Reducing risk of Type 2 diabetes in HIV: a mixed-methods investigation of the STOP-Diabetes diet and physical activity intervention.

AIM: To conduct a mixed-methods feasibility study of the effectiveness and acceptability of an individualized diet and physical activity intervention designed to reduce the risk of Type 2 diabetes experienced by people living with HIV. METHODS: Participants with impaired fasting glucose and HIV were invited to take part in a 6-month diet and physical activity intervention. Individualized advice to achieve 10 lifestyle goals was delivered monthly. Diabetes risk was assessed pre- and post-intervention by measurement of the glucose and insulin response to a 3-h meal tolerance test. Six-month change was analysed using paired t-tests. Research interviews exploring the acceptability of the intervention and factors influencing behaviour change were conducted with those who participated in the intervention, and those who declined participation. RESULTS: The intervention (n=28) significantly reduced the following: glucose and insulin, both fasting and postprandial incremental area under the curve (glucose 7.9% and 17.6%; insulin 22.7% and 31.4%, respectively); weight (4.6%); waist circumference (6.2%); systolic blood pressure (7.4%); and triglycerides (36.7%). Interview data demonstrated the acceptability of the intervention. However, participants expressed concern that deliberate weight loss might lead to disclosure of HIV status or association with AIDS-related illness. The belief that antiretroviral medications drove diabetes risk was associated with declining study participation or achieving fewer goals. CONCLUSIONS: We have demonstrated the beneficial effects of a lifestyle intervention in mitigating the increased risk of Type 2 diabetes associated with HIV. Future interventions should be designed to further reduce the unique barriers that prevent successful outcomes in this cohort.

Dietary patterns and bone mineral density in Brazilian postmenopausal women with osteoporosis: a cross-sectional study.

BACKGROUND/OBJECTIVES: The aim of this study was to investigate the association between dietary patterns and bone mineral density (BMD) in postmenopausal women with osteoporosis. SUBJECTS/METHODS: This cross-sectional study included 156 postmenopausal and osteoporotic Brazilian women aged over 45 years. BMD of lumbar spine, total femur (TF), femoral neck and of total body (TB), as well as body composition (fat and lean mass), was assessed by dual-energy X-ray absorptiometry. Body mass index and lifestyle information were also obtained. Dietary intake was assessed by using a 3-day food diary. Dietary patterns were obtained by principal component factor analysis. Adjusted multiple linear regression analysis was applied in order to evaluate the predictive effect of dietary patterns on BMD. Significance was set at P<0.05. RESULTS: Five patterns were retained: 'healthy', 'red meat and refined cereals', 'low-fat dairy', 'sweet foods, coffee and tea' and 'Western'. The 'sweet foods, coffee and tea' pattern was inversely associated with TF BMD (ß=-0.178; 95% CI: -0.039 to -0.000) and with TB BMD (ß=-0.320; 95% CI: -0.059 to -0.017) even after adjusting for energy and calcium intake, lean mass, age and postmenopausal time. CONCLUSIONS: A concomitant excessive consumption of sweet foods and caffeinated beverages appears to exert a negative effect on BMD even when the skeleton already presents some demineralization. Food and beverage intake is a modifiable factor that should not be neglected in the treatment of individuals with osteoporosis.

The influence of breakfast and dairy products on dietary calcium and vitamin D intake in postpubertal adolescents and young adults.

BACKGROUND: Given the importance of both calcium and vitamin D for bone health and the high prevalence of vitamin D from around the world, the present study aimed to evaluate calcium and vitamin D intake in a group of healthy Brazilian adolescents and young adults and to examine the influence of breakfast and dairy products in the total intake of these nutrients. METHODS: One hundred and sixty adolescents and young adults, aged 16-20 years old, from a public school, participated in the present study. Three-day dietary records were used to assess calcium and vitamin D intakes. Serum 25(OH)D levels were measured using a radioimmunoassay kit. The results were expressed as the mean (SD). RESULTS: Only 3.8% of the subjects met the daily adequate intake recommendation for calcium, and none for vitamin D [682.2 (132.2)mg day(-1) and 124.0 (28.0)IU day(-1) , respectively]. 25(OH)D serum levels were insufficient in 51.5% and deficient in 9.7% of the individuals [72.5 (22.3) nmol L(-1) ]. There was a significant positive correlation between dairy product intake with both calcium and vitamin D (r=0.597 and r =0.561, respectively; P=0.000). Adolescents who ate breakfast had a significant higher mean calcium, vitamin D and dairy product intake than adolescents who did not report this meal. CONCLUSIONS: The majority of adolescents and young adults did not consume recommended intakes of calcium and vitamin D and also presented 25(OH)D insufficiency. The results indicate that a regular breakfast and the consumption of dairy products represent important strategies in improving calcium and vitamin D intake in the diet.

Therapy for HIV: past, present, and future.

Initial therapies for HIV infection comprised nucleoside analogues, but as single or dual agents, they failed to prevent disease progression. When a new class of drug was introduced, the protease inhibitors, an effective triple therapy became possible-namely, highly active antiretroviral therapy, or HAART. HAART reduced viral replication almost completely and enabled immune system recovery. The probability of classical infections and tumors attributed to HIV were dramatically reduced, and life expectancy correspondingly increased. The initial disadvantages of HAART included the need for strict adherence to prevent drug resistance, the cost that initially precluded their widespread use in the developing world, and the short- and long-term side effects. One of the most disabling long-term complications was HIV lipodystrophy, which in extreme cases lead to severe peripheral fat wasting and central fat gain. In recent years, many of these disadvantages have been addressed: Once-daily drug combinations improve adherence; global access to HAART has been markedly improved; and new drugs enable patients to avoid many of the initial side effects. Future research will determine at what CD4 count HAART should be initiated, and new approaches such as immunotherapeutic HIV vaccines are being tested with the aim to delay or obviate the need for antiretroviral drugs.

Clinical markers of immunodeficiency and mechanism of immune reconstitution inflammatory syndrome and highly active antiretroviral therapy on HIV: workshop 3A.

Antiretroviral therapy (ART) has improved survival and changed the disease pattern of HIV infection. However, ART may cause serious side effects, such as metabolic and cardiovascular complications. In addition, immune reconstitution inflammatory syndrome (IRIS) is being increasingly reported in relation to ART. The article presents the consensus of a workshop around 4 key issues: (1) the differences in the response of adults and children to highly active antiretroviral therapy, (2) the mechanism of the new HIV entry inhibitors and its effect on oral markers, (3) the pathogenesis of IRIS and the contradictory findings of the possible oral lesions related with IRIS, (4) and the benefits and barriers associated with using ART in the developing and developed world. The consensus of the workshop was that there is a need for future studies on the oral manifestations of HIV in individuals treated with new ARTs-especially, children. IRIS was considered a promising field for future research; as such, workshop attendees recommended formulating an IRIS-oral lesions case definition and following strict criteria for its diagnosis.

Cardiovascular risk evaluation and antiretroviral therapy effects in an HIV cohort: implications for clinical management: the CREATE 1 study.

AIMS: The aim of this study is to determine the cardiovascular disease (CVD) risk profile of a large UK HIV cohort and how highly active antiretroviral therapy (HAART) affects this. METHODS: It is a cross-sectional study within a large inner city hospital and neighbouring district hospital. A total of 1021 HIV positive outpatients representative of the complete cohort and 990 who had no previous CVD were included in CVD risk analysis. We recorded demographics, HAART history and CVD risk factors. CVD and coronary heart disease (CHD) risks were calculated using the Framingham (1991) algorithm adjusted for family history. RESULTS: The non-CVD cohort (n = 990) was 74% men, 51% Caucasian and 73.1% were on HAART. Mean age was 41 +/- 9 years, systolic blood pressure 120 +/- 14 mmHg, total cholesterol 4.70 +/- 1.05 mmol/l, high-density lipoprotein-C 1.32 +/- 0.48 mmol/l and 37% smoked. Median CVD risk was 4 (0-56) % in men and 1.4 (0-37) % in women; CHD risks were 3.5 (0-36) % and 0.6 (0-16) %. CVD risk was > 20% in 6% of men and 1% of women and > 10% in 12% of men and 4% of women. CVD risk was higher in Caucasians than other ethnicities; the risk factor contributing most was raised cholesterol. For patients on their first HAART, increased CHD risk (26.2% vs. 6.5%; odds ratio 4.03, p < 0.001) was strongly related to the duration of therapy. CONCLUSIONS: Modifiable risk factors, especially cholesterol, and also duration of HAART, were key determinants of CVD risk. DISCUSSION: Regular CHD and/or CVD risk assessment should be performed on patients with HIV, especially during HAART therapy. The effect of different HAART regimens on CHD risk should be considered when selecting therapy.

Disseminated gonococcal infection in a homosexual man diagnosed by nucleic acid amplification testing from a skin lesion swab.

Disseminated gonococcal infection (DGI) often presents a diagnostic challenge. Through the novel application of molecular technology, a case is presented that suggests how the diagnostic sensitivity for this systemic complication of gonococcal infection can be improved. In a typical case of DGI seen in a homosexual man in whom all mucosal and blood specimens were culture negative, nucleic acid amplification testing (NAAT) helped to confirm the diagnosis. Both throat and skin lesion specimens tested positive for gonococcal DNA and this was confirmed with a supplementary porA pseudogene NAAT. The use of adjuvant NAAT assessment is recommended as part of the diagnostic work-up for suspected DGI cases.

Body composition changes in haemodialysis patients with secondary hyperparathyroidism after parathyroidectomy measured by conventional and vector bioimpedance analysis.

Considering the negative effects of secondary hyperparathyroidism (SHPT) in patients with chronic renal failure (CRF), the objective of the present study was to evaluate body composition changes using conventional and vector bioimpedance analysis in patients before and after parathyroidectomy (PTX). Twelve adult patients, mean age 43.4 (sd 12.7) years, were evaluated prior to and 6 months after PTX. Diets were assessed with 3 d dietary records, and mean energy, protein, calcium and phosphorus intake were estimated from these inventories. Weight, height, BMI and bioelectrical impedance were measured; and biochemical markers of nutritional status (albumin and total protein) and bone metabolism (calcium, phosphorus and intact parathyroid hormone) were determined. No significant differences were observed in mean energy, protein and phosphorus after surgery. There was a significant increase in calcium intake after PTX (382.3 (sd 209.6) mg to 656.6 (sd 313.8) mg; P<0.05). Mean weight, BMI, conventional bioelectrical impedance measurements, total body fat, lean body mass and total body water were unaffected by surgery. However, the phase angle and reactance significantly increased after PTX (5.0 degrees (sd 1.4) to 5.6 degrees (sd 1.3); 44.1 (sd 15.6) Omega to 57.1 (sd 14.4) Omega, respectively). The high levels of intact parathyroid hormone before surgery had a negative effect on total body fat (r -0.69, P<0.05). After PTX, the mean albumin significantly increased (3.9 (sd 0.4) g/dl to 4.2 (sd 0.6) g/dl; P<0.05). PTX for SHPT is associated with certain changes in laboratory values, dietary intake and body composition. The latter is best seen with bioimpedance vector analysis.

The basis for HIV immunotherapeutic vaccines.

The drug treatments introduced in recent years for HIV infection have enabled a marked reduction in morbidity and prolongation of life. These treatments, however, are often associated with acute and chronic toxicities, the development of resistant virus can limit their effectiveness, and they are too expensive and difficult to administer in most third world settings. A successful HIV immunotherapeutic vaccine has the potential to overcome these problems, and would be a valuable advance. The most promising approaches have induced the type of immune response found to correlate with reduced activity of HIV in man, especially cytotoxic T-cell responses, or have led to reduced HIV or SIV viral load and increased CD4 counts in non-human primates or man. The agents that have led to one or both of these effects have been selected for review, and include inactivated envelope depleted virus, recombinant envelope glycoprotein, DNA vaccines utilising HIV peptides or gene products, viral vectors, such as canarypox or attenuated vaccinia, with HIV core proteins. There are other approaches, such as alloimmunity, for which no candidate products yet exist, but which conceptually appear promising. Currently, however, only a few phase III studies of HIV therapeutic vaccines have been completed in man, and there has been a modest therapeutic effect. Further development of both existing and new candidates remains one of the key priorities in our fight against HIV.

Thalidomide is distributed into human semen after oral dosing.

As part of a double-blind placebo-controlled study of the effect of thalidomide on body weight and the viral load of human immunodeficiency virus-seropositive patients, plasma and semen samples were analyzed for the presence of thalidomide. Patients were orally dosed with 100 mg of thalidomide/day for 8 weeks. Blood samples were obtained at baseline and weeks 4, 8, and 12, and semen was obtained at baseline and weeks 4 and 8. Samples were extracted with solid-phase cartridges and analyzed by liquid chromatography/tandem mass spectrometry using atmospheric pressure chemical ionization in the negative ion mode. Two of four patients taking thalidomide were able to provide semen samples. Both had detectable levels of thalidomide in their plasma (10-350 ng/ml) and semen (10-250 ng/g) at weeks 4 and 8. There was an apparent correlation between plasma and semen levels. Semen levels could be significantly greater for therapeutic doses of more than 100 mg/day. Since the threshold dose for birth defects and thalidomide exposure is not known, male patients are advised to use barrier contraception.

In vivo evaluation of 111In-DTPA-N-TIMP-2 in Kaposi sarcoma associated with HIV infection.

Matrix metalloproteinases are the major agents responsible for the degradation of extracellular matrix and are produced at high levels by transformed and tumour cells, where they participate in the metastatic process by allowing local invasion. They are also more active at sites of new normal growth and angiogenesis. In the early stages of Kaposi sarcoma (KS), in vitro studies have demonstrated that vascular invasion can be inhibited by inhibitors of matrix metalloproteinases. Imaging of visceral and cutaneous KS presents a problem and therefore the potential use of a labelled inhibitor of metalloproteinases, N-TIMP-2, with indium-111 was thought to present a possible imaging tool. The biokinetics, dosimetry and potential for imaging with 111In-DTPA-N-TIMP-2 were assessed in five patients with HIV infection and KS. Between 103.1 and 108.0 MBq of this agent was injected into each patient, and the dynamic uptake over the kidneys was assessed, whole body scans were performed and blood samples were obtained. The clearance from the blood was rapid, with a first component half-time of 16.6+/-3.4 min and a second component half-time of 9.68+/-2.68 h. Two out of five patients experienced minor shivering but one of these patients was generally unwell before the study. The last three patients had no such problems. The tracer distributed predominantly to the kidneys and did not localise in other tissues. No KS lesions were clearly identified. 111In-DTPA-N-TIMP-2 can be successfully prepared and administered to patients safely, with a biodistribution and dosimetry which would allow its use as an imaging tracer. It is unlikely to be of use for imaging KS, but may have a role in other tumours that produce matrix metalloproteinases.

The relationships between ethnicity, sex, risk group, and virus load in human immunodeficiency virus type 1 antiretroviral-naive patients.

This cross-sectional study examined the relationships between ethnicity, sex, risk group, and virus load in human immunodeficiency virus type 1 (HIV-1) antiretroviral-naive patients. HIV-1 RNA levels were measured in 322 patients attending St. Thomas' Hospital between May 1997 and February 1999. By univariate analyses, only clinical status and CD4(+) cell count were related to virus load. In multivariate analysis, variables independently related to virus load were CD4(+) cell count (P=.001), being black African (P=.001), having a nonsexual risk for HIV infection (P=.03), and having AIDS (P=.05). Neither sex nor age was a significant predictor of initial virus load after adjusting for other variables. For a given CD4(+) cell count, black Africans and people who contracted HIV nonsexually presented with a virus load lower than that of patients in other groups. Because virus loads may need to be interpreted differently according to ethnicity, this may affect decisions on when to initiate antiretroviral therapy and how to interpret clinical trial results.

Highly active antiretroviral therapy normalizes the potential for MIP-1alpha production in HIV infection.

DESIGN: The CC chemokines RANTES, MIP-1alpha and MIP-1beta are ligands for CCR5, which has been identified as the principal co-receptor for macrophage tropic strains of HIV-1. This study investigated whether the inducible levels of RANTES, MIP-1alpha and MIP-1beta produced by cultured whole blood samples related to different rates of progression of HIV infection and to the introduction of Nelfinavir-based highly active anti-retroviral therapy (HAART). METHODS: Study subjects were HIV-positive and categorized as "slow progressors" (n= 8) or as "fast progressors" (n= 7); the latter group were treated with HAART. MIP-1alpha, MIP-1beta and RANTES production was determined using commercial ELISA kits. RESULTS: The inducible production of MIP-1alpha by whole blood cells in culture was significantly depressed in patients starting therapy compared with "slow progressors" and "normal donors". The levels of MIP-1alpha significantly increased with therapy at 12 weeks compared with pre-HAART levels (P= O.05) and became comparable to that of "normals" and "slow progressors". Differences in the inducible levels of MIP-1beta and RANTES for the separate subject groups were not significant. CONCLUSIONS: The increase in inducible MIP-1alpha production following HAART might suggest a role for the chemokines in HIV disease, either for monitoring the outcome of therapy of HIV disease, or as a direct therapeutic intervention.

HIV immunotherapeutic vaccines.

New combinations of antiretrovirals have improved the quality of life and length of survival of patients with HIV infection and AIDS, but they have significant disadvantages. These include considerable toxicity, the development of drug resistance and expense. Successful immunotherapeutic vaccination against HIV would overcome these problems. None of the approaches that have been tried so far have shown a sufficient effect on HIV replication or on immunorestoration to merit their introduction to clinical practice. The most developed agent thus far is Remune, a gp120 depleted whole killed HIV-1 vaccine that has shown marked cytotoxic T lymphocyte responses when administered to man. CD4 count and HIV-1 viral load responses have occurred, but have so far been disappointing in their magnitude. Remune is entering Phase III trials in North America, Europe and the Far East, to determine clinical efficacy. Immunization using recombinant HIV envelope proteins, such as rgp160, for example with VaxSyn, have failed to produce a therapeutic response. Similarly, agents using HIV core antigens, such as p24VLP, have also failed to work. Hence, newer strategies have been tried. Recombinant canarypox vaccines like ALVAC 1452 and highly attenuated vaccinia virus vaccines, such as NYVAC, have been used in combination with HIV genes and peptides. Preliminary results suggest that they might reduce the HIV replication rate, but this needs confirming in larger clinical trials. DNA vaccination has produced encouraging results in monkeys, but the success has not yet been repeated in humans. Other strategies at an early stage include the exploitation of the protective alloimmune response in man. Outside the immunotherapeutic area, other promising new strategies that are being developed in parallel, include the fusion inhibitors, such as T-20. The potential benefits from a successful immunotherapeutic vaccine dictate that this area should, and will receive priority.

Controlled management of public relations following a public health incident.

This paper describes the management of public relations following an outbreak of multidrug resistant TB at a London hospital. Eight patients were involved, all of the secondary cases occurred in HIV seropositive patients, and three cases died. The paper describes how the the Incident Committee undertook to recall contacts of the cases for screening, inform the general practitioners of all of the contacts about their patients' exposure, warn other organizations and professionals interested or involved in the management of HIV in the London area as to the nature of the incident, and establish a helpline, before informing a wider audience through the EPINET, Communicable Disease Report and national press.

Serologic evidence of human herpesvirus 8 transmission by homosexual but not heterosexual sex.

Epidemiologic studies link Kaposi's sarcoma with a sexually transmitted agent. Human herpesvirus 8 (HHV-8) is likely to be that agent, but routes of transmission are poorly described. A seroepidemiologic study was conducted to determine whether HHV-8 is transmitted sexually between heterosexuals. Sera from 2718 patients attending a sexually transmitted disease (STD) clinic were tested for antibodies to HHV-8 and herpes simplex virus type 2 (HSV-2). Information on sex partners in the previous 12 months and past STDs were obtained by questionnaire. Relationships between possible risk factors and HHV-8 infection were assessed by logistic regression. Overall, seroprevalence of HHV-8 was 7.3%. Independent risk factors for HHV-8 in the whole group were homo/bisexuality and birth in Africa and, among homo/bisexual men, a history of syphilis and HSV-2 and human immunodeficiency virus seropositivity. Among heterosexuals there was no evidence for sexual transmission; the only independent risk factor for HHV-8 seropositivity was birth in Africa.

Cytomegalovirus pp65 antigenaemia as an indicator of end-organ disease in AIDS.

We aim to assess the usefulness of the cytomegalovirus (CMV) pp65 antigenaemia test, also called the CMV direct antigen test (DAT), in the management of patients with advanced human immunodeficiency virus (HIV) infection; we studied all patients who had pp65 assays between 8 September 1995 and 30 August 1996. Twenty-three patients had 31 tests. The mean CD4 cell count was 20/mm3. The tests were negative in 16 patients, of whom 12 have not developed CMV end-organ disease after a mean follow up of 114 days (range 14-269 days), whilst the remaining 4 patients had previously treated CMV disease. Eleven patients had positive tests: 4 had active CMV disease, 2 subsequently developed CMV retinitis, 2 died within a fortnight of multi-drug resistant tuberculosis (MDR-TB), one was lost to follow up and 2 have remained disease-free. This test has a positive predictive value of 43% and a negative predictive value of 94%, Fisher's exact test P=0.03. The pp65 antigenaemia assay can be performed in a standard virology laboratory avoiding the problems associated with polymerase chain reaction (PCR), a result is available within 5 h, and it is semi-quantifiable. However, a large prospective study is required to determine the comparative value and roles of the pp65 antigenaemia assay and DNA PCR in the management of CMV disease, especially with regard to the use of primary prophylaxis and pre-emptive therapy.

An outbreak of multi-drug-resistant tuberculosis in a London teaching hospital.

We describe the epidemiology and control of a hospital outbreak of multi-drug-resistant tuberculosis (MDR-TB). A human immunodeficiency virus (HIV)-negative patient with drug-sensitive tuberculosis developed MDR-TB during a period of unsupervised therapy. She was admitted to an isolation room in a ward with HIV-positive patients, but the room, unbeknown to hospital staff, was at positive-pressure relative to the main ward. Seven HIV-positive contacts developed MDR-TB. The diagnosis in the second patient was delayed, partly because acid-fast bacilli in his sputum were assumed to be Mycobacterium avium-intracellulare. All the available Mycobacterium tuberculosis isolates were indistinguishable by molecular typing. Nearly 1400 staff and patient contacts were offered screening, but the screening programme detected only one of the cases. Despite therapy, the index patient and two of the contacts died. HIV-positive patients are more likely than others to develop tuberculosis after exposure, and the disease may progress more rapidly. In these patients the possibility that acid-fast bacilli may represent M. tuberculosis must always be considered. Patients with tuberculosis (suspected or proven) should not be nursed in the same wards as immunosuppressed patients, and should be isolated. MDR-TB cases must be isolated in negative-pressure rooms. Hospital side-rooms may be positive-pressure as a fire safety measure; infection control teams must be aware of the airflows in all isolation rooms, and must be consulted during the design of hospital buildings. Good communication between infection control teams and clinicians is important, and all medical and nursing staff must be aware of the principles of management of patients with proven or suspected tuberculosis and MDR-TB.