Biomedical subjects

Stephen Raffanti

Publications and source records attributed to Stephen Raffanti.

7 recordsLinked to original sources

PubMed2006

Drug transporter and metabolizing enzyme gene variants and nonnucleoside reverse-transcriptase inhibitor hepatotoxicity.

This nested case-control study examined relationships between MDR1, CYP2B6, and CYP3A4 variants and hepatotoxicity during antiretroviral therapy with either efavirenz- or nevirapine-containing regimens. Decreased risk of hepatotoxicity was associated with MDR1 3435C-->T (odds ratio, 0.254; P=.021). An interaction between MDR1 and hepatitis B surface antigen status predicted risk with 82% accuracy (P<.001).

Adult↗

PubMed2006

Time's up.

Explore the source record for details and available documents.

Anecdotes as Topic↗

PubMed2005

CD4 lymphocyte percentage predicts disease progression in HIV-infected patients initiating highly active antiretroviral therapy with CD4 lymphocyte counts >350 lymphocytes/mm3.

BACKGROUND: The optimal timing of highly active antiretroviral therapy (HAART) in human immunodeficiency virus (HIV)-infected patients with > or = 200 absolute CD4 lymphocytes/mm3 is unknown. CD4 lymphocyte percentage could add prognostic information. METHODS: Persons who initiated HAART between 1 January 1998 and 1 January 2003, received > or = 30 days of therapy, and had baseline CD4 lymphocyte data available were included in the study. The log-rank test for time to event and Cox proportional hazards models were used to determine predictors of a new acquired immunodeficiency syndrome-defining illness or death. RESULTS: A total of 788 patients met the inclusion criteria. At baseline, subjects had a median of 225 CD4 lymphocytes/mm3 and 17% CD4 lymphocytes. Subjects with < 17% CD4 lymphocytes had earlier disease progression, compared with subjects with > or = 17%, both in the entire cohort (P<.0001) and of those subjects with > 350 absolute CD4 lymphocytes/mm3 at baseline (P=.03). CD4 lymphocyte percentage < 17% was the strongest predictor of disease progression among subjects in this latter group (hazard ratio, 3.57; P=.045). CONCLUSIONS: In this cohort, CD4 lymphocyte percentage predicted disease progression in HIV-infected subjects who initiated therapy with > 350 CD4 lymphocytes/mm3. This information may help identify persons who will derive the greatest benefit from initiation of HAART.

Adolescent↗

PubMed2005

Prescribing of contraindicated protease inhibitor and statin combinations among HIV-infected persons.

HIV-1 protease inhibitors (PIs) contribute to hyperlipidemia in persons treated for HIV infection. There are potential drug-drug interactions between PIs and some statins, which are drugs frequently used to treat hyperlipidemia. We performed a retrospective cohort study using the TennCare program to determine prescribing rates of contraindicated combinations of PIs and statins in HIV-infected persons in Tennessee and to assess changes in prescribing after publication of treatment guidelines. Computerized files identified adult patients with antiretroviral prescriptions and overlapping prescriptions for PIs and statins from January 1, 1996 through June 30, 2002. A subset of these combinations was defined as contraindicated based on published guidelines. Changes in patterns of prescribing after publication of preliminary treatment guidelines were examined using a mixed-effects logistic regression model. There were 3448 persons who received PIs during the study period. The proportion of PI users receiving statins increased from 3.5% during January 1996 through December 2000 to 7.9% during January 2001 through June 2002 (P < 0.001). Contraindicated PI-statin use decreased from 42.0% of combinations to 20.8% during the same periods (P < 0.001). Use of PIs and statins has increased in the adult TennCare population. Contraindicated combinations have decreased but remain unacceptably high.

Adolescent↗

PubMed2003

Oxidant stress is increased during treatment of human immunodeficiency virus infection.

Some diseases and environmental exposures, including those that are risk factors for atherosclerosis, are associated with increased oxidant stress. The objective of this cross-sectional, observational study was to determine whether oxidant stress is increased during human immunodeficiency virus type 1 (HIV-1) infection or its therapy. To quantify oxidant stress, plasma F2 isoprostane (F2-IsoP) concentrations were determined by gas chromatography/mass spectroscopy. A total of 120 subjects were enrolled during routine primary care visits. The median CD4+ T cell count was 341 cells/mm3, the median HIV-1 RNA level was 3.4 log10 copies/mL, and 74% of patients were receiving antiretroviral therapy. Plasma F2-IsoP concentrations were 12-149 pg/mL (median, 31 pg/mL). In univariate analysis, higher F2-IsoP concentrations were associated with lower log10 plasma HIV-1 RNA levels (P=.009) and with efavirenz use (P=.02). Both factors remained associated with plasma F2-IsoP concentrations in multivariate analysis. Oxidant stress associated with therapeutic control of viral replication may have important implications for long-term complications of antiretroviral therapy.

Adult↗

PubMed2003

Implications of T-cell P-glycoprotein activity during HIV-1 infection and its therapy.

OBJECTIVES: P-glycoprotein (P-gp) may reduce antiretroviral efficacy by decreasing disposition of HIV-1 protease inhibitors into tissues and cells. In contrast, P-gp overexpression in vitro can inhibit HIV-1 replication, and some drugs induce P-gp expression. To explore which of these mechanisms predominate in vivo, this study characterized relationships between T-cell P-gp activity and clinical parameters in HIV-infected adults. METHODS: P-gp activity was quantified in total and naive CD4+ and CD8+ T cells of HIV-infected adults by flow cytometry using the substrate dye DiOC2(3). Demographic, virologic, immunologic, and treatment factors were obtained from medical records. Factors associated with P-gp activity were identified using multivariate linear regression. RESULTS: A total of 185 subjects (22% female; 34% African American) were studied, of whom 131 (71%) were receiving antiretroviral treatment. There was marked interindividual variability in P-gp activity. By multivariate analysis, higher CD4+ T-cell P-gp activity was associated with lower log10 HIV-1 RNA (P = 0.005), but not treatment or demographic factors. P-gp activity was correlated across T-cell subsets. CONCLUSIONS: The inverse relationship between P-gp activity and plasma HIV-1 RNA is most consistent with an inhibitory effect on viral replication rather than drug disposition. Antiretroviral drug class did not independently predict P-gp activity.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2003

Effects of ritonavir on indinavir pharmacokinetics in cerebrospinal fluid and plasma.

Therapeutic control of human immunodeficiency virus type 1 (HIV-1) in peripheral compartments does not assure control in the central nervous system. Inadequate drug penetration may provide a sanctuary from which resistant virus can emerge or allow development of psychomotor abnormalities. To characterize the effect of ritonavir on indinavir disposition into cerebrospinal fluid, seven HIV-infected adults underwent intensive sampling at steady-state while receiving twice-daily indinavir (800 mg) and ritonavir (100 mg). Serial cerebrospinal fluid and plasma samples were obtained at 10 time points from each subject. Free indinavir accounted for 98.6% of drug in cerebrospinal fluid and 55.9% in plasma. Mean cerebrospinal fluid C(max), C(min), and area under the concentration-time curve from 0 to 12 h (AUC(0-12)) values for free indinavir were 735 nM, 280 nM, and 6502 nM h(-1), respectively, and the free levels exceeded 100 nM in every sample. The cerebrospinal fluid/plasma AUC(0-12) ratio for free indinavir was 17.5% +/- 6.4%. This ratio was remarkably similar to results obtained in a previous study in which subjects received indinavir without ritonavir, indicating that ritonavir did not have a substantial direct effect on the barrier to indinavir penetration into cerebrospinal fluid. Low-dose ritonavir increases cerebrospinal fluid indinavir concentrations substantially more than 800 mg of indinavir given thrice daily without concomitant ritonavir, despite a lower total daily indinavir dose.

Adult↗