Tenofovir-associated renal and bone toxicity.

OBJECTIVES: The aims of the study were to describe the clinical presentation and renal and bone abnormalities in a case series of HIV-infected patients receiving treatment with tenofovir (TDF), and to recommend appropriate screening for toxicity related to TDF. METHODS: Patients were identified from referrals to a specialist HIV renal clinic. Patients were included if treatment with TDF was assessed as the primary cause of the renal function impairment and clinical data were available prior to and following discontinuation of TDF treatment. Data were collected from case note review and clinic databases. RESULTS: Twenty-two patients (1.6% of all those who received TDF) were identified with TDF-associated renal toxicity. All had normal serum creatinine prior to TDF therapy. All presented with proteinuria. On stopping TDF, renal function improved. Eight patients had confirmed Fanconi syndrome. Twelve patients presented with bone pain and osteomalacia was confirmed on an isotope bone scan in seven of these patients. The findings (in those patients tested) of tubular proteinuria, reduced tubular transport maximum of phosphate (TmP), and glycosuria were all consistent with the proximal tubule being the site of toxicity. CONCLUSION: Renal toxicity remains a concern in patients treated with TDF. Clinical presentation may be with renal dysfunction, Fanconi syndrome or osteomalacia. Our investigations suggest proximal tubular toxicity as a common pathogenic mechanism.

Evaluation of a home-delivery service for HIV-infected patients attending an inner London HIV treatment centre.

Home delivery (HD) of medication is a goal of the Department of Health's Pharmacy in the Future; Implementing the NHS Plan. We evaluated the safety and effectiveness of an HD service for antiretroviral therapy (ART). Patients on ART with stable viral load (VL) <50 were identified. Comparison was made between patients using HD and those using the clinic-based pharmacy (CP). The primary endpoint was HIV virological failure (VF) (HIV VL >400 copies/mL on two consecutive occasions). Secondary endpoints included frequency of outpatient attendances (OPA) and an incidence of adverse events. Cumulative incidences (CulmIn) for each outcome event were calculated. Incidence-rate ratios (IRR) were obtained using Poisson regression. Of 1663 patients identified; 450 received HD and 1213 used CP. CuImIn of VF was =4% in those using HD and =7% in those using CP (IRR [95% confidence intervals, CI] =0.53, 0.32-0.90). HD patients had fewer OPA, less frequent blood test monitoring and less frequent abnormal liver function results (IRR [95% CI]= 0.63 [0.59-0.67] and 0.59 [0.53-0.67], 0.68 [0.65-0.71] and 0.64 [0.53-0.78], respectively). Patients deemed stable enough on social, psychological and medical grounds to receive HD of ART had a lower risk of VF, fewer OPA and no increase in adverse events when compared with patients using CP.

Nodal domain statistics for quantum maps, percolation, and stochastic Loewner evolution.

We develop a percolation model for nodal domains in the eigenvectors of quantum chaotic torus maps. Our model follows directly from the assumption that the quantum maps are described by random matrix theory. Its accuracy in predicting statistical properties of the nodal domains is demonstrated for perturbed cat maps and supports the use of percolation theory to describe the wave functions of general Hamiltonian systems. We also demonstrate that the nodal domains of the perturbed cat maps obey the Cardy crossing formula and find evidence that the boundaries of the nodal domains are described by stochastic Loewner evolution with diffusion constant close to the expected value of 6, suggesting that quantum chaotic wave functions may exhibit conformal invariance in the semiclassical limit.

Overcoming subjectivity in assessing facial lipoatrophy: is there a role for three-dimensional laser scans?

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.

Is use of antiretroviral therapy among homosexual men associated with increased risk of transmission of HIV infection?

BACKGROUND/OBJECTIVE: There is concern that use of highly active antiretroviral therapy (HAART) may be linked to increased sexual risk behaviour among homosexual men. We investigated sexual risk behaviour in HIV positive homosexual men and the relation between use of HAART and risk of HIV transmission. METHODS: A cross sectional study of 420 HIV positive homosexual men attending a London outpatient clinic. Individual data were collected from computer assisted self interview, STI screening, and clinical and laboratory databases. RESULTS: Among all men, sexual behaviour associated with a high risk of HIV transmission was commonly reported. The most frequently reported type of partnership was casual partners only, and 22% reported unprotected anal intercourse with one or more new partners in the past month. Analysis of crude data showed that men on HAART had fewer sexual partners (median 9 versus 20, p=0.28), less unprotected anal intercourse (for example, 36% versus 27% had insertive unprotected anal intercourse with a new partner in the past year, p=0.03) and fewer acute sexually transmitted infections (33% versus 19%, p=0.004 in the past 12 months) than men not on HAART. Self assessed health status was similar between the two groups: 72% on HAART and 75% not on HAART rated their health as very or fairly good, (p=0.55). In multivariate analysis, differences in sexual risk behaviour between men on HAART and men not on HAART were attenuated by adjustment for age, time since HIV infection. CD4 count and self assessed health status. CONCLUSION: HIV positive homosexual men attending a London outpatient clinic commonly reported sexual behaviour with a high risk of HIV transmission. However, behavioural and clinical risk factors for HIV transmission were consistently lower in men on HAART than men not on HAART. Although use of HAART by homosexual men with generally good health is not associated with higher risk behaviours, effective risk reduction interventions targeting known HIV positive homosexual men are still urgently needed.

Enfuvirtide (Fuzeon): the first fusion inhibitor.

With the number of people living with HIV infection increasing and the problems of drug resistance and long-term toxicity associated with current antiretroviral agents continuing, there is a growing need for new therapy options. Enfuvirtide is the first fusion inhibitor, a new class of drug, to be licensed for the treatment of HIV infection and is a welcome addition to the arsenal of antiretrovirals. This paper, which is the result of a multidisciplinary discussion meeting, reviews current practice in treating HIV infection, the clinical data available on enfuvirtide and discusses its introduction into clinical practice. Data available to date indicate that enfuvirtide is appropriate for use in patients who have previously taken nucleoside reverse transcriptase inhibitor (NRTI), non-NRTI and protease inhibitor containing regimens and are either intolerant of them or have experienced virological failure. Enfuvirtide should ideally be used while the patient still has other active drug options available to them to combine with enfuvirtide in an effective therapy regimen.

Prophylaxis with a nevirapine-containing triple regimen after exposure to HIV-1.

Evidence suggests that nevirapine, a non-nucleoside reverse-transcriptase inhibitor, might be very effective in the prevention of HIV-1 integration and the reduction of risk of HIV-1 acquisition after exposure. We used a triple combination regimen, including nevirapine, for prophylaxis after occupational or sexual exposure to HIV-1 infection. Of 57 individuals who started therapy, only 41 returned for follow-up. Five had a grade three or four drug-induced hepatitis, two of whom also had a rash. This high rate of major adverse events raises concerns over the safety of such a regimen for its use in this population.

Social and behavioural factors associated with HIV seroconversion in homosexual men attending a central London STD clinic: a feasibility study.

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.

Presentation, pathology, and outcome of HIV associated renal disease in a specialist centre for HIV/AIDS.

OBJECTIVES: To describe the presentation, pathology, and outcome of biopsy proved renal disease in HIV infected patients at a central London HIV unit from 1992 to 1996. METHODS: Retrospective review of a computerised database and case notes to identify patients with renal disease confirmed by antemortem percutaneous renal biopsy or necropsy. RESULTS: 17 patients were identified, 13 had biopsy and four necropsy confirmed renal disease. Abnormalities included HIV associated nephropathy (HIVAN) in seven (41%) patients, membranous glomerulonephritis (GN) in four (23%), haemolytic uraemic syndrome (HUS) in two (12%), and interstitial nephritis, rhabdomyolysis, IgA nephropathy, and membranoproliferative GN in one patient each. Although renal disease was the first presentation of HIV disease in six (35%) patients the majority had advanced HIV disease (median CD4 count 40 x 10(6)/l). The commonest presentation was acute renal failure (ARF) in 10 (59%) patients, chronic renal failure (CRF) in five (29%), and proteinuria alone in two (12%). Although the majority of patients died during the study period (9/13) only three deaths were attributable to their renal disease. Survival ranged in those with HIVAN from 0 to 31 (median 10) months and, in those with membraneous GN from 1 to 46 (median 29) months. CONCLUSIONS: HIVAN was the commonest renal disease found in this group of patients; however, a variety of other pathologies were seen with variable outcomes. All cases of HIVAN were in patients of African or Afro-Caribbean origin and for the majority this was their first presentation of HIV disease. Nephrologists need to be aware of the possibility of HIV infection in patients presenting with renal disease.

Detection of human herpesvirus-8 DNA in oral ulcer tissues of HIV-infected individuals.

OBJECTIVE: To determine the frequency of detection of human herpesvirus-8 (HHV-8) in HIV-related oral ulcers. DESIGN: Analysis of archived biopsy material. METHODS: Nested polymerase chain reaction of DNA extracts. RESULTS: HHV-8 DNA was detected in six of 10 oral ulcers of HIV-positive patients without oral Kaposi's sarcoma (KS) lesions and five of 11 oral KS lesions. The positive non-KS samples were derived from various oral sites. CONCLUSIONS: In HIV-positive people, HHV-8 can infect oral tissues that are not affected by KS.