Antiretroviral treatment of men infected with human immunodeficiency virus type 1 reduces the incidence of heterosexual transmission. Italian Study Group on HIV Heterosexual Transmission.

OBJECTIVE: To determine the incidence of heterosexual human immunodeficiency virus type 1 disease transmission and the effect of zidovudine therapy on this risk of transmission. DESIGN: A cohort of 436 monogamous seronegative female sexual partners of human immunodeficiency virus type 1-infected males was followed up for 740 person-years with regular structured interviews and laboratory tests. PATIENTS: At enrollment of the women, 50% of their infected partners had one or more signs of disease progression (symptoms of acquired immunodeficiency syndrome, p24 antigen positivity, or CD4+ cell counts lower than 0.4 x 10(9)/L) and 15% were treated with zidovudine. MAIN OUTCOME MEASURE: Incidence rates of seroconversion were calculated and relative risks were estimated as incidence rate ratios. RESULTS: Twenty-seven women seroconverted during follow-up, and the incidence of seroconversion was 3.7 per 100 person-years. Seroconversion was about six times more frequent (relative risk, 5.8; 95% confidence interval, 2.2 to 15.3) in couples not using condoms. Men with signs of disease progression transmitted infection to their partners more frequently and were more frequently treated with zidovudine. When the risk of transmission was estimated accounting for disease progression, the rate of transmission in zidovudine-treated men was lower than in untreated men (relative risk, 0.5; 95% confidence interval, 0.1 to 0.9). CONCLUSION: Treatment of human immunodeficiency virus type-1 infected men with zidovudine reduces, but does not eliminate, heterosexual transmission of infection. Behavioral counseling that encourages sexual practices with a lower risk of transmission remains the most important method of prevention.

Detection of circulating p24 antigen-positive CD4+ cells during HIV infection by flow cytometry.

OBJECTIVES: To determine the amount of circulating CD4+ cells positive for intracellular p24 antigen during HIV infection, and to correlate the results with clinical, virological and therapeutic parameters. METHODS: Data were obtained from 24 anti-HIV-negative subjects (controls) and 47 anti-HIV-positive patients classified according to clinical diagnosis, serum p24-antigen assay results, and antiretroviral treatment with zidovudine, using a modified flow cytometric assay for the detection of intracellular HIV p24 antigen (p24-FCA) in circulating CD4+ lymphocytes. RESULTS: The proportion of CD4+ lymphocytes positive for p24-FCA correlated well with HIV infection (1.685 +/- 1.902 versus 0.160 +/- 0.152 in controls; P < 0.001) and clinical progression [Centers for Disease Control (CDC) stage II: 1.310 +/- 1.187; CDC stage III 1.145 +/- 1.442; CDC stage IVA/C2: 2.335 +/- 2.112; CDC stage IVC1: 2.066 +/- 2.420]. The percentage of CD4+ cells positive for HIV p24-FCA was inversely correlated with an absolute peripheral blood CD4+ lymphocyte count (Spearman's rank correlation = -0.324; P < 0.05). However, there was no statistically significant difference between patients in presence (n = 27; 1.938 +/- 2.095) or absence (n = 20; 1.343 +/- 1.594) of serum p24 Ag. The variable linked most strongly to the detection of intracellular p24 in anti-HIV-positive patients was zidovudine treatment: the proportion of p24-FCA-positive CD4+ lymphocytes was significantly lower (0.825 +/- 0.910) in the treated patients (n = 25) than in the untreated patients (n = 22; 2.662 +/- 2.248; P < 0.001). CONCLUSIONS: Our results suggest that CD4+ p24 Ag-FCA is a rapid and easy test for the identification of the proportion of CD4+ lymphocytes with intracellular p24 Ag, and that it could be more appropriate than serum p24 Ag assay in evaluating disease progression and efficacy of antiretroviral treatment.

Elevated plasma levels of vasoactive intestinal peptide in AIDS patients with refractory idiopathic diarrhoea. Effects of treatment with octreotide.

OBJECTIVE: To evaluate plasma levels of vasoactive intestinal peptide (VIP) in AIDS patients with refractory idiopathic diarrhoea, and to assess the role of treatment with octreotide. PATIENTS: Three AIDS patients were evaluated for severe watery diarrhoea of 2-6 months' duration, which was complicated by weight loss, weakness, and fluid and electrolyte abnormalities. They had not shown a significant response to several regimens of empirical antimicrobial chemotherapy, or symptomatic antidiarrhoeal treatment. METHODS: A complete diagnostic examination, including repeated microbiological evaluation and radiological, ultrasonographic, endoscopic and histological examination, was performed. Plasma levels of VIP were determined by radioimmunoassay and compared with concentrations in a group of healthy subjects. RESULTS: Since no clinically significant results were obtained from standard diagnostic evaluation and empirical therapeutical attempts, idiopathic refractory diarrhoea was diagnosed. Plasma concentrations of VIP were moderately elevated in all three subjects examined, with levels of 11.5, 17.5 and 9.5 pmol/l (values < 8.8 pmol/l in the control group). One patient received 50-100 micrograms octreotide three times daily subcutaneously for 6 months, resulting in complete resolution of diarrhoea and significant improvement in body weight and quality of life, together with a reduction in VIP concentration to within normal values. CONCLUSIONS: Although the somatostatin analogue octreotide has been used successfully in the management of both infectious and non-infectious AIDS-related diarrhoea, gastrointestinal neuroendocrine function and circulating humoral mediators of diarrhoea have not hitherto been investigated extensively in HIV-infected subjects. Our data on the association of idiopathic secretory diarrhoea and elevated plasma VIP levels provide a possible pathophysiological rationale for identifying AIDS patients whose refractory diarrhoea may be more responsive to octreotide treatment.

Man-to-woman sexual transmission of HIV: longitudinal study of 343 steady partners of infected men.

To study incidence and risk factors of heterosexually transmitted HIV infection, we followed a cohort of 343 seronegative women, stable, monogamous partners of infected men whose only risk of acquiring HIV was sexual exposure to the infected partner. Nineteen seroconversions occurred in 529.6 person years (py) of observation, yielding an incidence rate of 3.6 per 100 py. The incidence rate was 7.2 per 100 py among women who did not always use or never used condoms and 1.1 among those who always used them [relative risk (RR) 6.6, 95% confidence interval (CI) 1.9-21.9]. Anal sex was associated with a risk increase in only those women not always using condoms (RR 1.4, 95% CI 0.4-4.8). No seroconversions were observed among 22 women using oral contraceptives. One of the women using intrauterine devices seroconverted. In couples who did not always use condoms, seroconversions occurred more frequently in partners of men with symptomatic diseases, with a low CD4+ cell number (< 400 per mm3) or with a detectable p24 antigen. In couples not always using condoms and where the man had a low CD4+ cell count, the joint presence of blood viral antigens and AIDS symptoms conditioned a fivefold increased risk of seroconversion of the woman (RR 5.4, CI 1.4-20.3). At multivariate analysis, women with longer relationships (> or = 1 year) showed a lower risk of seroconversion (RR 0.3, CI 0.1-0.8), and those partners of men positive for p24 antigen in serum had an increased risk of seroconversion (RR = 4.0, CI 0.1-0.8).

Mortality among drug users in the AIDS era.

BACKGROUND: Infection with human immunodeficiency virus type 1 (HIV-1) causes progressive immune deficiency, the acquired immunodeficiency syndrome (AIDS), and death. Mortality, however, particularly with causes other than AIDS, deserves further study. A retrospective cohort study among drug users in Italy was performed to estimated absolute and proportional mortality rates due to AIDS and other causes, with or without HIV-1 infection. METHODS: All subjects who enrolled between January 1980 and July 1990 in the drug treatment programme in the Province of Bologna, Italy, were included in the cohort. Each subject was categorized for HIV-1 antibody status (positive, negative, untested), vital status (in 1990 by national surveillance), and causes of death (by death certificate). Data were analysed with actuarial and time-dependent covariate methods. RESULTS: There were 332 deaths among 4962 drug users who were followed for 21,130 person-years. This mortality rate (1.57 per 100 person-years) was increased 18-fold compared to the general population. Actuarial 10-year mortality estimates were 28.2% for the 2040 HIV-1 positive subjects, 12.1% for the 1859 HIV-1 untested subjects, and 2.5% for the 1063 HIV-1 negative subjects. AIDS contributed to 150 deaths, followed by drug overdose (64 deaths) and trauma (39 deaths). Compared to others in the cohort, mortality with AIDS and non-AIDS causes was reduced for HIV-1 negative subjects. In contrast, mortality for HIV-1 positive subjects was increased with AIDS, trauma, overdose, various bacterial infections, hepatitis, and cirrhosis. CONCLUSIONS: Mortality with HIV-1 infection was associated not only with opportunistic infections and malignancies but also with competing causes of death, particularly hepatic disease. Further investigation is needed to clarify whether alcohol, analgesics, hepatitis viruses, or other agents have enhanced hepatotoxicity for HIV-1 infected patients.

Vertical transmission of human immunodeficiency virus type 1. Prognostic value of IgA antibody to HIV-1 polypeptides during pregnancy.

In a retrospective study of 31 pregnant women infected with human immunodeficiency virus type 1 (HIV-1), nine (29%) infants presented unequivocal signs of HIV-1 infection (persistent p24 antigenemia and/or positive virus isolation). All serum samples obtained from the others, during pregnancy and on delivery, were studied for specific antibody (IgA) production by immunoblotting analysis to establish a possible link between the presence of a defined antibody class and mother-to-child viral transmission. The majority (16 of 22) of HIV-1-seropositive mothers who delivered uninfected children showed IgA antibody to low-molecular-weight HIV-1 polypeptides during pregnancy. Among those who delivered infected babies, only one showed a weak IgA reactivity to HIV-1 during pregnancy. Thus, our results suggest that immunoblotting study of IgA may be a diagnostic adjunct to predict the risk of mother-to-child HIV-1 transmission.

AZT plus methotrexate in HIV-related non-Hodgkin's lymphomas.

AZT is a thymidine analogue useful in the treatment of AIDS. It has been demonstrated that this compound can possess a significant antineoplastic activity when combined with de novo thymidylate synthesis inhibitors, such as 5-fluorouracil (5FU) and methotrexate (MTX). Here we report a review of our data concerning the efficacy and tolerance of the combination AZT + MTX in HIV-related non Hodgkin's lymphomas (NHL). Twenty-nine patients were treated, at weekly intervals, with three (patient 1 to 10) or six (patient 11 to 29) consecutive courses of MTX 1g/m2 and increasing doses of oral AZT (2, 4 and 6g/m2) with leucovorin rescue. Of 26 evaluable patients, a total (complete + partial) response rate of 77% was obtained. The median complete response duration was 16.8 months. There was one therapy-related death due to septic shock. Grade III-IV neutropenia was observed after 19% of the courses, but was prevented by G-CSF administration in 82/119 courses. Grade III-IV anemia was observed after 9% of the courses. In conclusion, the combination AZT + MTX was effective and well tolerated in our series of HIV-related NHL patients.

Four drug-HAART in primary HIV-1 infection: clinical benefits and virologic parameters.

BACKGROUND: From a theoretical standpoint, primary HIV infection (PHI) represents a great chance to modify the natural history of the disease. In this study we purposed a four drugs regimen with zidovudine, lamivudine, ritonavir and saquinavir to treat aggressively the infection and achieve a complete immune reconstitution. METHODS: This is an Italian multicentric open label study. Adult patients with PHI were eligible for the study if they met at least one clinical criterion and one laboratory criterion of the following. Clinical criteria: Signs and symptoms of acute retroviral syndrome within the past 70 days, exposure to HIV-1 within the last 3 months, a preceding negative antibody test within the past 6 months. Laboratory criteria: Detectable p24 antigen with neutralization in serum; detectable HIV-RNA in plasma; indeterminate Western blot test with negative or low positive value HIV antibody in ELISA test. RESULTS: Since April 1997 to April 1999 40 patients with PHI have been enrolled; 80% of this cohort referred symptoms related to acute antiretroviral syndrome. Treatment has been withdrawn in 17 patients (12 for intolerance, 3 for toxicity and 2 for failure). At baseline the mean CD4+ T cells count and CD4/CD8 ratio were 537 (range 55-1287) and 0.58 (range 0.1-1.03) and the mean plasma HIV-RNA level was 5.9 log copies/ml (range 3-7.15). Plasmatic HIV-1 RNA levels of all patients dropped below 200 copies/ml in 68% of patients at week 12, 81% at week 24, 93% after 12 months and 100% after 18 months. Immunological parameters have been improved and have achieved normal range since 6th month. CONCLUSIONS: A rapid virologic suppression and immunological reconstitution are associated with PHI therapy. However early treatment should be weighted against the potential disadvantages such as immediate adverse events (intolerance and drug toxicity) and long term manifestation (metabolic disorders).

Effects of dialysis membrane nature on intradialytic phagocytizing activity.

Blood-membrane contact in the extracorporeal circuit affects the activation of many biological systems. Among these, phagocytizing activity has been reported to be influenced by the nature of the hemodialysis membrane used, whether cellulosic or synthetic. This work reports on an ex-vivo, comparative test between cellulosics and synthetics concerning the effects of blood-membrane contact on the polymorphonucleate and monocyte phagocytizing function, both during and after the hemodialysis session. By means of flow cytometry, we evaluated the capacity for phagosoma formation and oxidative burst both in polymorphonucleates and monocytes. Ten hemodialysis patients were included in the study. Six separate dialysis procedures for each patient were considered, one per dialyzer (3 cellulosic and 3 synthetic membranes). Tests were performed at 15', 60', 210' and 4 hours after the session end. Comparative evaluation was made according to Student's t test. Polymorphonucleate phagocytosis and oxidative burst activation were globally more marked for synthetic than cellulosic membranes, tending to level out in the post-dialysis. This result could be affected by their functional exhaustion following pulmonary sequestration. Monocyte intradialytic phagocytosis and oxidative burst proved more activated by cellulosic membrane. All differences tended to vanish in the post-dialysis.

Cervical intraepithelial neoplasia in HIV seropositive patients.

In order to assess the frequency of cervical intraepithelial neoplasia (CIN) in a high risk population, 32 women infected with human immunodeficiency virus (HIV), with no AIDS-related symptoms, underwent colposcopic, cytologic and histologic examinations of the uterine cervix. In seven cases (21.9%) cervical smears showed dysplasia and in nine cases (28.1%) histologic evaluation indicated CIN. No invasive carcinomas were observed. In seven of the nine women CIN was associated with lesions due to human papillomavirus infection (HPV). These data confirm that HIV-positive women are at increased risk for developing neoplasias in the lower genital tract and are in need of regular and careful cytologic and, in particular, colposcopic and histologic examinations.

[Malignant tumors of the gastrointestinal autonomic nervous system (GAN tumors or plexosarcomas). Report of a case]. / I tumori maligni del sistema nervoso autonomo gastrointestinale (GAN tumors o plessosarcomi). Descrizione di un caso.

The plexosarcomas or gastrointestinal autonomic nerve tumors (GAN tumors) are very rare neoplasms originating from the gastrointestinal autonomic nervous system. They have been differentiated from the other gastrointestinal stromal tumors due to ultrastructural features showed by electronic microscopy. Their mesenteric localization rare than the gastric and intestinal localization, and it gives a very poor and specific clinical symptomatology. It's very difficult to make a correct diagnosis. The most important prognostic factors influencing the survival seem to be the tumor size and the mitotic activity. The authors describe a case of multiple Plexosarcomas occurred in a young patient one year after a surgical intervention for ileal resection to remove a benign schwannoma. This patient wasn't a carrier of multiple Neurofibromatosis. The diagnostic difficulties before surgical operation are stressed and the importance of surgery as the only diagnostic and therapeutic choice is underlined, even if local recurrences occurred in more than 50% of the treated cases.

[Thoracic lymphoma and AIDS]. / Lymphome thoracique et SIDA.

During the past 4 years, 122 patients with AIDS and 20 with thoracic lymphoma associated to AIDS were observed. There were 18 cases of non-Hodgkin's lymphoma, mostly at a high grade and a high b-cell stage (Burkitt's or Burkitt-like lymphoma) (16 cases). This prevalence reflects the general increase in the number of neoplasms secondary to immunosuppression, which goes along with the improvement of prevention and the control of opportunistic infections. Out of these 20 lymphomas in AIDS, 5 (25%) produced thoracic lesions; in 4 cases, the initial site of the disease was in a thoracic site. The frequency of such expressions is greater that reported in the literature. The radiological appearances are atypical relative to the classical signs of lymphoma in the general population, with predominantly nodular forms (60%) or peripheral, fast-growing masses that are likely to invade the thoracic wall. Isolate lymph node invasion is possible, as well as pleural effusion. Though not pathognomonic, this appearance is highly suggestive of lymphoma in AIDS (LDS) in HIV-positive patients. In all patients with pulmonary lymphoma, CT showed bilateral lesions in a greater number than plain radiography had shown, with morphological and CT appearances that allowed a correct approach of the diagnosis and an appropriate choice of the site of biopsy.

Sepsis-bacteraemia and other infections due to non-opportunistic bacterial pathogens in a consecutive series of 788 patients hospitalized for HIV infection.

A retrospective study was carried out to evaluate the incidence, etiology and role of non-opportunistic bacterial infections in a series of 788 consecutive HIV-infected patients hospitalized during the last 7 years; 71.9% of patients were i.v. drug addicts, 15.6% homo-bisexual men, 7.4% heterosexuals, 2.7% haemophiliacs and 2.4% children with vertically-acquired infection. According to the CDC classification of HIV infection, 71 patients were classified as CDC I-II, 148 as CDC III, and 569 (72.2%) as CDC IV. Diagnosis of bacterial infection was based on signs and symptoms, in association with the isolation of microorganisms consistent with the clinical picture. Two hundred and nineteen patients out of 788 (27.8%) (4 in CDC group I-II, 34 in CDC III and 181 in CDC IV), presented one or more episodes of non-opportunistic bacterial infection. The morbidity of these infections showed a significant correlation with the progression of HIV disease (CDC III vs. CDC I-II [p < 0.003] and CDC IV vs. CDC III [p < 0.05]), but no significant relation was found with age, sex or type of risk for HIV infection. The most frequent clinical picture was sepsis/bacteraemia (33.3%), followed by respiratory tract (23.8%), and genitourinary tract (20.8%) infections. A total of 399 bacterial pathogens were isolated in 303 different episodes of infection: 211 (52.9%) were gram-positive and 188 gram-negative, with Staphylococcus aureus (69 isolations), Staphylococcus epidermidis (50), and Pseudomonas spp. (48) as the major pathogens. Sepsis/bacteraemia was the most frequent clinical picture associated with growth of gram-positive pathogens, while detection of gram-negative bacteria appeared more significantly related with genitourinary or respiratory tract localizations. Bacterial infections in hospitalized HIV-infected patients, even though rarely life-threatening, need particular attention because of the high incidence and recurrence rate, the wide aetiological and clinical spectrum, the frequent microbial associations and the strict relationship with the progression of HIV disease.

[Clinical and immunologic test of the activity of a polymicrobial vaccine in patients with chronic bronchitis during a flare-up]. / Verifica clinica ed immunologica dell'attività di un vaccino polimicrobico in pazienti affetti da bronchite cronica in fase di riacutizzazione.

The authors evaluated the effect of an orally administered polymicrobial vaccine in a group of chronic bronchitis patients in order to assess its efficacy in preventing recurrent infections and as adjuvants during minor acute episodes. Compared to the control group, vaccinated patients had 1) a reduced number of flare-ups, and these were less severe and symptoms were improved; II) lymphocyte phenotype was not altered in any of the patients but nevertheless the response to skin tests for delayed sensitivity was improved in the vaccinated patients only; III) more rapid symptomatic improvement of flare-ups. The authors stress the improvement of cell-mediated lymphocyte function as a result of vaccination, probably due to macrophage activation and with resulting improvement of the clinical course of the bronchial disorder.

[Monitoring of several hematological parameters of the erythroid series in patients with HIV infection treated with zidovudine]. / Monitoraggio di alcuni parametri ematologici della serie eritroide in pazienti con infezione da HIV in trattamento con zidovudina.

Haematologic toxicity is the most common adverse effect related to long-term administration of zidovudine (AZT). We evaluated the kinetics of modifications of some haematologic parameters of erythroid series in 65 patients with HIV infection treated with AZT for a mean duration of 7.6 +/- 4.7 months (13 of them with a previous diagnosis of AIDS, 34 with ARC, 18 asymptomatic or with LAS/PGL), in order to correlate the observation and the evolution of these laboratory changes with the onset of severe anaemia. The development of macrocytosis occurs in a large majority of AZT-treated subjects, in spite of folate and vitamin B12 supplementation; the monitoring of erythrocytes distribution according to cellular volume and cellular haemoglobin concentration makes it possible to early recognize the occurrence of modification in erythropoiesis. There is no correlation between an elevated mean corpuscular volume and the development of severe anaemia (Hb less than or equal to 9 g/dl) in an individual patient; a fall in the reticulocyte count appears to be the earliest peripheral blood sign of the development of bone marrow toxicity.

[Linear psoriasis (linear psoriatic epidermal nevus) in a patient with HIV infection]. / Psoriasi lineare (nevo epidermico lineare-psoriasi) in paziente con infezione da HIV.

The Authors report a 24 year-old female who presented a linear localized epidermal nevus, from birth. Few months after a diagnosis of HIV infection (ARC WR 4) they observed the flaring-up of psoriasis both on the typical cutaneous sites, and on nevus, which looked like linear psoriasis.

Two-stage reimplantation for periprosthetic knee infection: Influence of host health status and infecting microorganism.

BACKGROUND: Two-stage revision is the gold standard treatment of TKA infection; nevertheless various factors may influence the success rate. The aim of our study was to assess the impact of the number of patient comorbidities together with virulence of infectious organism on prognosis of two-stage revision procedure in chronic peri-prosthetic knee infection; moreover we tried to demonstrate correlation between the presence of positive culture during re-implantation and re-infection rate. METHODS: Thirty-eight cases of two-staged revision procedures for infected total knee arthroplasty were prospectively followed. The presence of high virulence microorganisms on the culture result and the number (more than three) of comorbidities were used as major risk factors. All cases were divided into three groups: Group 1 (10 patients without major risk factors), Group 2 (18 patients with only one major risk factor), Group 3 (10 patients with both of major risk factors). RESULTS: After a mean follow-up of 65months (range 24-139months), there was infection recurrence in nine cases: four re-infections occurred with the same organism while five patients had re-infection with a different organism. Recurrence was higher in Group 3 (33% of the cases), lower in Group 2 (12% of the cases), whereas no infection occurred in Group 1. Finally in case of positive intraoperative cultures recurrence rate was 83%, whereas when specimens were negative we had only 12.5% of re-infections. CONCLUSIONS: Even if standard protocol of two-stage revision has demonstrated good results when treating low-virulence infections or patients without associated risk factors, its application to more challenging condition cannot be assumed. LEVEL OF EVIDENCE: Level IV, therapeutic study. See the Guidelines for Authors for a complete description of level of evidence.