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BACKGROUND: Randomized control studies have not shown an association between treatment with tenofovir (TDF) and clinically significant kidney toxicity. However, multiple cases of renal tubular toxicity have been described in patients with HIV treated with TDF. It is unclear whether spot urine protein- or albumin-creatinine ratio is a sufficiently sensitive screening test to detect subclinical renal tubular toxicity in patients with HIV. STUDY DESIGN: Cross-sectional. SETTING & PARTICIPANTS: 99 patients with HIV with serum creatinine levels < 1.70 mg/dL and dipstick-negative proteinuria; 19 were antiretroviral treatment (ART) naive, 47 were on a TDF regimen, and 33 were on ART, but with no history of TDF exposure. PREDICTOR OR FACTOR: Exposure to TDF. OUTCOMES: Spot urine concentrations of retinol-binding protein (RBP; a low-molecular-weight protein normally reabsorbed by the proximal tubule), N-acetyl-beta-D-glucosaminidase (NAG; a proximal tubule lysosomal enzyme), albumin (A; a marker of glomerular disease), and protein (P; a standard clinical screening test for kidney pathological states) expressed as a ratio to creatinine (C; U(RBP/C), U(NAG/C), U(A/C), and U(P/C), respectively). RESULTS: There were no significant differences in median U(A/C) (ART-naive, 7.3 mg/g [range, 0-245.8 mg/g]; TDF, 9.0 mg/g [range, 0.1-184.1 mg/g]; and non-TDF, 10.5 mg/g [range, 2.6-261.6 mg/g]; P = 0.8). U(RBP/C) excretion was significantly higher in the TDF group (median, 214.2 microg/g [range, 26.8-17,454.5 microg/g]) than in the ART-naive group (92.5 microg/g [range, 21.3-3,969.0 microg/g]; P = 0.03); there was also a trend toward higher values than in the non-TDF group (111.6 microg/g [range, 31.0-6,136.3 microg/g]; P = 0.08). U(NAG/C) excretion was significantly higher in both the TDF (median, 394.7 micromol/h/g [range, 140.5-10,851.3 micromol/h/g]; P = 0.01) and non-TDF (406.8 micromol/h/g [range, 12.4-8,485.8 micromol/h/g]; P = 0.03) groups compared with the ART-naive group (218.6 micromol/h/g [range, 56.5-2,876.1 micromol/h/g]). U(P/C) was significantly higher in the TDF (median, 123.9 mg/g [range, 53.1-566.4 mg/g]) than the non-TDF group (97.3 mg/g [range, 0-451.3 mg/g]; P = 0.03). The proportion of patients with evidence of tubular dysfunction (increased U(RBP/C) and/or U(NAG/C)) was considerably higher than the proportion with an increase in U(A/C) or U(P/C) in all groups: for ART-naive, 52.6% vs 31.6% vs 25.0%; for TDF, 80.9% vs 29.8% vs 52.2%; and for non-TDF, 81.8% vs 39.4% vs 30.0%. The level of agreement among the different urinary test results was low. LIMITATIONS: Causality cannot be established from single measurements of urinary markers in a cross-sectional study. CONCLUSIONS: Patients with HIV had high rates of subclinical proteinuria, but neither U(P/C) nor U(A/C) is sufficiently sensitive alone to detect many of these cases. Patients using TDF have increased U(RBP/C) and U(P/C); the significance of this will need to be determined from longer-term outcome studies. [ABSTRACT FROM AUTHOR]

BACKGROUND: Prevalence and incidence rates of lipodystrophy vary widely and frequently rely upon self- and/or clinician reports. Currently no validated assessment tool for facial lipoatrophy is available. AIMS AND OBJECTIVES: To illustrate that assessment of the severity of facial lipoatrophy by patients and clinicians is subjective. To evaluate the reproducibility of facial three-dimensional surface laser scans. METHODS: Twenty-three HIV-positive men were recruited from an inner London HIV outpatient clinic in September 2001. CD4 count, viral load, antiretroviral history and body mass index were recorded. Patients and clinicians independently assessed the severity of facial lipoatrophy on a four-point scale and the level agreement was measured. Seventeen of the 23 patients (73.9%) underwent two scans 1 week apart, which were then superimposed. The volume difference (mm3) and mean difference (mm) between the scans for five regions of the face were measured and compared with the self-reported grade of facial lipoatrophy. RESULTS: For each pair of clinicians (P=0.03, 0.005 and 0.0002, respectively), and for one patient-clinician pair (P=0.004), there was a significant systematic difference between the two sets of gradings of facial lipoatrophy. The level of disagreement was generally higher for patients reporting facial lipoatrophy (n=17) compared to those not reporting it (n=6). The mean volume difference and mean difference between any region were within 200 mm3 and 0.25 mm, respectively. Reproducibility was unaffected by the self-reported grade of facial lipoatrophy. CONCLUSIONS: Assessment of the severity of facial lipoatrophy by patients and clinicians is subjective. Three-dimensional facial laser scans are reproducible and may provide an objective tool for monitoring changes in facial lipoatrophy. [ABSTRACT FROM AUTHOR]

Introduction: Simultaneous treatment of HW and MTB can be complicated by drug interactions. Induction of the cytochrome P450 system by rifampicin (RIF) could lower plasma concentration leveis (PCL) of NNRTIs and possibly result in subtherapeutic levels. Aim: To measure real-time trough PCL of nevirapine (NVP) and efavirenz (EFV) in 12 patients taking both combination antiretroviral therapy (ARV) and twice-weekly RIF-containing Directly Observed Therapy (DOT). Methods: Nine patients on NVP 200mg bd and three on EFV 600mg od were studied. All patients received RIF 600mg DOT. NNRTI trough PCL were taken immediately prior to DOT, 24 hours post-DOT and on completion of DOT (controls). The PCL were taken 12 hours after last NVP dose and > 19 hours after last EFV dose. Results: Mean PCL of NVP (n=9) pr- and post-DOT were 3.91 µg/ mL and 4.4 µg/mL, respectively. The mean PCL of EFV (n = 3) preand post-DOT were 5.7 µtg/mL and 4.7 µg/mL, respectively. Five patients completed DOT and the mean PCL of NVP (n = 4) and EFV (n = 1) were 5.6 µg/mL and 2.2 µg/mL, respectively. Conclusion: In this small study all trough PCL of NNRTIs pre- and post-DOT and off DOT were within the normal range of historical controls, although significant interpatient variation did occur with EFV and RIF DOT. All patients had good surrogate marker response. Further NNRTI PCL monitoring of patients is needed to determine whether these drugs can be used concurrently. [ABSTRACT FROM AUTHOR]

Objective: Dyslipidaemia in HW-seropositive patients treated with highly active antiretroviral therapy (HAART) has been extensively described. The underlying derangement remains unclear. The physiology of the lipid metabolism of individuals treated with HAART was studied measuring lipid absorption, gastrointestinal lipid handling and lipid oxidation. Methods: The following groups were studied: six HIV+ individuais with established (2 years) lipidaemia on treatment with a protease inhibitor (PI); six age-matched healthy HIV-negative controls; seven HW-seropositive prior to treatment (study 1) and after 1 month (study 2) on a PI-containing regimen and again after 3 months (study 3). All patients were given a standard test meal containing 3.7 MJ, 45g lipid and 93g carbohydrate and 1g palmitic acid. Recovery of tracer in the breath as [sup 13]CO[sub 2] was determined hourly for 6 hours after the meal. Results: The rates of lipid absorption and oxidation were not significantly different between the (study 1) patient group and controls. However, the rate of lipid oxidation had increased by study 3 when compared with study 1. This rate was lower than in those who had established dyslipidaemia. Conclusion: Prior to commencing PI lipid metabolism in HIVseropositive males is normal. However, on a PI-containing regimen a progressive abnormality of lipid handling occurs in ali patients with decreased peripheral uptake of lipid and enhanced oxidation. [ABSTRACT FROM AUTHOR]

Objective: To review outcomes of HIV PEP regimens. Background: The recommended regimen of AZT, 3TC and indinavir (IDV) is often poorly tolerated. Mainly for reasons of compliance our policy from 11/97 has been to use D4T, 3TC and nevirapine (NVP). NVP is a potent inhibitor of HIV and intracellular therapeutic levels are rapidly achieved after a single dose. Methods: Retrospective case-note review between 1/97 and 6/99. Results: Eighty patients were considered for PEP. Of 67 who started: 34 followed occupational exposure (20 from known positive 'donors'), of whom 17 (50%) completed a 4-week course of PEP; 33 followed sexual exposure (24 from known positive 'donors'), of whom 22 (67%) completed. 0ne patient tested positive at baseline, one seroconverted by 6 months, having tested negative at 3 months; 46/67 (68.6%) received a NVP-based regimen: 28 (60.9%) completed; 10 (21.3%) reported minor and four (8.7%) major A/Es (ACTG toxicity criteria), one grade 4 hepatitis with a grade 3 rash, three grade 3 hepatitis, 13/67 (19.4%) had an IDVbased regimen: nine (69.2%) completed, seven (53.8%) reported minor A/Es; 7/67 (10.4%) received AZT/3TC, two (28.6%) completed; three (42.9%) reported minor A/Es. Conclusion: Documented completion of PEP regimens was no different between IDV- and NVP-containing regimens. Although a lower proportion experienced any A/Es with NVP, severe A/Es were only reported in those receiving D4T, 3TC and NVP, which is of concern in this population. Data are now being collected prospectively and policy is under review. [ABSTRACT FROM AUTHOR]

Objective: To determine any differences in the demographics of 100 people diagnosed with HIV in 1994 (pre-HAART) compared to 1998 (post-HAART). Method: Data were collected from an established database and supplemented from medical and counselling notes. Results: Mean age was 31 in 1994 and 34 in 1998. Most were male (74%, 78%) and Caucasian (67%, 68%). In 1994 the main risk groups were 62% homosexual and 34% heterosexual compared with 69% and 28% in 1998, 3% in both years were IDU. In 1994 19% had AIDS at the time of diagnosis, in 1998 this was 12%. The mean CD4 in 1994 was 445 (CI 374-516) and in 1998313 (CI 258367). Mean viral load in 1998 was 5.07 log[sub 10]. Most people tested via the Same Day Testing Clinic (73%, 74%). In 1994 34% had been tested previously and in 1998, 33%. In 1994 18% of the 100 were using condoms regularly, in 1998 22%. In 1994 20% had a known HIV+ partner and 19% in 1998. Conelusion: Very few differences were seen in those diagnosed HIV+ in the pre- and post-HAART era. Many people still present with relatively advanced disease at a stage when antivirals would be considered. Mean CD4 at presentation was lower in 1998. New sites and increased availability for testing do not seem to be impacting yet on where and when people present. Most people newly diagnosed in our service were still homosexual men. [ABSTRACT FROM AUTHOR]

An unmatched retrospective case control study was conducted to test the feasibility of investigating social and behavioural factors which may have contributed to recent HIV seroconversion in a group of homosexual men. Participants, recruited from a London sexually transmitted disease (STD) clinic, were sexually active and had had a negative HIV test with a subsequent test (positive (cases) or negative (controls)) within three to 15 months. Twenty cases and 22 controls were recruited between February and October 1995. There was no difference between cases and controls in: the number of regular or casual sexual partners, the proportion who were unaware of their regular partners' serostatus (cases 60%, controls 59%), or the proportion who had known HIV-positive regular partners (cases 20%, controls 23%). A significant difference in sexual behaviour was found only when the HIV status of partners, if known, was taken into account: cases were more likely than controls to have had unprotected receptive anal intercourse with a partner not known to be HIV-negative (OR = 5.5, CI = 1.15-29.50). Fifty per cent of the cases and 27% of the controls acquired acute STDs between the two HIV tests. All participants achieved high self-efficacy scores, but the controls believed their peers placed a greater value on safer sex. Cases cited emotional issues and the use of drugs and alcohol as contributing to their seroconversion, whereas controls cited a commitment to safer sex and the avoidance of high-risk situations as contributing to their remaining HIV-negative. The results illustrate the importance of acknowledging the concept of 'negotiated safety' in studies of sexual behaviour; seroconversion was only associated with unprotected sex with a partner not known to be HIV-negative. Despite high self-efficacy scores, indicating the skills to negotiate safer sex, high levels of unsafe anal intercourse were reported. Differences between cases and controls included the importance of safer sex, periods of emotional vulnerability, influence of peers and the appropriate use of condoms. There is a need for these results to be confirmed in a larger and more powerful study. [ABSTRACT FROM AUTHOR]