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Biomedical subjects

Michelle A Kendall

Publications and source records attributed to Michelle A Kendall.

9 recordsLinked to original sources
PubMed2006

A reduced frequency visit schedule underreports adverse events that resulted in dose modifications or treatment discontinuations in HIV/AIDS clinical trials: ACTG DACS 207.

BACKGROUND: Most large clinical trials for human immunodeficiency virus (HIV) conducted at university medical centers require intensive real-time monitoring, with clinic visits at least every 4 to 8 weeks. Investigating a reduced frequency visit schedule will help determine whether the current amount of monitoring is needed to ensure subject safety. If we can show that subjects may visit the clinic less often than every 8 weeks and not miss important laboratory-related drug toxicities, then it may be feasible to conduct large studies with simpler designs without compromising the subjects' health. METHODS: In a retrospective analysis, we examined 3385 study participants who were enrolled in one of four clinical trials conducted by the National Institute of Allergy and Infectious Disease AIDS Clinical Trials Group. Variables examined included age, sex, race, CD4 cell count, HIV antiretroviral use, and medications to treat or prevent selected HIV-associated opportunistic infections. RESULTS: Significantly more than the hypothesized 5% of clinic visits with at least one drug toxicity were missed when visits were either every 16 or 24 weeks instead of every 8 weeks (exact Poisson lower 95% confidence bounds = 9.7% and 9.2%, respectively). In both visit-skipping scenarios, there were no significant differences found in the rates of missed drug toxicities by sex or age. However, entry CD4 cell count, HIV antiretroviral use, and medications to treat or prevent two HIV-associated opportunistic infections significantly affected the expected mean number of missed drug toxicities. CONCLUSION: Study visits cannot be extended from every 8 weeks to every 16 or 24 weeks without potentially harming the subjects' health.

Adult↗
PubMed2006

Cytomegalovirus-specific immunity and protection against viremia and disease in HIV-infected patients in the era of highly active antiretroviral therapy.

To define the immune correlates of protection against cytomegalovirus (CMV) end-organ disease, CMV-specific interferon (IFN)- gamma enzyme-linked immunospot (ELISPOT) and CD8(+) and CD4(+) intracellular IFN- gamma synthesis assays were performed for subjects with CD4(+) cell counts of < or =50 cells/ microL who were enrolled in a prospective observational study of CMV infection in the era of highly active antiretroviral therapy. Of 87 subjects, 46 developed viremia, 14 developed end-organ disease, and 20 died. Positive ELISPOT assay results, but not positive results for CD4(+) or CD8(+) intracellular IFN- gamma synthesis, were associated with delayed development of viremia and CMV end-organ disease or death. CMV viremia did not appear to boost CMV-specific immunity. ELISPOT assays may be used to identify HIV-infected patients who might benefit from anti-CMV prophylactic interventions.

AIDS-Related Opportunistic Infections↗
PubMed2005

Carotid artery intima-media thickness and HIV infection: traditional risk factors overshadow impact of protease inhibitor exposure.

CONTEXT: The impact of HIV infection and exposure to antiretroviral therapy on the development of subclinical atherosclerosis is incompletely understood. OBJECTIVE: To compare intima-media thickness (IMT) of the carotid artery between HIV-infected subjects receiving protease inhibitor-containing regimens and subjects not receiving these regimens and to compare differences in the IMT of the carotid artery between HIV-infected subjects and HIV-uninfected subjects. METHODS: A prospective matched cohort study in university-based outpatient clinics. Groups of three individuals (triads) matched on the following characteristics were enrolled: age, sex, race/ethnicity, smoking status, blood pressure and menopausal status. Group 1, HIV-infected subjects with continuous use of protease inhibitor (PI) therapy for > or = 2 years; group 2, HIV-infected subjects without prior PI use; and group 3: HIV-uninfected. Ultrasonographers at six sites sent standardized ultrasound images to a central reading site for carotid IMT measurements. Carotid IMT was compared within the HIV-infected groups (1 and 2) and between the HIV-infected and uninfected groups in a matched analysis. RESULTS: One hundred and thirty-four individuals were enrolled in 45 triads. The median IMT in groups 1, 2 and 3 was 0.690, 0.712 and 0.698 mm, respectively. There were no statistically significant differences in IMT between groups 1 and 2, or in the combined HIV groups compared with the HIV uninfected group. Significant predictors of carotid IMT in a multivariate model included high-density lipoprotein (HDL) cholesterol, the interaction of HDL cholesterol and triglycerides, age and body mass index. CONCLUSIONS: We found no association between PI inhibitor exposure or HIV infection and carotid IMT.

Adult↗
PubMed2005

Pharmacokinetic interactions between indinavir plus ritonavir and calcium channel blockers.

BACKGROUND: Hypertension is an important modifiable cardiac risk factor in human immunodeficiency virus (HIV)-infected patients. Calcium channel blockers are substrates of cytochrome P450 3A and are commonly prescribed for hypertension. We evaluated potential bidirectional pharmacokinetic interactions between calcium channel blockers and coadministered indinavir and ritonavir. METHODS: Healthy HIV- seronegative subjects received 120 mg diltiazem daily or 5 mg amlodipine daily for days 1 to 7 and 20 to 26. All subjects received 100 mg ritonavir and 800 mg indinavir every 12 hours on days 8 to 26. Twenty-four-hour pharmacokinetic collection was performed on days 7 and 26, with 12-hour collection on day 19. RESULTS: Indinavir plus ritonavir increased the median amlodipine area under the curve from 0 to 24 hours (AUC) by 89.8%, from 122 to 230 ng.h/mL (n = 18, P < .0001), and increased the median diltiazem AUC by 26.5%, from 800 to 1060 ng.h/mL (n = 13, P = .06). Of 13 subjects, 2 (15%) had greater than 4-fold increases in diltiazem AUC. Desacetyldiltiazem AUC increased by 102.2% (P = .001), and desmethyldiltiazem AUC decreased by 27.4% (P = .01). Neither amlodipine nor diltiazem affected steady-state AUCs of the protease inhibitors. No serious cardiovascular adverse effects were observed. CONCLUSIONS: Indinavir plus ritonavir increases the AUCs of both amlodipine and diltiazem, which may result in an increased response. If coadministration is indicated, amlodipine or diltiazem should be initiated at low doses with careful titration to response and side effects.

Adolescent↗
PubMed2003

The predictive value of cytologic testing in women with the human immunodeficiency virus who have low-grade squamous cervical lesions: a substudy of a randomized, phase III chemoprevention trial.

OBJECTIVE: The purpose of this study was to determine whether the progression of low-grade squamous intraepithelial lesions of the cervix in women with the human immunodeficiency virus can be predicted reliably by standard cytologic testing. STUDY DESIGN: As part of a previously reported trial, 288 biopsy specimens were collected from 117 women with the human immunodeficiency virus. These specimens underwent central and local interpretation, which were compared and correlated with cytologic results. Ninety-two subjects had matched cytologic/histologic pairs at study termination, which were compared to determine whether cytologic testing was predictive of progression. RESULTS: Of the central histologic interpretations, 26 of 288 interpretations (9%) differed from local results, 97 of 246 cytologic/histologic pairs (39%) were discordant, and 21 subjects had progression to high-grade squamous intraepithelial lesions by histologic evidence. Cytologic testing showed high-grade squamous intraepithelial lesions in 4 of 21 specimens (sensitivity, 19%). The remaining cytologic specimens were either low-grade squamous intraepithelial lesions or were normal. CONCLUSION: This substudy of pathologic results from a randomized clinical trial suggests that, although the risk of progression of low-grade squamous intraepithelial lesions is low, follow-up cytologic testing is unreliable. Colposcopic evaluation with directed biopsies should be continued.

Antineoplastic Agents↗
PubMed2002

Isotretinoin for low-grade cervical dysplasia in human immunodeficiency virus-infected women.

OBJECTIVE: To estimate the efficacy of isotretinoin for prevention of progression of low-grade squamous intraepithelial lesions (SIL) of the cervix to high-grade lesions or invasive cervical cancer; to estimate the regression rate of low-grade SIL with isotretinoin and the toxicity of isotretinoin in this setting; and to correlate serum CD4 levels with progression of low-grade SIL. METHODS: A randomized, phase III, observation-controlled, multicenter trial was performed in which 117 human immunodeficiency virus (HIV)-positive women with low-grade SIL of the cervix received either oral isotretinoin at 0.5 mg/kg per day for 6 months or observation. Papanicolaou smears and colposcopy/biopsy were done at regular intervals during follow-up. The primary endpoint was progression to high-grade SIL or cervical cancer. RESULTS: Twenty-one of 102 women (20.6%) completing follow-up experienced progression to high-grade SIL, 13 in the observation group and eight in the isotretinoin group. This difference was not significant (P =.29). No cases of invasive cancer were seen. Baseline CD4 levels were lower than anticipated (median 329 cells/mm(3)), but not associated with time to progression (P =.36). Most subjects (63 of 102, 61.7%) used highly active antiretroviral therapy. Subjects under age 30 were more likely to progress than those older than 30 (P =.046). CONCLUSION: Isotretinoin was not associated with longer time to progression of low-grade SIL. This appears to be a chronic condition in HIV-positive women, with a low risk of progression and significant rate of resolution. As in the general population, observation without excisional therapy may be appropriate for HIV-positive women with low-grade SIL.

Adult↗