Audit of the management of antiretroviral treatment-naïve HIV patients in Greater Manchester, UK.

We evaluated the management of antiretroviral treatment (ART)-naïve HIV-positive patients in Greater Manchester against the 2005 British HIV association (BHIVA) guidelines. Fifty-seven HIV patients (median age 36 years, 61% males, 53% black Africans) commenced their first ART regimen between 1 October and 31 December 2005. Most of them presented with advanced HIV disease (74% had CD4 lymphocytes <200 and 33% were Centers for Disease Control and Prevention stage C) and 51% commenced ART within three months of their HIV diagnosis. Ninety-six percent had baseline laboratory investigations performed but only 53% had baseline blood pressure estimation. Only 25% had urinalysis performed. A combination of two nucleoside reverse transcriptase inhibitors (NRTI) and one non-NRTI was chosen in 76% of patients. Eighty-two percent of patients had a clinical review and blood tests within five weeks of starting treatment.

Thalidomide treatment for refractory HIV-associated colitis: a case series.

Thalidomide has been used as a treatment for various human immunodeficiency virus (HIV)-associated and non-HIV-associated illnesses, generally in cases in which inflammatory disease is refractory to standard therapy. Here, we discuss the successful use of thalidomide in 3 patients with severe, idiopathic HIV-associated colitis.

Pharmacologic optimization of protease inhibitors and nonnucleoside reverse transcriptase inhibitors (POPIN)--a randomized controlled trial of therapeutic drug monitoring and adherence support.

We evaluated the feasibility and effectiveness of therapeutic drug monitoring (TDM) and adherence support (collectively, AT) vs standard of care (SOC) in patients receiving HIV protease inhibitors (PIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs) within a nurse-led clinic. Primary end points were failure to achieve viral load of <50 copies/mL at 24 weeks, viral rebound, or development of treatment limiting toxicity. One hundred twenty-two patients (AT 63 and SOC 59) were followed-up every 12 weeks, for a median of 72 weeks. No difference was observed between arms in risk of reaching a study end point or between groups of patients with abnormal vs "therapeutic" drug concentrations. Interindividual variabilities (coefficient of variation) were the following: efavirenz, 77.5%; nevirapine, 74.5%; lopinavir, 73.4%; nelfinavir, 83.7%; indinavir, 80.8%; saquinavir, 112.4%. Intraindividual variabilities (median coefficient of variation) were the following: NNRTIs, approximately 25%; PIs, 48.4%. Despite persistently abnormal results in 26 of patients in the AT arm (38%), dosage adjustment was only undertaken in 9 patients (35%).A significant proportion of patients had drug concentrations outside the therapeutic range. The Pharmacologic Optimization of PIs and NNRTIs (POPIN) study confirms that TDM trials are complex to interpret and statistically underpowered, with effectiveness better assessed through the clinical utility of a TDM result, whether normal or abnormal. Although TDM of PIs and NNRTIs may be useful in selected patients, routine and unselected use is not supported by current evidence.

Lesson of the week: a new cause of treatable dementia.

CASE REPORT: A 69-year-old married British man presented with 4 months of falls and confusion. HIV antibody test, performed after exclusion of other diagnoses, was positive. Institution of triple antiretroviral therapy resulted in an almost complete recovery. DISCUSSION: HIV infection is now far more common than syphilis. It may be highly amenable to treatment and needs to be considered in the differential diagnosis of the older person with dementia.

Lipodystrophy in patients with HIV-1 infection: effect of stopping protease inhibitors on TNF-alpha and TNF-receptor levels, and on metabolic parameters.

OBJECTIVE: To evaluate the effects of stopping treatment with protease inhibitors (PIs) on tumour necrosis factor (TNF)-alpha and TNF-receptor levels, and on the metabolic and morphological abnormalities seen in patients with lipodystrophy. DESIGN: Longitudinal study. METHODS: Ten HIV-positive patients with lipodystrophy (LD) were studied whilst on PIs (LD1) and 3 months after stopping PIs (LD2) together with 10 HIV-positive subjects on PIs without LD (controls). TNF-alpha and TNF-receptor levels, insulin resistance parameters, lipid and hormonal profiles, body composition and fat distribution were measured in all subjects. RESULTS: TNF-alpha, TNF-receptor I (-RI) and TNF-RII levels were significantly lower in controls (P=0.02) than in subjects with LD, and there was a significant decrease in TNF-RI and TNF-RII levels (P=0.01 and 0.03, respectively) on stopping PIs. Insulin levels and the homeostasis model assessment for insulin resistance (HOMA-IR) index were significantly higher in LD1 subjects (P=0.02) than in controls but did not alter when PIs were stopped. Bioelectrical impedance analysis showed a significant decrease on stopping PIs but CT scans showed no significant difference in fat distribution. Apart from high-density lipoprotein, there was no change in lipid parameters on stopping PIs. There was no difference in the level of testosterone, sex hormone binding globulin and cortisol between the three groups. CONCLUSION: Our results show that TNF-alpha activity in patients with LD is modulated by PIs. This was not accompanied by significant changes in body habitus or insulin resistance, although this may have been a consequence of the short follow-up in this study.

TNF-alpha promoter region gene polymorphisms in HIV-positive patients with lipodystrophy.

OBJECTIVE: The pathogenic mechanisms underlying lipodystrophy in HIV-positive patients are largely unknown. TNF-alpha has many actions that are consistent with the features of lipodystrophy; therefore, an analysis was carried out to determine whether functionally active polymorphisms in the promoter region of the TNF-alpha gene are associated with the development of lipodystrophy. DESIGN: Genetic case-control association study. METHODS: Individuals were genotyped for the -238 and -308 polymorphisms in the TNF-alpha gene using polymerase chain reaction-restriction fragment length polymorphism analysis. The genotype and allele frequencies for 61 HIV-positive patients with lipodystrophy were compared with (a) 35 HIV-positive patients with no evidence of lipodystrophy and (b) 239 healthy HIV-negative individuals. RESULTS: The frequency of the variant rare -238 allele was significantly different (P = 0.01) in HIV-positive patients with lipodystrophy than in those without lipodystrophy. At the genotype level, a trend towards a difference between patients with and without lipodystrophy was observed (chi2 for linear trend 5.2, P = 0.02). For the -308 polymorphism, no difference was found in genotype and allele frequencies between HIV patients with and without lipodystrophy. CONCLUSIONS: The data suggest that the -238 (but not the -308) promoter region TNF-alpha gene polymorphism is a determinant in the development of HIV-related lipodystrophy. However, the results need to be confirmed in larger numbers of patients as well as in an ethnically diverse population.