Progress in HIV-1 therapy continues on upward track.
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Anti-HIV Agents↗
Biomedical subjects
J Montaner
Publications and source records attributed to J Montaner.
Mycobacterial lymphadenitis associated with the initiation of combination antiretroviral therapy.
OBJECTIVE: To characterize the impact of combination antiretroviral therapy on the clinical and laboratory features of mycobacterial lymphadenitis, we conducted a retrospective chart review of HIV-related mycobacterial lymphadenitis at St. Paul's hospital between 1989 and 1997. Among 52 evaluable patients, 12 presented within 12 weeks of initiating combination antiretroviral therapy (group 1, n = 12); the others developed lesions while receiving no antiretrovirals, monotherapy, or a stable combination regimen of >12 weeks duration (group 2, n = 40). RESULTS: Group 1 patients had higher absolute CD4 lymphocyte counts (median, 150 versus 20 cells/mm3, respectively; p = .001) and hemoglobin levels (median, 113 versus 88 g/L, respectively; p = .002) at the time of mycobacterial diagnosis. Clinical comparison showed that group 1 patients were more likely to develop a draining sinus (50% versus 0%; p < .001), but less often to have weight loss (17% versus 74%; p < .0001) or disease which was disseminated (25% versus 70%; p = .04) or caused by Mycobacterium tuberculosis (0% versus 33%; p = .04). CONCLUSIONS: Mycobacterial lymphadenitis developing within 12 weeks of initiating combination antiretroviral therapy is often localized Mycobacterium avium complex disease, associated with a relatively high CD4 count. The clinical course is often complicated by the development of a draining sinus. The close temporal association suggests that such treatment may unmask subclinical infection by enhancing the immune response to mycobacterial antigens.
AIDS-Related Opportunistic Infections↗
Atovaquone suspension compared with aerosolized pentamidine for prevention of Pneumocystis carinii pneumonia in human immunodeficiency virus-infected subjects intolerant of trimethoprim or sulfonamides.
Atovaquone suspensions (750 mg and 1500 mg once a day) were compared with aerosolized pentamidine (300 mg once a month) for the prevention of Pneumocystis carinii pneumonia (PCP) in subjects with human immunodeficiency virus (HIV) infection who were intolerant to trimethoprim or sulfonamides (or both). Median time using the assigned therapy was 6.6 months, and the median follow-up was 11.3 months. Intent-to-treat analyses (n=549) showed no statistically significant differences among subjects with regard to the incidence of PCP (26%, 22%, and 17%, respectively) or mortality (20%, 13%, and 18%, respectively). The incidence of treatment-limiting adverse events with atovaquone was significantly higher (P<.01). There was, however, no significant difference in the time using therapy. Incidences of PCP and death were higher in subjects receiving 750 mg of atovaquone than in subjects receiving 1500 mg. Atovaquone suspension at 1500 mg once a day has an efficacy similar to that of aerosolized pentamidine for prevention of PCP in HIV-infected subjects and is a safe, effective alternative in those who are intolerant to trimethoprim or sulfonamides.
AIDS-Related Opportunistic Infections↗
Impaired cerebrovascular reactivity as a risk marker for first-ever lacunar infarction: A case-control study.
BACKGROUND AND PURPOSE: Functional assessment of small arteries and arterioles could provide valuable information regarding the extent of diffuse arteriolosclerosis in patients with small-vessel disease. Therefore we attempted to clarify the role of cerebrovascular reactivity (CVR) as a risk marker for first-ever symptomatic lacunar infarction. METHODS: Forty-six patients with lacunar infarction and 46 sex- and age-matched control subjects were prospectively evaluated. Cerebral hemodynamics were studied with transcranial Doppler ultrasonography. CVR was examined by calculating the percent increase in mean flow velocity occurring after 15 mg/kg acetazolamide administration (Diamox test). RESULTS: CVR was significantly (P<0.0001, Student's t test) lower in cases (50.0+/-12. 7%) as compared with control subjects (65.2+/-12.4%). A multiple logistic regression analysis identified male sex (odds ratio [OR] 2. 3, P=0.02), age (OR 3.6, P<0.005), and the presence of lacunar infarction on magnetic resonance imaging (OR 5.3, P<0.001) as significant and independent factors associated with a reduction of CVR. Moreover, a cut-point of 55.6% (sensitivity 67%, specificity 82%) was established as the threshold value for distinguishing between pathological and normal CVR. CVR was significantly (P=0.02) lower in patients with multiple (46.38+/-12.6%) than with single (54. 83+/-11.58%) lacunar infarction. In addition, a trend of negative correlation was found between CVR and the number of lacunar infarctions (r=-0.26, P=0.08). In the multiple logistic model, history of hypertension (OR 7.24; 95% confidence interval 2.95 to 17. 79) and CVR (OR 0.8; 95% confidence interval 0.81 to 0.93) emerge as significant and independent predictors of first-ever lacunar infarction. CONCLUSIONS: These data suggest that impaired CVR is a risk marker for first-ever lacunar infarction.
Acetazolamide↗
An evaluation of the cost effectiveness of adding lamivudine to zidovudine-containing regimens in HIV infection. Canadian perspective.
BACKGROUND: A prospective cost-effectiveness analysis undertaken as part of the CAESAR (Canada, Australia, Europe, South Africa) placebo-controlled clinical trial showed that the addition of lamivudine to zidovudine-containing regimens for 1 year reduced progression of HIV infection to AIDS or death, as well as significantly reducing the number of hospitalisations, outpatient visits and the requirement for medications for HIV-related illness and adverse events. Data from all 1840 patients included in the 'intent-to-treat' population of the CAESAR trial were used for the present analysis. A Canadian third-party payer perspective was adopted, and all costs were adjusted to 1997 prices. RESULTS: The savings associated with reduced healthcare resource use in the CAESAR study were estimated to be 1123 Canadian dollars ($Can) per patient, over the year. These savings partly offset the cost of lamivudine. The analysis showed that the addition of lamivudine to zidovudine-containing regimens resulted in an incremental cost-effectiveness ratio of $Can 14,225 [95% confidence interval (CI): $Can4383 to $Can29,577] for progression to AIDS/death avoided and of $Can5631 (95%CI: $Can2010 to $Can12,929) for HIV-related illness avoided. CONCLUSIONS: Our findings indicate that treatments that slow the progression of HIV infection to AIDS or death have the potential to facilitate healthcare savings, which partly offset the drug acquisition costs. The results also demonstrate that it is possible to undertake economic evaluations in parallel with a major clinical end-point study.
Adult↗
Use of incentives to increase compliance for TB screening in a population of intravenous drug users. Vancouver Injection Drug Use Study Group.
SETTING: Intravenous drug users (IDUs) represent a high risk group for dual human immunodeficiency virus (HIV) and tuberculosis (TB) infection. Screening with TB skin testing has therefore been suggested in this group. Subjects' compliance for returning to have TB skin test results read is a major problem. In the setting of a needle exchange program we evaluated the role of financial incentives to increase compliance. METHODS: We evaluated the role of giving a small financial incentive of Can $5 to subjects if they returned to have their purified protein derivative (PPD) skin test read. IDUs who had previously been skin-tested were compared with IDUs drawn from a similar population who, prospectively, were offered a financial incentive. RESULTS: During the initial period 558 subjects were evaluated and no incentive was offered. During the second phase of the study 549 IDUs were assessed but were also offered Can $5 if they returned to have their skin test read. Use of incentives increased compliance from 43% to 78% (P = 0.001). During the same period three active cases of TB were also diagnosed. CONCLUSIONS: We suggest that use of financial incentives can increase the return of IDUs to have their skin tests read. Further studies are required to assess the efficacy of follow-up interventions, especially the use of isoniazid chemoprophylaxis.
Adult↗
[Electrocution: neurological complications].
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Aged↗
[Neuroimaging in cerebral ischemia].
A critical review about different neuroimaging techniques and its contribution to the field of cerebrovascular diseases is presented. The advances of neuroradiology have revolutionized stroke diagnosis. The inminence use of specific treatment for acute brain ischemia (neuroprotective and thrombolytic drugs) make neurologists become familiar with several imaging techniques that will also change stroke management. Nowadays, computed tomography is the mostly available technique for spanish neurologists in the acute phase, because of that, a suitable knowledge of early CT signs of acute infarction make possible use it in peak condition. Perfusion-and-diffusion-weighted magnetic resonance give such a lot of information for acute stroke, that at the near future, therapeutic decisions will be based on these findings. The role of other functional an angiography techniques is discussed.
Acute Disease↗
[Stroke: a stranger among the people].
INTRODUCTION: Lack of awareness of warning signs of stroke is a factor that contribute to late patient arrival to the emergency department. OBJECTIVE: The goal of this pilot study was to determine the baseline knowledge of stroke among the population (terminology, signs-symptoms, risk factors and attitude) prior to educational campaigns. PATIENTS AND METHODS: A population-based interview using closed-ended questions was conducted by neurologists among 100 users of the Vall d'Hebron's Primary Health Center, randomly sampled. RESULTS: In our population a 9% unknowns totally the disease, of the remainder, 42% has a good knowledge of signs-symptoms and 46% of risk factors. Only 22% of the sample has good global knowledge of the disease. If suffering a stroke this population should seek medical attention through 911 (46.2%) or come directly to the emergency department (50.5%). If symptoms were gone away, transient ischemic attack (TIA), appears a trend to contact primary physicians (59.3%). Respondents aged > 65 years were less likely to recognize symptoms (p = 0.001) and to consider stroke as an emergency. Respondents with an affected relative (50.5%) tend to locate more exactly the disease at the brain (p = 0.05) and to arrive earlier to the emergency department (p = 0.045), than those with non-affected relatives. CONCLUSIONS: Less than a quarter of our population have a good knowledge of the disease. Stroke is considered an emergency unlike TIA. The information about stroke is theoretically associated with early presentation to the emergency department. These results permit a redesign of the questionnaire to conduct a second phase of the study and generalize them for the Spanish population.
Adolescent↗
Selective cytotoxicity of lithium gamma-linolenic acid in human T cells chronically and productively infected with HIV.
We sought to extend observations of lithium gamma-linolenic acid (LiGLA)-associated selective cytotoxicity in different models of chronic HIV infection in vitro. In our initial experiments, 8E5, 8E5L and A3.01 cells were allowed to proliferate in the presence of 0-20 microg/ml LiGLA for 4 days. Similarly, OM-10.1 cells (with or without prior stimulation with tumour necrosis factor-alpha (TNF-alpha)) were grown with 0-5 microg/ml LiGLA for 10 days. Significant cytotoxicity was observed in productively infected 8E5 cells (100% cell death by day 2 at the highest concentration) as compared with latently infected 8E5L cells (50% cell death on days 2-4) and uninfected A3.01 cells. No drug-induced viral stimulation was observed in surviving cells. In fact, a mild direct antiviral effect may be present, independent of cytotoxicity. Maximum cytotoxicity to OM-10.1 cells was only observed when active viral replication was induced by TNF-alpha. Our preliminary results are encouraging and suggest that LiGLA should be retained as a candidate antiretroviral agent. Further work is underway to identify the specific mechanism underlying our observations.
Anti-HIV Agents↗
Species distribution in human immunodeficiency virus-related mycobacterial infections: implications for selection of initial treatment.
Management of mycobacterial infection is species specific; however, treatment is prompted by positive smears or cultures, often several weeks before species identification. The objective of this study was to determine the species distribution of mycobacterial isolates from various body sites in patients infected with human immunodeficiency virus (HIV). All mycobacterial isolates recovered at St. Paul's Hospital (Vancouver, British Columbia, Canada) from April 1989 to March 1993 were reviewed. Among 357 HIV-positive patients with mycobacterial infections, 64% (96) of the sputum isolates were Mycobacterium avium complex (MAC), 18% were Mycobacterium tuberculosis, and 17% were Mycobacterium kansasii. Lymph node involvement (25 patients) was due to either MAC (72%) or M. tuberculosis (24%). Two hundred ninety-eight episodes of mycobacteremia were due to MAC (98%), M. tuberculosis (1%), and M. kansasii (1%). Similarly, cultures of 84 bone marrow biopsy specimens (99%), 19 intestinal biopsy specimens (100%), and 30 stool specimens (97%) yielded predominantly MAC. These results have implications for initial therapy, particularly in areas where rapid methods for species identification are not readily available. Because of considerable geographic variation, development of guidelines for selection of initial therapy depends on regional determination of species distribution in HIV-related mycobacterial infections.
AIDS-Related Opportunistic Infections↗
HIV resistance to anti-viral drugs.
The use of zidovudine (ZDV) and other forms of nucleoside therapy, including dideoxyinosine (ddI), to treat HIV-infected individuals has led to both longer survival and improved quality of life. However, ZDV-resistant variants of HIV-1 can be isolated from patients undergoing prolonged therapy with this drug. HIV drug resistance against ZDV, ddI and other nucleosides is attributable to a series of point mutations within the pol gene of HIV-1 that encodes the viral enzyme, reverse transcriptase (RT). This is not surprising, since the virus is known to replicate at high rates in infected individuals; moreover the RT which mediates transcription of proviral DNA from viral genomic RNA is known to be highly error-prone. Thus, mutants of HIV-1, which possess a drug resistance phenotype and genotype, may be expected to emerge under the selective pressure of long-term anti-viral chemotherapy. HIV drug resistance occurs most commonly in individuals with low CD4 counts, who have progressed to more serious forms of disease. Moreover, viruses obtained from patients with AIDS generally display higher levels of resistance, relative to pre-treatment isolates, than do viruses from patients with more limited illness. Although observations of drug resistance can be correlated with disease progression and a weakened immune system, it is still unclear whether a cause and effect relationship exists. Current clinical research is designed to answer this question while testing the notion that combinations of nucleosides and immuno-stimulatory drugs may provide important clinical benefits.
Cross Reactions↗
Clinical correlates and molecular basis of HIV drug resistance.
It has been widely reported that zidovudine (ZDV)-resistant variants of human immunodeficiency virus type 1 (HIV-1) can be isolated from patients undergoing prolonged therapy with this drug. At the same time, treatment of HIV-infected individuals with ZDV and other forms of nucleotide therapy, including didanosine (ddI), have enabled patients to live longer than would otherwise be the case and to enjoy improved quality of life. HIV resistance to ZDV, ddI, and other nucleosides is attributable to a series of point mutations within the pol gene of HIV-1 that encodes the viral enzyme, reverse transcriptase (RT). This is not surprising as the virus is known to replicate at high rates in infected individuals; moreover the RT that mediates transcription of proviral DNA from viral genomic RNA is known to be highly error prone. Thus, mutants of HIV-1, which possess a drug-resistance phenotype and genotype, may be expected to emerge under the selective pressure of long-term antiviral chemotherapy. This article describes a novel mutation at site 184 within the pol gene that accounts for resistance against both ddI and zalcitibine (ddC). HIV drug resistance occurs most commonly in individuals with low CD4 cell counts who have progressed to more serious forms of disease. Moreover, viruses obtained from patients with AIDS generally display higher levels of resistance, relative to pretreatment isolates, than do viruses from patients with more-limited illness. Although observations of drug resistance can be correlated with disease progression and a weakened immune system, it is still unclear whether a cause-and-effect relationship exists. Because of the error-prone nature of viral RT and the fact that the HIV-1 genome can mutate efficiently, it can be anticipated that viral drug resistance may emerge for all forms of nucleotide therapy to be offered in the future. In addition, resistance may also become apparent with regard to drugs that block HIV replication by acting at sites within the viral replication cycle other than RT.
CD4-Positive T-Lymphocytes↗
Canadian multicenter azidothymidine trial: AZT pharmacokinetics.
The study objective was to describe the pharmacokinetics of azidothymidine (AZT) in a large population of early, asymptomatic human immunodeficiency virus (HIV)-infected individuals. The study design was a multicenter, prospective, descriptive single-dose pharmacokinetic study. Each of 66 fasting, male, HIV-infected homosexuals older than 18 years of age and in CDC classifications II, III, and IVC2 received a single 400-mg oral dose of AZT with subsequent pharmacokinetic measurements performed during an 8-h period for AZT and its major metabolite, glucuronylazidothymidine (GAZT). Results were obtained in 65 patients (36 smokers, 29 nonsmokers), of whom 3 were noted to have hepatic dysfunction. In those with normal hepatic function, the following parameters were described: AZT, area under the curve (AUC) +/- SD, 9.9 +/- 5.7 microM.h, maximum concentration (Cmax) +/- SD, 7.3 +/- 4.7 microM; time to maximum concentration (Tmax) +/- SD, 0.93 +/- 0.42 h, and half-life (t1/2) +/- SD, 1.0 +/- 0.8 h. Corresponding values for GAZT were: AUC +/- SD 35.7 +/- 10.3 microM.h, Cmax +/- SD 21.3 +/- 7.3 microM, Tmax +/- SD 1.2 +/- 0.50 h, t1/2 +/- SD 0.98 +/- 0.62 h, No significant differences were found in comparisons of study site, CDC classification of disease, smokers versus nonsmokers, and in patients with hepatic dysfunction, although a higher AUC and earlier Cmax for AZT was noted in the latter group. It is concluded that AZT pharmacokinetics are similar in patients with early asymptomatic HIV disease when compared with previous reports in patients with later disease.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Corticosteroids delay pneumonia in AIDS patients.
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Acquired Immunodeficiency Syndrome↗
Respiratory failure associated with the lipodystrophy syndrome in an HIV-positive patient with compromised lung function.
Protease inhibitors, used as treatment in human immunodeficiency virus (HIV) infection, are associated with a syndrome of peripheral lipodystrophy, central adiposity, hyperlipidemia and insulin resistance. An HIV-positive patient with chronic obstructive pulmonary disease is presented who developed the lipodystrophy syndrome that is associated with the use of protease inhibitors. It is postulated that the lipodystrophy syndrome further compromised his lung function, leading to respiratory failure. Patients who have pulmonary disease and are taking protease inhibitors require monitoring of clinical status and pulmonary function tests.
Adult↗
Plasma thrombin-activatable fibrinolytic inhibitor (TAFI) among healthy subjects and patients with vascular diseases: a validation study.
Thrombin activable fibrinolysis inhibitor antigen levels (TAFI Ag ) exhibit a great inter-individual variability in healthy populations. Our aim is to determine whether variability is due to physiologic variations depending on genetic control or due to validation of the method,in order to allow a better interpretation of the results inpatients with vascular diseases. With this purpose, we performed a strategy validation of specific ELISA method, Zymutest TAFI Ag Hyphen Biomed, base don a commercial monoclonal antibody. After methodology validation we have recently determined plasma TAFI Ag levels in several groups of diseases such as septic patients, menopause and cerebrovascular diseases. TAFI was finally determined in acute ischemic stroke to know its relationship with stroke evolution and response to thrombolytic treatments.
Adolescent↗