Biomedical subjects

Corklin R Steinhart

Publications and source records attributed to Corklin R Steinhart.

7 recordsLinked to original sources

PubMed2006

Efficacy of the protease inhibitors tipranavir plus ritonavir in treatment-experienced patients: 24-week analysis from the RESIST-1 trial.

BACKGROUND: Improved treatment options are needed for patients infected with multidrug-resistant human immunodeficiency virus type 1 (HIV-1). The nonpeptidic protease inhibitor tipranavir has demonstrated antiviral activity against many protease inhibitor-resistant HIV-1 isolates. The Randomized Evaluation of Strategic Intervention in multi-drug reSistant patients with Tipranavir (RESIST-1) trial is an ongoing, open-label study comparing the efficacy and safety of ritonavir-boosted tipranavir (TPV/r) with an investigator-selected ritonavir-boosted comparator protease inhibitor (CPI/r) in treatment-experienced, HIV-1-infected patients. METHODS: Six hundred twenty antiretroviral-experienced patients were treated at 125 sites in North America and Australia. Before randomization, all patients underwent genotypic resistance testing, which investigators used to select a CPI/r and an optimized background regimen. Patients were randomized to receive TPV/r or CPI/r and were stratified on the basis of preselected protease inhibitor and enfuvirtide use. Treatment response was defined as a confirmed reduction in the HIV-1 load of > or = 1 log10 less than the baseline level without treatment change at week 24. RESULTS: Mean baseline HIV-1 loads and CD4+ cell counts were 4.74 log10 copies/mL and 164 cells/mm3, respectively. At week 24, a total of 41.5% of patients in the TPV/r arm and 22.3% in the CPI/r arm had a > or = 1-log10 reduction in the HIV-1 load (intent-to-treat population; P<.0001). Mean increases in the CD4+ cell count of 54 and 24 cells/mm3 occurred in the TPV/r and CPI/r groups, respectively. Adverse events were slightly more common in the TPV/r group and included diarrhea, nausea, and vomiting. Elevations in alanine and aspartate aminotransferase levels and in cholesterol/triglyceride levels were more frequent in the TPV/r group. CONCLUSIONS: TPV/r demonstrated superior antiviral activity, compared with investigator-selected, ritonavir-boosted protease inhibitors, at week 24 in treatment-experienced patients with multidrug-resistant HIV-1 infection.

Adult↗

PubMed2005

Treating morphologic and metabolic complications in HIV-infected patients on antiretroviral therapy. A consensus statement of an advisory committee of the International Association of Physicians in AIDS Care.

OBJECTIVE: Clinicians are increasingly challenged by presentation of morphologic and metabolic complications in HIV-infected patients. These complications are associated with HIV infection and/or combination antiretroviral therapy. This Consensus Statement is intended to offer guidance to clinicians actively involved in HIV/AIDS care. PARTICIPANTS: Seven clinicians with expertise in HIV medicine were invited by the International Association of Physicians in AIDS Care (IAPAC) to serve on an ad hoc Advisory Committee. CONSENSUS PROCESS: IAPAC convened the Advisory Committee to develop a draft Consensus Statement. Each clinician was tasked with drafting a specific section of the Consensus Statement corresponding with his or her expertise around a morphologic and/or metabolic complication. Scientific and clinical research, and other data in published literature and abstracts from scientific conferences were considered by strength of evidence. This document represents the consensus agreement of the Advisory Committee.

Anti-HIV Agents↗

PubMed2004

A randomized study of emtricitabine and lamivudine in stably suppressed patients with HIV.

BACKGROUND: Once daily (QD) dosing facilitates regimen simplification and adherence to antiretroviral therapy. Emtricitabine (FTC) QD is a newly approved nucleoside reverse transcriptase inhibitor compared in this study to twice daily lamivudine (3TC BID). METHODS: Controlled, open label equivalence trial of 440 HIV-1-infected patients with plasma HIV-1 RNA stably suppressed on a regimen of 3TC 150 mg BID, stavudine or zidovudine, and a protease inhibitor or non-nucleoside reverse transcriptase inhibitor. Patients were randomized to continue their current regimen or replace 3TC with FTC 200 mg QD. If HIV-1 RNA levels were </= pound 400 copies/ml at 48 weeks in Protocol 303, patients could continue on FTC in Protocol 350. The primary analysis was based on virologic failure and response defined by plasma HIV-1 RNA suppression below 400 copies/ml. RESULTS: At baseline, the mean CD4 cell count was 525 (FTC) and 533 x 10(6) cells/l (3TC). At week 48 in Protocol 303, the probability of virologic failure was low, 7% (FTC) and 8% (3TC), and the probability of sustained viral suppression at week 48 was equivalent between treatment arms at both the 50 and 400 copies/ml thresholds. The mean increase in CD4+ T-cell percentage was 2.5% (FTC) and 1.7% (3TC). In Protocol 350, the probability of virologic failure was 11% after 4 years on FTC-containing highly active antiretroviral therapy (HAART). CONCLUSION: In stably suppressed patients, 200 mg emtricitabine QD was equivalent to 150 mg lamivudine BID. Emtricitabine-containing HAART was associated with a high rate of sustained virologic suppression during 4 years of follow-up.

Adult↗

PubMed2004

Atazanavir.

OBJECTIVE: To review the pharmacology, virology, pharmacokinetics, resistance profile, clinical efficacy, safety, and drug interactions of atazanavir. DATA SOURCES: A PubMed and NLMGateway search (1966-June 2004) utilizing the key words atazanavir and BMS-232632 was performed. Abstracts from scientific meetings, including the Conference on Retroviruses and Opportunistic Infections, International AIDS Society Conference on HIV Pathogenesis and Treatment, Interscience Conference on Antimicrobial Agents and Chemotherapy, and the Infectious Diseases Society of America, were also reviewed. STUDY SELECTION AND DATA EXTRACTION: All publications and meeting abstracts were reviewed, and information relevant to the formulary decision-making process was selected. DATA SYNTHESIS: Atazanavir is a once-daily protease inhibitor (PI) that received approval by the Food and Drug Administration in June 2003. In clinical trials in antiretroviral (ARV)-naïve patients, atazanavir had efficacy similar to that of efavirenz or nelfinavir. In ARV-experienced patients, atazanavir was inferior to lopinavir/ritonavir unless atazanavir was coadministered with low-dose ritonavir. Following failure of an atazanavir-containing regimen in ARV-naïve patients, a unique 150L mutation was seen. Atazanavir resistance is likely when resistance to >/=3 PIs is present. Atazanavir can cause increases in unconjugated bilirubin levels, which rarely leads to jaundice or scleral icterus. In contrast to comparators, atazanavir did not negatively impact the lipid profile. Similar to other PIs, atazanavir is metabolized by and inhibits CYP3A at clinically relevant concentrations; therefore, many potential drug interactions exist. CONCLUSIONS: Atazanavir is a once-daily PI that, unlike other PIs, does not negatively impact the lipid profile. Atazanavir may be particularly desirable in patients with hyperlipidemia or other coronary artery disease risk factors.

Atazanavir Sulfate↗

PubMed2004

Recent advances in the treatment of HIV/AIDS.

In industrialized countries, highly active antiretroviral therapy has resulted in significant reductions in morbidity and mortality in patients with HIV/AIDS. At the same time, the management of the HIV-infected individual has become exceedingly complex due to the increasing number of antiretroviral medications and resistance to them. New medications are needed that are effective against the drug-resistant virus. The key advances in the management of HIV/AIDS as seen through the eyes of a front-line HIV physician who has been actively involved in patient care, clinical drug trials and as an educator for the past 15 years will be discussed.

Acquired Immunodeficiency Syndrome↗

PubMed2004

Risks of cardiovascular disease in patients receiving antiretroviral therapy for HIV infection: implications for treatment.

As mortality rates decrease in the HIV/AIDS population because of antiretroviral therapies, modifiable risk factors for cardiovascular disease take on increased significance. There is compelling evidence that the patient population treated for HIV infection is at an increased risk for atherosclerotic cardiovascular disease. While a portion of this risk appears to be related to traditional cardiac risk factors, there is also evidence that iatrogenic factors play a role. Antiretroviral therapy has been associated with hypertriglyceridemia, hypercholesterolemia, and low high-density lipoprotein cholesterol levels. Insulin resistance and hyperglycemia are among the side effects reported with protease inhibitor (PI) use. Although a few studies report conflicting results, significant data suggest that antiretroviral therapy, particularly PI use, may be associated with a higher incidence of cardiovascular events. The management of cardiac risk will play an increasing role in the treatment of HIV/AIDS.

Anti-HIV Agents↗

PubMed2003

Tenofovir disoproxil fumarate in nucleoside-resistant HIV-1 infection: a randomized trial.

BACKGROUND: Resistance to antiretroviral agents remains a leading cause of treatment failure for patients infected with HIV-1. OBJECTIVE: To describe the efficacy and safety of tenofovir disoproxil fumarate (tenofovir DF) compared with placebo in patients with detectable viral replication despite current antiretroviral therapy. DESIGN: Randomized, double-blind, placebo-controlled study through 24 weeks. After 24 weeks, all patients received open-label tenofovir DF for the remainder of the 48-week study. SETTING: 75 North American, European, and Australian HIV clinics. PATIENTS: 552 HIV-1-infected adults who were receiving antiretroviral therapy and had stable HIV-1 RNA levels ranging from 400 to 10,000 copies/mL. MEASUREMENTS: Change in HIV-1 RNA level (time-weighted average from baseline through week 24); proportion of patients with grade 3 or 4 laboratory abnormalities and adverse events; and genotypic HIV-1 resistance testing in a separate substudy at baseline, week 24, and week 48. RESULTS: A statistically significant decrease in HIV-1 RNA level through week 24 (the primary end point) was observed in the tenofovir DF group versus the placebo group (-0.61 log10 copies/mL vs. -0.03 log10 copies/mL, respectively [P < 0.001]; difference, -0.58 log10 copies/mL [95% CI, -0.68 to -0.49 log10 copies/mL]). In a virologic substudy, 94% of 253 patients had plasma isolates expressing reverse transcriptase mutations associated with nucleoside resistance mutations at baseline. Through week 24, the incidence of clinical adverse events was similar between patients receiving placebo and those receiving tenofovir DF (14% vs. 13%). No evidence of tenofovir DF-related toxicity was seen through week 48. CONCLUSION: In treatment-experienced patients with suboptimal viral suppression, tenofovir DF significantly reduced HIV-1 RNA level and had a safety profile similar to that of placebo.

Adenine↗