PubMed Health⌕ Search

Biomedical subjects

Marianne Harris

Publications and source records attributed to Marianne Harris.

25 records · Page 2Linked to original sources
PubMed2002

Changes in mitochondrial DNA as a marker of nucleoside toxicity in HIV-infected patients.

BACKGROUND: Nucleoside analogues can induce toxic effects on mitochondria by inhibiting the human DNA polymerase gamma. The toxic effects can range from increased serum lactate levels to potentially fatal lactic acidosis. We studied changes in mitochondrial DNA relative to nuclear DNA in the peripheral-blood cells of patients with symptomatic, nucleoside-induced hyperlactatemia. METHODS: Total DNA was extracted from blood cells. A nuclear gene and a mitochondrial gene were quantified by real-time polymerase chain reaction. Three groups were studied: 24 controls not infected with the human immunodeficiency virus (HIV), 47 HIV-infected asymptomatic patients who had never been treated with antiretroviral drugs, and 8 HIV-infected patients who were receiving antiretroviral drugs and had symptomatic hyperlactatemia. The patients in the last group were studied longitudinally before, during, and after antiretroviral therapy. RESULTS: Symptomatic hyperlactatemia was associated with marked reductions in the ratios of mitochondrial to nuclear DNA, which, during therapy, averaged 68 percent lower than those of non-HIV-infected controls and 43 percent lower than those of HIV-infected asymptomatic patients never treated with antiretroviral drugs. After the discontinuation of antiretroviral therapy, there was a statistically significant increase in the ratio of mitochondrial to nuclear DNA (P=0.02). In the patients followed longitudinally, the decline in mitochondrial DNA preceded the increase in venous lactate levels. CONCLUSIONS: Mitochondrial DNA levels are significantly decreased in patients with symptomatic, nucleoside-related hyperlactatemia, an effect that resolves on the discontinuation of therapy.

Adult↗
PubMed2002

Management of HIV-infected Patients with Multidrug-resistant Virus.

Heavily pretreated HIV-infected patients with multidrug-resistant virus remain a clinical challenge to the treating physician. While the goal of therapy in such patients is still controversial, sustained immunologic and clinical benefit have only been demonstrated with complete suppression of plasma viral load below detectable levels. Expert use of resistance testing may help in the selection of the salvage regimen, and monitoring of plasma drug levels may help optimize the potency and tolerability, especially of complex, multiple drug regimens where adherence remains a critical determinant of treatment outcome. The potential roles of newer agents, adjuvants, treatment interruptions, and immune-based therapies remain under investigation.

Journal Article↗
PubMedDate not supplied

Case series assessing the safety of mycophenolate as part of multidrug rescue treatment regimens.

BACKGROUND: Mycophenolate mofetil (MMF), an inhibitor of lymphocyte proliferation, is emerging as a potential adjunct in the treatment of HIV-1 infection. By potentiating the activity of abacavir, MMF may improve antiviral efficacy. However, it may also lead to myelosuppression, such as was seen in patients taking hydroxyurea-containing regimens. PURPOSE: To assess the safety of MMF as adjunctive therapy for HIV infection. METHOD: Eighteen HIV-positive outpatients, given MMF (500 mg po bid) on a compassionate basis as part of their salvage therapy, were monitored for adverse effects. RESULTS: Five patients discontinued MMF between 26-68 days of follow-up due to adverse effects likely related to other factors. Among the remaining 13 patients, no new clinically significant cytopenias occurred over 107-154 days of follow-up. Three patients exhibited decreases in CD4 counts, despite decreases in plasma HIV-1 RNA. CONCLUSION: Short-term follow-up suggests that MMF (500 mg po bid) does not cause lymphocyte suppression. However, further studies are ongoing to determine its safety and efficacy profile in HIV infection.

Administration, Oral↗