Risk factors for cardiovascular disease in children infected with human immunodeficiency virus-1.

OBJECTIVE: To determine risk factors for cardiovascular disease (CVD) in children infected with human immunodeficiency virus (HIV) compared with nationally representative controls from 2003-2004 National Health and Nutrition Examination Survey (NHANES) data. STUDY DESIGN: A prospective, longitudinal analysis of CVD risk factors in 42 HIV-infected children compared with NHANES controls, with multivariable modeling of demographic, disease-specific, and treatment-related factors contributing to cardiac risk in the HIV cohort. RESULTS: The 42 children infected with HIV were initially an average of 10.1 years old; 68% were Centers for Disease Control and Prevention pediatric HIV disease stage B or C, and 76% were receiving highly active antiretroviral therapy (HAART). Compared with age- and sex-adjusted NHANES controls, the children infected with HIV had lower weight (-0.46 standard deviation [SD] vs +0.54 SD; P < .001), height (-0.62 SD vs +0.26 SD; P < .001), and body mass index (-0.09 SD vs +0.51 SD; P < .001), a higher level of triglycerides (136 mg/dL vs 90 mg/dL; P < .001), and a lower level of high-density lipoprotein (HDL) cholesterol (47 mg/dL vs 54 mg/dL; P < .001). Protease inhibitor therapy was independently associated with higher triglyceride (P = .02) and low-density lipoprotein cholesterol levels (P = .04) and lower HDL cholesterol level (P = .02); nonnucleoside reverse-transcriptase inhibitor therapy was associated with lower visceral fat (P = .01) and higher HDL cholesterol level (P = .005). CONCLUSIONS: Children infected with HIV have adverse cardiac risk profiles compared with NHANES controls. Antiretroviral therapy has a significant influence on these factors.

CD4+ cell count, viral load, and highly active antiretroviral therapy use are independent predictors of body composition alterations in HIV-infected adults: a longitudinal study.

BACKGROUND: To understand the concurrent effects of human immunodeficiency virus (HIV) infection, the immune system, and antiretroviral therapy on body composition alterations, we examined annualized composition changes in HIV-infected adults who were receiving stable antiretroviral therapy. METHODS: With use of data from the Nutrition For Healthy Living Study, we performed multivariate analyses using longitudinal models to evaluate the relationship of CD4+ cell count, viral load, and highly active antiretroviral therapy (HAART) or antiretroviral therapy (ART) with changes in trunk and extremity composition for 110 men and 42 women who provided data relating to 194 study intervals (i.e., intervals of time between 2 assessment visits). Of these intervals, 165 involved HAART use (89.7% involved protease inhibitor-based regimens), and 29 did not involve HAART use. Patients receiving HAART or ART (who had continuous use during the interval) were compared with HAART- or ART-naive subjects. RESULTS: The median length of intervals between visits was 12.9 months (interquartile range, 12.1-17.6 months). In models adjusted for HAART or ART use, baseline CD4+ cell count was positively associated with increased trunk fat (mean increase per year, 2.3% per 100 cells/mm3; 95% confidence interval [CI], 0.7%-3.9%]) and, in men, with increased extremity fat (mean increase per year, 1.8% per 100 cells/mm3; 95% CI, 0.6%-3.0%). Increase in CD4+ cell count predicted increased extremity lean mass (mean increase per year, 0.6% per 100 cells/mm3; 95% CI, 0.05%-1.1%). Higher baseline viral load predicted fat loss (trunk fat loss per year, -5.0% per log10 copies/mL; 95% CI, -9.4% to -0.7%; extremity fat loss per year, -3.4% per log10 copies/mL; 95% CI, -6.1% to -0.6%), as did zidovudine use (trunk fat loss per year, -10.8%; 95% CI, -20.4% to -1.4%; extremity fat loss per year, -4.9%; 95% CI, -9.8% to -0.01%). HAART use independently predicted decreased bone mineral content (extremity bone mineral content loss per year, -1.6%; 95% CI, -3.1% to -0.08%) but did not predict changes in fat or lean mass. Receipt of protease inhibitor-based HAART predicted a -1.9% decrease in extremity bone mineral content per year (95% CI, -3.6% to -0.2%), and zidovudine use predicted a -2.6% decrease in trunk bone mineral content per year (95% CI, -4.4% to -0.8%). CONCLUSIONS: Baseline viral load, CD4+ cell count, and change in CD4+ cell count predicted alterations in trunk fat, extremity fat, and lean mass. HAART use and zidovudine use were associated with bone loss, and zidovudine use was associated with fat loss, but HAART use was not associated with fat mass changes.

Pilot study of saquinavir and lopinavir/ritonavir twice daily in protease inhibitor-naive HIV-positive patients.

PURPOSE: Protease inhibitor (PI)-naive patients may have limited reverse transcriptase inhibitor (RTI) options due to resistance and/or toxicity. Effective, well-tolerated nucleoside reverse transcriptase inhibitor (NRTI)-sparing regimens are therefore needed. METHOD: This prospective study evaluated the efficacy and safety of saquinavir/lopinavir/ritonavir (1000/400/100 mg bid) in PI-naive patients over 48 weeks. The regimen could be intensified with NRTIs if patients did not achieve virologic suppression by 12 weeks. The primary study endpoint was virologic suppression at 48 weeks. Additional study objectives included assessment of safety, CD4 cell counts, blood lipids, PI trough levels, and anthropometrics. RESULTS: Of the 20 PI-naive study participants, 16 completed 48 weeks of study treatment, with no discontinuations attributed to virologic failure. Fourteen of 16 patients achieved virologic suppression with only the PIs; 2 patients required tenofovir intensification to achieve complete suppression. Median CD4 counts increased significantly over 48 weeks. Adverse events were generally mild and manageable. Extreme lipid elevations were uncommon, although moderate lipid elevations occurred in the majority of patients. Most patients reported some degree of central fat accumulation. CONCLUSION: Our study demonstrates that saquinavir/lopinavir/ritonavir 1000/400/100 mg bid with tenofovir intensification is a potent nucleoside-sparing regimen for PI-naive patients, associated with durable HIV suppression and improved CD4 cell counts. Fat accumulation and metabolic changes observed in this study warrant confirmation from ongoing trials.

Clinical evaluation and management of metabolic and morphologic abnormalities associated with human immunodeficiency virus.

In recent years, a spectrum of metabolic and morphologic alterations has emerged among patients infected with human immunodeficiency virus (HIV) receiving antiretroviral treatment. Changes observed include insulin resistance, dyslipidemia, abdominal and dorsocervical fat accumulation, and fat depletion in the extremities and in the face. The health consequences of these changes are not well understood but may include increased risk for diabetes, heart disease, and stroke. Therefore, clinicians that treat patients with HIV need current, practical information on management strategies and interventions for patients with manifestations of HIV-associated lipodystrophy. Literature is reviewed on the health consequences of insulin resistance, dyslipidemia, and alterations in body fat distribution in non-HIV populations to gain perspective on how such abnormalities might affect HIV-infected patients. We also suggest treatments and strategies to manage metabolic and morphologic changes in patients with HIV.

Nutrition treatment for HIV wasting: a prescription for food as Medicine.

BACKGROUND: The optimal nutrition approach for the promotion of weight gain in HIV-infected adults with wasting remains unclear. Previous dietary interventions report minimal success and provide inadequate information regarding the counseling approach, contact time, session format, and issues addressed with the subject. The methods we report were incorporated in a 12-week intervention trial for the reversal of HIV-wasting. METHODS: All subjects involved in the intervention trial for the reversal of HIV-wasting received weekly, customized, one-on-one counseling and an oral nutrition supplement (480 kcal/d with 30 g protein). The nutrition aims were to (1) increase caloric intake to surpass daily energy requirements by 500 kcal/d (suggested caloric intake: 40 to 50 kcal/kg current weight); (2) increase protein intake (1.6 to 1.8 g/kg current weight per day); and (3) identify foods that may exacerbate or curtail side effects associated with HIV. Also assessed were preconceptions, nutrition knowledge level and primary information source, and obstacles to healthy eating. Sessions, conducted by a nutritionist in an interactive, action-oriented learning approach, ranged from 30 to 60 minutes. RESULTS: At baseline, subjects harbored many misconceptions, reported numerous HIV-related side effects, and lacked practical nutrition strategies, all of which interfered with weight maintenance and health. The protocol strategies were acceptable to the patients (87% subjects completed all visits), with marked improvements in dietary intake, weight, and body composition, both during and after intervention. CONCLUSIONS: We describe a customized nutrition intervention that produces changes in energy intake, maintenance of appropriate protein intake, and the reversal of unintentional weight loss over 5 to 15 months. Sustained improvements occurred across a socioeconomically diverse population, despite persistent disease- and medication-associated side effects.

Switching to a protease inhibitor-containing, nucleoside-sparing regimen (lopinavir/ritonavir plus efavirenz) increases limb fat but raises serum lipid levels: results of a prospective randomized trial (AIDS clinical trial group 5125s).

BACKGROUND: Subcutaneous limb fat loss continues to be one the most troubling side effects of long-term antiretroviral regimens. Nucleoside analogues and protease inhibitors (PIs) have been linked to the development of this complication. METHODS: We evaluated the effects of nucleoside-sparing and PI-sparing regimens on fat distribution, bone mineral density, and metabolic parameters in 62 subjects, who were not selected for lipoatrophy, with advanced HIV (nadir CD4 count or=80,000 copies/mL) and an undetectable HIV viral load. Participants were randomized to switch their initial successful antiretroviral regimen to open-label lopinavir/ritonavir (LPV/r) at a dose of 533/133 mg twice a day and efavirenz (EFV) at a dose of 600 mg/d (the nucleoside-sparing arm) versus EFV and 2 nucleoside analogues (the PI-sparing arm). FINDINGS: At week 48, the median change in limb fat in the nucleoside-sparing arm was 562 g (6%, interquartile range [IQR]: -218-1186 g) versus a loss of -242 g (-4%, IQR: -539-452 g) in the nucleoside-containing PI-sparing arm (P = 0.086). At the time of last observation (median = 102 weeks, IQR: 73-152 weeks), a median gain of 782 g (10%, IQR: -380-1168 g) of limb fat was noted in the nonnucleoside arm (n = 22) versus a loss of 850 g (-15%, IQR: -1270 to -526 g) in the nucleoside-containing arm (n = 25; P = 0.002). INTERPRETATION: The switch to a nucleoside-sparing combination antiretroviral regimen (LPV/r + EFV) was associated with significant improvement in limb fat. These results provide additional evidence that nucleoside analogues are important in the progressive limb fat loss that characterizes antiretroviral treatment and that switching medications can significantly improve this complication. This option has to be carefully balanced with the potential to increase serum lipid levels and the trend to increase virologic failure.

The effect of micronutrient supplementation on disease progression and death in simian immunodeficiency virus-infected juvenile male rhesus macaques.

BACKGROUND: We investigated the impact that micronutrient supplementation has on the progression of simian acquired immunodeficiency syndrome (SAIDS). METHODS: Twenty-four simian immunodeficiency virus-infected juvenile male rhesus macaques were randomized into 2 groups. One group was given certified chow, and the other group was given chow and a supplement that contained 2-3 times the estimated nutritional requirement of micronutrients. Virological, immunological, and body composition measurements were taken every 4 weeks for 120 weeks. RESULTS: There was no difference between groups in weight gain, body mass index (BMI), crown-heel length, waist circumference, total tissue mass, lean mass, bone mineral content, or bone mineral density. The rhesus macaques on the supplemented diet had a higher death rate (hazard ratio, 2.39; P<.001) than those on the nonsupplemented diet; death in both groups was associated with a higher viral load set point during the early phase of infection. Additionally, higher body weight, BMI, crown-rump length, and lower viral load set point were protective from death in both groups. CONCLUSIONS: Micronutrient supplementation did not significantly alter the progression of SAIDS with respect to changes in body composition and immunological characteristics. A significantly higher rate of death was observed in rhesus macaques on the supplemented diet.

Insulin resistance in HIV-infected men and women in the nutrition for healthy living cohort.

OBJECTIVE: We evaluated insulin resistance (IR) in an HIV-infected cohort and compared our results with those of the National Health and Nutrition Examination Survey III (NHANES III). METHODS: Using a cross-sectional study design, we determined the Quantitative Insulin Sensitivity Check Index (QUICKI) in 378 nondiabetic participants in the Nutrition for Healthy Living (NFHL) study and evaluated the association of the QUICKI with demographic, socioeconomic, body composition, lipid, liver function, HIV-associated factors (CD4 cell count, viral load, highly active antiretroviral therapy type, and years infected), and injection drug use. The prevalence of IR (QUICKI <0.350) and the mean QUICKI were ascertained for nondiabetic persons aged 25 to 65 years in the NHANES III and compared with those in the NFHL study. RESULTS: Protease inhibitor (PI) highly active antiretroviral therapy (HAART) and nonnucleoside reverse transcriptase inhibitor (NNRTI) HAART were associated with worse IR in HIV-infected men. Greater waist circumference, triglycerides, age, and alanine aminotransferase were associated with worse IR, and higher high-density lipoprotein, low-density lipoprotein, and smoking were associated with less IR in the NFHL study; CD4 cell count, viral load, and years HIV infected were not associated with IR. There was no significant difference in the prevalence of IR in the NFHL study versus the NHANES III (51% vs. 47%; P = 0.27). NFHL participants were not more IR than NHANES III participants. CONCLUSIONS: IR in the NFHL study was quite common but not significantly different than in the NHANES III and was associated with similar factors as in the general population. PI HAART and NNRTI HAART were associated with worse IR in men.

A comparison of the clinical and cost-effectiveness of 3 intervention strategies for AIDS wasting.

OBJECTIVE: To compare oxandrolone (OX) or strength training with nutrition alone (NA) for AIDS wasting. SUBJECTS: Fifty patients with AIDS; 47 completing the study. INTERVENTIONS: Randomization to (1) NA with placebo pills, (2) nutrition with 10 mg of OX administered orally twice a day, or (3) nutrition with progressive resistance training (PRT) for 12 weeks. MAIN OUTCOME MEASURES: Midthigh cross-sectional muscle area (CSMA), physical functioning (PF), costs, and cost-effectiveness in dollars/quality-adjusted life-years (dollars/QALYs). RESULTS: The OX and PRT subjects had increases in CSMA (7.0% +/- 2.5%, P = 0.01; 5.0% +/- 2.0%, P = 0.04, respectively), although these increases did not differ significantly from the NA arm (NA: 1.0% +/- 1.0%; OX vs. NA: P = 0.09; PRT vs. NA: P = 0.26). Only PRT caused significant improvements in PF (mean +/- SE: 10.4 +/- 3.8 points on a 100-point scale) and 7 measures of strength (P values: 0.04 to <0.001). There were no overall differences between groups in PF change. Among patients with impaired baseline PF, however, OX was significantly less effective than NA and PRT was significantly better than NA. All treatments led to increases in protein intake and performance; NA and PRT also increased caloric intake. The institutional costs per subject in this trial were 983 dollars for NA, 3772 dollars for OX, and 3189 dollars for PRT. At a community-based level of intensity, the institutional costs per QALY were 45,000 dollars (range: 42,000 dollars-64,000 dollars) for NA, 147,000 dollars (range: 147,000 dollars-163,000 dollars) for OX, and 31,000 dollars (range: 21,000 dollars-44,000 dollars) for PRT. CONCLUSIONS: OX and PRT induce similar improvements in body composition, but PRT improves quality of life more than nutrition or OX, particularly among patients with impaired PF. PRT was the most cost-effective intervention, and OX was the least cost-effective intervention.