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Summary: The use of new potent protease inhibitor-based antiretroviral therapies in patients with human immunodeficiency virus (HIV) infection has been increasingly associated with cardiovascular risk factors, including hyperlipidaemia, fat redistribution syndrome, insulin resistance, and diabetes mellitus. The introduction of highly active antiretroviral therapy (HAART) in clinical practice has remarkably changed the natural history of HIV disease, leading to a notable extension of life expectancy, and prolonged lipid and glucose metabolism abnormalities are expected to lead to significant effects on the long-term prognosis and outcome of HIV-infected patients. Prediction modeling, surrogate markers and hard cardiovascular endpoints suggest an increased incidence of cardiovascular diseases in HIV-infected subjects receiving HAART, even though the absolute risk of cardiovascular complications remains still low, and must be balanced against the evident virological, immunological, and clinical benefits descending from combination antiretroviral therapy. Nevertheless, the assessment of cardiovascular risk should be performed on regular basis in HIV-positive individuals, especially after initiation or change of antiretroviral treatment. Appropriate lifestyle measures (including smoking cessation, dietary changes, and aerobic physical activity) are critical points, and switching HAART may be considered, although maintaining viremic control should be the main goal of therapy. Pharmacological treatment of dyslipidaemia (usually with statins and fibrates), and hyperglycaemia (with insulin-sensitizing agents and thiazolidinediones), becomes suitable when lifestyle modifications and switching therapy are ineffective or not applicable. [Copyright &y& Elsevier]

One thousand and eighty-one evaluable HIV-infected patients were assessed for pancreatic abnormalities in a prospective case–control study including the whole follow-up period of each patient (minimum 12 months). The 435 patients (40.2%), who experienced at least one episode of confirmed pancreatic laboratory abnormality had a longer duration of seropositivity, exposure to protease inhibitors, a more frequent immunodeficiency, AIDS, chronic liver and/or biliary disease and hypertriglyceridaemia, while no relation was found with antiretroviral administration, and the duration of type of nucleoside analogues, when compared with the 646 controls. High and prolonged laboratory alterations eventually associated with signs of organ involvement occurred in 166 cases (38.2%), and were related to the administration of didanosine, stavudine, lamivudine, pentamidine, cotrimoxazole or antitubercular/antimycobacterial therapy, cytotoxic chemotherapy, illicit substance or alcohol abuse, opportunistic infections, chronic liver and/or biliary disease, a protease inhibitor-based highly active antiretroviral therapy (HAART) and hypertriglyceridaemia (usually associated with HAART administration). No difference was noticed between the 46 patients with clinical and/or imaging evidence of pancreatic involvement and the 120 asymptomatic subjects. Although recurrences of enzyme alterations involved 69.6% of patients, only in 30.1% of cases did a change of the underlying antiretroviral or antimicrobial therapy become necessary. An acute, uncomplicated pancreatitis occurred in nine of the 46 symptomatic subjects (19.6%). A two to four week gabexate and/or octreotide administration (performed in 79 cases of 166, 47.6%), achieved a significant laboratory, clinical and imaging cure or improvement in 82.3% of cases, with a better success rate of combined (gabexate mesilate plus octreotide) vs. single (gabexate mesilate or ocreotide) therapy. Reduced disease recurrences and a better tolerability of antiretroviral regimens, were also noticed. [ABSTRACT FROM AUTHOR]

An extremely rare case report of HIV-associated gastric adenocarcinoma surgically treated in the year 1998 in a 37-year-old male patient already HIV positive for 10 years, with a complete post-surgery disease-free follow-up of eight years, is described. An international literature search allowed us to report the available details of the only nine cases of HIV-associated gastric cancer yet published. Seven occurred prior to the introduction of highly active antiretroviral therapy (HAART) and were burdened by a rapid disease evolution, while only two patients were reported after the introduction of HAART (like ours) and obtained surgical cure. Detailed data regarding complications, sequelae and overall survival are not given. Notably, even four of the nine published reports came from Japan, and an early disease development was usual (37–50 years of age at diagnosis). Due to its relevant differential diagnosis implications with many other HIV-related gastrointestinal disturbances caused by functional and organic diseases (drug-related disturbances, HIV infection itself, opportunistic infections, and Kaposi's sarcoma and malignant lymphomas being the most frequent disorders) and the possibility of maintaining an adequate life-expectancy when diagnosis and aggressive treatment are not delayed, gastric cancer should be considered carefully by all clinicians dealing with HIV disease. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Prostate cancer is a very infrequent occurrence in persons aged 55 years or less, and it has been rarely reported in HIV-infected patients (10 overall cases so far); therefore, an increased incidence compared with the general population has not been established, although a younger age seems more frequent among population with HIV disease. Case report: We report a case of metastatic prostate cancer occurred in a 53-year-old HIV-infected man, admitted due to non-specific signs, and symptoms: impaired general conditions, fever, weight loss, fatigue, and exertional dyspnea. A remarkable anemia and an aortic systolic murmur were the prominent initial findings, while AIDS-related conditions were not suspected due to a sustained CD4+ count and a contained viremia, which never required antiretroviral therapy. Repeated red blood cell transfusions and an empiric, combined antimicrobial therapy were promptly carried out, under the suspicion of infectious endocarditis, but no appreciable improvement of clinical conditions was achieved. Subsequently, our patient complained not only of an increasingly severe pain at the root of his left thigh, together with overcoming dysuria and urgency, but also urinary tract infection that was rapidly ruled out. During the diagnostic workup for an HIV-associated fever of undetermined origin, a bone marrow biopsy disclosed a metastatic prostatic cancer, with elevated prostate specific antigen (PSA) and acid phosphate levels. An abdominal–pelvic ultrasonography and computerized tomographic scan allowed to detect a dyshomogeneous endopelvic expansive mass with extrinsic compression of the urinary bladder, and involvement of the last lumbar vertebra, large portions of pelvis, and the proximal epiphysis of the right femur. A skeleton scintigraphy pointed out multiple hypercaptation (areas of concentrated traces of radioactivity) areas with involvement of cranial, cervical, dorsal, lumbar, and sacral vertebrae, as well as the pelvis and upper portions of both femurs. Despite therapeutic attempts, our patient deceased after seven weeks due to an overwhelming disseminated intravascular coagulation (DIC). Conclusions: The non-specific clinical presentation of our case (mimicking other generalized or focal illnesses), and the final, lethal complication (DIC) pose striking problems related to the differential diagnosis during HIV disease, while the rapid evolution into an advanced, complicated, and widely metastatic disease with extensive bone marrow invasion which preceded the appearance of local signs–symptoms, and the lethal overwhelming DIC, deserves attention by specialists who care for HIV-infected subjects. [Copyright &y& Elsevier]

Objective: The aim of this study is to evaluate the temporal trend of deaths in a cohort of intravenous (IV) drug users (IVDU) followed in a city in Northern Italy (Bologna), and to assess its relationship with HIV infection and AIDS, and availability of potent antiretroviral therapy. Methods: A total of 1214 IVDUs (mainly heroin addicts). 916 males and 298 females, attending an outpatient service for treatment and prevention of substance abuse between 1977 and November 1996, were enrolled into our observational cohort. Their vital status was ascertained up to December 31, 2002. Results: The large majority of enrolled subjects were born in the Bologna metropolitan area and surroundings; no extra-European immigrants were pres present. During the observation period. 271 IVDUs (22.3%) died, 211 males (23.0%), and 60 females (20.1 %). No death was recorded before 1984. Main death causes were as follows: AIDS (52.8% of deaths), heroin overdose (22.1%), street accidents (7.4%), decompensated liver cirrhosis (6.3%), and suicide (2.9%). The highest absolute number of deaths was observed between years 1991 and 1996. Crude mortality rate caused by AIDS was 10.0 per 1000 for males and 13.2 per 1000 for females; the rate of death due to other causes proved 11.1/1000 among males and 5.2/1000 among females. Conclusion: In most recent years, a sharp decrease in the number of AIDS related deaths, attributable to the increased use of potent antiretroviral regimens, was recorded among IVDUs, although overall mortality rate remained appreciable. [ABSTRACT FROM AUTHOR]

While the mean age of HIV/AIDS patients at first diagnosis is progressively rising, no updated epidemiological estimates, controlled clinical data, and randomized therapeutic trials, are available regarding clinical and laboratory response to antiretroviral therapy, safety of anti-HIV compounds and their associations, potential drug–drug interactions, short- and long-term toxicity, consequences on underlying disorders, or interactions with concomitant pharmacological regimens, in the elderly. The life expectancy of HIV-infected persons treated with highly active antiretroviral therapy (HAART) now approximates that of general population matched for age, while also AIDS definition itself has lost most of its epidemiological and clinical significance, thanks to the immunoreconstitution resulting from the large-scale use of potent HAART regimens. The increased survival of HIV-infected patients, the late recognition of other subjects with missed or delayed diagnosis are responsible for a further expected rise of mean age of HIV-infected individuals, so that the patient population aged 60–70 years or more is expected to increase in coming years. Unfortunately, the majority of therapeutic trials involving antiretroviral therapy, as well as antimicrobial chemoprophylaxis for AIDS-related opportunistic complications, have advanced age and/or concurrent end-organ disorders among main exclusion criteria, or the design of these studies does not allow to extrapolate data regarding older patients, compared with younger ones. The very limited data presently available seem to demonstrate that HAART has a virological efficacy in the elderly comparable with that of younger adults, but immunological recovery is often slower and blunted, although several studies clearly demonstrated that thymic function is preserved until late adult age. When facing an HIV-infected patient with advanced age, health care givers have to pay careful attention to eventual end-organ disorders, all possible pharmacological interactions, overlapping toxicity due to concurrent drug administration. All these issues may significantly interfere with HAART activity, patient’s adherence to prescribed medications, and frequency and severity of untoward effects. The guidelines of antiretroviral therapy and those of treatment and prophylaxis of AIDS-related diseases deserve appropriate updates, paralleling the increasing mean age of HIV-infected population. Moreover, epidemiological figures need an increased focus on older age, while clinical trials specifically targeting on the elderly population are mandatory to have reliable data on all aspects of HAART administration in advanced age. [Copyright &y& Elsevier]

The frequency, the microbiology and clinical features of AIDS-related primary episodes and relapses of cryptococcosis, before and after the introduction of highly active antiretroviral therapy (HAART), were compared. The study covered 58 cases diagnosed before the introduction of HAART, and eight episodes since 1997. Because of negative cultures, we sought a sensitive laboratory assay such as detection of polysaccharide antigen. Despite later diagnosis, there was reduced disease mortality. Clinical suspicion for HIV-associated cryptococcosis should be maintained in immunocompromised subjects. The introduction of HAART has led to significant clinical and laboratory changes of HIV-related cryptococcosis. [Copyright &y& Elsevier]

A wide range of abnormalities of lipid metabolism have been recently described in HIV-infected patients receiving a protease inhibitor (PI)-based highly active antiretroviral therapy, including hypertriglyceridaemia and hypercholesterolaemia. The increase of plasma lipid concentrations may involve up to 70–80% of HIV-positive subjects treated with a PI-containing regimen and are frequently (but not always) associated with the fat redistribution or the lipodystrophy syndrome. Multiple pathogenetic mechanisms by which antiretroviral agents lead to dyslipidaemia have been hypothesized, but they are still controversial. The potential clinicopathological consequences of HIV-associated hyperlipidaemia are not completely known, but several anecdotal observations report an increased risk of premature coronary artery diseases in young HIV-positive individuals receiving PIs, besides peripheral atherosclerosis and acute pancreatitis. A limited-to-significant improvement of increased triglyceride and cholesterol plasma levels was described in patients who replaced PIs with nevirapine, efavirenz or abacavir, but the risks of long-term toxicity and virological relapse of this treatment switching are not completely defined. A hypolipidaemic diet and regular physical exercise may act favorably on dyslipidaemia, but pharmacological therapy becomes necessary when hyperlipidaemia is severe or persists for a long time. The choice of hypolipidaemic drugs is problematic because of potential pharmacological interactions with antiretroviral compounds and other antimicrobial agents, associated with an increased risk of toxicity and intolerance. Statins are considered the first-line therapy for the PI-related hypercholesterolaemia, while fibrates are the cornerstone of drug therapy when predominant hypertriglyceridaemia is of concern. [Copyright &y& Elsevier]

Two hundred and twelve HIV-positive patients who started a new protease inhibitor (PI)-based antiretroviral regimen between January 1998 and December 2000 in our tertiary care centre were prospectively followed-up during a 12-month study period, in order to assess the incidence of hyperlipidaemia and related clinical adverse events. At the end of 1-year follow-up, PI-containing antiretroviral treatment led to a statistically significant increase in serum triglyceride levels (P<0.005) and total and LDL-cholesterol levels (P<0.05). The overall incidence of hypertriglyceridaemia and hypercholesterolaemia was 38.2 and 25%, respectively. The incidence of increased serum triglyceride levels was significantly higher in patients treated with ritonavir (66.6%) or lopinavir/ritonavir (60.7%), compared with other PIs (P<0.04). Clinical adverse events possibly related to the hyperlipidaemia (such as cardiovascular diseases or acute pancreatitis) were not observed during the entire 12 months study period. In conformity with other previously published studies, the very high incidence of hyperlipidaemia during a PI-based therapy recognised in our work raises a big concern about its potential clinico-pathological consequences and the most convenient pharmacological management of these metabolic imbalances. [Copyright &y& Elsevier]

Although HIV infection is often associated with several rheumatic diseases, the coexistence of this retroviral infection and systemic lupus erythematosus (SLE) is extremely uncommon. Generally, HIV-related immunosuppression improves SLE symptoms, and antiretroviral therapy may lead to an autoimmune disease flare subsequent to the increase of circulating CD4+ cell number. Two HIV-infected female patients with SLE and discoid lupus erythematosus (DLE) diagnosed a few months after the highly active antiretroviral therapy initiation, are described. To our knowledge, this is the second case of DLE and the twenty-seventh case of SLE reported to date in association with HIV infection. [ABSTRACT FROM AUTHOR]

An evaluation was made of the frequency of outcomes, the features, and one-year outcomes of the substitution, carried out because of failure or toxicity, of protease inhibitor (PI)-containing highly active antiretroviral therapy (HAART). Nine hundred and seventy-two HIV-infected patients were prospectively followed up since 1996, with the condition that they had a minimum 80% adherence to prescribed regimens. Four hundred and fifty-two changes occurred in 397 of the 876 evaluable patients (45.3%). Virological and/or immunological failure was of concern in 245 cases (54.2%). Interest in saquinavir had the greatest incidence and earliest occurrence (although the subsequent switch had a significantly better outcome than that of patients failing with other PIs); nelfinavir benefited from a shorter time to change and a worse long-term outcome (probably attributable to its predominant use in indinavir- and ritonavir-experienced patients); while indinavir showed the lowest overall frequency of substitution. Intolerance occurred in the remaining 207 cases (45.8%); with saquinavir being better tolerated than other PIs. A favourable outcome was obtained more frequently when poor tolerability was of concern, compared with therapeutic failure (P <0.008), while no significant differences were found according to prior antiretroviral experience and the subsequently selected HAART regimen. The overall one-year outcome per single substituted compound proved significantly better for patients who stopped using saquinavir and ritonavir, by contrast with those who stopped using indinavir and nelfinavir (P < 0.0008). A significantly shorter mean time to substitution was recognized for nelfinavir and saquinavir than with ritonavir and indinavir (P < 0.0001). When analysing the subset of patients experiencing HAART failure, a highly significant reverse relationship was demonstrated between mean time to failure, and rate of subsequent response to a modified antiretroviral regimen (P < 0.0001). When considering the different patterns of efficacy, durability, resistance induction, expected adherence, and safety of each antiretroviral drug, initial and subsequent therapeutic choices should be carefully balanced against expected benefits and risks. [ABSTRACT FROM AUTHOR]

Infective endocarditis associated with human immunodeficiency virus (HIV) infection occurs almost exclusively in intravenous (i.v.) drug users and usually involves the tricuspid valve, with an increased mortality rate among patients with a severe degree of immunosuppression. The first reported case of recurrent tricuspid endocarditis sustained by Streptococcus agalactiae and Enterococcus faecalis in an i.v. drug addict during HIV infection is presented. Antimicrobial therapy with i.v. ampicillin, gentamicin and teicoplanin led to complete clinical and echocardiographical recovery. [ABSTRACT FROM AUTHOR]

A possible association between carpal tunnel syndrome and HIV infection has been suggested only once until now. Two patients with HIV infection are described who presented confirmed carpal tunnel syndrome while on prolonged protease inhibitor-containing highly active antiretroviral therapy (HAART). Their disease course and long-term outcome after medical and/or surgical interventions is presented and discussed according to available evidence from the literature. In our patients, carpal tunnel syndrome occurred in apparent absence of all presumed risk factors of this disease and metabolic abnormalities potentially related to HIV protease inhibitor administration. [ABSTRACT FROM AUTHOR]

A case of isolated necrotizing cytomegalovirus (CMV) oophoritis disclosed only by necropsy studies in a patient with AIDS, is described. This unusual case report is discussed with a review of the literature dealing with CMV involvement of genital organs in the immunocompromised host, and in patients with HIV infection and AIDS. [ABSTRACT FROM AUTHOR]