Opportunistic infections and organ‐specific diseases in HIV‐1‐infected children: a cohort study (1990–2006)

Objectives

Highly active antiretroviral therapy (HAART) has dramatically changed the natural history of HIV infection in children, but there are few studies in the literature about the incidence of clinical manifestations after HAART in this population, compared with adults. The aim of this study was to describe the influence of the widespread use of HAART on the development of opportunistic infections and organ‐specific diseases in HIV‐infected children.

Methods

An observational study of a cohort of 366 vertically HIV‐infected children followed from 1990 to 2006 was carried out. According to the main antiretroviral protocol used, three calendar periods (CPs) were defined and compared: CP1 (1990–1996: no patients on HAART), CP2 (1997–1999: <60% on HAART) and CP3 (2000–2006: >60% on HAART).

Results

Children experienced a progressive increase in CD4 T cell count (P<0.05) and a decrease in HIV viral load from 1996 onwards (P<0.05). Similarly, rates of death, AIDS, opportunistic infections (bacteraemia, candidosis, cryptosporidiosis and bacterial pneumonia) and organ‐specific diseases (wasting syndrome, thrombocytopenia, cardiomyopathy, lymphoid interstitial pneumonia and HIV‐associated encephalopathy) were lower in CP2 and CP3 than in CP1.

Conclusions

This study provides evidence of improved clinical outcomes in HIV‐infected children over time and shows that mortality, AIDS, opportunistic infections and organ‐specific diseases declined as HAART was progressively instituted in this population.

     

Exercise‐related goals and self‐efficacy as correlates of aquatic exercise in individuals with arthritis

Objective

To examine whether aquatic exercise–related goals, task self‐efficacy, and scheduling self‐efficacy are predictive of aquatic exercise attendance in individuals with arthritis. A secondary objective was to determine whether high attendees differed from low attendees on goals and self‐efficacy.

Methods

The sample comprised 216 adults with arthritis (mean age 69.21 years). Measures included exercise‐related goal difficulty and specificity, task and scheduling self‐efficacy, and 8‐week aquatic exercise attendance.

Results

Results of a multiple hierarchical regression analysis were significant (P < 0.01). Goal difficulty, specificity, and task self‐efficacy were independent predictors of attendance (P < 0.05). A significant multivariate analysis of variance (P < 0.01) indicated that high attendees had higher task and scheduling self‐efficacy and lower goal difficulty than did low attendees (P < 0.05).

Conclusion

Support for the importance of exercise‐related goal setting and self‐efficacy was demonstrated. Implications pertain to the design of interventions to impact aquatic exercise.

     

Large particle hyaluronic acid for the treatment of facial lipoatrophy in HIV‐positive patients: 3‐year follow‐up study

Objectives

Facial lipoatrophy can be a stigmatizing side effect of antiretroviral (AVR) treatment for HIV‐infected patients. We sought to evaluate the long‐term efficacy and safety of a new formulation of hyaluronic acid that can be injected in larger amounts and into deeper skin layers during 3 years of follow‐up.

Methods

Twenty patients received injections of Restylane SubQ^™. Refill treatment was offered at 12 and 24 months. Treatment effects were evaluated using ultrasound, the Global Aesthetic Improvement Scale, visual analogue scale (VAS) and the Rosenberg self‐esteem scale.

Results

Seventeen patients remained at 36 months. Mean (± standard deviation) total cutaneous thickness increased from 6 ± 1 mm at baseline to 12 ± 1 mm (P<0.001) at 36 months. Response rate (total cutaneous thickness >10 mm) was 70%. Fifteen patients classified their facial appearance as very much or moderately improved. VAS increased from 39 ± 25 to 70 ± 20 (P<0.05) and higher self‐esteem scores were reported. Local swelling and tenderness after treatment was common. Persistent papules found in several patients after treatment were removed effectively with hyaluronidase injections. Three patients, treated only at baseline, still had higher total cutaneous thickness scores at 36 months.

Conclusions

Our results indicate that a large particle hyaluronic acid formulation is a durable and well‐tolerated dermal filler for treating HIV‐positive patients with facial lipoatrophy.

     

Long‐term high‐physiological‐dose growth hormone reduces intra‐abdominal fat in HIV‐infected patients with a neutral effect on glucose metabolism

Objectives

The aim of the study was to investigate the effect of long‐term high‐physiological‐dose recombinant human growth hormone (rhGH) therapy on fat distribution and glucose metabolism in HIV‐infected patients.

Methods

Forty‐six HIV‐infected Caucasian men on highly active antiretroviral therapy (HAART), with an age range of 21–60 years and no significant comorbidity, were included in this randomized, placebo‐controlled, double‐blind, single‐centre trial. Twenty‐eight subjects were randomized to 0.7 mg/day rhGH, and 18 subjects to placebo, administered as daily subcutaneous injections between 1 and 3 pm for 40 weeks. Endpoints included changes in visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), limb fat mass, percentage of limb fat, plasma lipids, insulin resistance and glucose tolerance.

Results

VAT and trunk fat mass decreased significantly in the GH group compared with the placebo group [−19 cm² (−11%) vs. 12 cm² (6%), P=0.03, and −548 g (−9%) vs. 353 g (6%), P<0.01, respectively]. The beneficial fat redistribution in the GH group occurred without concomitant changes in subcutaneous fat at the abdomen or extremities. rhGH therapy was well tolerated. Insulin resistance, glucose tolerance, and total plasma cholesterol and triglycerides did not significantly change during intervention.

Conclusions

Daily 0.7 mg rhGH treatment for 40 weeks reduced abdominal visceral fat and trunk fat mass in HIV‐infected patients. This treatment appeared to be safe with respect to glucose tolerance and insulin sensitivity.

     

Antibody levels correlate with creatine kinase levels and strength in anti–3‐hydroxy‐3‐methylglutaryl‐coenzyme A reductase–associated autoimmune myopathy

Objective

Autoantibodies recognizing 3‐hydroxy‐3‐methylglutaryl‐coenzyme A reductase (HMGCR) are found in patients with statin‐associated immune‐mediated necrotizing myopathy and, less commonly, in statin‐unexposed patients with autoimmune myopathy. The main objective of this study was to define the association of anti‐HMGCR antibody levels with disease activity.

Methods

Anti‐HMGCR levels, creatine kinase (CK) levels, and strength were assessed in anti‐HMGCR–positive patients. Associations of antibody level with CK level and strength at visit 1 were analyzed in 55 patients, 40 of whom were exposed to statins. In 12 statin‐exposed and 5 statin‐unexposed patients with serum from 5 serial visits, the evolution of antibody levels, CK levels, and strength was investigated.

Results

Antibody levels were associated with CK levels (P < 0.001), arm strength (P < 0.05), and leg strength (P < 0.05) at visit 1, but these associations were only significant among statin‐exposed patients in stratified analyses. With immunosuppressive treatment over 26.2 ± 12.6 months (mean ± SD), antibody levels declined (P < 0.05) and arm abduction strength improved (P < 0.05) in the 17 patients followed up longitudinally. The separate analysis showed that statin‐exposed patients developed decreased antibody levels (P < 0.01), decreased CK levels (P < 0.001), improved arm strength (P < 0.05), and improved hip flexion strength (P < 0.05) with treatment. Anti‐HMGCR antibody levels did not normalize in any patient.

Conclusion

In the entire cohort, initial anti‐HMGCR levels correlated with indicators of disease activity; with immunosuppressive treatment, antibody levels declined and arm strength improved. Statin‐exposed patients had significant improvements in CK levels and strength whereas statin‐unexposed patients did not, suggesting a phenotypic difference between statin‐exposed and statin‐unexposed anti‐HMGCR–positive patients.

     

Mid‐dosing interval concentration of atazanavir and virological outcome in patients treated for HIV‐1 infection

Objectives

We investigated the clinical significance of monitoring the mid‐dosing interval atazanavir (ATV) concentration (measured 12 ± 2 h after intake; C_{12 h}) in patients taking this drug once daily in the evening.

Methods

We retrospectively selected HIV‐infected patients harbouring ATV‐susceptible virus who underwent therapeutic drug monitoring (TDM) of ATV C_{12 h} during routine out‐patient visits, and we correlated C_{12 h} to the 24‐week virological response and toxicity.

Results

A total of 115 plasma samples from 86 patients (76.7% with baseline HIV RNA<50 HIV‐1 RNA copies/mL) were analysed. ATV plasma concentrations showed high inter‐individual variability. ATV plasma levels were higher in samples obtained from patients taking boosted regimens (P<0.001) and not concomitantly receiving acid‐reducing agents (P=0.007). In a multivariate model, ritonavir boosting, use of acid‐reducing agents and liver cirrhosis showed an independent association with ATV level. Virological response at 24 weeks was observed for 94 of the 115 samples (81.7%). We identified a concentration cut‐off of 0.23 mg/L which predicted virological response at 24 weeks: samples with a C_{12 h}≤0.23 mg/L showed virological failure in 41.2% of cases, whereas samples with a C_{12 h}>0.23 mg/L showed virological failure in 14.3% of cases (P=0.021). In multivariate analysis, C_{12 h}>0.23 mg/L was an independent predictor of virological response [odds ratio (OR) 4.23, P=0.031]. ATV levels correlated with concomitant unconjugated bilirubin levels (r=0.223, P=0.037), but a concentration cut‐off predictive of moderate/severe hyperbilirubinaemia could not be identified.

Conclusions

We identified a C_{12 h} efficacy threshold that predicted virological response; this could be useful for morning TDM in selected subjects receiving ATV in the evening. Results must be interpreted with caution given the retrospective design of the study.

     

Non‐medically supervised treatment interruptions among participants in a universally accessible antiretroviral therapy programme

Background

We examined clinical outcomes, patient characteristics and trends over time of non‐medically supervised treatment interruptions (TIs) from a free‐of‐charge antiretroviral therapy (ART) programme in British Columbia (BC), Canada.

Methods

Data from ART‐naïve individuals ≥18 years old who initiated triple combination highly active antiretroviral therapy (HAART) between January 2000 and June 2006 were analysed. Participants having ≥3 month gap in HAART coverage were defined as having a TI. Cox proportional hazards modelling was used to examine factors associated with TIs and to examine factors associated with resumption of treatment.

Results

A total of 1707 participants were study eligible and 643 (37.7%) experienced TIs. TIs within 1 year of ART initiation decreased from 29% of individuals in 2000 to 19% in 2006 (P<0.001). TIs were independently associated with a history of injection drug use (IDU) (P=0.02), higher baseline CD4 cell counts (P<0.001), hepatitis C co‐infection (P<0.001) and the use of nelfinavir (NFV) (P=0.04) or zidovudine (ZDV)/lamivudine (3TC) (P=0.009) in the primary HAART regimen. Male gender (P<0.001), older age (P<0.001), AIDS at baseline (P=0.008) and having a physician who had prescribed HAART to fewer patients (P=0.03) were protective against TIs. Four hundred and eighty‐eight (71.9%) participants eventually restarted ART with male patients and those who developed an AIDS‐defining illness prior to their TI more likely to restart therapy. Higher CD4 cell counts at the time of TI and unknown hepatitis C status were associated with a reduced likelihood of restarting ART.

Conclusion

Treatment interruptions were associated with younger, less ill, female and IDU participants. Most participants with interruptions eventually restarted therapy. Interruptions occurred less frequently in recent years.

     

Health‐related quality of life in juvenile‐onset systemic lupus erythematosus and its relationship to disease activity and damage

Objective

To assess the health‐related quality of life (HRQL) of patients with juvenile‐onset systemic lupus erythematosus (JSLE) and its relationship with disease activity and accumulated damage.

Methods

In this cross‐sectional study, HRQL was assessed using the Child Health Questionnaire (CHQ), disease activity using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), and accumulated damage using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI).

Results

A total of 297 patients were included. The mean ± SD physical and psychosocial summary scores of the CHQ were 40.2 ± 15.0 and 44.8 ± 10.7, respectively. The most impaired CHQ subscales were global health, general health perceptions, and parent impact–emotional. The SLEDAI score was significantly correlated with both the physical summary score (r = ?0.29, P < 0.0001) and psychosocial summary score (r = ?0.25, P < 0.0001), whereas the SDI score was significantly correlated only with the physical summary score (r = ?0.23, P = 0.0001).

Conclusion

We found that patients with JSLE have significant impairment of their HRQL, particularly in the physical domain. HRQL may be affected by both disease activity and accumulated damage, particularly in the renal, central nervous, and musculoskeletal systems.

     

Effects of a stress‐reduction program on psychological function,pain, and physical function of systemic lupus erythematosus patients: A randomized controlled trial

Objective

To assess the effects of a stress‐reduction program on pain, psychological function, and physical function in persons with systemic lupus erythematosus (SLE) who experience pain.

Methods

Ninety‐two SLE patients were assigned randomly to receive either biofeedback‐assisted cognitive‐behavioral treatment (BF/CBT), a symptom‐monitoring support (SMS) intervention, or usual medical care (UC) alone.

Results

BF/CBT participants had significantly greater reductions in pain and psychological dysfunction compared with the SMS group (pain, P = 0.044; psychological functioning, P < 0.001) and the UC group (pain, P = 0.028; psychological functioning, P < 0.001). BF/CBT had significantly greater improvement in perceived physical function compared with UC (P = 0.035), and improvement relative to SMS was marginally significant (P = 0.097). At a 9‐month followup evaluation, BF/CBT continued to exhibit relative benefit compared with UC in psychological functioning (P = 0.023).

Conclusion

This study supports the utility of a brief stress management program for short‐term improvement in pain, psychological function, and perceived physical function among persons with SLE who experience pain.

     

Anti–topoisomerase I (Anti–Scl‐70) antibodies in patients with systemic lupus erythematosus

Objective

To investigate the presence and clinical significance of anti–Scl‐70 antibodies in patients with systemic lupus erythematosus (SLE).

Methods

Levels of antibodies against Scl‐70 were determined by a commercial clinical enzyme‐linked immunosorbent assay (ELISA) during routine evaluation. Results were verified by an additional ELISA with a characterized bovine Scl‐70, by ELISA with a recombinant human topoisomerase I, by Western blot, and by double diffusion in agar gel. Disease activity was estimated retrospectively by the Systemic Lupus Activity Measure (SLAM).

Results

Of 128 consecutive SLE patients, 25% were positive for anti–Scl‐70 antibody; this antibody activity was cognate in nature. No SLE patient could be classified as also having systemic sclerosis. The levels of anti–Scl‐70 were significantly correlated with the SLAM score for the entire cohort (r = 0.563, P < 0.001) and for 7 individual patients with multiple longitudinal measurements (r = 0.755–0.951, P < 0.001; n = 6) (r = 0.378, P < 0.05; n = 1). A significant correlation was also found between the levels of anti–Scl‐70 and anti–double‐stranded DNA antibodies (r = 0.558, P < 0.001). Patients with anti–Scl‐70 had significantly higher risk of pulmonary hypertension (P < 0.01) and renal involvement (P < 0.001) than patients without this antibody.

Conclusion

Anti–Scl‐70 antibody is present in a significant subset of patients with SLE. For this subset, it offers a good correlate of disease activity and suggests increased risk for pulmonary hypertension and nephritis.

     

Juvenile‐onset ankylosing spondylitis is associated with worse functional outcomes than adult‐onset ankylosing spondylitis

Objective

To compare functional outcome of patients with juvenile‐onset ankylosing spondylitis (JoAS; defined as AS with symptom onset before 16 years of age) with that of patients with adult‐onset AS (AoAS) and to identify variables associated with a poor functional outcome of JoAS.

Methods

A cross‐sectional study was performed of 326 JoAS patients who participated in a postal survey conducted by the Spondylitis Association of America. This cohort was compared with 2,021 AoAS patients who participated in the same survey. Simple and multiple logistic regression analyses were performed to identify differences with respect to clinical features, demographic features, and functional outcome (defined by the Bath Ankylosing Spondylitis Functional Index [BASFI]) between the 2 groups. A validation cohort of 255 AS patients was also surveyed.

Results

The mean ± SD BASFI score (controlled for disease duration) for JoAS was 51.3 ± 1.5 compared with 46.4 ± 0.6 for AoAS (P < 0.0001). Multiple logistic regression identified only age (P < 0.0001) and income status (P < 0.0001) as factors associated with functional impairment.

Conclusion

It appears that JoAS is a progressive disease and is associated with significant delay in diagnosis and worse functional outcome compared with AoAS. Furthermore, women do worse than men with JoAS. This would argue for the importance of early diagnosis and treatment of AS, particularly in the subgroup of patients with JoAS.

     

Effects of teriparatide versus alendronate for treating glucocorticoid‐induced osteoporosis: Thirty‐six–month results of a randomized,double‐blind,controlled trial

Objective

To compare the bone anabolic drug teriparatide (20 μg/day) with the antiresorptive drug alendronate (10 mg/day) for treating glucocorticoid‐induced osteoporosis (OP).

Methods

This was a 36‐month, randomized, double‐blind, controlled trial in 428 subjects with OP (ages 22–89 years) who had received ≥5 mg/day of prednisone equivalent for ≥3 months preceding screening. Measures included changes in lumbar spine and hip bone mineral density (BMD), changes in bone biomarkers, fracture incidence, and safety.

Results

Increases in BMD from baseline were significantly greater in the teriparatide group than in the alendronate group, and at 36 months were 11.0% versus 5.3% for lumbar spine, 5.2% versus 2.7% for total hip, and 6.3% versus 3.4% for femoral neck (P < 0.001 for all). In the teriparatide group, median percent increases from baseline in N‐terminal type I procollagen propeptide (PINP) and osteocalcin (OC) levels were significant from 1 to 36 months (P < 0.01), and increases in levels of C‐terminal telopeptide of type I collagen (CTX) were significant from 1 to 6 months (P < 0.01). In the alendronate group, median percent decreases in PINP, OC, and CTX were significant by 6 months and remained below baseline through 36 months (P < 0.001). Fewer subjects had vertebral fractures in the teriparatide group than in the alendronate group (3 [1.7%] of 173 versus 13 [7.7%] of 169; P = 0.007), with most occurring during the first 18 months. There was no significant difference between groups in the incidence of nonvertebral fractures (16 [7.5%] of 214 subjects taking teriparatide versus 15 [7.0%] of 214 subjects taking alendronate; P = 0.843). More subjects in the teriparatide group (21%) versus the alendronate group (7%) had elevated predose serum calcium concentrations (P < 0.001).

Conclusion

Our findings indicate that subjects with glucocorticoid‐induced OP treated with teriparatide for 36 months had greater increases in BMD and fewer new vertebral fractures than subjects treated with alendronate.

     

Health‐related quality of life in systemic sclerosis as measured by the short form 36: Relationship with clinical and biologic markers

Objective

To evaluate health‐related quality of life (HRQOL) in patients with systemic sclerosis (SSc) using the Short Form 36 (SF‐36) and to correlate SF‐36 scores with clinical and biologic markers.

Methods

The SF‐36 was administered to 24 controls and 24 SSc patients. SSc patients also were evaluated for subset (limited SSc [lSSc] and diffuse SSc [dSSc]), age, disease duration, angiotensin‐converting enzyme (ACE) levels, autoantibodies, and skin and internal organ involvement.

Results

The physical summary score (PSS) was lower in SSc patients than in controls (P < 0.05), whereas the mental summary score (MSS) was higher in dSSc than in lSSc patients (P < 0.05). Five of 8 single SF‐36 domain scores were lower in SSc patients than in controls (P < 0.05). Vitality was higher in dSSc than in controls (P < 0.001). In SSc, elder age correlated with lower PSS; low ACE levels and high skin score correlated with higher general mental health and role limitations due to physical problems, respectively (P < 0.05). Patients with heart involvement had higher scores in general health perceptions (P < 0.05).

Conclusion

The SF‐36 shows that HRQOL is impaired in patients with SSc. Higher scores in MSS and vitality in patients with dSSc and correlations of high SF‐36 scores with specific organ involvement suggest that SSc patients with severe disease are more able to cope with HRQOL modification.

     

Nonconcordance between subclinical atherosclerosis and the calculated Framingham risk score in HIV‐infected patients: relationships with serum markers of oxidation and inflammation

Objectives

HIV‐infected patients show an increased cardiovascular disease (CVD) risk resulting, essentially, from metabolic disturbances related to chronic infection and antiretroviral treatments. The aims of this study were: (1) to evaluate the agreement between the CVD risk estimated using the Framingham risk score (FRS) and the observed presence of subclinical atherosclerosis in HIV‐infected patients; (2) to investigate the relationships between CVD and plasma biomarkers of oxidation and inflammation.

Methods

Atherosclerosis was evaluated in 187 HIV‐infected patients by measuring the carotid intima‐media thickness (CIMT). CVD risk was estimated using the FRS. We also measured the circulating levels of interleukin‐6, monocyte chemoattractant protein‐1 (MCP‐1) and oxidized low‐density lipoprotein (LDL), and paraoxonase‐1 activity and concentration.

Results

There was a weak, albeit statistically significant, agreement between FRS and CIMT (κ=0.229, P<0.001). A high proportion of patients with an estimated low risk had subclinical atherosclerosis (n=66; 56.4%). In a multivariate analysis, the presence of subclinical atherosclerosis in this subgroup of patients was associated with age [odds ratio (OR) 1.285; 95% confidence interval (CI) 1.084–1.524; P=0.004], body mass index (OR 0.799; 95% CI 0.642–0.994; P=0.044), MCP‐1 (OR 1.027; 95% CI 1.004–1.050; P=0.020) and oxidized LDL (OR 1.026; 95% CI 1.001–1.051; P=0.041).

Conclusion

FRS underestimated the presence of subclinical atherosclerosis in HIV‐infected patients. The increased CVD risk was related, in part, to the chronic oxidative stress and inflammatory status associated with this patient population.

     

Risk genotypes in folate‐dependent enzymes and their association with methotrexate‐related side effects in rheumatoid arthritis

Objective

Methotrexate (MTX) is an antifolate agent that is often associated with toxicity. This study investigated whether risk genotypes for folate‐dependent enzymes are associated with the toxicity of MTX in patients with rheumatoid arthritis (RA).

Methods

Blood was collected for analysis in a muticenter, cross‐sectional study of RA patients who had been receiving MTX for at least 1 month prior to enrollment, and side effects occurring at the time of a single study visit were recorded. Low‐penetrance risk genotypes in methylenetetrahydrofolate reductase (MTHFR) 677TT, thymidylate synthase (TSER) *2/*2 (variable number of tandem repeats), amino imidazole ribonucleotide transformylase (ATIC) 347GG, and serine hydroxymethyltransferase (SHMT1) 1420CC were measured and summed to constitute the toxicogenetic index specific to each patient. Statistical analyses consisted of logistic regression models with clustered‐center effects, and associations with risk genotypes were expressed as adjusted odds ratios (ORs).

Results

Among 214 patients enrolled at 4 study sites, a total of 67 patients (31%) presented with a side effect (gastrointestinal event, headache, lethargy, alopecia, cough, or dyspnea). Risk genotypes associated with side effects in the central nervous system were MTHFR 677TT (OR 3.3, P < 0.01) and SHMT1 1420CC (OR 2.4, P < 0.05). ATIC 347GG was associated with gastrointestinal side effects (OR 3.0, P < 0.01), while TSER*2/*2 (OR 5.4, P < 0.01) and SHMT1 1420CC (OR 3.2, P < 0.01) were associated with alopecia. The toxicogenetic index ranged from 0 to 3 (median 1). An index of 3 was associated with an ∼7‐fold higher likelihood of having a side effect compared with an index of 0 (P < 0.01).

Conclusion

These data suggest that a composite index of the cumulative risk genotypes in folate‐dependent enzymes may be an effective means of profiling RA patients who develop side effects to MTX.

     

Effect of simplification from protease inhibitors to boosted atazanavir‐based regimens in real‐life conditions

Background

Atazanavir (ATV) boosted with ritonavir (ATV/r) is a potent, well‐tolerated, once‐daily protease inhibitor (PI). Few data are available on this agent as a treatment simplification option for patients taking other PIs.

Objective

The aim of the study was to determine the effectiveness and safety of ATV‐containing regimens in patients who have simplified their antiretroviral treatment.

Methods

SIMPATAZ was a multicentre, prospective, noninterventional study in patients who had undetectable HIV RNA on their current PI‐containing therapy and who were switched to an ATV/r‐based regimen. Patients underwent a routine physical examination, and data were collected on HIV RNA levels, CD4 cell counts, liver function, lipid parameters, adverse reactions, adherence to treatment and patient satisfaction.

Results

A total of 183 patients were enrolled in the study and included in the analysis (80% were male, 29% had AIDS, and 52% were coinfected with HIV and hepatitis B virus or hepatitis C virus). The median baseline CD4 count was 514 cells/μL. Median exposure to previous HIV therapy was 8 years, and 32% of patients had a history of PI failures. Lopinavir boosted with ritonavir was the most frequent PI replaced (62%) and tenofovir+lamivudine /emtricitabine the backbone most used during the study (29%). The study drug was discontinued early by 25 patients (14%), two of whom discontinued as a result of adverse events (Hodgkin lymphoma and vomiting). Two patients died (lung cancer and myocardial infarction). At month 12, 93% of the study population had an undetectable HIV RNA viral load. Hyperbilirubinaemia >3 mg/dL and increased alanine aminotransferase levels>200 IU/L were observed in 38.5% and 4.4% of patients, respectively. Median changes from baseline to month 12 in total cholesterol, triglycerides and low‐density lipoprotein cholesterol were ?13 mg/dL (?7%; P<0.0001), ?19 mg/dL (?13%; P<0.0001) and ?7 mg/dL (?6%; P=0.021), respectively.

Conclusions

In a real‐world setting, switching from other PIs to ATV/r is a well‐tolerated and safe option for improving the lipid profile and for retaining virological response in controlled pretreated patients.

     

Individuals with high total cholesterol/hdl cholesterol ratios are insulin resistant

Jeppesen J, Facchini FS, Reaven GM. (The Department of Medicine, Stanford University School of Medicine, Stanford, and Shaman Pharmaceuticals Inc., South San Francisco, CA, USA). Individuals with high total cholesterol/hdl cholesterol ratios are insulin resistant. Journal of Internal Medicine 1998; 243 : 293–98.

Objectives

To define the pathophysiologic characteristics of patients at high risk for coronary heart disease due to an increased ratio of total cholesterol (TC) to high density lipoprotein-cholesterol (HDL-C).

Design

Cross-sectional.

Setting

Clinical Research Center.

Subjects

One hundred-20 healthy, non-diabetic, normotensive, volunteers were screened for this study. From this pool, 40 individuals (20 females and 20 males) with the highest and the lowest TC/HDL-C ratios were selected for comparison.

Main Outcome Measures

Values for body mass index (BMI), ratio of waist to hip girth (WHR), and blood pressure were obtained on all patients. In addition, measurements were made of fasting lipid and lipoprotein concentrations, plasma glucose and insulin responses to an oral glucose challenge, and insulin resistance as assessed by the insulin suppression test.

Results

Age, BMI, and WHR were the same in the two groups. However, the group with a high TC/HDL-C ratio had higher (P < 0.05) systolic and diastolic blood pressures. In addition, patients with a high TC/HDL-C ratio had significantly higher (P < 0.001) very low density (VLDL) and low density lipoprotein (LDL)-cholesterol concentrations and lower HDL-cholesterol concentrations, with significant (P < 0.001) correlations between the TC/HDL-C ratio and VLDL (r= 0.60), LDL (r= 0.54), and HDL (r=? 0.73) cholesterol concentrations. Patients with a high TC/HDL-C ratio were also significantly (P < 0.05–0.001) more insulin resistant, glucose intolerant with a greater plasma insulin response to oral glucose, and hypertriglyceridemic.

Conclusions

The results indicate that an increase in LDL-cholesterol concentration is not necessarily the major contributor to a high ratio of TC/HDL-C. Furthermore, individuals with this epidemiologic designation are insulin resistant, and liable to all the other abnormalities associated with this metaboic defect.

     

Treatment of rheumatoid arthritis with the selective costimulation modulator abatacept: Twelve‐month results of a phase iib,double‐blind,randomized, placebo‐controlled trial

Objective

To determine the clinical efficacy, safety, and immunogenicity of abatacept (CTLA‐4Ig), a selective costimulation modulator, in patients with rheumatoid arthritis (RA) that has remained active despite methotrexate (MTX) therapy.

Methods

This was a 12‐month, multicenter, randomized, double‐blind, placebo‐controlled study. A total of 339 patients with active RA despite MTX therapy were randomly assigned to receive 10 mg/kg abatacept (n = 115), 2 mg/kg abatacept (n = 105), or placebo (n = 119). This report focuses on the results observed at month 12 of a phase IIb trial.

Results

A significantly greater percentage of patients treated with 10 mg/kg abatacept met the American College of Rheumatology 20% improvement criteria (achieved an ACR20 response) at 1 year compared with patients who received placebo (62.6% versus 36.1%; P < 0.001). Greater percentages of patients treated with 10 mg/kg abatacept also achieved ACR50 responses (41.7% versus 20.2%; P < 0.001) and ACR70 responses (20.9% versus 7.6%; P = 0.003) compared with patients who received placebo. For patients treated with 10 mg/kg abatacept, there were also statistically significant and clinically important improvements in modified Health Assessment Questionnaire scores compared with patients who received placebo (49.6% versus 27.7%; P < 0.001). Abatacept at a dosage of 10 mg/kg elicited an increase in rates of remission (Disease Activity Score in 28 joints of <2.6) compared with placebo at 1 year (34.8% versus 10.1%; P < 0.001). The incidence of adverse events was comparable between the groups, and no significant formation of neutralizing antibodies was noted.

Conclusion

Abatacept was associated with significant reductions in disease activity and improvements in physical function that were maintained over the course of 12 months in patients with RA that had remained active despite MTX treatment. Abatacept was found to be well tolerated and safe over the course of 1 year. Abatacept in combination with MTX has the potential to play an important role in future RA therapy.

     

Mode of delivery in HIV‐infected pregnant women and prevention of mother‐to‐child transmission: changing practices in Western Europe

Objectives

The aim of the study was to examine temporal and geographical patterns of mode of delivery in the European Collaborative Study (ECS), identify factors associated with elective caesarean section (CS) delivery in the highly active antiretroviral therapy (HAART) era and explore associations between mode of delivery and mother‐to‐child transmission (MTCT).

Methods

The ECS is a cohort study in which HIV‐infected pregnant women are enrolled and their infants prospectively followed. Data on 5238 mother–child pairs (MCPs) enrolled in Western European ECS sites between 1985 and 2007 were analysed.

Results

The elective CS rate increased from 16% in 1985–1993 to 67% in 1999–2001, declining to 51% by 2005–2007. In 2002–2004, 10% of infants were delivered vaginally, increasing to 34% by 2005–2007. During the HAART era, women in Belgium, the United Kingdom and the Netherlands were less likely to deliver by elective CS than those in Italy and Spain [adjusted odds ratio (AOR) 0.07; 95% confidence interval (CI) 0.04–0.12]. The MTCT rate in 2005–2007 was 1%. Among MCPs with maternal HIV RNA<400 HIV‐1 RNA copies/mL (n=960), elective CS was associated with 80% decreased MTCT risk (AOR 0.20; 95% CI 0.05–0.65) adjusting for HAART and prematurity. Two infants born to 559 women with viral loads <50 copies/mL were infected, one of whom was delivered by elective CS (MTCT rate 0.4%; 95% CI 0.04–1.29).

Conclusions

Our findings suggest that elective CS prevents MTCT even at low maternal viral loads, but the study was insufficiently powered to enable a conclusion to be drawn as to whether this applies for viral loads <50 copies/mL. Diverging mode of delivery patterns in Europe reflect uncertainties regarding the risk–benefit balance of elective CS for women on successful HAART.