Hepatitis C virus coinfection independently increases the risk of cardiovascular disease in HIV-positive patients.

Patients infected with HIV are at increased risk for cardiovascular disease despite successful antiretroviral therapy. Likewise, chronic hepatitis C virus (HCV) infection is associated with extrahepatic complications, including cardiovascular disease. However the risk of cardiovascular disease has not been formally examined in HIV/HCV-coinfected patients. A retrospective study was carried out to assess the influence of HCV coinfection on the risk of cardiovascular events in a large cohort of HIV-infected patients recruited since year 2004. A composite event of cardiovascular disease was used as an endpoint, including myocardial infarction, angina pectoris, stroke or death due to any of them. A total of 1136 patients (567 HIV-monoinfected, 70 HCV-monoinfected and 499 HIV/HCV-coinfected) were analysed. Mean age was 42.7 years, 79% were males, and 46% were former injection drug users. Over a mean follow-up of 79.4 ± 21 months, 3 patients died due to cardiovascular disease, whereas 29 suffered a first episode of coronary ischaemia or stroke. HIV/HCV-coinfected patients had a greater incidence of cardiovascular disease events and/or death than HIV-monoinfected individuals (4% vs 1.2%, P = 0.004) and HCV-monoinfected persons (4% vs 1.4%, P = 0.5). After adjusting for demographics, virological parameters and classical cardiovascular disease risk factors (smoking, hypertension, diabetes, high LDL cholesterol), both HIV/HCV coinfection (HR 2.91; CI 95%: 1.19-7.12; P = 0.02) and hypertension (HR 3.65; CI 95%: 1.34-9.94; P = 0.01) were independently associated with cardiovascular disease events and/or death in HIV-infected patients. Chronic hepatitis C and hypertension are independently associated with increased cardiovascular disease risk in HIV-infected patients. Therefore, treatment of chronic hepatitis C should be prioritized in HIV/HCV-coinfected patients regardless of any liver fibrosis staging.

Changes in liver fibrosis in HIV/HCV-coinfected patients following different outcomes with peginterferon plus ribavirin therapy.

There is scarce information about the impact of antiviral treatment on subsequent progression of liver fibrosis in HIV-infected patients with chronic hepatitis C who experience different outcomes following peginterferon-ribavirin therapy. We conducted a retrospective study of a cohort of HIV/HCV-coinfected patients with longitudinal assessment of liver fibrosis using elastometry. Patients were split out into four groups according to the prior peginterferon-ribavirin response: sustained virological response (SVR), relapse (R), partial response (PR) and null response (NR). A group of untreated, coinfected patients was taken as control. Significant liver fibrosis progression (sLFP) was defined as a shift from baseline Metavir estimates ≤ F2 to F3-F4, or by >30% increase in liver stiffness in patients with baseline F3-F4. Conversely, significant liver fibrosis regression (sLFR) was defined as a shift from baseline Metavir estimates F3-F4 to ≤ F2, or by >30% reduction in liver stiffness in patients that kept on F3-F4. A total of 498 HIV/HCV-coinfected patients were examined. They were classified as follows: 138 (27.7%) SVR, 40 (8%) R, 61 (12.2%) PR, 71 (14.3%) NR and 188 (37.8%) naive. After a mean follow-up of 53.3 months, sLFP occurred less frequently in patients with SVR (7.2%) compared with R (25%; P = 0.002), PR (23%; P = 0.002), NR (29.6%; P < 0.001) and naïve (19.7%; P = 0.002). Conversely, sLFR was 26.1% in SVR compared with 10% in R (P = 0.03), 14.8% in PR (P = 0.06), 16.9% in NR (P = 0.07) and 10.6% in naïve (P < 0.001). Sustained clearance of serum HCV-RNA following a course of antiviral treatment is the major determinant of liver fibrosis regression in HIV/HCV-coinfected patients.

Association of low-density lipoprotein receptor genotypes with hepatitis C viral load.

Several data suggest that low-density lipoprotein receptor (LDLR) is a co-receptor for hepatitis C virus (HCV). Soluble LDLR can inhibit HCV infectivity; greater plasma low-density lipoprotein levels are associated with treatment success; LDLR genotypes have a synergistic impact on the likelihood of achieving SVR with Peg-IFN plus RBV, as well as on viral kinetics after starting treatment. The objective of this study was to assess the impact of genetic polymorphisms in genes related to cholesterol synthesis and transport pathways on pre-treatment plasma HCV viral load (VL). A total of 442 patients infected with HCV and treatment naive were prospectively recruited. One hundred forty-four SNPs located in 40 genes from the cholesterol synthesis/transport and IL28B were genotyped and analyzed for genetic association with pre-treatment plasma HCV VL. SNPs rs1433099 and rs2569540 of LDLR showed association with plasma HCV VL (P=4 × 10(-4) and P=2 × 10(-3)) in patients infected with genotypes 1 and 4. A haplotype including the last three exons of LDLR showed association with the cutoff level of 600 000 IU ml(-1) VL for genotypes 1 and 4 (OR=0.27; P=8 × 10(-6)), as well as a quantitative VL (mean±s.d.: 6.19±0.9 vs CC+CG 5.58±1.1 logIU ml(-1), P=8 × 10(-5)). LDLR genotypes are a major genetic factor influencing HCV VL in patients infected with genotypes 1 and 4.

Treatment of chronic hepatitis C in HIV-infected patients with compensated liver cirrhosis.

The greatest benefit of hepatitis C virus (HCV) therapy is seen in cirrhotics attaining sustained virological response (SVR). However, concerns about toxicity and poorer responses often discourage treatment of cirrhotics. This may be particularly relevant in HIV-HCV-coinfected patients, in whom progression of liver fibrosis is faster and treatment responses lower. This is a retrospective analysis of HIV-HCV-coinfected patients who had received peginterferon-ribavirin therapy at our institution. Individuals naïve for interferon in whom liver fibrosis had been assessed using elastometry within the year before being treated were chosen. Response rates and toxicities were compared in cirrhotics (>14.5 KPa) and noncirrhotics. Patients with previous liver decompensation were excluded. Overall, 41 cirrhotics and 190 noncirrhotics entered the study. Groups were similar in age, gender, HCV genotypes and baseline serum HCV-RNA. SVR occurred at similar rates in cirrhotic and noncirrhotics, either considered by intention-to-treat (39%vs 45%; P = 0.4) or as treated (50%vs 52%, P = 0.8). In multivariate analysis (odds ratio, 95% CI, P), SVR was associated with HCV genotypes 2-3 (5, 2.9-11, <0.01) and lower serum HCV-RNA (2, 1.4-3.03 for every log decrease, <0.01) but not with cirrhosis (1.2, 0.4-3.6, 0.6). Treatment discontinuations because of adverse events tended to be more common in cirrhotics than in noncirrhotics (17%vs 12%; P = 0.2), but only severe thrombocytopenia was more frequent in cirrhotics than in non-cirrhotics (20%vs 3% at week 24; P < 0.01). Response to peginterferon-ribavirin therapy is similar in HIV-HCV coinfected patients with and without liver cirrhosis. Therefore, treatment must be encouraged in all compensated cirrhotic patients, although closer monitoring and management of side effects, mainly thrombocytopenia, may be warranted.

Hepatitis C virus (HCV) treatment uptake and changes in the prevalence of HCV genotypes in HIV/HCV-coinfected patients.

The efficacy of current hepatitis C therapy in HIV/HCV-coinfected patients is largely dependent on HCV genotype. The annual prevalence of HCV genotypes/subtypes and their influence on HCV clearance with antiviral treatment were examined in a dynamic cohort of HIV/HCV-coinfected patients followed up in Madrid since 2000. Patients entered the cohort at first visit and left the cohort when HCV clearance was achieved with HCV therapy or when follow-up was interrupted for any reason, including death. A total of 672 HIV/HCV-coinfected patients constituted the cohort. The mean follow-up time was 5.5 years, corresponding to 4108 patient-years. Mean age at entry was 37 years, and 73% were men and 86% were intravenous drug users. Overall distribution of HCV genotypes was as follows: 57.1% HCV-1 (1a: 29.2%, 1b: 20.4%, unknown: 7.6%), 1.3% HCV-2, 25.4% HCV-3 and 15.9% HCV-4. A total of 274 (40.8%) patients were treated with peginterferon-ribavirin, of whom 116 (42.3%) achieved HCV clearance following 1-3 courses of therapy. The proportion of HCV-1/4 rose from 71.7% in 2000 to 76.8% in 2008, whereas the proportion of HCV-2/3 fell from 28.1% in 2000 to 23.2% in 2008. The yearly prevalence increased for HCV-1 (R(2) : 0.92, b: 0.59, P < 0.001) and HCV-4 (R(2) : 0.77, b: 0.33, P < 0.005) and conversely diminished for HCV-3 (R(2) : 0.94, b: -0.82, P < 0.001). In summary, the prevalence of HCV-1 and HCV-4 has increased over the last decade in HIV/HCV-coinfected patients, whereas conversely it has declined for HCV-3, in association with the wider use of HCV therapy (41%) in this population.

Risk factors for advanced liver fibrosis in HIV-infected individuals: role of antiretroviral drugs and insulin resistance.

Liver damage may result from multiple factors in HIV-infected patients. The availability of reliable noninvasive tools to measure liver fibrosis has permitted the screening of large patient populations. Cross-sectional study of all consecutive HIV outpatients who underwent examination by transient elastometry (FibroScan) at one HIV reference clinic during 2007. Advanced liver fibrosis (ALF) was defined as hepatic stiffness >9.5 kilopascals, which corresponds to Metavir stages F3-F4 in the liver biopsy. A total of 681 consecutive HIV-infected patients (64% injecting drug users; mean age 43; 78% male; 98% on antiretroviral therapy) had at least one valid FibroScan evaluation. ALF was diagnosed in 215 (32%) of them. In the univariate analysis, ALF was significantly associated with older age, low CD4 counts, chronic hepatitis C, past alcohol abuse, elevated ALT, high triglycerides, low cholesterol, high homeostasis model assessment (HOMA) index and exposure to didanosine and/or stavudine. In a multivariate model (OR, 95% CI), chronic hepatitis C (2.83, 1.57-5.08), past alcohol abuse (2.26, 1.37-3.74), exposure to didanosine and/or stavudine (1.85, 1.14-3.01), high HOMA index (1.25, 1.04-1.51), older age (1.09, 1.05-1.14) and elevated ALT (1.04, 1.03-1.06) remained as independently associated with ALF. Therefore, in addition to chronic hepatitis C and alcohol abuse, insulin resistance and/or exposure to dideoxy-nucleosides may contribute to ALF in HIV-infected patients.

Predictors of severe hepatic steatosis using abdominal ultrasound in HIV-infected patients.

OBJECTIVE: Multiple factors may lead to hepatic steatosis (HS) in HIV-positive patients. HS may result in severe liver damage on its own and/or by accelerating the progression of chronic viral hepatitis B or C. METHODS: The sensitivity/specificity of liver ultrasound (US) to recognize severe HS is above 85%. A cross-sectional case-control study of all HIV out-patients who underwent liver US since 2004 was conducted at our institution. RESULTS: Eight hundred and thirty (36.1%) out of 2300 HIV-positive patients on regular follow-up underwent liver US during the study period. Severe HS was diagnosed in 108 (13%) patients. A total of 117 matched HIV controls lacking HS were selected randomly. In patients with severe HS, we found significantly higher values of body mass index (BMI), plasma viral load, serum glucose, alkaline phosphatase, triglycerides and low-density lipoprotein cholesterol, as well as significantly higher prevalence of diabetes, elevated alcohol consumption, lipohypertrophy and advanced liver fibrosis. Furthermore, a trend towards longer exposure to nucleoside analogues was noticed. In the multivariate analysis, only elevated alcohol consumption [odds ratio (OR) 7, P=0.013], lipohypertrophy (OR 5.3, P=0.008), plasma viral load (OR 2.1, P=0.02), BMI (OR 1.2, P=0.013) and serum glucose (OR 1.03, P=0.027) were significantly associated with severe HS. CONCLUSIONS: Severe HS in HIV-positive patients is associated with predisposing factors that are similar to those of HIV-negative individuals. However, its characteristic association with elevated plasma viral load might suggest a direct involvement of HIV in liver fat deposition. Therefore, the benefit of controlling HIV replication with antiretroviral therapy should be balanced against its effect of occasionally inducing metabolic abnormalities and lipodystrophy.

Level, phenotype and activation status of CD4+FoxP3+ regulatory T cells in patients chronically infected with human immunodeficiency virus and/or hepatitis C virus.

CD4(+) regulatory T (T(reg)) cells have been involved in impaired immunity and persistence of viral infections. Herein, we report the level, phenotype and activation status of T(reg) cells in patients chronically infected with human immunodeficiency virus (HIV) and/or hepatitis C virus (HCV). Expression of CD25, CD45RA, CD27, CD127 and CD38 was assessed on these cells using polychromatic flow cytometry in 20 healthy controls, 20 HIV-monoinfected, 20 HCV-monoinfected and 31 HIV/HCV-co-infected patients. T(reg) cells were defined as CD4(+)forkhead box P3 (FoxP3)(+). The percentage of T(reg) cells was increased significantly in HIV patients compared with controls. Moreover, there was a significant inverse correlation between CD4 counts and T(reg) cell levels. Fewer than 50% of T(reg) cells expressed CD25, with differences in terms of CD127 expression between CD25(+) and CD25((-)) T(reg) cells. CD4(+)Foxp3(+) T(reg) cells displayed predominantly a central memory phenotype (CD45RA(-)CD27(+)), without differences between patients and healthy controls. Activated T(reg) cells were increased in HIV patients, particularly considering the central memory subset. In summary, HIV infection, but not HCV, induces an up-regulation of highly activated T(reg) cells, which increases in parallel with CD4 depletion. Hypothetically, this might contribute to the accelerated course of HCV-related liver disease in HIV-immunosuppressed patients.

Liver cirrhosis in HIV-infected patients: prevalence, aetiology and clinical outcome.

Liver disease is frequently seen in HIV+ patients as a result of coinfection with hepatitis B (HBV) or C (HCV) viruses, alcohol abuse and/or exposure to hepatotoxic drugs. The aim of this study was to assess the prevalence of liver cirrhosis, its main causes and clinical presentation in HIV+ patients. Observational, cross-sectional, retrospective study of all HIV+ individuals followed at one reference HIV outpatient clinic in Madrid. Liver fibrosis was measured in all cases using transient elastometry (FibroScan). All 2168 HIV+ patients on regular follow-up (76% males, 46% injecting drug users) were successfully examined by FibroScan) between October 2004 and August 2006. Liver cirrhosis was recognized in 181 (overall prevalence, 8.3%), and the main aetiologies were HCV, 82.3%; HBV, 1.6%; dual HBV/HCV, 2.8%; and triple HBV/HCV/ hepatitis delta virus (HDV) infection, 6.6%. The prevalence of cirrhosis differed among patients with distinct chronic viral hepatitis: HCV, 19.2%; HBV, 6.1%; HBV/HCV, 41.7%; and HBV/HCV/HDV, 66.7%. In 12 patients with cirrhosis (6.7%), no definite aetiology was recognized. Overall, cirrhotics had lower mean CD4 counts than noncirrhotics (408 vs 528 cells/microL respectively; P = 0.02), despite similar proportion of subjects with undetectable viraemia on highly active antiretroviral therapy. Clinical manifestations of liver cirrhosis were: splenomegaly, 61.5%; oesophageal varices, 59.8%; ascites, 22.6%; encephalopathy, 12.1%; and variceal bleeding, 6.1%. Liver cirrhosis and hepatic decompensation events are relatively frequent in HIV+ individuals. Chronic HCV and alcohol abuse, but not chronic HBV, play a major role. Transient elastometry may allow the identification of a significant number of HIV+ individuals with asymptomatic liver cirrhosis.

Liver fibrosis on account of chronic hepatitis C is more severe in HIV-positive than HIV-negative patients despite antiretroviral therapy.

The recent availability of non-invasive tools to measure liver fibrosis has allowed examination of its extent and determination of predictors in all patients with chronic hepatitis C virus (HCV) infection. On the other hand, most information on hepatic fibrosis in HCV/human immunodeficiency virus (HIV)-coinfected patients has been derived from liver biopsies taken before highly active antiretroviral therapy (HAART) was widely available. All consecutive HCV patients with elevated aminotransferases seen during the last 3 years were evaluated and liver fibrosis measured using transient elastography (FibroScan) and biochemical indexes. Patients were split according to their HIV serostatus. A total of 656 (69.6%) HCV-monoinfected and 287 (30.4%) HIV/HCV-coinfected patients were assessed. Mean CD4 count of coinfected patients was 493 cells/muL and 88% were under HAART (mean time, 4.2 +/- 2.4 years). Advanced liver fibrosis or cirrhosis was recognized in 39% of the coinfected and 18% of the monoinfected patients (P < 0.005). A good correlation was found between FibroScan) and biochemical indexes [AST to platelet ratio index (r = 0.405, P < 0.0001), FIB-4 (r = 0.393, P < 0.0001) and Forns (r = 0.407, P < 0.0001)], regardless of the HIV status. In the multivariate analysis, age >45 years, body mass index (BMI) >25 kg/m(2), and HIV infection were independently associated with advanced liver fibrosis or cirrhosis. HIV/HCV-coinfected patients have more advanced liver fibrosis than HCV-monoinfected patients despite the immunologic benefit of HAART.

Prevalence of M. tuberculosis infection and tuberculosis disease among HIV-infected people in Spain.

OBJECTIVE: To study the prevalence of Mycobacterium tuberculosis infection (MTBI) and past/current tuberculosis (TB) among human immunodeficiency virus (HIV) infected persons in Spain. DESIGN: Longitudinal study conducted between 2000 and 2003 at 10 HIV hospital-based clinics. Data were drawn from clinical records. Associations were measured using odds ratios (ORs) and their 95% confidence intervals (95%CI). RESULTS: Of the 1242 persons who met the eligibility criteria, most were male (75%), aged <40 years (75%) and unemployed (40%). HIV infection occurred through intravenous drug use (53%), heterosexual sex (29%) and sex between men (16%). In the initial evaluation, 315 subjects had evidence of MTBI: 84 (6.8%) had a history of TB, 23 (1.8%) current TB and 208 (16.8%) latent tuberculosis infection (LTBI). MTBI was associated with male sex, age 30-49 years, contact with a TB case, homelessness, poor education, and negatively with CD4 <100 cells/mm(3). Among subjects with MTBI, past/current TB was associated with retirement/disability (OR 6, 95%CI 1.6-22.5), CD4 <200 cells/mm(3) (OR 9.7, 95%CI 3.8-24.6), viral load >55,000 copies (OR 5.3, 95%CI 1.4-20.0), and negatively, with skilled work (OR 0.4, 95%CI 0.1-1.0) or administrative/managerial/professional work (OR 0.05, 95%CI 0.01-0.4). CONCLUSION: Social context has an impact on the effectiveness of HIV and TB control programmes even in industrialised countries with free access to health care.

Critical role of ribavirin for the achievement of early virological response to HCV therapy in HCV/HIV-coinfected patients.

The response to hepatitis C virus (HCV) therapy seems to be lower in HCV/HIV-coinfected patients than in HCV-monoinfected individuals. Given that most pivotal trials conducted in coinfected patients have used the combination of pegylated interferon (pegIFN) along with fixed low doses (800 mg/day) of ribavirin (RBV), it is unclear whether HIV itself and/or suboptimal RBV exposure could explain this poorer outcome. Two well-defined end points of early virological response were evaluated in Peginterferon Ribavirina España Coinfección (PRESCO), a multicentre trial in which the combination of pegIFN plus RBV (1000 mg if body weight <75 kg and 1200 mg if >75 kg) was prescribed to coinfected patients. For comparisons, we used unpublished data from early kinetics in two other large trials, one performed in HIV-negative patients [Pegasys International Study Group (PISG)] in which RBV 1000-1200 mg/day was used and another [AIDS Pegasys Ribavirin Coinfection Trial (APRICOT)] in which HIV-positive patients received fixed low RBV doses (800 mg/day). A total of 348 HCV/HIV-coinfected patients from the PRESCO trial were analysed as well as all patients treated with pegIFN plus RBV, who completed 12 weeks of therapy in the comparative studies (435 in PISG and 268 in APRICOT). Negative serum HCV-RNA at week 4 (which has the highest positive predictive value of sustained virological response, SVR) was attained in 33.3%, 31.2% and 13% of treated patients with HCV genotype 1, respectively, in PRESCO, PISG and APRICOT. For HCV genotypes 2/3, responses were 83.7%, 84.2% and 37%, respectively. A decline lower than 2 log(10) at week 12 (which has the highest negative predictive value of SVR) was seen in 25.5%, 19.5% and 37% of HCV genotype-1-infected patients, and in 2.1%, 2.9% and 12% of genotypes-2/3-infected patients, respectively. Prescription of high RBV doses enhances the early virological response to HCV therapy in HCV/HIV-coinfected patients, with results approaching those seen in HCV-monoinfected patients.

Inhibitory quotient as a prognostic factor of response to a salvage antiretroviral therapy containing ritonavir-boosted saquinavir. The CIVSA Study.

BACKGROUND: The addition of a low dose of ritonavir to protease inhibitors (PIs) has become a widespread strategy to improve PI pharmacokinetics. As resistance is a major barrier to long-term suppression, in salvage therapy genotype and/or phenotype scoring is currently used to predict the response. We evaluated the relationship between the saquinavir (SQV) inhibitory quotient (IQ) (virtual and genotypic) and virological response. METHODS: Eligible patients were on a PI-containing highly active antiretroviral therapy (HAART) regimen excluding SQV and had a viral load >5000 HIV-1 RNA copies/mL. The PI was switched to SQV/ritonavir (RTV) 1000/100 mg twice a day (bid) and the same two backbone nucleoside reverse transcriptase inhibitors (NRTIs) were maintained at least until week 4, when the resistance test results became available. Genotype and virtual phenotype were determined at baseline, while the SQV trough plasma concentration was determined at week 4. RESULTS: Fifty-three patients were included in the study. Mean baseline viral load and CD4 count were 137,693 copies/mL and 263 cells/microL, respectively, the mean number of previous PIs was 2.3 and the mean number of protease gene mutations (PGMs) was 4.1. Using an on-treatment analysis, at week 16 the mean increase in CD4 count was 70.9 cells/microL, viral load was <200 copies/mL in 17 out of 37 patients (45.9%), and 30 out of 45 patients (66.7%) were considered virological responders (VRs) (viral load <200 copies/mL or viral load declined > or =1 log(10) at week 16). Median virtual phenotype was 1.3 (0.6-6.9). Baseline differences were detected between VR and non-VR populations: the mean numbers of PGMs were 3.2 and 5.8 (P<0.05), the mean numbers of SQV-associated mutations were 2 and 3.8 (P<0.05), and the mean CD4 counts were 365.9 and 184.3 cells/microL (P<0.05), respectively. Mean SQV trough concentrations at week 4 were 1.1 and 1.0 microg/mL (not significant), and mean virtual IQs were 0.7 and 0.1 (P<0.01), respectively. Multivariate analysis showed that baseline PGMs >5 or SQV-associated mutations>5, virtual phenotype, baseline viral load >50,000 copies/mL, and virtual IQ <0.5, but not genotypic IQ, were the variables independently associated with non-VR. CONCLUSION: In heavily pretreated patients, the use of SQV virtual IQ or alternatively virtual phenotype, as well as PGMs, is a useful tool for the prediction of virological response.

Interferon alpha treatment of chronic hepatitis C in HIV-infected patients receiving zidovudine: efficacy, tolerance and response related factors.

BACKGROUND/AIMS: In our area most of the human immunodeficiency virus (HIV) infected patients are intravenous drug users; HIV and hepatitis C virus infections often coexist in these patients. Due to the repercussions of both infections, we designed a trial to evaluate the efficacy, response-related factors and tolerance during an eight-month regime of recombinant interferon alpha-2b on hepatitis C virus infection. METHODOLOGY: We included 79 patients in an open, prospective and multicentric trial with zidovudine and interferon alpha-2b. Response to interferon treatment was evaluated by biochemical and histopathological criteria. RESULTS: A complete response (alanine aminotransferase normalization) was obtained in 57.4% of patients. The significant response-related factors were: degree of histopathological activity, CD4+ cell number and initial leukocyte number. CONCLUSIONS: Recombinant interferon therapy seems to be effective for chronic hepatitis C in HIV infected patients; the best response was in those with active chronic hepatitis and CD4+ cell counts > or = 200/mm3. General tolerance was variable, although side effects were not different from those seen in non-HIV patients. The most common side effect was flu-like syndrome (constitutional manifestations), with no interference on treatment continuity; however, hematological toxicity prevents the indiscriminate use of interferon.

Induction of neutralizing antibodies against human immunodeficiency virus type 1 using synthetic peptide constructs containing an immunodominant T-helper cell determinant from vpr.

Identification of immunodominant T-helper-cell determinants after natural infection is an important step in the design of immunogens for potential use in vaccination. Using cells from human immunodeficiency virus type 1 (HIV-1)-infected individuals and a panel of peptides encompassing the sequence of the regulatory protein vpr from HIV-1, we identified the T-helper determinant QLLFIHFRIGCRHSR, which is active in 37.5% of these individuals. To gain insight on the efficacy of this peptide in helping induce neutralizing antibodies against a B-cell determinant (BD), we synthesized constructs containing B- and T-cell determinants and tested them in BALB/c mice, the highest responders to the T-cell determinant moiety among several strains tested. These immunogens induced antibodies against two chosen B-cell determinants from HIV-1IIIB gp160 (amino acids 310-322 from the V3 loop of gp120 and 736-751 from gp41) that were able to neutralize HIV-1 infection in vitro. The highest neutralization titer against HIV-1IIIB was obtained by immunization with the homopolymer of the construct containing the T-cell epitope from vpr and the B-cell epitope from the V3 loop. We believe that the immunodominant T-cell determinant from vpr is a promising epitope to consider in the design of future peptide vaccines.

[Lymphocyte subpopulations, neopterin, and beta-2-microglobulin: relationship with clinical stage, risk of progression to AIDS and presence of active infection in HIV infection]. / Subpoblaciones linfocitarias, neopterina y beta-2-microglobulina: relación con estadio clínico, riesgo de progresión a sida y presencia de infección activa en la infección por VIH.

BACKGROUND: The aim of the present study was to evaluate the relation between the number of CD4 lymphocytes, the CD4/CD8 ratio and the plasma levels of neopterin and beta-2 microglobulin, and the clinical status, risk of progression without of active opportunistic infections, among HIV-infected patients. METHODS: Seventy-two patients infected by HIV in different clinical groups were evaluated upon entering the study and following a mean follow up of 6 months for the parameters studied. RESULTS: The values of CD4 lymphocytes and neopterin were related with the clinical status according to the CDC's classification, with no significant differences existing in the beta-2 microglobulin level. The CD4 count as well as the neopterin and the beta-2 microglobulin levels differed significantly when classified to the patients with regard to the risk of progression to AIDS throughout the study. The presence of active opportunistic infections was related with significantly higher concentrations of neopterin without differences recorded for the remaining parameters. CONCLUSIONS: The parameters studied are good markers or both clinical status and/or the risk of short-term progression to AIDS. Neopterin levels are high during acute infections. Therefore, its prognostic value should be cautiously evaluated in this situation.

[Clinico-epidemiological study of botulism poisoning in La Rioja (1979-1990)]. / Estudio clinicoepidemiológico de la intoxicación botulínica en La Rioja (1979-1990).

BACKGROUND: The aim of the present study was to evaluate botulinic poisoning requiring hospital admission in La Rioja (Spain) during one decade from a clinical-epidemiologic point of view. METHODS: Chart records from patients admitted to the departments of Internal Medicine, Neurology, the ICU, and the Neurophysiology and Preventive Medicine files of the reference hospital between 1979 and 1990 were retrospectively reviewed. RESULTS: Fifteen cases were identified. Home preserves of vegetables were most frequently the foods responsible for the poisoning. The presentation as a sole case constituted half of this series. The most frequent symptomatology was neuro-ophthalmologic and digestive. All the cases were type B. Neurophysiologic studies were compatible with the diagnosis in all the cases in which they were performed. Two cases (13.3%) required intensive care and death occurred in one (6.6%). CONCLUSIONS: a) The habit of home preserves was responsible for the presentation of botulism in this environment. b) Early diagnosis was based on complementary clinical tests together with the neurophysiologic study. c) The mild forms were most frequent. Death in this series was 6.6%.

[HIV infection in an autonomous Spanish community (La Rioja). Features, trends and conclusions applicable to other regions]. / Estudio de la infección por VIH en una comunidad autónoma española (La Rioja). Características, tendencias y conclusiones aplicables a otras regiones.

BACKGROUND: The epidemiologic characteristics of HIV infection in La Rioja (Spain) were studied and the future tendencies of the same analyzed. METHODS: The data from official Health sources were collected and analyzed. RESULTS: In La Rioja, the 5th region in Spain regarding to AIDS incidence, the duplication time of the number of cases continues to shorten. The number in December 1991 was 81. The heterosexual route of infection was 5% of the cases of AIDS up to December 1990 and in 1991 it was 15%, while, with regards to the total number of seropositive subjects, the number rose from 0.3% in December 1990 to 10% in 1991. One thousand one hundred fifty-one seropositive patients were detected in December 1991 representing seroprevalence of 0.34% which reaches 1.14% in the age range between 18-32 years. Mean hospital stay was 23.6 days with 3,032 hospital stays calculated for 1991 representing 8.3 occupied beds/day. There are presently 92 patients undergoing antiviral treatment. Between 43-69 new cases of AIDS have been calculated for 1992. CONCLUSIONS: 1) Medical care should be provided to a greater number of seropositive people to avoid early deterioration. 2) The increase in heterosexual infection is alarming. 3) The need for rehabilitation centers for drug abusers and social alternatives to prostitution is clear. 4) Organized campaigns pointing out and returning the dignity and value of life and therewith the role of human sexuality are needed. 5) Alternative means to conventional hospitalization is required.

Renal prostacyclin influences renal function in non-azotemic cirrhotic patients treated with furosemide.

The influence of prostaglandins on renal function changes induced by furosemide was analyzed in 21 non-azotemic cirrhotic patients with ascites. Patients were studied in two periods of 120 min immediately before and after furosemide infusion (20 mg, ev). Furosemide caused an increase in creatinine clearance in 15 patients (group A: 99 +/- 7 vs. 129 +/- 5 ml/min; mean +/- S.E.) and a reduction in the remaining six (group B: 102 +/- 13 vs. 71 +/- 9 ml/min). Parallel changes were observed in the urinary excretion of 6-Keto-prostaglandin-F1 alpha (metabolite of renal prostacyclin) which augmented after furosemide in 14 of the 15 patients from group A (478 +/- 107 vs. 1034 +/- 159 pg/min, p less than 0.001) and decreased in all patients from group B (1032 +/- 240 vs. 548 +/- 136 pg/min, p less than 0.05). In contrast, the urinary excretion of prostaglandin E2 was stimulated by furosemide in all patients (group A, 92 +/- 19 vs. 448 +/- 60 pg/min, p less than 0.001; and group B, 209 +/- 63 vs. 361 +/- 25 pg/min, p less than 0.05). In all of the patients furosemide-induced changes (post- minus pre-furosemide values) in creatinine clearance were closely correlated in a direct and linear fashion with those in 6-Keto-prostaglandin-F1 alpha (r = 0.74; p less than 0.001). These changes were associated with a higher furosemide-induced natriuresis in group A than in group B (641 +/- 68 vs. 302 +/- 46 mumol/min, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)