Biomedical subjects
Simon Paul
Publications and source records attributed to Simon Paul.
Brief report: efficacy and treatment-limiting toxicity with the concurrent use of lopinavir/ritonavir and a third protease inhibitor in treatment-experienced HIV-infected patients.
To investigate the efficacy and tolerability of using lopinavir/ritonavir concurrently with a third protease inhibitor (PI), the authors reviewed the medical records of 47 HIV-infected patients treated with antiretroviral regimens containing lopinavir/ritonavir and amprenavir, saquinavir, indinavir, or nelfinavir. The baseline mean HIV RNA level was 4.6 log(10) copies/mL, and the median CD4 cell count was 123/mm3. By week 40, one patient (2%) was lost to follow-up, and 21 (44%) discontinued their lopinavir/ritonavir plus a third PI regimens: 4 (8%) due to virologic failure as determined by the clinician; 13 (28%) due to toxicity; and 4 (8%) due to social reasons. By intent-to-treat analysis, 12 (26%) of 47 patients had an HIV RNA level of less than 400 copies/mL at 40 weeks. By multivariate analysis, factors associated with virologic response were no prior lopinavir exposure (p =.03) and no prior exposure to nonnucleoside reverse transcriptase inhibitors among patients taking a nonnucleoside reverse transcriptase inhibitor (p =.05). Some HIV-infected patients concurrently treated with lopinavir/ritonavir and a third PI have viral suppression; many eventually discontinue therapy because of toxicity or virologic failure.
Urinary 8-hydroxy-2'-deoxyguanosine, a metabolite of oxidized DNA, is not elevated in HIV patients on combination antiretroviral therapy.
Mitochondrial toxicity of nucleoside analogues has been proposed to be the etiology of a range of side-effects from antiretroviral therapy of HIV infection. In this study, urinary 8-hydroxy-2'-deoxyguanosine (8OH2'dG), a metabolite of oxidized DNA, was measured to determine if antiretroviral therapy leads to oxidative damage to DNA. A cross-sectional study was carried out measuring urinary 8OH2'dG in three groups of HIV-infected patients: (1) antiretroviral medication naïve, (2) patients on antiretroviral medications without lipodystrophy and (3) patients on antiretroviral medications with lipodystrophy. Twenty-five patients were enrolled in each group. The mean spot urinary 8OH2'dG measurements per mg creatinine for the three groups were: antiretroviral naïve 4.27 +/- 0.61 (ng 8OH2'dG/mg creatinine +/- SEM), on antiretroviral medications without lipodystrophy 2.88 +/- 0.26, and on antiretroviral medications with lipodystrophy 3.27 +/- 0.30. The differences between the means of the three groups is not statistically significant (p = 0.055), and these results are not significantly different from reported values for healthy controls [A carbon column-based liquid chromatography electrochemical approach to routine 8-hydroxy-2-deoxyguanosine measurements in urine and other biologic matrices: a one-year evaluation of methods. Free Radical Biology and Medicine 27 (1999) 647-666].
Impact of antiretroviral therapy on decreasing hospitalization rates of HIV-infected patients in 2001.
Effective antiretroviral therapy initially resulted in large decreases in hospitalization rates of HIV-infected patients. The goal of this study was to determine whether these gains were being maintained in 2001. A cross-sectional study of hospital admission characteristics during four time periods was performed. All patients receiving care at the HIV clinics of New York Presbyterian Hospital-Cornell Medical Center (NYPH) in New York City were included. In 1995, 883 outpatients were receiving care for HIV infection at NYPH; this increased to 1990 outpatients by 2001. Demographic and laboratory information was obtained for these outpatients, and diagnoses were recorded for all patients requiring hospitalization on at NYPH during the time periods January 1 through June 30, in 1995, 1997, 1999, and 2001. The incidence of hospital admission declined in all four time periods: 1995 (95 per 100 patient-years [pt-yr]), 1997 (48 per 100 pt-yr), 1999 (38 per 100 pt-yr, p < 0.05), and 2001 (25 per 100 pt-yr). The incidence of bacterial pneumonia and opportunistic infections (OIs) decreased in all four time periods. The median hospitalization were CD4(+) cell count for outpatients increased from 231 (1995) to 364 (2001). Important predictors of hospitalization were CD4(+) < 200, and IVDU as an HIV risk factor. Since 1995 and the introduction of highly active antiretroviral therapy, continuing increases in CD4(+) cell counts of outpatients has been reflected in persistent declines in hospitalization rates. Large decreases in OIs and pneumonia have been minimally offset by stable rates of hospital admissions for diagnoses such as hepatitis, cirrhosis, and cellulitis.
Prioritization of medical problems to improve adherence.
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