Relationship between IgM antibody to human cytomegalovirus, virus load, donor and recipient serostatus, and administration of methylprednisolone as risk factors for cytomegalovirus disease after liver transplantation

A retrospective study was performed on a selected cohort of 40 liver transplant recipients derived from the previous prospective follow-up of 162 liver transplant patients. The criterion for selection of this cohort was the presence of human cytomegalovirus (HCMV) DNAemia after transplantation, as determined by qualitative polymerase chain reaction (PCR). These 40 patients were followed longitudinally by quantitative PCR and by the new recombinant antigen-based AxSYM immunoassay for IgM to HCMV. The detection of IgM to CMV after transplantation was significantly associated with the development of HCMV disease in patients who had evidence of active HCMV replication in the blood by PCR (P=.01). On the basis of multivariate logistic regression analyses, the maximum titer of IgM detected after transplantation was a risk factor that was independent of augmented methylprednisolone and donor seropositivity. However, in multivariate analyses, elevated virus load continued to be the predominant risk factor for progression to HCMV disease.     

Reasons for modification and discontinuation of antiretrovirals: results from a single treatment centre

OBJECTIVE: To describe the reasons for, and factors associated with, modification and discontinuation of highly active antiretroviral therapy (HAART) regimens at a single clinic. SUBJECTS: A total of 556 patients who started HAART at the Royal Free Hospital were included in analyses. Modification was defined as stopping or switching any antiretrovirals in the regimen, whereas discontinuation was defined as the simultaneous stopping of all antiretrovirals included in the initial regimen. Reasons were classified as immunological/virological failure (IVF) and toxicities and patient choice/poor compliance (TPC). RESULTS: The median CD4 count at starting HAART was 171 x 10(6) cells/l and viral load 5.07 log copies/ml. During a median follow-up of 14.2 months, 247 patients (44.4%) modified their HAART regimen, 72 due to IVF (29.1%) and 159 due to TPC (64.4%) and a total of 148 patients (26.6%) discontinued HAART. Older patients were less likely to modify HAART [relative hazard (RH), 0.73 per 10 years; P = 0.0008], as were previously treatment-naive patients (RH, 0.65; P = 0.0050), those in a clinical trial (RH, 0.64; P = 0.027) and those who started nelfinavir (RH, 0.57; P = 0.035). Patients who started with four or more drugs (RH, 2.21, P < 0.0001), who included ritonavir in the initial regimen (RH, 1.41; P = 0.035) or who had higher viral loads during follow-up (RH per log increase, 1.51; P < 0.0001) were more likely to modify HAART. CONCLUSIONS: There was a high rate of modification and discontinuation of HAART regimens in the first 12 months, particularly due to toxicities, patient choice or poor compliance.     

Reduced bone mineral density in HIV-positive individuals

A total of 105 HIV-positive patients underwent dual-energy X-ray absorbtiometry (DEXA) scan to assess bone mineral density (BMD). The prevalence of reduced BMD was found to be 71% and was higher in patients who had ever been treated with protease inhibitors (PI). Our results suggest a possible association between PI and reduced BMD, and further complicate the debate regarding when to commence treatment of HIV and with what agents to start.     

Pre-travel preparation and outcome of HIV-infected travellers from a UK clinic

Objectives. To review the pre-travel preparations and travel health outcomes of HIV-infected individuals. Methods. A prospective questionnaire-based study among English speaking adults with HIV infection attending an outpatient clinic from July to November 2000. Results. Baseline and follow-up questionnaire data were available for 34 individuals whose median CD4 count was 451 cells/mm(3). Eleven of these (32%) had sought travel advice before departure. Eight (23.5%) had been vaccinated or were planning vaccination against at least one condition and 17 (50%) listed travel-specific medications they planned to take with them. Those who were travelling to Africa were more likely to be vaccinated than those who were not travelling to Africa (3/4 vs 5/30, respectively, P=0.03). Those travelling to Europe were less likely to be vaccinated than those who were not (1/16 vs 7/18, P=0.04). The median duration of travel was 14 days (1-180). Fifteen subjects (44%) became ill while abroad. Those who became ill abroad were more likely to have visited Asia (P=0.003) and less likely to have visited the Americas (P=0.02) than those who did not become ill abroad. In addition, they tended to have stayed abroad for longer periods (P=0.07) and had visited more countries (P=0.04) than those who did not become ill abroad. Sixteen individuals (47%) reported illness on their return to the UK. Conclusions. HIV-infected travellers have an increased susceptibility to opportunistic and other travel-related infections and the need for appropriate advice, vaccination and prophylactic therapy is important. Health care provision in this field is in need of uniform guidelines to coordinate travel health management for this particular high risk group.     

Beta-2 microglobulin as a predictor of prognosis in HIV-infected men with haemophilia: a proposed strategy for use in clinical care

Summary Whilst the prognostic value of serum beta-2 microglobulin (s-β₂m) is well documented, the lack of a simple strategy for its use means that it is rarely ever measured in clinical practice. The prognosis associated with s-β₂m at two different points in HIV infection, as defined by the CD4 count, was studied in a cohort of 111 men with haemophilia registered at the Royal Free Hospital School of Medicine, London. At CD4 counts of 0·5 and 0·2 × 10⁹/1, a raised s-β₂m level was significantly associated with an increased risk of developing AIDS (P= 0·002 and 0·022 respectively, adjusted for the patient's age). Kaplan-Meier progression rates to AIDS by 4·5 years after a CD4 count of 0·5 × 10⁹/1 were 57% (95% CI 32–82%) in those with s-β₂m levels of 3 mg/1 or more, but 20% (95% CI 4–36%) in those with s-β₂m levels of less than 3 mg/1. By 3·5 years after a CD4 count of 0·2 × 10⁹/1, Kaplan-Meier progression rates to AIDS were 75% (95% CI 52–98%) in those with s-β₂m levels of 3·8 mg/1 or more, and 47% (95% CI 29–66%) in those with s-β₂m levels of less than 3·8 mg/1. In the absence of acute viral infections, a raised s-β₂m indicates those who will tend to progress to AIDS more rapidly than those with lower s-β₂m levels and the same CD4 count. S-β₂m levels in general are likely to be higher in haemophilia patients than in other, nonhaemophilic risk groups. Whilst care should be taken, therefore, when applying our chosen cut-off values to nonhaemophilic patients, our findings support the introduction of prophylaxis and antiviral therapies at a higher CD4 count in those with raised s-β₂m levels relative to other patients in the same risk group whilst delaying treatment in those with lower CD4 counts, but relatively normal s-β₂m levels.     

An audit of antiretroviral treatment use in HIV-infected patients in a London clinic: the limitations of observational databases when auditing antiretroviral treatment use

Objective

To audit the use of antiretroviral (ARV) treatment in a large treatment clinic in the UK against the British HIV Association (BHIVA) ARV treatment guidelines.

Methods

All patients under follow‐up between 1st January 2000 and 1st January 2001 were included. The most recent CD4 count and HIV RNA level prior to 1st January 2001, and the nadir CD4 count and peak HIV RNA level over follow‐up, were used to identify which patients should be receiving HAART according to the guidelines.

Results

One thousand two hundred and sixty‐four patients were included in the analysis (63.8% homosexual, 29.0% heterosexual risk; 72.9% white; 79.2% male). Almost half of patients had ever had a CD4 count below 200 cells/µL and over 80% had previously had a viral load above 4 log₁₀ HIV‐1 RNA copies/mL. Under 2000 BHIVA guidelines, treatment would be recommended in 77.4% patients. Overall, 819 patients were receiving ARV therapy. Two hundred and eighty‐five patients were not receiving treatment when guidelines suggest they should (including 33 patients who were receiving regimens not recommended in the guidelines). These patients were younger, less likely to be homosexual and had higher CD4 nadirs than those who were receiving ARV treatment. Almost half of these patients had previously received ARV therapy but were not currently receiving it.

Conclusion

Only a small proportion of patients at our centre were not receiving ARV treatment in line with national guidelines. While genuine reasons may exist for these departures from optimal care, this may simply reflect the limitations of using observational databases when auditing treatment use in a clinic setting.