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Biomedical subjects

S Vella

Publications and source records attributed to S Vella.

At least 55 records · Page 3Linked to original sources
PubMed1999

The relationship between ritonavir plasma levels and side-effects: implications for therapeutic drug monitoring.

OBJECTIVES: To assess whether the neurological or gastrointestinal adverse effects of ritonavir correlate with parameters of ritonavir systemic exposure. METHODS: Peak (Cmax) and trough (Cmin) ritonavir plasma levels were compared in 11 patients experiencing side-effects (group A) versus 10 patients without side-effects (group B). Ritonavir was administered with the following escalation dosing scheme: 300, 400, 500 mg twice a day for 3, 4, and 5 days, respectively, then the full dose of 600 mg twice a day. Blood sampling was done in group A within 24 h of the occurrence of side-effects and in group B after at least 3 days of the full dosage regimen. RESULTS: Both Cmax and Cmax were significantly higher (Mann-Whitney U test) in patients with side-effects. Cmax was [median (interquartile range)] 26.7 (22.7-33.3) mg/l versus 16.2 (13.4-17.0) mg/l (P = 0.001) and Cmin was 12.6 (9.1-13.9) versus 7.5 (4.9-8.6) mg/l (P = 0.002). CONCLUSION: Patients with higher ritonavir concentrations are at a higher risk of experiencing neurological or gastrointestinal side-effects. Individualization of the dosage regimen, e.g. a downward titration of the ritonavir dose in patients with side-effects, guided by plasma level monitoring, may result in a substantial increase in the percentage of patients tolerating ritonavir without increasing the risk of treatment failure as a result of suboptimal systemic exposure.

Adult↗
PubMed1999

[Objective value of adenotonsillectomy in the child. A prospective study of incidence of tonsillitis, snoring, pulse oximetry and polysomnography and general development before and after adenotonsillectomy].

65 children were analysed prospectively before and after adeno-tonsillectomy to determine the incidence of upper airway infections, snoring and nocturnal obstructive symptoms. The weight and height percentiles were also determined before and after adeno-tonsillectomy. The Oxygen Desaturation Index (ODI) was measured in 27 children suspected of having a sleep apnea syndrome. In six of these children polysomnographic studies were carried out. A statistically significant reduction (p < 0,005) of upper airway infections could be seen six to twelve months after adeno-tonsillectomy. In 25 children (38%), we observed a postoperative weight gain and in eight cases (12%) a height gain. The obstructive symptoms, especially snoring and respiratory apneas, disappeared or were significantly reduced in 90% of the cases after adeno-tonsillectomy. All preoperatively pathological ODI and AHI normalised after the operation (p < 0,005).

Adenoidectomy↗
PubMed1999

Thymus volume correlates with the progression of vertical HIV infection.

BACKGROUND: The thymus is the organ responsible for the maturation and selection of T lymphocytes and is thus pivotal in allowing the development of a functional immune system. Because in HIV infection cell-mediated immune responses are severely impaired, we studied the role of thymus in the control of the progression of HIV infection to AIDS. METHODS: Thymic volume was analysed by magnetic resonance imaging in 31 vertically HIV-infected children. Plasma HIV viral load and phenotypic and functional cellular immunity-defining parameters were examined in the same patients. RESULTS: Thymic volume was not correlated with age or nutritional status; thymic volume was nevertheless correlated with CD4 T-lymphocyte counts and with the percentage and absolute number of CD45RA+CD62L+ (naive) T lymphocytes. In addition, the ability of peripheral blood mononuclear cells to proliferate upon tetanus stimulation was directly proportional to thymic volume. Finally, a negative correlation was detected between thymic volume and HIV viral load. CONCLUSION: Because low HIV plasma viraemia and preserved immune function are favourable prognostic indices in HIV disease, these data indicate that an immunological, thymic-dependent control of the progression of HIV infection might be possible, at least in vertically transmitted HIV infection.

CD4-Positive T-Lymphocytes↗
PubMed1999

A randomized, double-blind trial on the use of a triple combination including nevirapine, a nonnucleoside reverse transcriptase HIV inhibitor, in antiretroviral-naive patients with advanced disease.

The immunologic and virologic activity of nevirapine in combination with two nucleosides (zidovudine [ZDV] and didanosine [ddI]) was evaluated in antiretroviral-naive patients with a CD4 count <200/mm3 or clinical AIDS. In all, 68 patients were enrolled in a 48-week double-blind, placebo-controlled trial. A group of 32 patients received ZDV + ddI + nevirapine, and 36 patients received ZDV + ddI. Primary efficacy parameters were the activity on HIV-1 RNA and on peripheral blood CD4+ cells, with differences between groups analyzed by the Wilcoxon's nonparametric two-sample test. Baseline RNA was high in both treatment groups (median values, 5.8 and 5.7 log10). RNA and CD4 responses were significantly higher with the triple combination (median RNA reductions, 2.69 versus 1.05 log10 at 24 weeks and 1.97 versus 1.20 log10 at 48 weeks; median CD4 increases, 81 versus 64 cells/mm3 at 24 weeks and 101 versus 27 cells/mm3 at 48 weeks). This study demonstrates that a triple combination of ZDV + ddI + nevirapine used as first-line regimen in antiretroviral-naive patients can induce sustained virologic and immunologic response in patients with low CD4 count or a previous diagnosis of AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Clinical and immuno-virologic characterization of the efficacy of stavudine, lamivudine, and indinavir in human immunodeficiency virus infection.

Clinical, virologic, and immunologic outcomes were analyzed in children with vertically transmitted human immunodeficiency virus (HIV) infection (n = 25) and clinical symptoms and evidence of immunosuppression to establish the efficacy of 18 months' treatment with stavudine, lamivudine, and indinavir. Children were naive for treatment with protease inhibitors and lamivudine and had minimal exposure to stavudine. At 1, 6, 12, and 18 months, the proportions of patients with HIV-RNA <400 copies/mL were 79%, 100%, 94%, 87% in Centers for Disease Control and Prevention (CDC) immunologic class 2 and 50%, 67%, 67%, 72% in CDC immunologic class 3. At 12 months, the median CD4(+) count and percent increased significantly in both CDC immunologic class groups, but to a greater extent in the class 3 group. In the 12- to 18-month period, there were no significant changes within the groups. In both groups there was a steady increase in the proportion and number of children with positive skin test responses. Children in class 2 were more likely to have a positive delayed-type hypersensitivity response and a greater number of positive responses. Lymphocyte proliferative response to recall antigens improved significantly in all patients. The rate of increase in positive test results was faster in children in class 2 than in those in class 3. Only minor clinical events occurred during 18 months of therapy. Potent antiretroviral therapy achieves a sustained benefit in HIV-infected children, but immune reconstitution is more likely achieved in children with less advanced disease.

Adolescent↗
PubMed1999

Circulating antineutrophil autoantibodies in a child with isolated central nervous system vasculitis.

An 8-year old girl with history of twisted neck and painful swelling on the left side of the neck was found to have malfunction of glossopharyngeal and hypoglossal nerves on the left side. Magnetic resonance angiography revealed a giant aneurysm of the internal carotid artery surrounded by a widespread inflammatory tumor. Cerebral angiography disclosed a large, false aneurysm with almost complete compression of the internal carotid artery. Circulating antineutrophil cytoplasmic autoantibodies (titer 1:2560) and high levels of antibodies against antiproteinase 3 were detectable. This observation indicates that these autoantibodies may be a diagnostic tool in children in whom an undiagnosed central nervous system inflammatory disease is present.

Angiography, Digital Subtraction↗
PubMed1999

Longitudinal human immunodeficiency virus type 1 load in the italian seroconversion study: correlates and temporal trends of virus load.

A prospective study of 149 human immunodeficiency virus type 1 (HIV-1) seroconverters was conducted to describe trends and correlates of HIV-1 load after seroconversion and over time. HIV-1 load was quantified from frozen sera by reverse transcriptase-polymerase chain reaction. High early virus load was associated with lower CD4 cell counts and male sex but not with age at seroconversion or injection drug use. Early virus load predicted progression to clinical AIDS and AIDS/<200 CD4 cells/microL. Virus load exhibited a decline of 52% by 18 months after seroconversion then increased 23% annually (95% confidence interval, 13%-33%). Men and those developing AIDS during follow-up had higher virus loads over the course of disease. Persons who developed AIDS had a steeper virus load slope than those who were AIDS-free (P=.01). In long-term follow-up, virus load exhibited a gradual and sustained increase over time. Virus load and annual increase are strong predictors of disease progression.

Acquired Immunodeficiency Syndrome↗
PubMed1999

HIV-HCV RNA loads and liver failure in coinfected patients with coagulopathy.

BACKGROUND AND OBJECTIVE: The aim of this study was to measure contemporaneously HCV-RNA load, HIV-RNA load and CD4+ lymphocyte count in HCV/HIV coinfected patients with coagulopathy and to examine the relationship between these parameters and the liver failure. DESIGN AND METHODS: A cross-sectional study was performed on 54 patients with severe coagulopathy: 39 HCV/HIV coinfected and 15 HCV+/HIV- comparable for age and HCV exposure time. HCV-RNA and HIV-RNA load, CD4+ lymphocyte count, biochemical and ultrasonographic parameters were evaluated at the time of entry to the study. RESULTS: Mean HCV-RNA load was significantly higher in coinfected patients (643,872 717,687 copies/mL) than in HCV+/HIV- (mean 161,573 276,896 copies/mL) (p = 0.01). The 39 HCV/HIV coinfected patients had a mean HIV-RNA load of 205,913 456,311 copies/mL (range 4,000-2,500,000) and a mean CD4+ lymphocyte count of 206.5171/microL (range 5-693). Five of the 39 (12.8%) coinfected patients had liver failure. In these five patients the mean HCV-RNA load (770,200 996,426 copies/mL) was high but not significantly different from that in the 34 HCV+/HIV+ patients (623,496 682,239 copies/mL) without liver failure (p = 1.0). Coinfected patients with liver failure had a significantly higher HIV-RNA load (mean 764, 599 978,542 copies/mL) and lower CD4+ lymphocyte count (mean 52.655. 6/microL) than those observed in coinfected patients without liver failure (p = 0.007 and p = 0.03, respectively). A significant inverse correlation was found between CD4+ lymphocyte count and HIV-RNA load (r = -0.37, p = 0.01). INTERPRETATION AND CONCLUSIONS: HCV-RNA load is significantly higher in HIV+ than in HIV- patients with coagulopathy. Liver failure was found only in the HCV/HIV coinfected patients with severe immunodepression, expressed either by low CD4+ lymphocyte count or by high HIV-RNA load.

Adult↗
PubMed1998

Changing patterns of mortality across Europe in patients infected with HIV-1. EuroSIDA Study Group.

BACKGROUND: The introduction of combination antiretroviral therapy and protease inhibitors has led to reports of falling mortality rates among people infected with HIV-1. We examined the change in these mortality rates of HIV-1-infected patients across Europe during 1994-98, and assessed the extent to which changes can be explained by the use of new therapeutic regimens. METHODS: We analysed data from EuroSIDA, which is a prospective, observational, European, multicentre cohort of 4270 HIV-1-infected patients. We compared death rates in each 6 month period from September, 1994, to March, 1998. FINDINGS: By March, 1998, 1215 patients had died. The mortality rate from March to September, 1995, was 23.3 deaths per 100 person-years of follow-up (95% CI 20.6-26.0), and fell to 4.1 per 100 person-years of follow-up (2.3-5.9) between September, 1997, and March, 1998. From March to September, 1997, the death rate was 65.4 per 100 person-years of follow-up for those on no treatment, 7.5 per 100 person-years of follow-up for patients on dual therapy, and 3.4 per 100 person-years of follow-up for patients on triple-combination therapy. Compared with patients who were followed up from September, 1994, to March, 1995, patients seen between September, 1997, and March, 1998, had a relative hazard of death of 0.16 (0.08-0.32), which rose to 0.90 (0.50-1.64) after adjustment for treatment. INTERPRETATION: Death rates across Europe among patients infected with HIV-1 have been falling since September, 1995, and at the beginning of 1998 were less than a fifth of their previous level. A large proportion of the reduction in mortality could be explained by new treatments or combinations of treatments.

Adult↗
PubMed1998

Estimates of the virological benefit of antiretroviral therapy are both assay- and analysis-dependent.

OBJECTIVE: To assess the potential discrepancies in reported changes in plasma viral load (PVL) depending on how values below the detection limit of the assay are handled in the data analysis phase of a randomized controlled clinical trial. DESIGN: Data from a recently completed clinical trial comparing combinations of zidovudine, didanosine and nevirapine were analysed. In this trial, PVL was measured using an assay with a lower quantification limit of 400 HIV-1 RNA copies/ml initially. All PVL values less than 500 copies/ml were retested with a more sensitive assay with a lower quantification limit of 20 copies/ml. METHODS: Several summary measures for assessing change in PVL were calculated using three different methods to adjust for PVL values less than the quantification limit of the assay. The differences between these measures were evaluated. RESULTS: We found that the magnitude of the discrepancy between summary measures used to report changes in PVL depended on the proportion of subjects with PVL less than the quantification limit of the assay, how those observations were handled in the data analysis, and the relative difference between the quantification limits of the conventional and more sensitive assay. CONCLUSION: The lack of consensus in reporting of PVL data in the literature makes the interpretation of published trial results difficult. In the absence of agreement on the most appropriate summary measure of PVL data, we recommend that all summaries include information on the quantification limit of the assay used, the proportion of observations at or below the quantification limit and how these observations were handled in the data analysis.

Analysis of Variance↗
PubMed1998

Suppression of plasma viral load below 20 copies/ml is required to achieve a long-term response to therapy.

BACKGROUND: Current guidelines state that the goal of antiretroviral therapy for HIV-infected individuals is to suppress plasma viral load (pVL) to below 400 copies/ml. METHODS: Predictors of achieving and maintaining pVL suppression were examined in a randomized trial of combinations of zidovudine, nevirapine and didanosine in patients with CD4+ T cell counts of between 200 and 600 x 10(6) cells/l who were naive to antiretroviral therapy and AIDS-free at enrolment. RESULTS: One hundred and four patients had pVL > 500 copies/ml at baseline and a pVL nadir below 500 copies/ml. Of these, 77 patients experienced an increase in pVL above 500 copies/ml. The median number of days of pVL suppression to below 500 copies/ml was 285 (42) for patients with pVL nadir < or = (>) 20 copies/ml (P = 00.0001). The relative risk of an increase in pVL above 500 copies/ml associated with a pVL nadir below 20 copies/ml was 0.11 (P = 0.0001). The relative risks of an increase in pVL above 5000 copies/ml associated with a pVL nadir below 20 copies/ml or between 20 and 400 copies/ml were 0.05 [95% confidence interval (CI), 0.02-0.12] and 0.37 (95% CI, 0.23-0.61) respectively, compared with individuals with a pVL nadir > 400 copies/ml. Individuals with a pVL nadir < or = 20 copies/ml were at a significantly lower risk of virologic failure than individuals with a pVL nadir of between 21 and 400 copies/ml (P = 0.0001). CONCLUSIONS: Our results demonstrate that suppression of pVL below 20 copies/ml is necessary to achieve a long-term antiretroviral response. Our data support the need for a revision of current therapeutic guidelines for the management of HIV infection.

Anti-HIV Agents↗
PubMed1998

Antiretroviral therapy for HIV infection in 1998: updated recommendations of the International AIDS Society-USA Panel.

OBJECTIVE: To provide recommendations for antiretroviral therapy based on information available in mid-1998. PARTICIPANTS: An international panel of physicians with expertise in antiretroviral research and care of patients with human immunodeficiency virus (HIV) infection, first convened by the International AIDS Society-USA in December 1995. EVIDENCE: The panel reviewed available clinical and basic science study results (including phase 3 controlled trials; clinical, virologic, and immunologic end point data; data presented at research conferences; and studies of HIV pathophysiology); opinions of panel members were also considered. Recommendations were limited to drugs available in mid-1998. CONSENSUS PROCESS: Panel members monitor new clinical research reports and interim results. The full panel meets regularly to discuss how the new information may change treatment recommendations. Updated recommendations are developed through consensus of the entire panel at each stage of development. CONCLUSIONS: Accumulating data from clinical and pathogenesis studies continue to support early institution of potent antiretroviral therapy in patients with HIV infection. A variety of combination regimens show potency, expanding choices for initial regimens for individual patients. Plasma HIV RNA assays with increased sensitivity are important in monitoring therapeutic response; however, more data are needed to determine precisely the HIV RNA levels that define treatment failure. Long-term adverse drug effects are beginning to emerge, requiring ongoing attention. Some issues regarding optimal long-term approaches to antiretroviral management are unresolved. The increased complexity in HIV management requires ongoing monitoring of new data for optimal treatment of HIV infection.

Anti-HIV Agents↗
PubMed1998

Antiretroviral drug resistance testing in adults with HIV infection: implications for clinical management. International AIDS Society--USA Panel.

OBJECTIVES: To review current knowledge of the biology and clinical implications of human immunodeficiency virus (HIV) resistance to antiretroviral drugs, describe assays for measuring resistance, and assess their use in clinical practice. PARTICIPANTS: The International AIDS Society-USA assembled a panel of 13 physicians with expertise in basic science, clinical research, and patient care relevant to HIV resistance to antiretroviral drugs. EVIDENCE: We reviewed available data from published reports and presented at national and international research conferences. Basic science research, clinical trial results, and expert opinions were used to form the basis of this report. Data on methods for and characteristics of specific genotypic and phenotypic assays were obtained from manufacturers and service providers. CONSENSUS PROCESS: The panel met regularly between October 1997 and April 1998. Panel subgroups developed and discussed different sections of the report before discussing them with the entire panel. Conclusions and suggested approaches to the use of resistance testing were determined by group consensus. CONCLUSIONS: Plasma HIV RNA level and CD4+ cell count are the primary values that should be used to guide the initiation of antiretroviral therapy and subsequent changes in therapy. Possible causes of treatment failure other than development of drug resistance that should be considered are adherence, drug potency, and pharmacokinetic issues. Genotypic and phenotypic testing for HIV resistance to antiretroviral drugs may prove useful for individual patient management. Assays under development need validation, standardization, and a clearer definition of their clinical roles. Possible current roles of resistance testing for choosing an initial regimen or changing antiretroviral therapy, as well as possible implications of the presence or absence of phenotypic resistance and genotypic changes, are discussed.

Anti-HIV Agents↗
PubMed1998

Induction-maintenance antiretroviral therapy: proof of concept.

OBJECTIVE: To investigate the concept of aggressive initial combination therapy followed by reduction to a less demanding maintenance regimen with respect to its potential for sustaining viral suppression. DESIGN: Durable viral suppression to < 20 HIV RNA copies/ml plasma was achieved with zidovudine-nevirapine-didanosine (ZDV-NVP-ddl) therapy. Potential for sustained antiviral response was explored for patients who began with ZDV-NVP-ddl and subsequently interrupted ddl. METHODS: Antiretroviral-naive patients were treated with ZDV-NVP, ZDV-ddl, or ZDV-NVP-ddl. Viral load was measured with the Amplicor assay (limit of quantification 400 copies/ml) and by the Ultra Direct assay (limit of quantification 20 copies/ml) when the Amplicor result was < 500 copies/ml. Treatment adherence for each drug was recorded, including all dose adjustments. RESULTS: Five patients who had begun treatment with ZDV-NVP-ddl discontinued ddl for at least 6 weeks after achieving viral load levels below detection. All were documented to have sustained their viral load at < 20 copies/ml during the ddl interruption. Two patients permanently discontinued ddl, both with sustained viral load below detection for more than 1 year while treated with ZDV NVP. In contrast, no patient initially receiving ZDV-NVP was able to maintain viral load below detection for sustained periods; none had viral load below detection after week 12 of treatment. CONCLUSIONS: After induction with ZDV-NVP-ddl, patients were able to sustain viral suppression with a regimen (ZDV NVP) that was only transiently effective as initial therapy. There was no evidence of virologic escape, even with the most sensitive measure of plasma viral load.

Anti-HIV Agents↗