Kristin Mondy

Alendronate, vitamin D, and calcium for the treatment of osteopenia/osteoporosis associated with HIV infection

Background:Osteopenia and osteoporosis are frequent complications of HIV infection and/or its treatment. Alendronate is the only bisphosphonate approved for the treatment of osteoporosis in men and women. We conducted a 48-week prospective, randomized, open-label study to evaluate the effects of alendronate, vitamin D, and calcium supplementation on bone mineral density (BMD) in patients with HIV infection. Methods:Thirty-one HIV-infected subjects with lumbar spine BMD t-scores less than −1.0 on antiretroviral therapy for a minimum of 6 months were randomized to receive (n = 15) or not to receive (n = 16) 70 mg of alendronate weekly for 48 weeks. All subjects received calcium (1000 mg daily as calcium carbonate) and vitamin D supplementation (400 IU daily). The study was powered to detect 3% changes in BMD in the lumbar spine within arms at 48 weeks. Results:Thirty-one patients were enrolled; most were male, with an average length of HIV infection of 8 years. Eighty-four percent had an HIV RNA load below 400 copies/mL, with a current median CD4+ T-cell count of 561 cells/mm3 (median nadir CD4 cell count of 167 cells/mm3). At baseline, the median t-score in the lumbar spine was −1.52 and the median t-score in the hip was −1.02. Alendronate in combination with vitamin D and calcium increased lumbar spine BMD by 5.2% (95% confidence interval [CI]: 1.3-6.4) at 48 weeks compared with an increase of 1.3% (95% CI: −2.4 to 4.0) in subjects receiving vitamin D and calcium alone. One subject discontinued treatment in each arm. There were no serious adverse events. Conclusions:Alendronate, vitamin D, and calcium are safe and potentially useful in the treatment of osteopenia/osteoporosis associated with HIV infection.

Aging and HIV Infection: A Comparison Between Older HIV-Infected Persons and the General Population

Abstract Background: As HIV-infected persons age, the relative contribution of HIV infection, combination antiretroviral therapy (cART), and the normal aging process to the frequent comorbidities is unknown.Methods: We prospectively evaluated comorbidities, cardiovascular risk, cognitive function, and anthropomorphic and laboratory parameters of HIV-infected persons aged 50 years and over in two US urban clinics. Results were compared to controls from the National Health and Nutrition Examination Survey (NHANES) matched 1:1 by age, race, gender, smoking status, and body mass index (BMI).Results: We enrolled 122 HIV-infected persons; median age 55 years, 83% male, 57% Caucasian, 39% current smokers, mean BMI 26 kg/m2, and 92% on cART. Compared to controls, HIV-infected persons had a higher prevalence of hypertension (54% vs 38%), hypertriglyceridemia (51% vs 33%), low bone mineral density (BMD) (39% vs 0%), and lipodystrophy and greater receipt of antihypertensive and lipid-lowering medications (all Ps < .05). Groups were similar in prevalence of coronary heart disease, diabetes mellitus, chronic viral hepatitis, non-AIDS-defining malignancies and Framingham Risk and cognitive function scores.Conclusions: Older HIV-infected persons have a higher prevalence of hypertension, hypertriglyceridemia, low BMD, and lipodystrophy than matched controls, suggesting that HIV and treatment-related factors exceed “normal” aging in the development of those problems.

Niacin in HIV-infected individuals with hyperlipidemia receiving potent antiretroviral therapy

BACKGROUND Extended release (ER)-niacin therapy, which has been associated with reduced glucose tolerance in human immunodeficiency virus (HIV)-seronegative individuals, has not been evaluated in the HIV-infected population. METHODS This open, prospective trial evaluated the safety and efficacy of ER-niacin therapy for antiretroviral therapy-associated dyslipidemia. Fourteen individuals received ER-niacin at maximum doses of 2000 mg per day for 14 weeks. RESULTS Significant reductions in serum levels of triglycerides (P=.02), total cholesterol (P=.005), and non-HDL cholesterol (P=.04) were seen after ER-niacin therapy. Seven of 11 subjects were glucose intolerant after ER-niacin therapy; for 3 of these subjects, this was a new finding. Beta-cell sensitivity to basal glucose levels increased significantly without concomitant increase in overall glucose disposition indices. The values for the homeostasis model of insulin resistance index increased significantly (P=.005). CONCLUSION ER-niacins role in the treatment of antiretroviral therapy-associated dyslipidemia requires further evaluation, but the results of this pilot study indicate that it is safe and tolerated and provides a valuable treatment option.

Factors associated with renal dysfunction within an urban HIV-infected cohort in the era of highly active antiretroviral therapy

Kidney disease remains a prevalent problem in HIV care. The contribution of highly active antiretroviral therapy (HAART), HIV disease factors and traditional factors needs further evaluation.

Development of Appropriate Coronary Heart Disease Risk Prediction Models in HIV-Infected Patients

Prediction equations for coronary heart disease (CHD) risk are useful tools that inform clinicians and patients about the absolute risk for developing CHD. A basic principle in CHD prevention is that the intensity of risk-reducing interventions should be based on the individual patient’s absolute CHD risk. In the current era of human immunodeficiency virus (HIV) infection and highly active antiretroviral therapy (HAART), knowing one’s CHD risk and acting to reduce it have become imperative to long-term survival. Given the increased life expectancy as a result of HAART, more HIV-infected persons will experience complications not related to HIV per se and will reach an age at which they are at increased risk for developing CHD. However, existing CHD risk prediction equations were not developed in HIV-infected adults or children. In the general population, CHD risk prediction models derived from the Framingham Heart Study estimate the risk of total CHD (angina pectoris, myocardial infarction [MI], CHD death)1 or estimate the risk for hard CHD end points (MI, CHD).2 The traditional risk factors used to predict CHD risk and how risk factor alterations affect CHD outcomes in HIV-infected and HIV-seronegative people are summarized in the Table. The estimates of the relative effects of traditional risk factors on CHD outcomes appear similar between HIV- and non–HIV-infected patients. However, they are based on only 2 studies in HIV-infected patients. Although traditional CHD risk factors may operate in the same manner in HIV patients as in the general population, there may still be a need to identify and evaluate HIV-specific CHD risk factors and equations, to refine existing CHD prediction equations, and to develop new HIV-specific CHD prediction equations for adults, adolescents, and children. To date, Framingham CHD risk predictions have performed reasonably well when applied to HIV-infected patients. We need to evaluate …

Insulin resistance predicts endothelial dysfunction and cardiovascular risk in HIV-infected persons on long-term highly active antiretroviral therapy.

Objective:Cardiovascular disease risk among persons with HIV is likely multifactorial, thus testing a variety of available noninvasive vascular ultrasound and other surrogate tests may yield differing results. To address this issue, we assessed multiple metabolic and clinical predictors of endothelial function and carotid intima–media thickness in HIV-infected subjects and compared results with HIV-negative controls. Design:Prospective, cross-sectional study of 50 HIV-infected, healthy adults on stable highly active antiretroviral therapy matched to 50 HIV-negative controls by age, sex, race, and body mass index. Methods:Flow-mediated vasodilation of the brachial artery, carotid intima–media thickness, dual energy X-ray absorptiometry (HIV-infected subjects), and fasting insulin, lipids, and oral glucose tolerance tests were performed. Results were compared between HIV-infected and control groups. Results:Fifty percent of subjects were African–American with 34% women. Among HIV-infected, mean CD4 cell count was 547 cells/μl; 90% had HIV RNA less than 50 copies/ml. There were no significant differences between HIV-infected and control subjects with regard to brachial artery flow-mediated vasodilation or carotid intima–media thickness. In multivariate analyses of the HIV cohort, independent predictors of endothelial dysfunction (lower flow-mediated vasodilation) were increasing insulin resistance, greater alcohol consumption, and higher baseline brachial artery diameter (P < 0.05); predictors of increased carotid intima–media thickness were hypertension, higher trunk/limb fat ratio, and insulin resistance (P < 0.05). Conclusion:In this HIV cohort on modern highly active antiretroviral therapy with well controlled HIV, there were no significant differences with regard to preclinical markers of cardiovascular disease. Insulin resistance was a strong predictor of impaired brachial artery flow-mediated vasodilation and increased carotid intima–media thickness, and may be an important cardiovascular disease risk factor in the HIV population.

Patterns of primary antiretroviral drug resistance in antiretroviral-naive HIV-1-infected individuals in a midwest university clinic.

A total of 192 HIV-1-infected antiretroviral-naive individuals had genotyping performed in our midwest university clinic between 2003 and 2005. The overall prevalence of resistance with either a reverse transcriptase or major protease mutation was 18%. There did not seem to be a significant difference in primary resistance patterns between different modes of HIV transmission (heterosexual versus men who have sex with men), gender or between white and African-American individuals.

Exercise training augments the peripheral insulin sensitizing effects of pioglitazone in HIV-infected adults with insulin resistance and central adiposity

The prevalence and incidence of insulin resistance and type 2 diabetes mellitus (DM) are higher in people treated for human immunodeficiency virus-1 (HIV) infection than in the general population. Identifying safe and effective interventions is a high priority. We evaluated whether the peroxisome proliferator-activated receptor-γ agonist pioglitazone with exercise training improves central and peripheral insulin sensitivity more than pioglitazone alone in HIV-infected adults with insulin resistance and central adiposity. Forty-four HIV-infected adults with baseline insulin resistance and central adiposity were randomly assigned to 4 mo of pioglitazone (30 mg/day) with or without supervised, progressive aerobic, and resistance exercise training (1.5-2 h/day, 3 days/wk). The hyperinsulinemic euglycemic clamp was used to evaluate alterations in central and peripheral insulin sensitivity. Thirty-nine participants completed the study. Hepatic insulin sensitivity improved similarly in both groups. Exercise training augmented the beneficial effects of pioglitazone on peripheral insulin sensitivity. Greater improvements in peripheral insulin sensitivity were associated with reductions in total body and limb adipose content rather than increases in limb adiposity or pioglitazone-induced increases in adiponectin concentration. We conclude that supplementing pioglitazone with increased physical activity improved insulin sensitivity more effectively than pioglitazone alone in HIV-infected adults with insulin resistance and central adiposity. Pioglitazone alone did not significantly increase limb adipose content. Potential cardiovascular benefits of these interventions in HIV need investigation.

Inappropriate use of antifungal medications in a tertiary care center in Thailand: A prospective study

The incidence and factors associated with inappropriate use of antifungal medications were studied in a Thai tertiary care center. The incidence of inappropriate antifungal use was 74% (in 42 of 57 patients). Isolation of Candida species from urine (P = .004) was a risk factor, whereas receipt of an infectious diseases consultation (P = .004) was protective.

Effect of Postpartum HIV Treatment Discontinuation on Long-Term Maternal Outcome

Background. Long-term maternal outcomes after postpartum antiretroviral therapy (ART) discontinuation are unknown. Methods. Retrospective review of pregnancies in HIV-infected women on treatment between 1997 and 2005. Women were grouped by postpartum ART use and followed until new opportunistic infection (OI), death or last clinic visit. Results. Of 172 pregnancies, postpartum ART discontinuation occurred in 123 (71.5%) women and was associated with greater parity, no partner during pregnancy, and no indication for OI prophylaxis or preconception ART in multivariate analysis (P < .05). Median follow-up was 32.5 months after delivery. There were 12 OIs and 2 deaths; 10 OIs and both deaths occurred in women who had discontinued ART. Conclusion. Postpartum ART discontinuation is common, especially among those with less advanced HIV disease, but may leave women at increased risk of long term adverse outcomes. This study highlights the need for larger longitudinal studies to determine appropriate recommendations for postpartum ART administration.