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)

Presentations at the Fifth Conference on Retroviruses and Opportunistic Infections focused on new and novel HIV treatments. Four new agents in advanced testing are described: abacavir (1592), efavirenz (DMP-266), adefovir dipivoxil (bis-POM PMEA), and amprenavir (141W94). Other new drugs are being developed; however, the drugs are not as far along in the testing and approval process. The new drugs include integrase inhibitors, zinc finger inhibitors, cyclams and bycyclams, fusion inhibitors, and CKR-5 gene therapy. A summary of each drug is provided.
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PMID:Novel approaches for the treatment of HIV. 1136 50

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

Efavirenz is a non-nucleoside reverse transcriptase inhibitor (NNRTI) used in the treatment of patients with HIV infection. Both US and British treatment guidelines for HIV infection recommend NNRTI- or protease inhibitor-based combinations [i.e. with nucleoside reverse transcriptase inhibitors (NRTIs)] as first-line treatmentoptions in the management of HIV disease. Results of a pivotal randomised study (DMP 266-006) comparing efavirenz- versus indinavir-based triple combination therapy in patients with HIV infection (the majority of whom were antiretroviral therapy-naive) showed the efavirenz-based regimen was better tolerated and had greater success in achieving reductions in viral load below the limit of detection. These and other clinical data were incorporated into economic models in 2 analyses, one conducted in the US and the other in Canada. The US analysis examined long term clinical and economic outcomes predicted on the basis of response (viral load and CD4+ cell counts), tolerability and willingness to adhere to therapy. The efavirenz-based regimen was the dominant treatment strategy as it was predicted to improve survival and reduce direct medical costs in the US healthcare system. Compared with the indinavir-containing regimen, survival was increased by 11% (absolute difference) and cumulative costs were reduced by $US10,326 per patient (1998 discounted costs) at 5 years after starting treatment with efavirenz-based therapy. The Canadian analysis was conducted from the perspective of the Ontario healthcare system. This study did not consider differences in clinical efficacy between treatment groups, costs of study medication or outcomes beyond 1 year--all factors that would have favoured the efavirenz-based regimen. Of the 2 treatment options, the efavirenz-based regimen was associated with 7.4% lower average annual medical care costs, primarily because of greater costs associated with adverse clinical events with the indinavir-based regimen. In conclusion, current treatment guidelines for HIV infection recognise efavirenz-based combination regimens as a first-line treatment option. A pivotal comparative clinical trial (DMP 266-006) showed a significantly greater virological response to efavirenz- than indinavir-based triple combination therapy, and the efavirenz-based regimen was better tolerated. These clinical data are supported by pharmacoeconomic analyses conducted in the US and Canada, both of which showed lower medical care costs with the efavirenz-based regimen. The US analysis also predicted long term health benefits, such as improved survival, with efavirenz- versus indinavir-based triple combination therapy. These results must be weighed against the inherent difficulties of predicting long term treatment failure rates from short term data, and the limited number of pharmacoeconomic analyses conducted with efavirenz to date.
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PMID:Efavirenz: a pharmacoeconomic review of its use in HIV infection. 1138 58

An HIV-positive patient presented with pulmonary tuberculosis as her AIDS-defining diagnosis in 1993 and was effectively treated with 12 months of standard antituberculosis medications (isoniazide, rifampin, and pyrazinamide for 2 months). She received zidovudine for 6 weeks at the time of her diagnosis; however, because of patient preference, she has not received subsequent standard HIV medications (7 years). Her CD4 count at the time of diagnosis (1993) was 297/microL. Monthly passive immunotherapy was administered (fresh frozen plasma from HIV-negative blood donors with a significant titer for the anti-vasoactive intestinal peptide [VIP]/NTM antibody) from December 1993 to June 1994. Her CD4 count increased to > 400/microL during the passive immunotherapy and has remained stable for the past 6 years. The rational for the use of anti-VIP/NTM antibodies preparations in HIV, the possible mode of action of anti-VIP/NTM antibodies, the use of Ig preparations, and the role of exercise as a natural source of anti-VIP/NTM antibodies are discussed. This case report supports the potential therapeutic use of anti-VIP antibodies for treatment of HIV disease.
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PMID:The role of passive immunization in hiv-positive patients : a case report. 1150 75

Virtually all the compounds that are currently used, or under advanced clinical trial, for the treatment of HIV infections, belong to one of the following classes: (i) nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs): i.e., zidovudine (AZT), didanosine (ddI), zalcitabine (ddC), stavudine (d4T), lamivudine (3TC), abacavir (ABC), emtricitabine [(-)FTC], tenofovir (PMPA) disoproxil fumarate; (ii) non-nucleoside reverse transcriptase inhibitors (NNRTIs): i.e., nevirapine, delavirdine, efavirenz, emivirine (MKC-442); and (iii) protease inhibitors (PIs): i.e., saquinavir, ritonavir, indinavir, nelfinavir, amprenavir, and lopinavir. In addition to the reverse transcriptase and protease step, various other events in the HIV replicative cycle are potential targets for chemotherapeutic intervention: (i) viral adsorption, through binding to the viral envelope glycoprotein gp120 (polysulfates, polysulfonates, polyoxometalates, zintevir, negatively charged albumins, cosalane analogues); (ii) viral entry, through blockade of the viral coreceptors CXCR4 and CCR5 [bicyclams (i.e. AMD3100), polyphemusins (T22), TAK-779, MIP-1 alpha LD78 beta isoform]; (iii) virus-cell fusion, through binding to the viral glycoprotein gp41 [T-20 (DP-178), T-1249 (DP-107), siamycins, betulinic acid derivatives]; (iv) viral assembly and disassembly, through NCp7 zinc finger-targeted agents [2,2'-dithiobisbenzamides (DIBAs), azadicarbonamide (ADA) and NCp7 peptide mimics]; (v) proviral DNA integration, through integrase inhibitors such as L-chicoric acid and diketo acids (i.e. L-731,988); (vi) viral mRNA transcription, through inhibitors of the transcription (transactivation) process (fluoroquinolone K-12, Streptomyces product EM2487, temacrazine, CGP64222). Also, in recent years new NRTIs, NNRTIs and PIs have been developed that possess respectively improved metabolic characteristics (i.e. phosphoramidate and cyclosaligenyl pronucleotides of d4T), or increased activity against NNRTI-resistant HIV strains [second generation NNRTIs, such as capravirine and the novel quinoxaline, quinazolinone, phenylethylthiazolylthiourea (PETT) and emivirine (MKC-442) analogues], or, as in the case of PIs, a different, non-peptidic scaffold [i.e. cyclic urea (DMP 450), 4-hydroxy-2-pyrone (tipranavir)]. Given the multitude of molecular targets with which anti-HIV agents can interact, one should be cautious in extrapolating from cell-free enzymatic assays to the mode of action of these agents in intact cells. A number of compounds (i.e. zintevir and L-chicoric acid, on the one hand; and CGP64222 on the other hand) have recently been found to interact with virus-cell binding and viral entry in contrast to their proposed modes of action targeted at the integrase and transactivation process, respectively.
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PMID:New developments in anti-HIV chemotherapy. 1156 82

Protease inhibitors block the protease enzyme of HIV-1. When new viral particles break off from an infected cell, protease cuts long protein strands into the parts needed to assemble a mature virus. When protease is blocked, the new viral particles cannot mature. Protease inhibitors being tested in humans include Atazanavir, GW433908, L-756,423, Mozenavir(DMP-450), Tipranavir and more. Several firms are trying to develop a new type of protease inhibitor that will be the more favorable pharmacokinetic and resistance profiles compared with currently available drugs. We cannot expect that every one of the drugs listed in this paper will be successfully developed. However, it is likely that significant clinical advancements can be made with those that are proven to be active and safe for patients in need.
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PMID:[New HIV-1 protease inhibitors in development]. 1196 88

A great deal of study has gone into the assessment of the epidemiology of NTM infection and disease in many different parts of the world. Review of the available studies provides insight into the frequency of this clinical problem as well as important limitations in current data. Study methods have varied greatly, undoubtedly leading to differing biases. In general, reported rates of infection and disease are likely underestimates, with the former probably less accurate than the latter, given that people without significant symptoms are not likely to have intensive investigations to detect infection. Pulmonary NTM is a problem with differing rates in various parts of the world. North American rates of infection and disease have been reported to range from approximately 1-15 per 100,000 and 0.1-2 per 100,000, respectively (see Table 1). Rates have been observed to increase with coincident decreases in TB. MAC has been reported most commonly, followed by rapid growers and M kansasii. Generally similar rates have been reported in European studies, with the exception of extremely high rates in an area of the Czech Republic where mining is the dominant industry (see Table 2). These studies have also shown marked geographic variability in prevalence. The only available population-based studies have been in South Africa and report extremely high rates of infection, three orders of magnitude greater than studies from other parts of the world (see Table 3). This undoubtedly reflects the select population with an extremely high rate of TB and resultant bronchiectasis leading to NTM infection. Rates in Japan and Australia were similar to those reported in Europe and North America and also show significant increases over time (see Table 3). Specific risk factors have been identified in several studies. CF and HIV, mentioned above, are two important high-risk groups. Other important factors include underlying chronic lung disease, work in the mining industry, warm climate, advancing age, and male sex. Aside from HIV and CF, mining with associated high rates of pneumoconiosis and previous TB may be the most important historically, reported in studies worldwide [63]. A recurring observation is the increase in rates of infection and disease. The reason for this is unclear but may be caused by any of several contributing factors. The possibility exists that the apparent increase is either spurious or less significant than studies would suggest. Changes in clinician awareness leading to increased investigations, or laboratory methods leading to isolation and identification of previously unnoticed organisms, could play a role in this trend, and studies have been published that support [67] and refute [31] this argument. We believe such factors may contribute to but do not explain the significant increases that have been observed. A true increase could be related to the host, the pathogen, or some interaction between the two. Host changes leading to increased susceptibility could play an important role, with increased numbers of patients with inadequate defenses from diseases such as HIV infection, malignancy, or simply advanced age [31]. An increase in susceptibility could also relate to the decrease in infection with two other mycobacteria. It has been speculated that infection with TB [29,38] and Bacillus Calmette-Guerin (BCG) [19,68] may provide cross-immunity protecting against NTM infection. Many investigations have observed decreasing rates of TB concomitant with the increases in NTM. In addition, studies from Sweden [68] and the Czech Republic [19] have found that children who were not vaccinated with BCG had a far higher rate of extrapulmonary NTM infection. Potential changes in the pathogens include increases in NTM virulence, and it has been argued that this should be considered as a possible contributing factor [69]. Finally, an interaction between the host and pathogen could involve a major increase in pathogen exposure or potential inoculum size. This may be occurring secondary to the increase in popularity of showering as a form of bathing [66], a habit that greatly increases respiratory exposure to water contaminants. Several limitations of our review should be noted. We reviewed English-language reports and abstracts, probably leading to fewer data from non-English speaking regions, which may explain the paucity of studies from Africa, Eastern Europe, and most Asian nations. The heterogeneity of study methods in identifying cases and the lack of a uniformly applied definition of disease makes it difficult to compare rates between studies. Finally, the lack of systematic reporting of NTM infection in most nations limits the ability to derive accurate estimates of infection and disease. Regardless, there are more than adequate data to conclude that NTM disease rates vary widely depending on population and geographic location. NTM disease is clearly a major problem in certain groups, including patients with underlying lung disease and also in individuals with impaired immunity. The rates of NTM infection and disease are increasing, so the problem will likely continue to grow and become a far more important issue than current rates suggest.
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PMID:Epidemiology of human pulmonary infection with nontuberculous mycobacteria. 1237 Sep 92

The reduction in disseminated NTM infections caused by HAART is one of the success stories in the history of HIV in the developed world. Despite this success, these diseases still occur and may have atypical presentations in patients receiving HAART. Clinicians treating HIV-infected patients must remain familiar with the diagnosis and treatment of these diseases and implement prevention strategies when indicated.
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PMID:Nontuberculous mycobacteria in the HIV infected patient. 1237 Oct 2

HIV is a major health problem in Thailand. These patients are vulnerable to opportunistic infections, especially Mycobacterium tuberculosis and MAC infection. However, NTM was considered a rare disease in Thailand before the AIDS era. In this study, there were 38 HIV seropositive patients with NTM (other than MAC) identified from clinical specimens during the 3 year period 1998-2000 at Siriraj Hospital, which has a higher prevalence than the previous report. Among these patients, 29 cases were likely to have had definite infection from NTM, 5 cases possibly had NTM as a pathogen, and 4 cases had NTM as colonization. The most common site of infection was the lung (87%) and most common symptoms were cough (62.2%), fever (34.2%), weight loss (42.1%), and lymphadenopathy (5.3%). The outcome was poor because many NTM are not susceptible to standard medication for tuberculosis which is the empirical treatment for the majority of HIV seropositive patients with a clinical finding suspected of mycobacterial infection. The fatality rate was as high as 58.6 per cent. Awareness of NTM as a potential pathogen in HIV seropositive patientsand adjustment of medications even before the availability of culture results may improve the outcome of treatment of NTM infection in HIV seropositive patients.
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PMID:Infection due to nontuberculous Mycobacterium other than MAC in AIDS patients at Siriraj hospital during 1998-2000: saprophyte vs pathogen. 1240 9

[reaction: see text] The utility of functionalized 1,4-diamines, produced via a temporary phosphorus tether (P-tether)/ring-closing metathesis (RCM)/hydrolysis sequence, is demonstrated in the synthesis of structurally diverse DMP 323 analogues. These 1,4-diamines are transformed into various seven-membered heterocycles via insertion of the appropriate nuclei "X". Subsequent derivatization generates heterocyclic diols that are similar in structure to DMP 323, a notable member of a class of highly potent inhibitors of HIV protease.
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PMID:A concise route to structurally diverse DMP 323 analogues via highly functionalized 1,4-diamines. 1248 58


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