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      Prevalence of HIV-Associated Metabolic Abnormalities among Patients Taking First-Line Antiretroviral Therapy in Uganda

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          Abstract

          Introduction. While the introduction of highly active antiretroviral therapy decreased HIV-related morbidity and mortality rates in the sub-Saharan Africa, a subsequent increase in metabolic abnormalities has been observed. We sought to determine the prevalence of HIV-associated metabolic abnormalities among patients on first-line antiretroviral therapy (ART) in an ART clinic in Kampala, Uganda. Methods. Four hundred forty-two consecutive patients on first-line ART for at least 12 months were screened for eligibility in a cross-sectional study, and 423 were enrolled. Pre-ART patient characteristics were abstracted from medical charts, examinations included anthropometric measurement and physical assessment for lipodystrophy. Results. The prevalence of hyperglycemia and dyslipidemia was 16.3% (69/423) and 81.5% (345/423), respectively. Prevalence of dyslipidemia between stavudine- and zidovudine-based regimens (91% versus 72%; P < 0.001). Being on stavudine (aOR 4.79, 95%, 2.45–9.38) and peak body weight (aOR 1.44, 95% CI 1.05–1.97) were independent risk factors for dylipidemia. Stavudine (aOR 0.50, 95% CI  0.27–0.93) use was associated with lower risk for hyperglycemia while, and older age (aOR 1.31, 95% CI 1.11–1.56) and having a family history of DM (aOR 2.18, 95% CI 1.10–4.34) were independent risk factors for hyperglycemia. Conclusions. HIV-associated metabolic complications were prevalent among patients on thymidine analogue-containing ART regimens. Screening for lipid and glucose abnormalities should be considered in ART patients because of cardiovascular risks.

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          Cardiovascular disease risk factors in HIV patients--association with antiretroviral therapy. Results from the DAD study.

          To determine the prevalence of risk factors for cardiovascular disease (CVD) among HIV-infected persons, and to investigate any association between such risk factors, stage of HIV disease, and use of antiretroviral therapies. Baseline data from 17,852 subjects enrolled in DAD, a prospective multinational cohort study initiated in 1999. Cross-sectional analyses of CVD risk factors at baseline. The data collected includes data on demographic variables, cigarette smoking, diabetes mellitus, hypertension, dyslipidaemia, body mass index, stage of HIV infection, antiretroviral therapy. Almost 25% of the study population were at an age where there is an appreciable risk of CVD, with those receiving a protease inhibitor (PI) and/or non-nucleoside reverse transcriptase inhibitor (NNRTI) tending to be older. 1.4% had a previous history of CVD and 51.5% were cigarette smokers. Increased prevalence of elevated total cholesterol (> or = 6.2 mmol/l) was observed among subjects receiving an NNRTI but no PI [odds ratio (OR), 1.79; 95% confidence interval (CI), 1.45-2.22], PI but no NNRTI (OR, 2.35; 95% CI, 1.92-2.87), or NNRTI + PI (OR, 5.48; 95% CI, 4.34-6.91) compared to the prevalence among antiretroviral therapy (ART)-naive subjects. Subjects who have discontinued ART as well as subjects receiving nucleoside reverse transcriptase inhibitors had similar cholesterol levels to treatment-naive subjects. Higher CD4 cell count, lower plasma HIV RNA levels, clinical signs of lipodystrophy, longer exposure times to NNRTI and PI, and older age were all also associated with elevated total cholesterol level. HIV-infected persons exhibit multiple known risk factors for CVD. Of specific concern is the fact that use of the NNRTI and PI drug classes (alone and especially in combination), particularly among older subjects with normalized CD4 cell counts and suppressed HIV replication, was associated with a lipid profile known to increase the risk of coronary heart disease.
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              Changes in mitochondrial DNA as a marker of nucleoside toxicity in HIV-infected patients.

              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. 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. 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. Mitochondrial DNA levels are significantly decreased in patients with symptomatic, nucleoside-related hyperlactatemia, an effect that resolves on the discontinuation of therapy.
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                Author and article information

                Journal
                ISRN AIDS
                ISRN AIDS
                ISRN.AIDS
                ISRN AIDS
                International Scholarly Research Network
                2090-939X
                2012
                23 August 2012
                : 2012
                : 960178
                Affiliations
                1School of Medicine, Makerere University College of Health Sciences, P.O. Box 7072, Kampala, Uganda
                2Research Department, Infectious Diseases Institute, Makerere University College of Health Sciences, P.O. Box 22418, Kampala, Uganda
                3Institute of Tropical Medicine, Nationalestraat 155, University of Antwerp, Antwerp, Belgium
                4Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
                Author notes

                Academic Editors: O. Andersen, L. Belec, and L. Gray

                Article
                10.5402/2012/960178
                3767451
                24052885
                786a0697-4b9d-4f57-bb4d-ce5b36c8308c
                Copyright © 2012 Bernard Omech et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 18 May 2012
                : 25 June 2012
                Categories
                Research Article

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