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.

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.

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.

Disseminated strongyloidiasis in AIDS: uncommon but important.

Disseminated Strongyloides stercoralis infection is a rare and severe but treatable complication of AIDS. We present a case where this infection was successfully treated and review the available literature. Cases may present many years after they have left an area endemic for Strongyloides infection, emphasizing the need for a full travel history. Symptoms are typically gastrointestinal and pulmonary, with infiltrates often seen on chest radiography. Diagnosis requires stool examination and biopsy of affected sites. Treatment with repeated courses of thiabendazole (25 mg/kg twice daily for 5 days) was successful in our case, but maintenance regimens have not yet been defined. The relative rarity of this complication of AIDS suggests that, where both infections are present, disseminated strongyloidiasis only arises either when HIV-induced immunodeficiency is profound or, possibly, when it is accompanied by impaired granulopoiesis.

Adverse effects of drugs used in the management of opportunistic infections associated with HIV infection.

Pneumocystis carinii pneumonia (PCP) is one of the most common AIDS-defining diagnoses. First-line therapy is cotrimoxazole (trimethoprim-sulfamethoxazole), despite a high incidence of toxic effects, and a greater incidence of hypersensitivity reactions among HIV-positive patients compared with the seronegative population. Alternative agents such as intravenous pentamidine, or clindamycin with primaquine, and trimethoprim with dapsone, also have a wide range of serious adverse effects, but remain treatment options. Atovaquone appears promising for the treatment of both PCP and toxoplasmosis, and has a lower reported incidence of toxicity than the alternative agents. The most toxic antifungal drugs are reserved for serious infections, such as cryptococcal meningitis. Liposomal amphotericin B has less renal toxicity than standard formulations, and exemplifies that new formulations of existing drugs, although often expensive, may have a better adverse effect profile. There are 2 different drugs currently available for cytomegalovirus (CMV) infections, ganciclovir and foscarnet. Both have a high incidence of serious adverse effects; ganciclovir mainly causes bone marrow toxicity and foscarnet leads to renal toxicity. The drugs used for mycobacterial infection (including mycobacteria as well as tuberculosis) have a wide range of adverse effects, particularly skin rashes and drug-induced hepatitis. Some of these compounds are quite new, such as rifabutin and clarithromycin, and it is important to be ever vigilant for previously unreported adverse effects.

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.

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.

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.

Cytomegalovirus infection in AIDS. Patterns of disease, response to therapy and trends in survival.

Among 347 AIDS patients seen at St Mary's Hospital, London between 1983 and 1989, cytomegalovirus (CMV) disease was observed in 75 (22%). Of these, 58 (77%) had CMV retinitis, 26 (35%) CMV colitis, and 12 (16%) had CMV infection diagnosed at other sites. Relapse occurred in 71%. A favourable response to the use of ganciclovir as induction therapy for CMV retinitis was observed in 92%. Relapse of CMV retinitis occurred in 54% at a median time of 97 days. Neutropenia was the most frequent and serious side-effect of ganciclovir, 76% patients having neutrophil counts less than 1.0 x 10(9)/l and 48% less than 0.5 x 10(9)/l at some stage of therapy. Thrombocytopenia was also common, and platelet counts of less than 50 x 10(9)/l occurred in 43% patients on ganciclovir. The concurrent use of zidovudine made the development of severe neutropenia and thrombocytopenia more likely. Median survival following the diagnosis of CMV disease increased from 5-8 months between 1984 and 1987, to over 12 months in 1988. Patients with CMV colitis had a worse prognosis than patients with CMV retinitis, with median survival of 4.5 and 7 months respectively. In conclusion, CMV is an important opportunist infection in AIDS and both the disease and its treatment cause considerable morbidity. Hence, it is important to develop more effective and less toxic forms of therapy for CMV infection.

A pilot phase II study of the safety and immunogenicity of HIV p17/p24:VLP (p24-VLP) in asymptomatic HIV seropositive subjects.

The aim of this phase II study was to evaluate the safety, immunogenicity and tolerability of the yeast-derived virus-like particle immunogen, Ty.p24.VLP (p24-VLP), in HIV-antibody-positive asymptomatic volunteers. Fifteen informed and consented volunteers, with p24 Antibody titres >1/100, p24 Antigen <20 pg/l, and CD4>350 x 10(9)/l were enrolled. Five were immunized with aluminium hydroxide placebo, five with 25 microg, and five with 100 microg p24-VLP in Alum adjuvant at weeks 0 and 4 by the intramuscular route. Patients were followed for 16 weeks post vaccination and the main outcome assessments were CD4 and CD8 lymphocyte counts, p24 antigen and antibody, Ty antibody and quantitative viral cultures. No serious adverse events were observed in any of the groups. There were increases in CD4 counts in the treated groups but not in the controls, although these changes were not statistically significant. There were no significant intrasubject or intergroup changes in the other parameters, such as p24 antigen and antibody. No pattern of change in plasma viraemia was detected, and most cultures were negative. Therefore we conclude that p24-VLP immunizations of 25 microg and 100 microg are well tolerated, and the CD4 changes are encouraging, but higher doses and larger numbers are required to see if there are significant humoral or cellular responses, and extended phase II studies are now in progress.

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.

Chlamydia trachomatis as a possible cofactor for Kaposi's sarcoma in AIDS.

AIDS-associated Kaposi's sarcoma (KS) is much more frequent in patients acquiring HIV infection via the sexual route. Epidemiological studies have confirmed the likely involvement of a sexually acquired cofactor in the pathogenesis of this form of KS. We have formulated a set of postulates, epidemiological and experimental, to fit a single unifying hypothetical agent. Chlamydia trachomatis is one of 3 agents to fit the epidemiological criteria. Our data suggest a possible association between increased IgG serum antibody to C. trachomatis and the occurrence of KS. Conversely, higher titres of IgG serum antibody to C. pneumoniae were associated with the absence of KS. We feel that it is important to study further the relationship between C. trachomatis and KS.

Changing disease patterns in patients with AIDS in a referral centre in the United Kingdom: the changing face of AIDS.

OBJECTIVE: To study the changes in morbidity, mortality, and survival patterns in a population of patients with AIDS in the United Kingdom from 1982 to 1989. DESIGN: A retrospective analysis of inpatient and outpatient records of patients with AIDS. SUBJECTS: 347 Patients with AIDS, predominantly homosexual or bisexual men. SETTING: Departments of immunology and genitourinary medicine, St Mary's Hospital, London. MAIN OUTCOME MEASURES: Presenting diagnosis of AIDS, occurrence of other opportunist diseases, cause of death, and survival since AIDS was diagnosed, in particular for those patients with Pneumocystis carinii pneumonia or Kaposi's sarcoma. RESULTS: The overall proportion of patients who developed P carinii pneumonia dropped from 56% (20/36) in 1984 to 24% (46/194) in 1989, although it has remained the index diagnosis in about half of new patients. Kaposi's sarcoma has decreased as index diagnosis from 30% (20/67) to 20% (15/74) over the same period, though the prevalence has remained constant at around 35%. P carinii pneumonia accounted for 46% (16/35) of known causes of death in 1986 but only 3% (1/31) in 1989. Conversely, deaths due to Kaposi's sarcoma rose from 14% (1/7) to 32% (10/31) between 1984 and 1989. Lymphoma accounted for an increased proportion of deaths among these patients with 16% (5/31) of deaths in 1989. Their median survival increased from 10 months in 1984-6 to 20 months in 1987. CONCLUSIONS: The changing patterns of disease in patients with AIDS have important implications both for health care provision and future medical research. Medical and nursing provision must be made for the increased morbidity of these diseases and the increased survival of these patients. Research should now be directed towards developing effective treatments for the opportunist infections which are currently more difficult to treat, the secondary malignancies of AIDS, as well as more effective immunorestorative treatments. Future changes in disease patterns must be recognised at an early stage so that resources can be adequately planned and allocated.