Denise L. Jacobson

Patient-reported nonadherence to HAART is related to protease inhibitor levels.

Objective: To compare self‐reported nonadherence with antiretroviral therapy (ART) with predose plasma levels of protease inhibitor (PI). Design: A cross‐sectional study of consecutive patients from a university‐based HIV clinic in Rome, Italy, was conducted. One hundred and forty HIV‐infected patients were prescribed regimens containing ritonavir or indinavir. A patient questionnaire assessing knowledge of treatment regimen, adherence behavior, reasons for taking and missing therapy, factors influencing adherence, and health behaviors was administered. A predose PI plasma level was measured concurrently. Results: By patient report, 12% missed at least one dose “yesterday,” and 24% missed doses in the last 3 days; 14% had a predose plasma concentration below the assay limit of quantitation (2 ritonavir and 18 indinavir samples). Confusion, poor psychological well‐being, long office wait, running out of drugs between visits, having relatives to remind the patient to take medication, children, and alteration of sense of taste were related to unquantifiable predose levels of PI. In multivariable analysis, reported nonadherence (odds ratio [OR], 15.8; 95% confidence interval [CI], 4.0‐63.3) and confusion (OR, 9.9; 95% CI, 1.4‐69.6) were related to unquantifiable predose levels of PI. Conclusion: Self‐report of missing a dose of antiretroviral medication “yesterday” was related to an unmeasurable plasma PI level.

Incidence of metabolic syndrome in a cohort of HIV-infected adults and prevalence relative to the US population (National Health and Nutrition Examination Survey).

Background:Metabolic syndrome increases the risk of cardiovascular outcomes and type II diabetes. Most of the metabolic abnormalities defining metabolic syndrome are observed in HIV. Objective:To determine the incidence and risk factors for metabolic syndrome in HIV-infected adults in the Nutrition for Healthy Living (NFHL) study (2000-2003) and prevalence relative to the findings of the National Health and Nutrition Examination Survey (NHANES) (1999-2002). Methods:Metabolic syndrome is ≥3 of the following: hypertriglyceridemia, low high-density lipoprotein (HDL) cholesterol, hypertension, abdominal obesity, and high serum glucose. The baseline prevalence of metabolic syndrome in the NFHL study (n = 477) was compared to that in the NHANES (n = 1876), adjusted for age, race, gender, poverty, exercise, and diet. Results:Almost one quarter of NFHL subjects had metabolic syndrome. Most with metabolic syndrome (77%) had low HDL and hypertriglyceridemia plus ≥1 additional abnormality. The prevalence of metabolic syndrome was significantly lower in HAART and non-HAART users compared with NHANES participants unadjusted for body mass index (BMI). After adjustment for BMI, it was no longer significant but the trend remained. The incidence of metabolic syndrome in the NFHL study was higher with increasing viral load, higher BMI, higher trunk-to-limb fat ratio, and Kaletra (lopinavir/ritonavir) or didanosine (ddI) use and lower among college-educated persons. Conclusions:Metabolic syndrome is mostly diagnosed through low HDL and high triglycerides in HIV. The risk of developing the syndrome is related to HIV, specific medications, and body fat.

Immune Response to Influenza Vaccine in Children With Inflammatory Bowel Disease

OBJECTIVES:Patients with inflammatory bowel disease (IBD) frequently receive immunosuppressive therapy. The immune response in these patients to vaccines has not been well studied. We conducted a prospective, open label study to evaluate the serologic response to influenza vaccine in children with IBD.METHODS:Serum was obtained from 146 children and young adults with IBD (96 Crohns disease, 47 ulcerative colitis, and 3 indeterminate colitis) for baseline influenza titer, immediately followed by immunization with trivalent (A/Solomon Islands/3/2006 (H1N1), A/Wisconsin/67/2005 (H3N2), and B/Malaysia/2506/2004 (B)) inactivated influenza vaccine. Patients returned for repeat titers 3–9 weeks later. Seroprotection against each influenza strain was defined as hemagglutination inhibition titer ≥40. Patients were categorized as nonimmunosuppressed (NIS; aminosalicylates only, antibiotics only, or no therapy) or immunosuppressed (IS; any immunosuppressive agent). IS patients were further subcategorized as: (i) tacrolimus, (ii) tumor necrosis factor-α (TNF-α) inhibitor, (3) immunomodulator, and (4) corticosteroids only.RESULTS:More patients were seroprotected against strains A/H1N1 and A/H3N2 than B strain (P<0.02), regardless of immunosuppression status. The proportion of seroprotected patients and geometric mean titers at post-vaccination were similar between NIS and IS groups for all three strains. Subanalysis of patients not seroprotected at baseline showed that those receiving anti-TNF therapy were less likely to be seroprotected against strain B (14%) compared to patients in the NIS group (39%, P=0.025). There were no serious vaccine-associated adverse events.CONCLUSIONS:Influenza vaccination produces a high prevalence of seroprotection in IBD patients, particularly against A strains. The vaccine is well tolerated. Routine influenza vaccination in IBD patients is recommended, irrespective of whether patients receive immunosuppressive medications.

Prevalence of, Evolution of, and Risk Factors for Fat Atrophy and Fat Deposition in a Cohort of HIV-Infected Men and Women

BACKGROUND At present, no uniform definition of human immunodeficiency virus (HIV)-associated lipoatrophy exists. The risk factors for fat atrophy (FA) and central fat deposition (FD) are multifactorial. We assessed the evolution and predictors of FA and FD in HIV-infected men and women. METHODS Participants (n = 452) were evaluated at baseline (starting in November 1998) and 1 year later. FA was defined as triceps skin-fold measurement less than the 10th percentile on the National Health and Nutrition Examination Survey for sex and age. FD was defined as a waist-to-hip ratio of > 0.95 for men and of > 0.85 for women. Predictors of the baseline prevalence of FA and FD and new cases of each syndrome after 1 year were determined. RESULTS The baseline prevalences of FA, FD, and combined FA and FD were 35%, 44%, and 14%, respectively. Twenty-two percent of subjects had newly developed FA at 1 year, and 16% of subjects with FA at baseline did not have it at 1 year. Also, 23% of subjects had newly developed FD at 1 year, and 15% of those with FD at baseline did not have it at 1 year. The risk of developing new FA was increased among participants with low triceps skin-fold values (P < .001), smaller hips (P < .001), higher nadir HIV load (P = .006), abacavir use (P < .001), stavudine use (P < .001), and use of highly active antiretroviral therapy (P = .002). The risk of developing new FD was higher among women (P < .001) and among participants with greater body fat levels (P = .005) and higher triglyceride levels (P < .001), and it was lower among those with a high school education (P = .003) and higher triceps skin-fold values (P = .026). CONCLUSIONS FA and FD are common in HIV-infected patients, but may change over time in the individual. FA and FD appear to be different syndromes, because risk factors for the development differ, and the prevalence of the combined syndrome differs from the prevalences of the 2 independent syndromes.

Safety of tenofovir use during pregnancy: Early growth outcomes in HIV-exposed uninfected infants

Objective:To evaluate the association of tenofovir disoproxil fumarate (TDF) use during pregnancy with early growth parameters in HIV-exposed, uninfected (HEU) infants. Design:US-based prospective cohort study of HEU children to examine potential adverse effects of prenatal TDF exposure. Methods:We evaluated the association of maternal TDF use during pregnancy with small for gestational age (SGA); low birth weight (LBW, <2.5 kg); weight-for-age z-scores (WAZ), length-for-age z-scores (LAZ), and head circumference-for-age (HCAZ) z-scores at newborn visit; and LAZ, HCAZ, and WAZ at age 1 year. Logistic regression models for LBW and SGA were fit, adjusting for maternal and sociodemographic factors. Adjusted linear regression models were used to evaluate LAZ, WAZ, and HCAZ by TDF exposure. Results:Of 2029 enrolled children with maternal antiretroviral information, TDF was used by 449 (21%) HIV-infected mothers, increasing from 14% in 2003 to 43% in 2010. There was no difference between those exposed to combination regimens with vs. without TDF for SGA, LBW, and newborn LAZ and HCAZ. However, at age 1 year, infants exposed to combination regimens with TDF had significantly lower adjusted mean LAZ and HCAZ than those without TDF (LAZ: −0.17 vs. −0.03, P = 0.04; HCAZ: 0.17 vs. 0.42, P = 0.02). Conclusion:TDF use during pregnancy was not associated with increased risk for LBW or SGA. The slightly lower mean LAZ and HCAZ observed at age 1 year in TDF-exposed infants are of uncertain significance but underscore the need for additional studies of growth outcomes after TDF use during pregnancy.

Incident depression symptoms are associated with poorer HAART adherence: a longitudinal analysis from the Nutrition for Healthy Living Study.

Objective:To determine the relationship between incident depression symptoms and suboptimal adherence to HIV highly active antiretroviral therapy (HAART). Methods:Participants in a cohort study of persons with HIV on HAART with at least 4 consecutive semiannual study visits were included (n = 225). Incident depression was defined as having 2 visits with a negative depression screening test followed by 2 visits with a positive test. Comparison group participants had 4 consecutive visits with a negative depression screening test. Suboptimal adherence was defined as missing >5% of HAART doses in the past 7 days. We compared suboptimal adherence rates in those with and without incident depression symptoms and estimated the relative risk and 95% confidence intervals of suboptimal adherence at visit 4 in those adherent at baseline (n = 177), controlling for sociodemographic, behavioral, and clinical variables. Results:Twenty-two percent developed depression symptoms. Those developing depression symptoms had higher rates of suboptimal adherence at follow-up (45.1% vs. 25.9%, P < 0.01). Among those with optimal baseline adherence, those with incident depression were nearly 2 times more likely to develop suboptimal adherence (Adjusted relative risk =1.8, 95% confidence interval =1.1 to 3.0) at follow-up. Conclusion:Incident depression symptoms were associated with subsequent suboptimal HAART adherence. Ongoing aggressive screening for, and treatment of, depression may improve HAART outcomes.

Metabolic Syndrome and Subclinical Atherosclerosis in Patients Infected with HIV

BACKGROUND The present study examines the association between carotid and coronary atherosclerosis and metabolic syndrome in human immunodeficiency virus (HIV)-infected adults. METHODS We measured the common and internal carotid intima-media thickness (c-IMT) using B-mode ultrasonography, and we measured coronary artery calcium (CAC) using high-resolution, electrocardiographic, synchronized, computed tomography, for 314 HIV-infected men and women. Metabolic syndrome was defined by National Cholesterol Education Program/Adult Treatment Panel III criteria. We compared the c-IMT measurements and CAC scores of patients with metabolic syndrome with the scores of those without metabolic syndrome using a Wilcoxon test for continuous variables and a chi2 test for categorical variables. To examine the association between surrogate markers and metabolic syndrome, we used logistic regression analysis. RESULTS Participants with metabolic syndrome were more likely to have a common c-IMT measurement >0.8 mm than were those without metabolic syndrome (17% vs.7%; P=.009), but both groups were equally likely to have an internal c-IMT measurement >1.0 mm (20% vs. 13%; P=.15). Any positive CAC score was more likely to occur for participants with metabolic syndrome (80.3% vs. 46.7%; P<.0001). In a multivariate model adjusted for sex, age, ethnicity, and smoking status, participants with metabolic syndrome were more likely than those without metabolic syndrome to have an abnormal common c-IMT measurement (odds ratio [OR], 2.9; P=.020) and detectable CAC scores (OR, 4.9; P<.0001) but not a higher internal c-IMT measurement (OR, 1.6; P=.255). CONCLUSION Our study demonstrates that HIV-infected individuals with metabolic syndrome may be at increased risk for subclinical atherosclerosis and supports screening for metabolic syndrome among HIV-infected patients at risk for cardiovascular disease.

Morphologic and metabolic abnormalities in vertically HIV-infected children and youth.

Objective:To compare the distribution of lipid and glucose abnormalities and altered fat distribution among vertically HIV-infected patients and controls. Design:Cross-sectional multicenter study on HIV-infected (HIV-positive) patients, 7–24 years of age, stratified by Tanner stage and protease inhibitor use (protease inhibitor, n = 161 and non- protease inhibitor, n = 79) and seronegative controls (HIV-negative, n = 146). Methods:Measurements included fasting lipids, glucose, insulin, 2-h oral glucose tolerance test, dual-energy X-ray absorptiometry, anthropometry, and antiretroviral therapy and medical histories. Multiple linear regression models were used to compare distributions between HIV-positive and HIV-negative groups. Results:Both HIV-positive groups had long exposures to antiretroviral therapy. Protease inhibitor and nonprotease inhibitor groups had similar current CD4 cell count and HIV-1 RNA, but the protease inhibitor group had lower nadir CD4 cell count, higher peak HIV-1 RNA, and more advanced Centers for Disease Control disease stage. In adjusted analyses, both HIV-positive groups had significantly lower mean Z scores for height, weight, BMI, and total and limb fat than the HIV-negative group. Mean triglycerides were significantly higher and high-density lipoprotein cholesterol lower in both HIV-positive groups relative to the HIV-negative group. The protease inhibitor group also had significantly higher mean total, low-density lipoprotein, and non-high density lipoprotein cholesterol. Mean fasting insulin was higher in both HIV-positive groups, and 2-h glucose and insulin were higher in the protease inhibitor group. Ritonavir was associated with increasing dyslipidemia and altered glucose metabolism. Conclusion:In a large group of vertically HIV-infected children and youth with extensive antiretroviral therapy exposure, height, weight, and total and limb fat were lower than in controls. There was a high prevalence of lipid abnormalities among those on protease inhibitors and evidence of developing insulin resistance, factors that may accelerate lifetime risk for cardiovascular disease.

Evolution and predictors of change in total bone mineral density over time in HIV-infected men and women in the Nutrition for Healthy Living Study

Background:Osteopenia is common in the era of effective antiretroviral therapy (ART), yet the etiology is unclear. We evaluated the association of host factors, disease severity, and ART to changes in total body bone mineral density (total BMD) over time in HIV-infected men (n = 283) and women (n = 96). Methods:Total BMD was measured annually by whole-body dual-energy absorptiometry (DXA), and medical, dietary, and behavioral history was collected. The median time from first to last DXA was 2.5 years (range 0.9-6.8 years). Using a repeated measures regression model, we identified variables independently associated with percent change in total BMD between consecutive DXA exams (n = 799 intervals), adjusted for age, race, sex, menopause, and smoking. We estimated percent change in total BMD over an average interval (1 year) standardized for representative levels of each determinant in males, premenopausal women, and postmenopausal women. Results:Median baseline age, CD4, and viral load were 42 years, 364 cells per cubic millimeter, and 2.7 log10 copies per milliliter, respectively. The estimated change in total BMD for those not on ART was −0.37% per year [95% confidence interval (CI) −0.76 to −0.02] for men, −0.08% per year (95% CI −0.49 to 0.33) for premenopausal women, and −1.07% per year (95% CI −1.86 to −0.28) for postmenopausal women. Greater loss of total BMD was associated with lower albumin, lower body mass index, prednisone/hydrocortisone use, tenofovir use, and longer duration of didanosine. Strength training and long duration of d4T and saquinavir prevented or mitigated bone loss. For those on ART for 3 years (not including the above agents), the rate of loss was −0.57% per year (95% CI −1.00 to −0.14) for men, −0.28% (95% CI −0.71 to 0.15) for premenopausal women, and −1.27% (95% CI −2.07 to −0.47) for postmenopausal women. Postmenopausal women had greater loss than premenopausal women and men. Conclusions:Low body weight, low albumin, catabolic steroid use, and menopause may accelerate bone loss, and strength training may be protective. Tenofovir and didanosine may also have a deleterious effect on BMD.

Effectiveness of a Home-Based Exercise Intervention for HIV-Infected Adults: A Randomized Trial

The authors conducted a randomized controlled trial to assess the impact of a 15-week (20 minutes three times per week) home-based aerobic exercise intervention versus usual care on the physical endurance, immune status, and self-reported health status of 99 HIV-infected adults. In the exercise group, there was no improvement in physical endurance or health-related quality of life (HRQOL), except in the Medical Outcomes Study-HIV Health Survey Overall Health subscale (difference = 12.1, 95% confidence interval = 2.0-22.2, p = .02). Although physical endurance levels were maintained at baseline levels in the intervention group and declined in the control group, differences between the groups were small and not significant. There were also no significant changes in CD4+ T-lymphocyte counts. Exercise appears to be safe in HIV-infected patients. Improvements in physical endurance and HRQOL might result if the exercise protocol is longer or progressive. Further research is needed to establish guidelines for exercise in patients on highly active antiretroviral therapy.