A case-control study of risk factors for hepatitis C infection in patients with unexplained routes of infection.

Twenty to 40% of hepatitis C virus (HCV)-infected patients do not have a recognized parenteral risk factor, suggesting that still-unidentified modes of transmission exist. In order to investigate potential routes of HCV transmission for patients with no recognized parenteral risk factor, we conducted a multicentre case-control study. A total of 450 HCV-seropositive patients with no history of transfusion or intravenous drug use and 757 controls were recruited from the general population and matched for sex, age, geographical residence and number of chronic diseases. All subjects answered an interviewer-administered questionnaire on potential risk factors for HCV. Eighty per cent of cases had chronic hepatitis or cirrhosis. Respective percentages of genotypes 1, 2, 3, 4 and 5 were 65, 14, 11, 5 and 4. Among the 66 items considered, multivariate analysis identified 15 independent risk factors for HCV infection: nosocomial [admission to medical (odds ratio, OR = 2.1) or surgical ward (OR = 1.7), digestive endoscopy (OR = 1.9), abortion (OR = 1.7)], outpatient treatments [cutaneous ulcer and wound care (OR = 10.1), diathermy (OR = 3.0), gamma globulin (OR = 1.7), intravenous (OR = 1.7) or intramuscular (OR = 1.4) injections, varicose vein sclerotherapy (OR = 1.6), acupuncture (OR = 1.5)] and lifestyle-associated [intranasal cocaine use (OR = 4.5), practice of contact sports (OR = 2.3), beauty treatments (OR = 2.0), professional pedicure/manicure (OR = 1.7)]. These factors could explain 73% of community-acquired hepatitis C. In conclusion, for patients with unexplained routes of HCV infection, our data incriminate previously unidentified risk factors (abortions, some dermatological procedures, outpatient injections, contact sports, beauty treatments, professional pedicure/manicure) and confirm those already recognized (hospitalization, digestive endoscopy, acupuncture and intranasal cocaine use).

Knowledge, attitudes, belief and practice related to HIV/AIDS among young people in Ho Chi Minh City, Vietnam.

The HIV infection rate has shown a rapid increase among the young people in Vietnam. In order to inform an HIV education prevention program, we have conducted a knowledge, attitudes, beliefs and practices (KABP) survey among 902 young vietnamese people in Ho Chi Minh City (HCMC) in 1999. Results show that overall knowledge about HIV, sexually transmitted diseases and safe sex is good. A minority of them (11%) declare having sexual activity. Eighty percent of those sexually active use condoms. This rather optimistic picture needs to be confirmed by qualitative measures of sexual behavior among the youth of HCMC. Gender specific interventions should be developed since there appear to be significant differences of knowledge, beliefs and practices between males and females. Other groups of young people should be investigated in order to have a better picture of the Vietnamese context at a time of expansion of the Aids epidemic.

MIKADO: a multicentre, open-label pilot study to evaluate the antiretroviral activity and safety of saquinavir with stavudine and zalcitabine.

BACKGROUND: Since eradication of HIV is unlikely, long-term management of the disease necessitates careful evaluation of the combinations of currently available drugs to determine the most potent and useful rational sequencing of regimens. OBJECTIVE: To determine the antiretroviral efficacy and tolerability of saquinavir soft gelatin capsule (SQV-SGC) plus zalcitabine (ddC) and stavudine (d4T), as first-line treatment in HIV-infected patients. DESIGN: Multicentre, open-label, non-comparative study. PATIENTS AND METHODS: Thirty-five asymptomatic, HIV-infected adults with no prior antiretroviral treatment, a CD4 count > or =250 cells/microL and baseline > or = 5000 HIV RNA copies/mL were included in the study. Patients received SQV-SGC 1200 mg three times a day (tid), ddC 0.75 mg tid and d4T 30 or 40 mg twice a day (bid) for 24 weeks. Plasma HIV RNA, CD4 and CD8 cell counts, HIV reverse transcriptase and protease resistance genotypes, SQV plasma concentration and tolerability were evaluated. RESULTS: At baseline, median HIV RNA (interquartile range) was 4.99 (4.81-5.48) log10 copies/mL, and median CD4 count was 370 (318-504) cells/microL (n = 35). At week 24, the median decrease in HIV RNA was 3.05 (2.19-3.68) log10 copies/mL. A viral load below the level of quantification (200 copies/mL and 20 copies/mL) was achieved in 63% and 34% of patients, respectively (intent-to-treat analysis). The only mutations detected were L90M substitutions in two patients. At week 24, the median CD4 count increased (P < 0.0001), and CD8 cell counts decreased (P < 0.0001), relative to baseline. In total, there were five cases of peripheral neuropathy (14%). Mean triglyceride and cholesterol levels remained within normal ranges. CONCLUSIONS: Triple therapy with SQV-SGC plus ddC and d4T is a reasonably well tolerated regimen that markedly and rapidly reduces viral load with immunological improvement. This combination is an effective additional therapeutic option, with an efficacy that compares favourably to other triple regimens used in HIV treatment.

Mortality among human immunodeficiency virus-infected patients with cirrhosis or hepatocellular carcinoma due to hepatitis C virus in French Departments of Internal Medicine/Infectious Diseases, in 1995 and 1997.

Several studies have suggested that the progression of hepatitis C virus (HCV) infection is more severe in patients infected by the human immunodeficiency virus (HIV). Two national retrospective multicenter cohort surveys were performed in France that included 17,487 HIV-infected patients during 1995 and 26,497 during 1997. The following data was evaluated: total number of deaths; number of deaths linked to AIDS, cirrhosis, or hepatocellular carcinoma (HCC); and number of deaths related to other (non-HCV--linked) causes. In 1995, the causes of death were as follows: AIDS, 1307 (7.47%); cirrhosis or HCC, 21 (0.12%); and other (non-HCV--linked) causes, 99 (0.56%). In 1997, the causes of deaths were as follows: AIDS, 459 (1.73%); cirrhosis or HCC 36 (0.13%); and other (non-HCV--linked) causes, 48 (0.18%). Comparative results between the 1995 and 1997 surveys showed a dramatic decrease in AIDS-related mortality rates (7.47% vs. 1.73%; P<.001) but not in HCV-related mortality rates (0.06% vs. 0.07%; P=.79). In France, despite the high prevalence of HCV infection in HIV-positive patients, the mortality rate in 1995 and 1997 caused by HCV-related cirrhosis or HCC was low.

Adhesive capsulitis of shoulder and treatment with protease inhibitors in patients with human immunodeficiency virus infection: report of 8 cases.

OBJECTIVE: To describe our experience with human immunodeficiency virus (HIV) infected patients receiving protease inhibitor therapy who presented with adhesive capsulitis of the shoulder. METHODS: Between July 1996 and December 1999, 8 HIV-infected patients (7 male) treated with protease inhibitors who presented with adhesive capsulitis of the shoulder were retrospectively identified. Diagnosis of adhesive capsulitis relied on clinical features including shoulder pain and both active and passive restricted range of motion (ROM). All available clinical and radiographic data were reviewed. RESULTS: Onset of symptoms was insidious, and at presentation, patients complained of shoulder pain, which was bilateral in 4 of the 8 cases. Physical examination showed global restriction of active and passive ROM of the glenohumeral joint. The mean delay between initiation of HIV protease inhibitors and onset of shoulder pain was 14 months (range 2 to 36). The protease inhibitor therapy always included indinavir. No underlying condition associated with secondary adhesive capsulitis of the shoulder, including shoulder trauma, diabetes mellitus, thyroid disease, pulmonary or cardiac diseases could be identified. In all 8 patients, despite continuation of therapy with indinavir, both shoulder pain and restricted ROM completely resolved, after a mean disease course of 7.4 months. CONCLUSION: Adhesive capsulitis of shoulder seems to be a new adverse event of HIV protease inhibitor therapy. In all reported cases, patients were treated with indinavir. Further observations will be necessary to confirm adhesive capsulitis as a side effect.

Long-term outcome and treatment modifications in a prospective cohort of human immunodeficiency virus type 1-infected patients on triple-drug antiretroviral regimens. Triest Cohort Investigators.

We designed a cohort in order to assess the long-term effects of triple-drug antiretroviral combinations in 608 patients infected with human immunodeficiency virus type 1 (HIV-1). We recruited patients who had been previously treated with nucleoside analogues as well as treatment-naive patients who were starting triple-drug antiretroviral combinations consisting of nucleoside analogues, either alone or in combination with a protease inhibitor. After a median follow-up time of 22 months, the incidence rates of acquired immune deficiency syndrome-defining events and death were, respectively, 6.9 (95% confidence interval [CI], 5.3-8.8) and 2.9 (95% CI, 1.9-4.2) per 100 person-years. Advanced clinical stage of disease (P=.004), a low CD4(+) cell count (P=.002), and a low quality-of-life score (P=.001) at baseline were independent predictors of clinical progression. The initial triple-drug combination was modified a total of 647 times in 321 patients. The only independent predictor of treatment modification was previous exposure to a nucleoside analogue in patients who did not receive a new nucleoside analogue at inclusion (P=.001). Plasma HIV RNA values below 500 copies/mL were obtained in 88% of the treatment-naive patients and in 57% of the previously treated patients (P<.001). Compared with previously treated patients who received > or = 1 new nucleoside analogue at enrollment, previously treated patients who did not receive a new nucleoside analogue at enrollment were twice as likely to have plasma HIV RNA values >500 copies/mL at the last visit (adjusted odds ratio [OR], 1.8; 95% confidence interval [CI], 1.2-2.8), and the antiretroviral-naive patients were significantly less likely to have plasma HIV RNA values >500 copies/mL at the last visit (adjusted OR, 0.2; 95% CI, 0.1-0.4).

The cumulative occurrence of resistance mutations in the HIV-1 protease gene is associated with failure of salvage therapy with ritonavir and saquinavir in protease inhibitor-experienced patients.

Salvage therapy with ritonavir (RTV) and saquinavir (SQV) failed to achieve virological and immunological improvement in 24 HIV-infected patients who discontinued triple therapy with RTV or indinavir (IDV) because of failure or intolerance to treatment. Changes in the HIV-1 protease gene sequence were analyzed prospectively in 14 patients. No primary protease mutation was found prior to the use of protease inhibitors. After 7 months of treatment with IDV or RTV, primary resistance mutations at codons pol 46 and/or pol 82 were observed in 11 of 13 patients. After 16 weeks on RTV-SQV, novel primary mutations related to SQV emerged in 7 of 13 patients, together with an increase in the number of secondary resistance mutations. Our observations indicate that the cumulative occurrence of resistance mutations in the protease gene was associated with failure of antiretroviral therapy. The presence of mutations to a first protease inhibitor may represent a risk factor for the failure of a subsequent treatment with a second line protease inhibitor.

[Leiomyosarcoma of the superior vena cava: diagnosis by endovascular biopsy]. / Leiomyosarcome de la veine cave superieure: diagnostic par biopsies endovasculaires.

We report the case of a 69-year-old woman with leiomyosarcoma of the superior vena cava presenting with acute superior vena cava syndrome (SVCS). CT and MRI failed to fully characterize the endovascular process. Percutaneous endovascular biopsy, followed by metallic stent placement to treat the SVCS, confirmed the diagnosis. Symptoms resolved within 48 hours and surgical resection of the tumor was performed one month later. Unfortunately the patient died two weeks later because of intracranial hemorrhage.

[Agranulocytosis in acute hepatitis B in an HIV seropositive patient]. / Agranulocytose au cours d'une hépatite B aiguë chez un patient séropositif pour le VIH.

BACKGROUND: During the course of acute hepatitis B, hematology disorders are common though they are generally mild and occur early. Agranulocytosis is exceptional and occurs late in the disease course. CASE REPORT: We report a case of agranulocytosis which developed 3 weeks after onset of acute hepatitis B in an HIV-positive patient. Peripheral and central hematological disorders led to the diagnosis. Agranulocytosis developed during the cytolytic phase of the primary hepatitis B infection and regressed after administration of hematopoietic growth factors. DISCUSSION: It is sometimes difficult to establish the causal effect of hepatitis B in the development of agranulocytosis in patients with an HIV co-infection who are on a multiple drug regimen and subject to multiple bacterial, viral or parasite infections.

Extrahepatic manifestations associated with hepatitis C virus infection. A prospective multicenter study of 321 patients. The GERMIVIC. Groupe d'Etude et de Recherche en Medecine Interne et Maladies Infectieuses sur le Virus de l'Hepatite C.

From January 1996 to January 1997, 321 patients with an average age of 46 +/- 16 years and chronically infected with hepatitis C virus (HCV) were prospectively enrolled in a study designed to determine the prevalence of extrahepatic manifestations associated with HCV infection in a large cohort of HCV patients, to identify associations between clinical and biologic manifestations, and to compare the results obtained in human immunodeficiency virus (HIV)-positive versus HIV-negative subsets. In a cross-sectional study, clinical extrahepatic manifestations, viral coinfections with HIV and/or hepatitis B virus, connective tissue diseases, and a wide panel of autoantibodies were assessed. Thirty-eight percent (122/321) of patients presented at least 1 clinical extrahepatic manifestation including arthralgia (60/321, 19%), skin manifestations (55/321, 17%), xerostomia (40/321, 12%), xerophthalmia (32/321, 10%), and sensory neuropathy (28/321, 9%). Main biologic abnormalities were mixed cryoglobulins (110/196, 56%), thrombocytopenia (50/291, 17%), and the presence of the following autoantibodies: antinuclear (123/302, 41%), rheumatoid factor (107/280, 38%), anticardiolipin (79/298, 27%), antithyroglobulin (36/287, 13%) and antismooth muscle cell (27/288, 9%). At least 1 autoantibody was present in 210/302 (70%) of sera. By multivariate logistic regression analysis, 4 parameters were significantly associated with cryoglobulin positivity: systemic vasculitis (p = 0.01, odds ratio OR[ = 17.3), HIV positivity (p = 0.0006, OR = 10.2), rheumatoid factor positivity (p = 0.01, OR = 2.8), and sicca syndrome (p = 0.03, OR = 0.27). A definite connective tissue disease was noted in 44 patients (14%), mainly symptomatic mixed cryoglobulinemia and systemic vasculitis, HIV coinfection (23%) was associated with 3 parameters: anticardiolipin (p = 0.003, OR = 4.18), thrombocytopenia (p = 0.01, OR = 3.56), and arthralgia or myalgia (p = 0.017, OR = 0.23). HIV-positive patients presented more severe histologic lesions (p = 0.0004). Extrahepatic clinical manifestations in HCV patients involve primarily the skin and joints. The most frequent immunologic abnormalities include mixed cryoglobulins, rheumatoid factor, antinuclear, anticardiolipin, and antithyroglobulin antibodies. Cryoglobulin positivity is associated with systemic vasculitis and rheumatoid factor and HIV positivity. HIV coinfection is associated with arthralgia or myalgia, anticardiolipin antibodies, and thrombocytopenia.

The VIRGO study: nevirapine, didanosine and stavudine combination therapy in antiretroviral-naive HIV-1-infected adults.

The virological and immunological efficacy of the triple regimen containing nevirapine (once or twice daily), didanosine (once daily) and stavudine, in antiretroviral-naive patients infected with HIV-1, was evaluated in an open-label, prospective, non-randomized, multi-centre, 52-week study. The first 60 patients (VIRGO I) received nevirapine as the standard dose, 200 mg twice daily; the subsequent 40 patients (VIRGO II) received nevirapine at a dose of 400 mg once daily. All patients received 400 mg of didanosine once daily and 40 mg of stavudine twice daily, adjusted for body weight. At baseline, the median CD4 cell count and plasma viral load (pVL) were 414 cells/mm3 and 4.59 log10 copies/ml in VIRGO I, and 412 cells/mm3 and 4.87 log10 copies/ml in VIRGO II. Using an intent-to-treat, 'non-completer equals failure', analysis, 78% (95% CI, 68-88%) of patients in VIRGO I and 68% (95% CI, 53-83%) of those in VIRGO II had a pVL <500 copies/ml at 24 weeks; the proportions achieving a pVL of <50 copies/ml were 62% (95% CI, 50-74%) and 50% (95% CI, 35-65%), respectively. The week 24 median CD4 cell count increase was 168 cells/mm3 (VIRGO I) and 139 cells/mm3 (VIRGO II). At week 52, 39/45 (87%) of VIRGO I patients had pVL <500 copies/ml and 30/45 (67%) <50 copies/ml. Of the 100 patients, 44 experienced grade 2 to 4 adverse events; 20 permanently discontinued study medication because of an adverse event. Combination therapy with the three reverse transcriptase (RT) inhibitors stavudine, once-daily didanosine and either once- or twice-daily nevirapine could be considered as an alternative option for first-line antiretroviral therapy.

Digital necrosis revealing ovarian cancer.

We describe a 57-year-old woman who developed permanent acrocyanosis of all fingers rapidly leading to distal necrosis, revealing an ovarian cancer (OC). Seven similar published cases are reviewed. Digital ischaemia was bilateral, severe and frequently complicated by digital necrosis. OC was of epithelial origin and disseminated at the time of diagnosis. Initial treatment of OC usually resulted in improvement of digital ischaemia. A possible OC should be looked for in women aged 45 years or more presenting with severe digital ischaemia of recent onset.

[1977 mortality rate in HIV-infected patients presenting with hepatitis C cirrhosis. Results of the GERMIVC multicenter survey conducted in French departments of internal medicine or infectious disease]. / Mortalité par cirrhose virale C chez les patients infectés par le VIH dans les services de médecine interne et de pathologie infectieuse en 1997. Enquête multicentrique GERMIVIC. (Groupe d'étude sur le virus C). (Société nationale française de médecine interne). (Société de pathologie Infectieuse de langue française).

PURPOSE: Hepatitis C (HCV) has a high prevalence (10-30%) among human immunodeficiency virus (HIV)-infected patients. However, little information is available regarding the impact of hepatitis C on survival. The objective of our study was to determine the incidence of hepatitis C-related deaths in HIV-HCV co-infected patients. METHODS: The study was a retrospective (1-year), multicenter cohort survey conducted in 63 departments of either internal medicine or infectious diseases in France. It included 26,497 HIV-infected patients, of whom 4,465 (16.8%) presented coinfection due to the hepatitis C virus. The following parameters were studied for the year 1997: total number of deaths, number of deaths related to either AIDS, cirrhosis, hepatocellular carcinoma, or other causes. RESULTS: Among the 26,497 patients, 543 deaths (incidence: 2%) were observed in 1997; 543 deaths were due to AIDS (incidence: 1.7%), 36 to cirrhosis and/or hepatocellular carcinoma (incidence: 0.13%), and 48 (incidence: 0.18%) to another cause. In the subgroup including 4,465 HIV-HCV-coinfected patients, 29 deaths (incidence: 0.64%) were due to either HCV-related cirrhosis or hepatocellular carcinoma. These results were compared with those of a previous similar survey conducted in 1995, before the era of highly active antiretroviral therapy. The only significant difference is the dramatic regression of deaths due to AIDS. CONCLUSION: The impact of hepatitis C virus on the mortality among HIV-infected patients whose follow-up took place in departments of either internal medicine or infectious diseases in France was very low in 1997. The expected increase in the life span in these patients could modify these results in the future, due to recent improvements in the HIV infection treatment.

Hepatitis C in France: a national survey in the Departments of Internal Medicine and Infectious Diseases. The GERMIVIC (Joint Study Group on Hepatitis C virus of the French National Society of Internal Medicine and the French Society of Infectious Diseases).

Infection with Hepatitis C virus is a significant public health problem that has important clinical and financial consequences. Understanding of the epidemiology of HCV is needed to help define future therapeutic and preventive strategies. So far, the importance and characteristics of the epidemics have been best appreciated in specialist units dealing with liver disease. The purpose of our study was to survey the number and characteristics of hepatitis C antibody positive patients in Departments of Internal Medicine and Infectious Diseases. We conducted a multicentre national prospective analysis of all positive HCV-antibody patients, either inpatient or outpatient, reported over a period of one month across France. Two thousand and two cases were identified. Epidemiological, clinical and therapeutic characteristics are described. Risk factors were identified in 86%. For 10% of the patients, hepatitis C seropositivity was discovered during the period of survey. At the time of first diagnosis, 47% of patients presented with no clinical or biological abnormality. Coinfection with HIV was frequent (59%). Only 20.3% of the patients had received or were receiving a treatment with interferon. Within the limits of the methodology used, this study shows that Hepatitis C infection is a substantial clinical problem in French Departments of Internal Medicine and Infectious Diseases. Our findings may help the public health authorities in better appreciating the impact of hepatitis C and making policy decisions.