Impact of hepatitis C virus infection on the risk of death of alcohol-dependent patients.

Hepatitis C virus (HCV) infection is frequent among patients with alcohol use disorders. We aimed to analyse the impact of HCV infection on survival of patients seeking treatment for alcohol use. This was a longitudinal study in a cohort of patients who abused alcohol recruited in two detoxification units. Socio-demographic and alcohol use characteristics, liver function tests for the assessment of alcohol-related liver disease and HCV and HIV infection serologies were obtained at admission. Patients were followed until December 2008; causes of death were ascertained through clinical records and death registry. Cox models were used to analyse predictors of death. A total of 675 patients (79.7% men) were admitted; age at admission was 43.5 years (IQR: 37.9-50.2 years), duration of alcohol abuse was 18 years (IQR: 11-24 years), and median alcohol consumption was 200 g/day (IQR: 120-275 g/day). Distribution of patients according to viral infections was as follows: 75.7% without HCV or HIV infection, 14.7% HCV infection alone and 8.1% HCV/HIV coinfection. Median follow-up was 3.1 years (IQR: 1.5-5.1 years) accounting for 2,345 person-years. At the end of study, 78 patients (11.4%) had died. In the multivariate analysis, age at admission (HR = 1.71, 95%CI: 1.05-2.80), alcohol-related liver disease (HR = 3.55, 95%CI: 1.93-6.53) and HCV/HIV co-infection (HR = 3.86 95%CI: 2.10-7.11) were predictors of death. Younger patients (≤43 years) with HCV infection were more likely to die than those without viral infections (HR = 3.1, 95%CI: 1.3-7.3; P = 0.007). Among patients with alcohol-related liver disease, mortality rate was high, irrespective of viral infections. These data show that HCV infection confers a worse prognosis in patients with alcohol use disorders.

Use of highly active antiretroviral therapy is increasing in HIV positive severe drug users.

BACKGROUND: Substance abuse greatly impacts the effectiveness of highly active antiretroviral therapy (HAART). We analyzed antiretroviral use in drug users positive for human immunodeficiency virus (HIV) that sought substance abuse treatment. METHODS: This cross-sectional study recruited 705 patients HIV positive (74.6% men) between 1997 and 2007. Patients were grouped by calendar periods when different HAART regimens were available in Spain (p1: 1997-1999, n=299; p2: 2000-2003, n=249; and p3: 2004-2007, n=157). RESULTS: The mean age at admission was 34 years; 94.7% had a past history of injection drug use (IDU) and 67.7% were current IDUs. The average CD4 cell count was 399 cells/µL [interquartile range:203-632 cells/µL]. Lifetime prevalence of antiretroviral use was 59.4% (416/705; p1: 48.1%; p2: 64.6%; p3: 72.6%; p<0.05). The overall prevalence of antiretroviral use at admission was 40.7% (p1: 31.4%; p2: 41.0%; p3: 58.0%; p<0.05). In multivariate logistic regression analysis, age, calendar period, and non-IDU were predictors of antiretroviral use at admission. Among those taking antiretrovirals, 21.6% were on suboptimal HAART, mostly in the p1 group. Overall, 44.6% of patients were taking protease inhibitor and non-nucleoside reverse transcriptase inhibitor (PI-NNRTI), 21.9% were taking NRTI-NNRTI, and 9.4% were taking three NRTIs. Although not significant, the three-NRTI regimen was associated with CD4 >350 cells/µL and HIV RNA <400 copies/mL. CONCLUSIONS: HAART use is steadily increasing in HIV positive heavy drug users. However, part of this population remains antiretroviral therapy-naïve despite advanced immunodeficiency. Interventions that focus on integrating substance abuse with HIV/AIDS treatments are needed.

Impact of hepatitis C virus coinfection on immune restoration during successful antiretroviral therapy in chronic human immunodeficiency virus type 1 disease.

The effect of coinfection with hepatitis C virus (HCV) on immune restoration in 39 human immunodeficiency virus (HIV)-infected patients during treatment with combined antiretroviral therapy (cART) was prospectively evaluated. After 48 weeks of treatment, HCV-coinfected patients had lower increases in CD4% (P = .05), total CD4+ (P = .01), and naïve CD4+ (P = .06) T cells than did single-infected subjects. Higher baseline naïve CD4+ T-cell levels were associated with better CD4+ (P = .05) and naïve CD4+ (P < .001) T-cell recovery. After a 4-year follow up, the differences disappeared (median CD4+ increase: 291 and 306 cells for HCV-positive and HCV-negative patients, respectively, P = .9). No significant differences were seen in memory CD4+ T cells (P = .30), and CD8+ cells expressing CD38 (P = .10) and CD28 (P = .73). These results suggest that, independently of other factors, infection with HCV blunts early CD4+ T-cell recovery in HIV-infected patients treated with combined antiretroviral therapy (cART). However, as good control of viral replication is maintained, satisfactory long-term immune restoration can nonetheless be achieved.

Detection of hepatitis C virus antibodies in oral fluid specimens for prevalence studies.

Within the framework of hepatitis C virus (HCV) prevalence monitoring, we evaluated oral fluid (OF), which is richer in IgG than whole saliva, as a possible alternative to serum for the detection of HCV antibodies. Paired OF and serum samples were collected from 90 individuals, including 45 HCV-positives and 45 HCV-negatives. The detection of HCV antibodies in both serum and OF was performed using the Ortho HCV 3.0 SAVe enzyme-linked immunosorbent assay (ELISA) (Ortho-Clinical Diagnostics, Inc., Raritan, NJ), but a modified, more sensitive protocol was used to process OF. The sensitivity and specificity of this assay were 86.67% (95% confidence interval (CI): 72.51-94.46%) and 100% (95% CI: 90.20-99.80%) in OF and 100% in serum. The correlation obtained between both types of clinical specimens was excellent (k: 0.87, 95% CI: 0.66-1.07). However, the negative predictive value (NPV) of the assay in OF decreased with the prevalence of HCV infection in the population studied. Our results suggest that the modified Ortho HCV 3.0 SAVe ELISA is suitable for the detection of HCV antibodies in OF for epidemiological studies. Using this assay, we observed an unadjusted anti-HCV prevalence of 78.6% among a population of intravenous drug users; when adjusted to account for assay sensitivity, this prevalence may be closer to 90%.

Evaluation of a commercial enzyme immunoassay for HIV screening in urine.

A cross-sectional study was conducted to evaluate the utility of a commercial enzyme immunoassay (EIA) as a screening test for detecting HIV-1 antibody in urine in a population at risk for HIV infection in Catalonia, Spain. Paired urine and serum samples were collected consecutively from 99 patients who attended two drug-dependency treatment centres and 151 patients who attended a sexually transmitted diseases (STD) clinic in Barcelona. Antibodies against HIV in urine samples were detected using the Calypte HIV-1 Urine EIA (Calypte Biomedical Corporation, Berkeley, CA, USA) and confirmed by urine-based Western blot (WB) analysis. Sera were analysed using Bioelisa HIV-1+2 EIA (Biokit Laboratories, Barcelona, Spain), and the results were verified using serum-based WB analysis. Results of both urine and serum testing were available for 246 of 250 participants. For 52 individuals the results of both urine and serum testing were positive and for five the results were discordant (2 with urine-negative/serum-positive results and 3 with urine-positive/serum-negative results). The respective sensitivity and specificity values obtained for the urine EIA were 100% and 96.2% for intravenous drug users (IDUs) and 80% and 99.3% for persons attending the STD clinic. According to the 1997 UNAIDS/WHO strategy I recommendations, these values are acceptable for surveillance purposes, particularly in populations with a high prevalence of HIV infection.

Prevalence and distribution of HHV-8 in different subpopulations, with and without HIV infection, in Spain.

OBJECTIVE: To estimate the seroprevalence of HHV-8 in several Spanish subpopulations with different risk levels of acquiring HIV-1 infection and from different geographical regions. DESIGN: Cross-sectional seroprevalence study. METHODS: A total of 1699 serum samples from blood donors (613), children under the age of 12 years (100), injecting drug users (IDU) (382), heterosexuals attending a sexually transmitted disease (STD) clinic (273) and homosexual men attending a STD clinic or a HIV-based hospital unit (331) were analysed for anti-HHV-8 antibodies. The presence of antibodies against HHV-8 was tested with an indirect immunofluorescence assay (IFA). A subsample of HHV-8-positive samples was also tested for antibody titre against HHV-8. RESULTS: The overall seroprevalence of antibodies against HHV-8 for the blood donor population was 6.5% (7.0% in Andalusia, 8.0% in Catalonia and 4.5% in the Basque Country). None of the children tested positive for HHV-8. The HHV-8 prevalence was 86.7% in HIV-positive homosexual men and 28.0% in HIV-negative homosexual men (P < 0.001). Of heterosexual men attending STD clinics, 17.2% tested positive for HHV-8; 11.5% of IDU tested positive for HHV-8. HHV-8 antibody titres by groups parallel the distribution of HHV-8 prevalence. No association between HHV-8 antibody titres and CD4 cell count or HIV viral load was identified. CONCLUSIONS: The HHV-8 prevalence among blood donors in Spain is higher than in Northern Europe and the USA, but is similar to that in Northern Italy. The distribution of HHV-8 is compatible with a sexually transmitted agent. The distribution of HHV-8 correlates with that of Kaposi's sarcoma but factors other than HHV-8 seem to explain the Kaposi sarcoma distribution.

Twice-weekly maintenance therapy with sulfadiazine-pyrimethamine to prevent recurrent toxoplasmic encephalitis in patients with AIDS. Spanish Toxoplasmosis Study Group.

OBJECTIVE: To evaluate the efficacy of twice-weekly maintenance therapy with sulfadiazine-pyrimethamine to prevent toxoplasmic encephalitis relapse in patients with the acquired immunodeficiency syndrome (AIDS). DESIGN: Randomized, open, multicenter trial. Patients were randomly assigned to receive sulfadiazine (500 mg) four times per day plus pyrimethamine (25 mg) plus folinic acid (15 mg) either daily (n = 60) or twice weekly (n = 45). SETTING: 8 university teaching hospitals. PATIENTS: Between February 1990 and June 1993, 105 patients with HIV infection were enrolled after each had had resolution of an acute episode of toxoplasmic encephalitis treated with sulfadiazine (1 g four times per day) plus pyrimethamine (50 mg/d) plus folinic acid (15 mg/d) for 4 to 8 weeks. MEASUREMENTS: Clinical and biological evaluations done every 30 to 60 days. End points were toxoplasmic encephalitis relapse, death, and interruption of therapy due to adverse reactions. RESULTS: After a median follow-up period of 11 months (range, 1 to 39 months), patients receiving the twice-weekly regimen had a higher rate of relapse then patients receiving the daily regimen (19.5 compared with 4.4 per 100 patient-years; incidence rate ratio, 4.36 [95% CI, 1.05 to 25.5]; P = 0.024). The estimated cumulative percentages of relapse at 12 months were 30% and 6%, respectively (P = 0.029), with an adjusted risk ratio (adjusted for age, sex, risk behavior, previous diagnosis of AIDS, Pneumocystis carinii pneumonia prophylaxis before initial episode of toxoplasmosis, CD4 cell count, baseline number of brain lesions, radiologic sequelae, and antiretroviral therapy during follow-up) of 5.6 (CI, 1.2 to 25.6; P = 0.028). Patients receiving the twice-weekly regimen had 1.6 times (CI, 0.9 to 2.9 times; P = 0.11) the adjusted risk for death of patients receiving the daily regimen. No statistical differences were found in the patients who stopped receiving the regimens due to adverse effects. No patient developed P. carinii pneumonia during the study period, even though 17 patients (10 receiving the daily regimen and 7 receiving the twice-weekly regimen) had had an episode of P. carinii pneumonia before study entry. CONCLUSIONS: At the given doses, a combination of sulfadiazine, pyrimethamine, and folinic acid was less effective when administered twice weekly than when administered daily, although the twice-weekly regimen was much more effective than historic controls.

Efficacy of acute phase and maintenance therapy with itraconazole in an AIDS patient with sporotrichosis.

An AIDS patient with sporotrichosis who improved with itraconazole therapy after consecutive failure of ketoconazole, saturated solution of potassium iodide, fluconazole and amphotericin B is presented. In addition, long-term therapy with high doses of itraconazole was well tolerated and effective in avoiding relapse. Itraconazole may be suitable for use in HIV-infected patients with sporotrichosis, who probably require chronic suppressive therapy to prevent relapse of symptomatic disease.

Thrice-weekly cotrimoxazole is better than weekly dapsone-pyrimethamine for the primary prevention of Pneumocystis carinii pneumonia in HIV-infected patients.

OBJECTIVE: To compare the efficacy and safety of two intermittent regimens for the simultaneous primary prevention of Pneumocystis carinii pneumonia (PCP) and toxoplasmosis in HIV-infected patients. DESIGN: Prospective randomized open trial. SETTING: HIV outpatient clinic of an Infectious Disease Service and a 1000-bed university teaching hospital. PATIENTS: A total of 166 HIV-infected patients with a CD4 cell count < 200 x 10(6)/l or a CD4 percentage < 20%, without previous PCP or toxoplasmosis. INTERVENTION: Patients were randomized to oral (1) cotrimoxazole [160 mg trimethoprim (TMP) and 800 mg sulphamethoxazole (SMX)] twice a day on Mondays, Wednesdays and Fridays (n = 81), or (2) dapsone (100 mg) plus pyrimethamine (25 mg) (DP) once a week (n = 85). MAIN OUTCOME MEASURES: Clinical and biological evaluation was performed every 30-60 days. End-points were PCP, toxoplasmosis and death. Adverse reactions were considered as defined in the protocol. RESULTS: After a mean follow-up of 380 days, intention-to-treat analysis revealed that DP patients had a higher rate of PCP [13 out of 85 (15.2%) versus three out of 81 (3.7%); P = 0.01]. The cumulative rates of PCP at 12 and 24 months were 5 and 42% for DP patients and 3 and 10% for TMP-SMX patients, respectively (Mantel-Cox, P = 0.0007). Of the 29 patients who died during follow-up, 14 were in the TMP-SMX group and 15 in the DP group (not significant). Two patients in the TMP-SMX group and three in the DP group developed toxoplasmosis (not significant). Adverse reactions were common (66.7% of TMP-SMX patients and 42.4% of DP patients; P = 0.001). However, only 12.3% of TMP-SMX patients and 2.3% of DP patients (P = 0.01) had to discontinue therapy because of toxicity. CONCLUSIONS: At the given doses, DP was inferior to TMP-SMX in preventing first episodes of PCP. Although more patients and a longer follow-up are required, the regimens appeared to prevent toxoplasmosis equally well.

Low-dose interferon alpha combined with zidovudine in patients with AIDS-associated Kaposi's sarcoma.

Forty patients with AIDS-associated Kaposi's sarcoma (KS) treated with the combination of interferon alpha-2b (IFN-alpha) 10-20 MU day-1 and zidovudine (ZDV), 500-800 mg day-1, were evaluated for safety and efficacy. Eighteen patients (45%) had an overall response (CR+PR) at 3 months and a response persisting for a median of 14 (3-27) months. Patients with a CD4 count of less than 300 mm-3, prior to opportunistic infections or constitutional symptoms, were less likely to respond. However, between 28.5% and 36% of patients with a low CD4 count did respond to combined therapy. This is higher than would be predicted from single agent IFN-alpha therapy. Twelve of 28 patients (42.8%) receiving 10 MU day-1 of IFN-alpha (low dose) had an overall response. In addition, patients tolerated this dose of IFN-alpha better, presenting fewer flu-like symptoms and displayed a trend toward less anaemia. p24 antigen decreased in six out of nine evaluable cases, four of whom were treated with low-dose IFN-alpha. Low-dose IFN-alpha plus ZDV seems to be a useful and well-tolerated therapy for KS with antitumoral and antiviral activity. Patients without 'bad prognostic markers' are most likely to show improvement.

[Cytomegalovirus disease in patients with acquired immunodeficiency syndrome. Report of 63 cases]. / Enfermedad por citomegalovirus en pacientes afectados del síndrome de inmunodeficiencia adquirida. A propósito de 63 episodios.

BACKGROUND: The aim of the present was to study the clinical and therapeutic characteristics of patients with the human immunodeficiency virus (HIV) with disease by the cytomegalovirus (DCMV) observed between 1984-1990. Some concrete aspects such as viremia by the cytomegalovirus (CMV) without focal disease or the profitability of cultures of different samples as predictors of DCMV were analyzed. METHODS: The clinical records of the patients diagnosed with DCMV as well as cultures of blood, saliva, and urine CMV of the global collective of patients with HIV were retrospectively studied. RESULTS: Sixty-three episodes of DCMV were collected in 41 patients corresponding to 29 episodes of retinitis by CMV (46%), 8 with digestive involvement (13%), 7 with lung involvement (11%), 18 with fever without focality and viremia by CMV 9 (29%) and 1 of encephalitis by CMV (1.5%). Eighty percent of the patients had been previously diagnosed of AIDS. The mean of CD4 lymphocytes was 43 cells/mm3 and the estimated probability of survival at 12 month was 18%. In 89% of the episodes of retinitis and 87% with digestive involvement improvement was achieved with treatment. Retinitis developed a posteriori in 38% of the patients with viremia without focality. During the period studied, 105/244 (43%) of the patients with the HIV showed some sample positive for CMV. Sixty-four percent of the patients with positive cultures in urine and/or saliva did not present DCMV after prolonged follow up. CONCLUSIONS: Cytomegalovirus disease is produced in advanced phases of infection by the human immunodeficiency virus. Response to treatment was good in cases of retinitis, digestive involvement and symptomatic viremia without focality. The symptomatic viremia by cytomegalovirus constitutes a predictor of localized disease. Positivity of urine and saliva cultures has slight predictive value for cytomegalovirus disease in patients with the human immunodeficiency virus.

[Lumbosacral polyradiculomyelitis caused by cytomegalovirus in a patient with acquired immunodeficiency syndrome]. / Polirradiculomielitis lumbosacra por citomegalovirus en un paciente con síndrome de inmunodeficiencia adquirida.

The case of a HIV positive patient with lumbosacral polyradiculomyelitis by cytomegalovirus (PLS-CMV) is presented. The patient was a homosexual male receiving maintainance treatment with foscarnet for previous corioretinitis by CMV who consulted for paraparesia and sphincter disorders of a 3 week evolution. Neutrophilic pleocytosis and high levels of glucose and proteins were observed on LCR and CMV isolated discarding other entities. The LCR normalized upon treatment with gancyclovir although serious residual paraparesia persisted. PLS-CMV is an infrequent entity of typical clinic and liquoral characteristics. Recognition of the same is important since favorable response depends on early anti-CMV treatment.

[Changes in the small cerebral vessels in the acquired immunodeficiency syndrome]. / Alteraciones de los pequeños vasos cerebrales en el síndrome de inmunodeficiencia adquirida.

In the necropsy exam of the brains of 13 patients with acquired immune deficiency syndrome (AIDS) cerebrovascular lesions were seen in 5 cases, three of them having AIDS encephalopathy. Hyalinosis was noted in 3 cases, and endarteritis obliterans and fibrinoid necrosis in one case each; both of them had associated perivascular lymphocytic infiltrates. Cerebral infarction was observed in one case, but no hemorrhages were seen. The neuropathological anomalies in four children affected with the AIDS are reported too, being an extensive calcified vasculopathy and changes suggesting active AIDS encephalopathy the main findings.

Gallium-67 scan for distinguishing follicular hyperplasia from other AIDS-associated diseases in lymph nodes.

We have studied gallium-67 citrate scan (Ga-67) in the diagnosis of lymphadenopathy in patients with HIV-associated symptoms. Thirty HIV-infected patients with lymphadenopathy, fever and/or weight loss were evaluated with Ga-67. Lymph-node biopsy and/or needle aspirations were done in all patients. Twelve of 17 patients with grade 2 or 3 Ga-67 (uptake equal to or greater than that in the liver) had mycobacteriosis, three had lymphoma, one had Kaposi's sarcoma plus Castleman's disease and one had follicular hyperplasia. The three patients with grade 1 Ga-67 (uptake greater than that in soft tissue but less than that in the liver) had follicular hyperplasia. Of the 10 patients with grade 0 Ga-67 (less than or equal to that in soft tissue), nine had follicular hyperplasia and one had Kaposi's sarcoma. Sixteen of 17 patients with grade 2 or 3 Ga-67 versus one of 13 with Ga-67 grade 1 or 0 had diseases other than follicular hyperplasia (P less than 0.0001). Ga-67 may be a practical diagnostic tool in HIV-infected patients with lymphadenopathy and constitutional symptoms. A grade 1 or 0 Ga-67 suggests the presence of follicular hyperplasia, and lymph-node biopsy may be avoided unless Kaposi's sarcoma is suspected.

[Ocular toxoplasmosis in patients with acquired immunodeficiency syndrome]. / Toxoplasmosis ocular en pacientes con síndrome de inmunodeficiencia adquirida.

Ocular toxoplasmosis is an uncommonly reported complication in patients with acquired immunodeficiency syndrome. Three patients with human immunodeficiency virus (HIV) infection and ocular toxoplasmosis are reported. In two of them, cerebral toxoplasmosis was associated. Ocular involvement presented as exudative chorioretinitis, bilateral in 2 cases and unilateral in 1. The diagnosis was made on the basis of ocular disease associated with lesions consistent with toxoplasmosis of central nervous system (CNS) and response to antitoxoplasma treatment in one case, and ocular disease with rising antitoxoplasma serologic titers in the remaining two. Initial therapy included pyrimethamine plus sulfadiazine in 2 cases and pyrimethamine plus clindamycin in 1. The 2 patients treated with sulfadiazine showed hypersensitivity features, and clindamycin had to be substituted. The response to therapy was favorable, although one patient died few days after the development of CNS lesions. When chorioretinitis develops in a patient with HIV infection, ocular toxoplasmosis should be considered. As CNS involvement is commonly associated and relapse after the withdrawal of therapy is likely, these patients should be treated as those with isolated toxoplasma encephalitis.