erythema multiforme and not unusually induces xerostomia, again by an unknown mechanism. Xerostomia may be seen in up to one-third of patients taking didanosine. Taste abnormalities are common with the protease inhibitors and oral and perioral paraesthesia can be a disturbing adverse effect. Ritonavir in particular can give rise to circumoral paraesthesia in over 25% of patients. Indinavir can also produce cheilitis.
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PMID:Orofacial effects of antiretroviral therapies. 1157 69

Indinavir is a viral protease inhibitor used for the treatment of HIV infection. Unconjugated hyperbilirubinemia develops in up to 25% of patients receiving indinavir, prompting drug discontinuation and further clinical evaluation in some instances. We postulated that this side-effect is due to indinavir-mediated impairment of bilirubin UDP-glucuronosyltransferase (UGT) activity and would be most pronounced in individuals with reduced hepatic enzyme levels, as occurs in approximately 10% of the population manifesting Gilbert's syndrome. This hypothesis was tested in vitro, in the Gunn rat model of UGT deficiency, and in HIV-infected patients with and without the Gilbert's polymorphism. Indinavir was found to competitively inhibit UGT enzymatic activity (K(I) = 183 microM) while concomitantly inducing hepatic bilirubin UGT mRNA and protein expression. Although oral indinavir increased plasma bilirubin levels in wild-type and heterozygous Gunn rats, the mean rise was significantly greater in the latter group of animals. Similarly, serum bilirubin increased by a mean of 0.34 mg/dl in indinavir-treated HIV patients lacking the Gilbert's polymorphism versus 1.45 mg/dl in those who were either heterozygous or homozygous for the mutant allele. Whereas saquinavir also competitively inhibits UGT activity, this drug has not been associated with hyperbilirubinemia, most likely because of the higher K(I) (360 microM) and substantially lower therapeutic levels as compared with indinavir. Taken together, these findings indicate that elevations in serum-unconjugated bilirubin associated with indinavir treatment result from direct inhibition of bilirubin-conjugating activity.
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PMID:Mechanism of indinavir-induced hyperbilirubinemia. 1198 77

In the last five years, as HAART has become standard therapy in HIV seropositive or AIDS patients, changes have been noted in the numbers and types of opportunistic fungal infections in these cohorts of patients. Particularly, oropharyngeal candidiasis have become rare in HIV infected patients since the introduction of new anti-HIV drugs of the protease inhibitors type. At the Immunology Institute of the Universidad Central de Venezuela the most frequent protease inhibitors (PIs) used for the treatment of these patients have been: Nelfinavir (Viracept, Roche), Indinavir (Crixivan Merck), Ritonavir (Norvir, Abbott), Saquinavir (Fortovase, Roche). Recently, we observed that recurrent candidiasis was less frequent and no Candida could be isolated in our patients. A direct relation to the PIs was suspected. In order to assess the "in vitro" antifungal activity of the afore mentioned protease inhibitors on Candida sp., we used both the well diffusion test and the NCCLS broth microdilution test to assay 100 Candida sp. isolates from HIV seropositive or AIDS patients with syntomatic oropharyngeal Candida infection. In general, the data obtained with the well diffusion test were in agreement with those obtained by the broth microdilution test. All 100 isolates were susceptible to Saquinavir and 32 were susceptible to Indinavir using the NCCLS microdilution test, while 97 were susceptible to Saquinavir and 52 to Indinavir by the well diffusion test. From 17 C. albicans resistant to fluconazole, all were susceptible to Saquinavir by the NCCLS micromethod and 16 by the well diffusion test. Our results showed anticandidal activity "in vitro" of PIs, mainly Saquinavir.
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PMID:"In vitro" antifungal activity of protease inhibitors. 1181 41


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