Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The frequency of drug-resistant human immunodeficiency virus type 1 (HIV-1) variants in virus populations not previously exposed to drug was determined in vitro by using HIV-1RF and the protease inhibitor SC-55389A. Two variants with single mutations responsible for drug resistance (V82A and N88S) were quantifiably isolated after only one round of replication, yielding a crude frequency estimate of at least 1 SC-55389A-resistant variant per 3.5 x 10(5) wild-type infectious units.
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PMID:Estimate of the frequency of human immunodeficiency virus type 1 protease inhibitor resistance within unselected virus populations in vitro. 952 15

Inhibiting human immunodeficiency virus (HIV) replication with potent antiretroviral therapy may result in improved immune function, and this may lead to favorable outcomes, independent of changes in CD4+ lymphocyte count. The effect of combination protease inhibitor therapy (ritonavir plus saquinavir) on functional measures of cell-mediated immunity in 41 HIV-infected patients from one center of a multicenter trial was investigated. After 24 weeks, median plasma virus load decreased from 4.74 log10 copies/mL to below the detection limit of the assay (2.30 log10), and mean CD4+ lymphocyte count increased from 284 cells/microL to 413 cells/microL. Proliferative responses to phytohemagglutinin developed in 21 of 34 patients in whom responses were absent at baseline. Increases were observed in interleukin-2, -12, and -10 production and in the expression of CD28 on CD8+ lymphocytes. Initiation of potent anti-HIV therapy results in a degree of immune restoration, suggesting that HIV-induced immune suppression is a dynamic and potentially reversible process.
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PMID:Improvement in cell-mediated immune function during potent anti-human immunodeficiency virus therapy with ritonavir plus saquinavir. 953 61

RANTES has been found to suppress human immunodeficiency virus type 1 (HIV-1) replication. To further elucidate the role of this chemokine in HIV-1 infection, RANTES levels were analyzed in serum and platelet-free plasma (PFP) in 53 HIV-1-infected patients and 20 controls. RANTES levels were significantly elevated in both serum and PFP in all clinical stages of HIV-1 infection, with the highest levels in CDC groups A and B. In longitudinal testing, the progressors were characterized by a pronounced decline in serum levels over time; the nonprogressors, however, had only a slight reduction or an increase in RANTES levels. During 16 weeks of indinavir therapy, there was an increase in circulating RANTES levels and enhanced release of RANTES from stimulated CD8+ lymphocytes. The decline in RANTES levels along with disease progression is compatible with RANTES having a beneficial role in HIV-1-infected patients. The increase in RANTES levels during protease inhibitor-containing regimens may represent a previously unrecognized immunologic effect of such therapy.
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PMID:Circulating levels of RANTES in human immunodeficiency virus type 1 infection: effect of potent antiretroviral therapy. 953 90

Ten subjects received 600 to 1,200 mg of the human immunodeficiency virus type 1 (HIV-1) protease inhibitor ritonavir per day. Following 2 weeks of therapy, plasma HIV RNA levels decreased by a mean of 1. 57 (range, 0.89 to 1.96) log units. With continued therapy, HIV RNA levels began to rise in eight subjects. The initial rise in plasma RNA levels was temporally associated with the development and quantitative increase in the V82 resistance mutation. Doubling times of the V82A mutant virus were estimated to be 2.4 to 4.8 days. An L63P/A mutation was commonly present at baseline even in subjects with a durable virologic response. The concomitant acquisition of an L63P/A mutation with the V82A/F mutation at the time when plasma RNA levels rebounded suggests a role for the L63P/A mutation in improving the fitness of the V82A/F mutation. Subsequent additional genotypic changes at codons 54 and 84 were often associated with further increases in plasma RNA levels. Ongoing viral replication in the presence of drugs resulted in the appearance of additional genotypic changes, including the L90M saquinavir resistance mutation, and decreased phenotypic susceptibility. The relative fitness of the protease V82A ritonavir resistance mutation and reverse transcriptase T215Y/F zidovudine resistance mutation following drug withdrawal were estimated to be 96 to 98% that of the wild type. Durability of the virologic response was associated with plasma RNA levels at the nadir. A virologic response beyond 60 days was not observed unless plasma HIV RNA levels were suppressed below 2,000 copies/ml, consistent with estimates from V82A doubling times for selection of a single resistance mutation to dominate the replicating population.
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PMID:Genotypic changes in human immunodeficiency virus type 1 associated with loss of suppression of plasma viral RNA levels in subjects treated with ritonavir (Norvir) monotherapy. 957 87

Kaposi's sarcoma (KS) is the most common neoplasm affecting people with the human immunodeficiency virus (HIV) infection. The skin is the most common site of disease; however, KS can also involve visceral organs such as the lungs, leading to severe morbidity and contributing to death in almost 30% of patients with the acquired immunodeficiency syndrome (AIDS). New antiretroviral strategies incorporating combination nucleoside analogues with a protease inhibitor lead to increased circulating CD4+ lymphocyte counts, decreased plasma levels of HIV, and decreased mortality from AIDS-defining opportunistic infections. The effects of highly active antiretroviral therapy (HAART) on AIDS-associated KS remain largely unknown. Herein the case of an antiretroviral-naive man with advanced AIDS (CD4+ helper T-lymphocyte count, 35/mm3; HIV viral RNA quantification, more than 800,000 copies/mL), and symptomatic pulmonary KS is described. After HAART was initiated, his CD4+ cell count increased fourfold, his HIV-viral load decreased to nondetectable levels, and the pulmonary KS regressed dramatically. To my knowledge, this report represents the first documented case of pulmonary KS regression after the initiation of HAART. Although this finding is preliminary, if confirmed by other clinicians, the effect of potent antiretrovirals on KS growth and development will have important implications on the manner in which KS is staged and treated.
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PMID:Regression of acquired immunodeficiency syndrome-related pulmonary Kaposi's sarcoma after highly active antiretroviral therapy. 958 84

The suppression of human immunodeficiency virus (HIV) replication and elevation in CD4 cells observed with protease inhibitor combination regimens known as HAART (highly active antiretroviral therapy) may allow AIDS patients to undergo an immune recovery that allows them to suppress the progression of cytomegalovirus (CMV) retinitis. Eleven AIDS patients receiving HAART with healed CMV retinitis in whom CMV-specific maintenance therapy was discontinued were studied. Median CD4 cell counts were 42 before the initiation of HAART and 183 at discontinuation of anti-CMV therapy. While a median 1.1 log10 drop in plasma HIV-1 RNA was obtained between starting HAART and withdrawal of maintenance therapy for CMV, only 3 of 11 patients maintained plasma HIV RNA below the limits of detection. Reactivation of CMV retinitis after withdrawal of anti-CMV therapy did not occur in any of the patients observed for a median of 156 days (range, 92-558).
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PMID:Lack of reactivation of cytomegalovirus (CMV) retinitis after stopping CMV maintenance therapy in AIDS patients with sustained elevations in CD4 T cells in response to highly active antiretroviral therapy. 1072 May 61

The clinical course of 37 Enterocytozoon bieneusi-infected acquired immunodeficiency syndrome patients with diarrhea was studied. Parasite clearance was seen in 15 patients (40.5%). Clearance of E. bieneusi resulted in a 25-100% reduction in episodes of diarrhea, suggesting that microsporidia are true pathogens. Univariate and multivariate proportional hazards analyses revealed that peripheral blood CD4 cell counts > or = 100/mm3, the use of two or more antiretroviral medications, and use of a protease inhibitor were statistically associated with decreased time to clearance of E. bieneusi. Specific anti-microsporidial therapy (albendazole) was not associated with parasite eradication. Factors related to immunocompetence and human immunodeficiency virus suppression appeared to be important in the clearance of E. bieneusi.
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PMID:Modification of the clinical course of intestinal microsporidiosis in acquired immunodeficiency syndrome patients by immune status and anti-human immunodeficiency virus therapy. 959 40

There is a low risk of infection with the human immunodeficiency virus (HIV) for HCW through exposure in the work place. The mean risk of infection with HIV after a percutaneous exposure is 0.3%. This risk can be considerably higher depending on various factors: for example, a deep percutaneous injury or the source patient being in an end stage of HIV infection. Despite compliance with adequate precautions, it is not always possible for HCW to avoid injuries. This fact has made intervention desirable after such exposure. Zidovudine (AZT) was available as the first effective drug for treatment of HIV infection. Also, animal experiments have shown efficacy in prophylactic use of zidovudine. Therefore, since the beginning of the 90's, there has been an increased use of postexposure prophylaxis with zidovudine for exposed HCW, and during this period of use more evidence has come up to show the efficacy of PEP. In fact, a large retrospective case-control study showed a 81% reduction of HIV transmission to exposed HCW in the zidovudine treated group after percutaneous exposure. Based upon this impressive evidence and other data which indicate the efficacy of PEP, postexposure prophylaxis has become a standard procedure in the health care setting after a significant exposure to HIV. A combination of three antiretroviral drugs, usually including a protease inhibitor, is used today. Based on our current pathogenetic understanding, PEP should be started as soon as possible after exposure to HIV. There are effective tools for preventing HIV transmission in the general population. However, these tools do not provide universal protection: rupture of condoms, needle sharing and unprotected intercourse with a HIV infected person are situations at risk of HIV transmission. In spite of a different mode of exposure when compared to the health care setting, PEP in timely application is believed to be efficacious. To date there is no controlled data to support PEP in such situations; however, PEP with a combination of antiretroviral drugs after anal, oral (with ejaculation) or vaginal intercourse and needle sharing with a HIV-positive partner is recommended for a minimum of two weeks. There are reservations in recommending PEP after unprotected sexual intercourse with a partner of unknown serostatus.
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PMID:[Post-exposure HIV prevention within and outside the hospital]. 964 26

Protease inhibitors are an important new class of agents for the treatment of human immunodeficiency virus (HIV) infection. The purpose of our trial was to determine the feasibility of combining the protease inhibitor saquinavir with a 96-hour continuous intravenous infusion of cyclophosphamide (800 mg/M2), doxorubicin (50 mg/M2, and etoposide (240 mg/M2) (CDE) plus filgrastim in patients with non-Hodgkin's lymphoma associated with HIV infection. The effect of saquinavir on CDE-induced myelosuppression, CD4 lymphopenia, and non-hematologic toxicity was also sought. Twelve patients with HIV-related lymphoma received CDE every 28 or more days. All patients received saquinavir (600mg PO TID), filgrastim and Pneumocystis carinii and fungal prophylaxis. Patients also received either stavudine (n = 2) or both stavudine and didanosine (n = 10). Toxicity was analyzed using the NCI Common Toxicity Criteria for each cycle and the data were compared with the data from our prior study of CDE plus didanosine. An interim analysis was performed after accrual of the first 12 patients in order to assess toxicity. Severe (grade 3 or 4) mucositis occurred in eight of 12 patients (67%) treated with CDE plus saquinavir compared with three of 25 patients (12%) in our prior study treated with CDE without saquinavir (P < 0.001). In logistic regression analysis, saquinavir use was the only factor associated with a significantly greater risk of severe mucositis (relative risk 7.9; P = 0.03). Saquinavir use was not associated with a significant difference in the incidence of febrile neutropenia, prolonged neutropenia, chemotherapy dose reduction, or in the degree of myelosuppression. The decrease in CD4 lymphocytes for patients treated with saquinavir (absolute decrease of 23/microL, or a 26% decrease from baseline) was significantly less than for patients treated without saquinavir in the prior study (absolute decrease of 91/microL, or 42% decrease from baseline; P = 0.05). Four of 10 patients (40%) treated with saquinavir had an increase in CD4 lymphocytes of > or = 10/microL compared with none of 25 patients (0%) treated without saquinavir (P < 0.001). Combination of the protease inhibitor saquinavir with infusional CDE in patients with HIV-associated lymphoma was associated with a significant increase in the incidence of severe mucositis. This finding suggests that saquinavir may alter the metabolism of one of more of the cytotoxic agents in the CDE regimen, and underscores the need for careful investigation regarding the use of the protease inhibitors in patients receiving chemotherapy.
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PMID:Saquinavir enhances the mucosal toxicity of infusional cyclophosphamide, doxorubicin, and etoposide in patients with HIV-associated non-Hodgkin's lymphoma. 964 31

In HIV/AIDS illness the reverse transcriptase and protease enzymes of human immunodeficiency virus (HIV) are currently the agents of antiretroviral therapy. Nucleoside analogues were the first group of drugs which exerted antiviral activity in humans. More recently protease inhibitors have provided new approaches in the treatment of HIV-infection and AIDS. Impressive clinical results have been obtained with combined therapies of three antiretroviral drugs, including one protease inhibitor. It is worth to mention that apart from the above, many new compounds are under development, including the vaccine against HIV.
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PMID:[HIV protease inhibitors (new possibilities in the treatment of HIV infection and AIDS)]. 965 65


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