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Kimberly Y Smith

Publications and source records attributed to Kimberly Y Smith.

14 recordsLinked to original sources
PubMed2004

Recognizing and managing common toxicities in patients receiving antiretroviral therapy.

Each of the 3 traditional classes of antiretroviral drugs (nucleoside/nucleotide reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors, and protease inhibitors [PIs]) has characteristic sets of toxicities that are not found with the other drug classes. On the other hand, lipodystrophy, which was thought to be specific to PIs, is now known to be common to all 3 classes of drugs. An understanding of the drug-specific, class-specific, and general toxicities and side effects of antiretroviral drugs will help the clinician tailor treatment regimens to individual patients.

Black or African American↗
PubMed2003

HIV-1-infected antiretroviral-treated patients with prolonged partial viral suppression: clinical, virologic, and immunologic course.

The long-term feasibility of a drug conservation strategy that allows low-level viral replication is unknown. We performed a retrospective study of treated HIV-infected patients with stable detectable viral replication (<10000 copies/mL [low-level viremia]) and compared their clinical, virologic and immunologic courses with those of treated patients with undetectable viremia and viremia (>or=10000 copies/mL [high-level viremia]). Viral reverse transcriptase and protease genotype and HIV-specific CD4 T-cell responses were determined using patient-derived samples. Clinical and immunologic benefits were maintained in patients with partial virologic suppression ( or=2 classes of antiretroviral medications. HIV-specific CD4+ T-cell immunity was detected in most subjects with low-level and undetectable viremia and may have a role in controlling viremia in the setting of partial suppression.

Adult↗
PubMed2003

Role of Baseline pol Genotype in HIV-1 Fitness Evolution.

Viral fitness can be modified upon development of antiretroviral drug resistance, usually by selection of compensatory mutations. In this study, we have used HIV-1 isolates from individuals receiving a protease inhibitor (PI)-based regimen to analyze the impact of basal genetic background on viral fitness evolution. Paired plasma samples and HIV-1 isolates were obtained from 10 PI-naive HIV-infected individuals enrolled in 2 different studies of combination antiretroviral therapy. Genomic regions from pol and env were sequenced. Viral fitness was measured using growth competition experiments followed by heteroduplex tracking analysis. Baseline genotypic analyses of pol showed that 9 of 10 viruses had a different degree of secondary mutations in the protease gene at codons associated with PI resistance (i.e., 10I, 36I, 63P, 71T, and 77I). After 48 weeks of PI-based therapy, a strong correlation was observed between protease genetic divergence and viral fitness difference (r = 0.78, P = 0.03), but not with reverse transcription or Env divergence, suggesting that genotypic changes in the protease gene were driving HIV-1 evolution in these patients. As expected, an inverse correlation was observed between the number of protease and reverse transcription primary mutations and viral fitness (r = -0.65, P < 0.0001). However, our results suggest that the preexistence of secondary mutations in protease genetic background may have implications in HIV-1 fitness evolution and virologic response to antiretroviral therapy.

Acquired Immunodeficiency Syndrome↗
PubMed2003

Optimizing care for African-American HIV-positive patients.

The African-American community has been disproportionately affected HIV/AIDS, as noted by higher reported rates of HIV infection, higher proportion of AIDS cases, and more deaths caused by complications of AIDS than whites and other ethnic groups. In addition, epidemiologic trends suggest that African Americans with HIV infection are more often diagnosed later in the course of HIV disease than whites. Numerous reasons account for this disparity, including the lack of perception of risk and knowledge about HIV transmission as well as a delays in HIV testing and diagnosis in the African-American community. Understanding the important considerations in the management of HIV infection in the African-American patient may create awareness among health care professionals and broaden the knowledge of HIV-infected patients within the African-American community.

Black or African American↗
PubMed2002

Limited immune restoration after 3 years' suppression of HIV-1 replication in patients with moderately advanced disease.

OBJECTIVE: To describe the magnitude of immune restoration after long-term control of HIV-1 replication. DESIGN Prospective study of immune restoration in patients starting highly active antiretroviral therapy (HAART). METHODS: Patients with moderately advanced HIV-1 infection (CD4 cells between 100 x 10 and 300 x 10 /l) who enrolled in a trial of HAART and who had suppression of HIV-1 replication during 3 years of therapy were evaluated for phenotypic and functional indices of immune restoration. RESULTS: Almost all immune restoration achieved occurred during the first year. The median CD4 lymphocyte count increased by 159 x 10 cells/l during the first year (P < 0.001); CD4 lymphocyte rises during the second and third years were not significant. Most decreases in activation antigen expression (CD38/HLA-DR) on CD4 and CD8 lymphocytes occurred during the first year, and after 3 years, patient lymphocytes were still abnormally activated. The proportion of CD4 lymphocytes expressing CD28 increased during the first and second years, but even after 3 years, CD28 expression on CD4 cells remained abnormally low. Lymphocyte proliferative responses to normalized during the first 12 weeks of HAART while responses to tetanus increased only after immunization and enhanced responses to HIV-1 p24 antigen were not observed. CONCLUSIONS: Immune restoration was incomplete in patients who started HAART with moderately advanced HIV-1 disease and most changes occurred during the first year. These data suggest that this degree of suppression of HIV-1 replication alone will not suffice to restore immune competence. The clinical significance of incomplete reconstitution of CD4 lymphocyte number, phenotype, and proliferative function in HIV-1 infection remains to be determined.

Adult↗
PubMed2002

Electron beam computed tomography for assessment of coronary artery disease in HIV-infected men receiving antiretroviral therapy.

Hyperlipidemia has been seen in patients receiving protease inhibitor-based antiretroviral therapy, prompting concern that such patients are at risk for accelerated coronary artery disease (CAD). To assess the risk of CAD in antiretroviral-treated HIV-infected men, we quantified coronary artery calcium (CAC), a sensitive and established marker of subclinical CAD, using electron beam computed tomography (EBCT) of coronary vessels. Sixty HIV-infected men who met the following criteria (cases) were enrolled in the study: age of 40 years or older; naive to antiretroviral therapy or use of a stable antiretroviral regimen for >or=6 months (mean duration, 25.9 months; 41 patients were receiving protease inhibitor therapy); and no known CAD or no use of lipid-lowering agents. EBCT-derived CAC scores, serum lipid levels, history of antiretroviral therapy, and risk factors for CAD were obtained. Each case was compared with three age-, sex-, and race-matched HIV-negative controls randomly selected from a database including >9000 patients who had undergone EBCT. We determined differences in the proportion of cases and controls with CAC scores of >0 (detectable calcium) and clinically significant CAC for age range. There were no statistically significant differences between the number of cases and controls with detectable CAC (33% and 39%, respectively) and clinically significant CAC (18% and 17%, respectively). This study suggests that the rate of coronary atherosclerosis among HIV-infected patients who receive short-term antiretroviral therapy with or without protease inhibitors is not higher than that among age-, sex-, and race-matched HIV-negative controls. These results need to be confirmed in larger long-term studies, with controls well matched for coronary risk factors.

Adult↗
PubMed2002

Selected metabolic and morphologic complications associated with highly active antiretroviral therapy.

Metabolic and morphologic changes have been described in patients with human immunodeficiency virus (HIV) infection. In the short term, these disorders can be debilitating and may require medical intervention, including alterations in antiretroviral therapy regimens. The long-term consequences have not been fully realized, but are important, particularly in the era of durable HIV disease management with highly active antiretroviral therapy. This review focuses on 3 of the important morphologic or metabolic changes, namely alterations in body fat distribution, dyslipidemia, and lactic acidosis. The prevalence of each of these disorders remains unknown due to varied definitions and difficulty in recognition of the conditions for both the patient and the clinician. Treatment regimens directed at these abnormalities are being developed, but clinical trials are needed to fully ascertain the efficacy and safety of such interventions.

Acidosis, Lactic↗
PubMed2002

A pilot study of the safety and efficacy of cholestin in treating HIV-related dyslipidemia.

OBJECTIVE: We collected preliminary safety and efficacy data on the effects of Cholestin, a statin-containing dietary supplement, in individuals with dsylipidemia related to human immunodeficiency virus. METHODS: Fourteen adults with dsylipidemia related to human immunodeficiency virus characterized by hypercholesterolemia, hypertriacylglycerolemia, or both participated in a randomized, double-blind, placebo-controlled pilot study in an infectious disease clinic based in an academic medical center. Participants were randomly assigned to receive 1.2 g of Cholestin twice daily (n = 7) or placebo (n = 7) for 8 wk. The main outcome measures were safety (hepatic function tests, plasma human immunodeficiency virus-1 RNA levels, CD4(+) cell counts, adverse effects) and efficacy (fasting serum cholesterol: total, high- and low-density lipoproteins, and fasting serum triacylglycerols). Safety and efficacy outcomes were evaluated at 2- and 8-wk intervals. RESULTS: Twelve participants (n = 6 per group) completed the 8-wk treatment protocol. After 8 wk of treatment with Cholestin, there were significant declines from baseline in mean (+/- standard error of the mean) fasting total cholesterol (-30.8 +/- 8.8 versus 7.7 +/- 5.6; P = 0.01) and low-density lipoprotein cholesterol (-32.2 +/- 7.2 versus 26.3 +/- 14.2; P = 0.01) versus placebo. Moreover, the decline in fasting total cholesterol was significant (-40.2 +/- 4.8 versus 2.8 +/- 11.9; P = 0.006) after 2 wk of therapy, at which time the low-density lipoprotein cholesterol approached significance (-30.2 +/- 7.4 versus 4.4 +/- 15.2; P = 0.068). High-density lipoprotein cholesterol and triacylglycerol levels did not change at either time point. No adverse effects were seen with Cholestin. CONCLUSIONS: Cholestin may safely lower total and low-density lipoprotein cholesterol in patients with dsylipidemia related to human immunodeficiency virus. Larger and longer-term trials of this approach are warranted.

Adult↗