Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

During 27 months treatment with 400 mg didanosine and 80 mg stavudine daily but no protease inhibitor therapy, a 50-y-old HIV-positive woman gradually lost 13 kg in weight, her arms, legs and buttocks decreased in volume and she experienced fatigue and polyneuropathy. Laboratory tests showed slight increases in plasma lactate and liver enzyme levels. Eighteen months after withdrawal of antiretroviral drug, the patient was free of fatigue and polyneuropathy and had regained 7 kg in weight as well as most of the volume of her arms, legs and buttocks.
 ...
PMID:Clinical and laboratory signs of mitochondrial dysfunction secondary to nucleoside analogue antiretroviral therapy are reversible. 1151 73

The difference between adherence to non- nucleoside reverse transcriptase inhibitor (NNRTI) and protease inhibitor (PI)-based regimens was investigated. Better adherence was found in NNRTI-treated patients, especially when efavirenz was included in the regimen, compared with single PI-treated patients and in those with CD4 cell counts less than 200 x 10(6)/l. By contrast, younger age, self-report of active drug use, fatigue or vomiting negatively affected adherence. Self-reported sexual dysfunction was significantly associated with non-adherence only in PI-treated individuals.
 ...
PMID:Adherence to highly active antiretroviral therapy is better in patients receiving non-nucleoside reverse transcriptase inhibitor-containing regimens than in those receiving protease inhibitor-containing regimens. 1270 Apr 67

Antiretroviral agents may participate in drug interactions that influence the efficacy and toxicity of other antiretrovirals, as well as pharmacologic treatments of coincident or complicating diseases. The viral protease inhibitor, ritonavir, may cause drug interactions by inhibiting the activity of cytochrome P450-3A (CYP3A) isoforms. In a single-dose, blinded, four-way crossover study, 10 healthy volunteer subjects received 50 mg of trazodone hydrochloride or matching placebo concurrent with low-dose ritonavir (four doses of 200 mg each) or with placebo. Compared to the control condition, ritonavir significantly reduced apparent oral clearance of trazodone (155 +/- 23 vs. 75 +/- 12 ml/min, p < 0.001), prolonged elimination half-life (6.7 +/- 0.7 vs. 14.9 +/- 3.9 h, p < 0.05), and increased peak plasma concentrations (842 +/- 64 vs. 1125 +/- 111 ng/ml, p < 0.05) (mean +/- SE). Coadministration of trazodone with ritonavir increased sedation, fatigue, and performance impairment compared to trazodone plus placebo; differences reached significance only for the digitsymbol substitution test. Three subjects experienced nausea, dizziness, or hypotension when trazodone was given with ritonavir; 1 of these subjects also experienced syncope. Thus short-term low-dose administration of ritonavir impairs oral clearance of trazodone and increases the occurrence of adverse reactions. The findings are consistent with impairment of CYP3A-mediated trazodone metabolism by ritonavir.
 ...
PMID:Short-term exposure to low-dose ritonavir impairs clearance and enhances adverse effects of trazodone. 1272 62

The triple combination tablet containing lamivudine (150 mg), zidovudine (300 mg) and abacavir (300 mg, as abacavir sulfate) is a new formulation of three nucleoside analogue reverse transcriptase inhibitors. Two studies in treatment-naive patients (one double-blind, one nonblind) have reported that lamivudine/zidovudine (dual combination tablet) plus abacavir showed efficacy similar to that of lamivudine/zidovudine plus indinavir. In both studies, similar numbers of patients in each treatment group had plasma HIV RNA levels </=400 copies/mL at week 48 (51% vs 51% and 64% vs 50%). In treatment-experienced patients with baseline plasma HIV RNA levels <50 copies/mL, switching to lamivudine/zidovudine/abacavir (triple combination tablet) was as effective as remaining on highly active antiretroviral treatment (mainly protease inhibitor [PI]-based). Virological failure, the primary endpoint, defined as two consecutive plasma HIV RNA values >400 copies/mL, was reported in 22% of patients in both treatment groups at week 48. Treatment-naive patients receiving lamivudine/zidovudine/abacavir combination therapy experienced several adverse events, including nausea, malaise/fatigue and vomiting.
 ...
PMID:Lamivudine/zidovudine/abacavir: triple combination tablet. 1274 41

Enfuvirtide is a novel antiretroviral that blocks HIV-1 cell fusion and viral entry. This Phase II, controlled, open-label, randomized, multicentre dose-ranging trial explored the safety, antiviral activity and pharmacokinetics of enfuvirtide, administered by subcutaneous (s.c.) injection, in 71 HIV-1-infected, protease inhibitor-experienced, non-nucleoside reverse transcriptase inhibitor (NNRTI)-naive adults for 48 weeks. Study participants were randomized to receive enfuvirtide at a deliverable dose of 45, 67.5 or 90 mg twice daily; the 45 mg twice daily dose required 2 injections/day, while the higher doses required 4 injections/day. A background oral antiretroviral (ARV) regimen of abacavir (300 mg twice daily), amprenavir (1200 mg twice daily), ritonavir (200 mg twice daily) and efavirenz (600 mg once daily) was provided with enfuvirtide. A control group received the background ARV regimen alone. All potential participants underwent an HIV genotype at screen to ensure a homogenous population and to exclude patients with evidence of genotypic resistance to NNRTIs. Overall, the tolerability of the combination of abacavir, amprenavir, ritonavir, efavirenz and enfuvirtide was generally comparable to control through 48 weeks. No enfuvirtide dose-dependent adverse events (AEs) were observed across treatment groups. Injection site reactions (ISRs) occurred at least once in 68.5% of the enfuvirtide-treated population, and most ISRs were mild to moderate in severity, with no apparent dose relationship. Excluding ISRs, the most common treatment-emergent AEs were nausea, diarrhoea, dizziness and fatigue; with no clinically significant differences in the incidence of AEs observed between the control and enfuvirtide groups. Each treatment group benefited from ARV therapy, with a trend of increasing antiviral and immunological activity associated with increasing enfuvirtide dose. At 48 weeks, the median HIV-1 RNA change from baseline for the ITT population was -2.24 log10 copies/ml for the combined enfuvirtide groups compared with -1.87 log10 copies/ml for the control group. In addition, 54.9% of patients in the enfuvirtide group achieved HIV-1 RNA < or = 400 copies/ml versus 36.8% of patients in the control group. These results indicate that enfuvirtide has a favourable safety profile and is a promising new antiviral agent for HIV-infected patients who have been on previously failing ARV regimens.
 ...
PMID:A controlled Phase II trial assessing three doses of enfuvirtide (T-20) in combination with abacavir, amprenavir, ritonavir and efavirenz in non-nucleoside reverse transcriptase inhibitor-naive HIV-infected adults. 1451 96

With the advent of potent combination antiretroviral therapy (ART), there has been a reduction in the incidence of wasting. However, few studies have investigated specific body composition changes associated with these treatments. This study aimed to investigate longitudinally the association of increasingly potent ART with changes in body cell mass and wasting utilizing bioelectric impedance analysis (BIA). In this longitudinal cohort study, 159 HIV-positive men were assessed semiannually from 1995 to 1997 for body composition utilizing BIA, CD4 lymphocyte count, HIV viral load, medical and depressive symptoms. Wasting was defined as body cell mass/height below the 90th percentile based on HIV positive norms. ART potency at each visit was scored utilizing published clinical guidelines, ranging from 1 (0-1 antiretrovirals) to 5 (3 or more antiretrovirals including a potent protease inhibitor). Viral resistance testing was not used. The mixed-effects model and the generalized estimating equations approaches were used to determine longitudinal correlates of body cell mass and of wasting, respectively. Over the 2 years of follow-up, potent combination ART use increased from 6% to 79%. Concurrently, a significant increase in mean body cell mass and a reduction in prevalence of wasting were seen, while total body weight, fat mass, and total body water did not change. Increasingly potent ART was associated with significant increases in body cell mass and reduction in wasting. Other significant correlates of increased body cell mass included higher CD4 count and decreased severity of HIV-related symptoms, fatigue and depression. The current study found that higher potency ART taken for relatively short term (2 years) was associated with an increase in body cell mass and a reduction in wasting and that these changes were associated with both medical (CD4, HIV symptoms) and behavioral (fatigue, depression) improvements. One caveat is this study did not distinguish among types of potent ART regimens. Given only some antiretrovirals appear linked to many body composition changes, regardless of their effect on viral load, it may be the type of regimen used that accounted for the relationship seen between viral load and body composition changes.
 ...
PMID:Increase in body cell mass and decrease in wasting are associated with increasing potency of antiretroviral therapy for HIV infection. 1585 93

(1) The current first-line treatment for HIV infection is a combination of at least two nucleoside (or nucleotide) inhibitors of HIV reverse transcriptase, and one non nucleoside inhibitor or at least one HIV protease inhibitor. (2) Emtricitabine is the eighth nucleoside/nucleotide inhibitor to be marketed in France. It has a similar chemical structure to lamivudine. (3) Evaluation of emtricitabine use in adults contains data from four comparative trials, two in treatment-naive patients and two in patients who were already receiving a virologically effective treatment. Emtricitabine combination therapy was no more effective than lamivudine combination therapy on either viral load or the CD4+ lymphocyte count. (4) Only non comparative trials are available in children. (5) In clinical trials, the adverse effects of emtricitabine were similar to those of lamivudine, including headache, pain, fatigue, fever, abdominal pain, nausea, vomiting, and diarrhea. (6) Viral strains resistant to emtricitabine are also resistant to lamivudine, and vice versa. (7) Emtricitabine, like other nucleoside inhibitors (lamivudine, didanosine, tenofovir), can be taken once a day by mouth. (8) In practice, emtricitabine is indistinguishable from lamivudine and does not offer any advance for patients living with HIV/AIDS.
 ...
PMID:Emtricitabine: new preparation. An antiretroviral very similar to lamivudine. 1587 41

The efficacy, safety, and pharmacokinetics of three doses of tipranavir/ritonavir (TPV/r) in highly treatment-experienced human immunodeficiency virus (HIV)-1-infected patients with protease inhibitor (PI)-resistant isolates were evaluated. A 24-week multicenter, double-blind, randomized, dose-finding trial was conducted. All patients were three-drug class experienced and had taken at least two PI-based regimens. All had at least one primary PI mutation and had plasma HIV-RNA > 1000 copies/ml. Patients remained on their background non-PI antiretroviral medications for the first 14 days. After this 14-day period of functional TPV/r monotherapy, the background antiretroviral medications were optimized based on treatment history and the screening genotype. A total of 216 patients were randomized. All groups [TPV/r 500 mg/100 mg (n = 73), 500 mg/200 mg (n = 72), and 750 mg/200 mg (n = 71) twice daily] achieved an approximate 1 log10 reduction in the median HIV-RNA at week 2. A significant reduction was sustained through 24 weeks in the TPV/r 500 mg/200 mg and 750 mg/200 mg groups. The 500 mg/200 mg dose achieved optimal median TPV trough concentrations and lower interpatient variability. The most frequently reported adverse events (AEs) were diarrhea, nausea, vomiting, fatigue, and headache. The TPV/r 750 mg/200 mg group had the highest rate of grade 3 or 4 laboratory abnormalities and study discontinuations due to AEs. All doses of TPV/r tested in this study were associated with HIV-1 viral load reductions through 24 weeks. The 500 mg/200 mg dose achieved the best efficacy, safety, and pharmacokinetic profile in this highly treatment-experienced population and was selected for the pivotal phase 3 studies.
 ...
PMID:Efficacy and safety of three doses of tipranavir boosted with ritonavir in treatment-experienced HIV type-1 infected patients. 1726 50

A 14-year-old female with perinatally acquired HIV on boosted protease inhibitor (PI) therapy with atazanavir and ritonavir rapidly developed cushingoid features with excessive weight gain and moon facies within 2 weeks of receiving inhaled fluticasone/salmeterol for asthma treatment. Soon after discontinuing PIs and inhaled steroid, she required hospitalization for dyspnea, headache, muscle weakness, and extreme fatigue requiring hydrocortisone replacement therapy for presumed adrenal insufficiency. Cushing syndrome and adrenal suppression were very likely caused by elevated steroid systemic concentrations resulting from the cytochrome p450 interaction between the protease inhibitors and fluticasone. The Naranjo probability scale score of 5 suggests that the event was probably drug related. This is the first case report of fluticasone and PI-induced Cushing syndrome and adrenal suppression in a pediatric patient without a history of recent or concomitant treatment with systemic steroid therapy. Additionally, this case is unique as it is the most rapid (<2 weeks) presentation documented, thus far. Health care professionals should be conscious of this important drug-drug interaction in HIV-infected children and adolescents and be aware that rapid onset of hypercortisolism and adrenal suppression are possible.
 ...
PMID:Cushing syndrome and severe adrenal suppression caused by fluticasone and protease inhibitor combination in an HIV-infected adolescent. 1759 45

The incidence of acute promyelocytic leukemia (APL) in patients with HIV is exceedingly rare, making the establishment of therapeutic approaches challenging and often individualized. We report the case of a 43-year-old female who presented with fatigue and malaise, and was concurrently diagnosed with APL and HIV. Induction and consolidation with all-trans-retinoic acid (ATRA), idarubicin, and mitoxantrone were initiated in conjunction with highly active anti-retroviral therapy (HAART) consisting of tenofovir/emtricitabine, fosamprenavir, and raltegravir. A complete morphologic, cytogenetic, and molecular response was achieved post-induction. Therapeutic strategies should consider overlapping effects of current agents in targeting both pathologies. ATRA has been found to induce apoptosis in HIV-infected leukemic cells, and protease inhibitor therapy has furthermore been reported to be synergistic with ATRA in inducing differentiation of APL cell lines. Pending further investigation, regimens with protease inhibitor backbones may represent a viable first-line strategy for patients elected to receive HAART in addition to ATRA and standard chemotherapy.
 ...
PMID:Acute promyelocytic leukemia in HIV-infected adults: a case report and review of therapeutic considerations. 2185 51


<< Previous 1 2 3 4 Next >>