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Biomedical subjects

G Sirera

Publications and source records attributed to G Sirera.

At least 19 recordsLinked to original sources
PubMed2003

Time on antiretroviral therapy is a protective factor for liver fibrosis in HIV and hepatitis C virus (HCV) co-infected patients.

To assess the factors associated with liver fibrosis in human immunodeficiency virus and hepatitis C virus (HIV/HCV) co-infected patients eligible for anti-HCV therapy, we performed an observational, single-centred, cross-sectional study of 180 HIV/HCV co-infected patients who underwent liver biopsy between May 1998 and November 2001. A total of 126 patients with a known date of HCV infection were evaluated. Liver fibrosis was defined as a Knodell stage of fibrosis 1-4. The mean age was 36.7 (3.8) years, 81% were male and had a mean age of 20.5 (3.8) years at HCV infection. Mean CD4 cell count and plasma HIV-1 RNA load at the time of biopsy were 552 cell/mm3 (239) and 2.5 log10 (0.9), respectively; 118 patients had been on antiretroviral therapy (ART) for a median of 45 months (Q1-Q3: 21-75) and 84 on protease inhibitor for a median of 12.0 months (Q1-Q3: 0-29.5); 55 had an AIDS event or a CD4 cell count nadir < 200 cells/mm3 prior to biopsy. Median histological activity index was 6 and 27% had a Knodell stage of fibrosis 0. On the multivariate analysis time on ART (OR for 6 months extra: 0.954, 95% CI: 0.859-0.994), CD4 cell count at the time of liver biopsy (OR for 100 cells/mL increase: 0.740, 95% CI: 0.670-0.905), age at HCV infection acquisition (OR for 5 years extra: 2.594, 95% CI: 1.326-5.133) and alcohol intake (> 50 g/day) (OR: 2.73, 95% CI: 1.108-6.731) were associated with liver fibrosis. Hence ART should be a priority in HIV/HCV co-infected patients eligible for anti-HCV treatment as it is a protective factor for liver fibrosis.

Adult↗
PubMed2002

A nested polymerase chain reaction (Ln-PCR) for diagnosing and monitoring Leishmania infantum infection in patients co-infected with human immunodeficiency virus.

We investigated a Leishmania-specific nested polymerase chain reaction (Ln-PCR) for the diagnosis and treatment monitoring of L. infantum infections in patients co-infected with human immunodeficiency virus (HIV). Peripheral blood and bone marrow samples from 89 HIV patients in Spain suspected of having leishmaniasis were examined by different diagnostic techniques (Ln-PCR, microscopy, NNN culture and indirect fluorescent antibody test). The sensitivity of Ln-PCR compared with microscopy and culture of bone marrow was 95.45% using blood and 100% when using bone marrow. 38 of these patients with confirmed leishmaniasis were entered in a chemotherapy trial (reported elsewhere), and samples from them were collected before treatment, one month after treatment ended and during follow-up (1-20 months), and examined similarly. Ln-PCR was shown to be a good method for testing efficacy of treatment and for predicting relapses after treatment (relapses were predicted on average 5 months earlier than when using classical diagnostic techniques). We suggest that Ln-PCR (especially using peripheral blood) should be the technique of choice for diagnosis, monitoring the success of treatment, and predicting relapses in patients with HIV and suspected or confirmed L. infantum infection.

AIDS-Related Opportunistic Infections↗
PubMed2002

Initiation, changes in use and effectiveness of highly active anti-retroviral therapy in a cohort of injecting drug users.

The prevalence of anti-retroviral therapy (ART) use over time and the incidence of AIDS in a cohort of HIV-seroconverting injecting drug users (IDUs) were assessed by means of a hospital-based study of IDUs with a well documented date of HIV infection. Use of ART and clinical endpoints were assessed by hospital records. Three calendar periods (before 1992, 1992-6 and 1997-2000) were defined as corresponding to modalities of ART available. Prevalence of ART usage in each calendar period, changes in medication and, hazard of AIDS in patients reaching the same duration of HIV infection at different calendar periods were analysed. In total, 132 IDUs with a median age of 23 years at seroconversion were followed up for 6.8 years (median) (range 0.2-15.7). At the end of the study, 58 patients (44%) had developed AIDS. Before the introduction of highly active anti-retroviral therapy (HAART) 12% of patients were on ART. Starting in 1997, an increasing proportion were receiving HAART with a prevalence of 39.5% by January 2000. Taking 1992-6 as the reference category the relative hazard of AIDS during 1997-2000 was 0.42 (95% CI, 0.1-1.1) (P = 0.09). A 40% penetration of HAART in a cohort of IDUs with known dates of seroconversion resulted in a 58 % reduction of the hazard of AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed2001

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.

AIDS-Related Opportunistic Infections↗
PubMed2000

Prospective randomized two-Arm controlled study to determine the efficacy of a specific intervention to improve long-term adherence to highly active antiretroviral therapy.

BACKGROUND: Nearly perfect compliance seems to be indispensable to obtain the maximum benefit from highly active antiretroviral therapy (HAART). Interventions to ensure a high level of adherence during a relatively long-term period of therapy are necessary. METHODS: This is a prospective, randomized, two-arm controlled study including patients starting their first-or second-line HAART who were randomized to receive psychoeducative intervention to implement adherence (experimental group [EG]) or a usual medical follow-up (control group [CG]). We aimed to study the efficacy of a psychoeducative intervention to ensure long-term adherence to HAART, its relation with the virologic efficacy of treatment, and to determine the variables related to long-term adherence. Visits were made at weeks 0, 4, 24, and 48 for data collection. Self-reported adherence was registered at each visit and its veracity was tested by randomized blood analyses performed without previous warning to 40% of patients. Appropriate adherence was defined as the consumption of >/=95% of medication prescribed. Statistical analyses were performed both by the as treated (AT) and the intention to treat missing = failure (ITT) methods. RESULTS: In all, 116 patients were included. At week 48, 94% of patients in the EG versus 69% controls achieved adherence >/=95% (p =.008); 89% of patients in the EG versus 66% controls had HIV-1 RNA levels <400 copies/ml (p =.026). Overall, 85% of patients with adherence >/=95% but only 45% of those with adherence <95% had viral load (VL) <400 copies/ml (p =. 008). In multivariate analysis, variables significantly related to adherence were having received a psychoeducative intervention (odds ratio [OR], 6.58; p =.04), poor effort to take medication (OR, 5.38; p =.03), and high self-perceived capacity to follow the regimen (OR, 13.76; p =.04). Self-reported adherence and drug plasma levels coincided in 93% of cases. However, differences in adherence did not reach statistical significance in the ITT analysis although a clear tendency toward benefit was observed in EG. CONCLUSIONS: Specific and maintained psychoeducative interventions based on excellence on clinical practice are useful to keep high levels of adherence as well as high levels of viral suppression. There is a clear relation between high adherence levels and virologic success. Assessment of certain specific variables related to adherence may be helpful to monitor patient's compliance in the clinical setting.

Adult↗
PubMed2000

Mortality of HIV-positive and HIV-negative heroin abusers as a function of duration of injecting drug use.

OBJECTIVE: To determine the incidence of mortality of injecting drug users as a function of the duration of injecting drugs and HIV status, and to assess how these effects vary according to age at initiation and calendar period (before and after 1992). METHODS AND DESIGN: Cohort of 376 intravenous heroin users admitted to detoxification between February 1987 and January 1990. SETTING: Patients referred from outpatient clinics of metropolitan Barcelona. Duration and characteristics of drug use were determined by interviews. Blood samples were collected during admission and analyzed for HIV, CD4+ cell count and different biologic parameters. Assessment of vital status and causes of death were obtained by hospital charts, death certificates, and autopsies. RESULTS: The study population consisted of 299 men and 77 women, whose mean age at entry was 26 years, mean duration of injecting drug use before admission 6.1 years; HIV seroprevalence at entry 70.2%. By the end of the follow-up (median 5.6 years), 21.8% of individuals had died (26.6% in HIV-positive, and 10.7% in HIV-negative injecting users). Based on Kaplan-Meier estimates, 10%, 20%, and 30% of HIV negative patients died by 8.7, 11.3 and 14.3 years, respectively, after initiating injecting drugs. The corresponding survival times for the seropositives were substantially lower: 6.6, 8.5, and 11.6 years, respectively. Overall, the survival time was significantly (p < .05) decreased by 22% in HIV-positive injecting drug users. Older age at initiation of injecting drug use was significantly (p < .05) associated with mortality in HIV-positive heroin users but it showed the opposite direction among HIV-negative people. Death rates in HIV-positive patients of the same duration of drug use were similar in periods before and after 1992 (relative hazard (RH) = 0.97; 95% confidence interval: 0.58-1.61). Although not statistically significant, the hazard of death in HIV-negative injecting drug users was substantially lower after 1992 (RH = 0.59). CONCLUSIONS: Before introduction of potent antiretroviral therapies, HIV infection further increased rates of mortality that had already been heightened by injecting drug use. Furthermore, HIV infection modifies the effect of age at initiation and eliminates the seemingly downward trend of mortality in HIV-negative people.

Adolescent↗
PubMed2000

Structured treatment interruption in chronically HIV-1 infected patients after long-term viral suppression.

OBJECTIVE: To investigate the virological and immunological impact of a structured treatment interruption (STI) in a cohort of HIV-1 chronically infected patients with a further long-lasting effective virus suppression. METHODS: Twelve HIV-1 chronically infected adults who had maintained viral suppression (< 20 copies/ml) for more than 2 years, as well as a CD4:CD8 ratio > 1 for a median time of 22 months, were included in the study. Participants interrupted their antiretroviral treatment during a maximum period of 30 days or until a viral load rebound > 3000 copies/ml was detected. The same prior antiretroviral regimen was resumed after STI. Kinetics of plasma viral rebound was evaluated every 2 days during the treatment interruption period. Flow cytometry and cell proliferation assays were performed before and after STI. Genotypic resistance was assessed at the time of treatment resumption. RESULTS: No adverse events occurred during the interruption period. In two patients no viral rebound was detected after 30 days of treatment interruption. In the remaining 10 patients, viral load became detectable (> 20 copies/ml) at a median time of 14 days after treatment interruption. Afterwards, viral load increased exponentially with a mean t1/2 of 1.6 days. Treatment was successfully resumed in all patients. No resistance-conferring mutations associated with the pre-interruption antiretroviral regimen were detected. The percentage of CD4 and CD8 lymphocytes did not vary during the STI period; however, the level of expression of T-cell activation antigen CD38 on CD8 T cells increased significantly in response to viral rebound. Four patients gained T-helper cell responses to recall antigens (tuberculin and tetanus toxoid), two of who developed an HIV-specific response to p24. CONCLUSIONS: STI in chronically HIV-1-infected patients is not associated with reductions in CD4 T lymphocytes or to clinical complications in this group of patients after 2 years of effective plasma viral suppression. Viral load rebounds in most but not all patients, without evidence of selection of resistance-conferring mutations. Thereafter, viraemia can be effectively controlled by antiretroviral agent reintroduction. HIV-specific T-helper cell responses may be achieved after one cycle of treatment interruption suggesting some degree of immune-stimulation. These data do not discard consecutive cycles of STI as a therapeutic strategy to boost HIV-specific immunity in order to maintain viral replication under effective control.

Adult↗
PubMed2000

[Hodgkin's disease in patients infected by the human immunodeficiency virus. Study of fifteen cases].

BACKGROUND: In spite of not being considered as an AIDS defining illness, Hodgkin's disease (HD) has specific clinical and biological features in HIV-infected patients. PATIENTS AND METHODS: Study of clinicopathologic and analytic characteristics, Epstein-Barr virus (EBV) detection (polymerase chain reaction), and prognosis in 15 patients with HD and HIV infection. RESULTS: Thirteen patients had B symptoms, 10 extranodal involvement and 12 advanced HD. The most frequent histologic subtypes were mixed cellularity (6) and lymphocyte depletion (6). The mean (SD) of CD4 lymphocytes was 0.10 (0.08) x 10(9)/l. The presence of EBV in lymph node biopsy was demonstrated in 3 out of 4 patients investigated. Complete remission (CR) was achieved in 7 out of 14 treated cases (50%), the median overall survival was 26 months and the 2 year event-free survival probability was 60%. CONCLUSIONS: In HIV-infected patients, HD presents in advanced stages, unfavourable histologic subtypes, frequent extranodal involvement and B symptoms. The prognosis is poor, mainly because of a low CR rate.

Adult↗
PubMed2000

Prevalence and route of transmission of infection with a novel DNA virus (TTV), hepatitis C virus, and hepatitis G virus in patients infected with HIV.

OBJECTIVES: To evaluate the prevalence, route of transmission and clinical significance that current co-infection with TT virus (TTV), hepatitis C virus (HCV), and hepatitis G virus (HGV) have in HIV-1-infected patients. DESIGN: Presence of TTV, HCV, and HGV was analyzed in plasma samples from 160 HIV-1-infected patients with parenteral (38 intravenous drug users [IVDUs] and 41 patients with hemophilia) or sexual (39 homosexuals and 42 heterosexuals) risk of exposure, and in 168 volunteer blood donors. Alanine aminotransferase (ALT) levels and CD4+ counts were also analyzed. METHODS: HCV and HGV RNA were detected by specific reverse transcriptase (RT) nested polymerase chain reaction (PCR) and TTV DNA by specific heminested PCR. RESULTS: TTV DNA was detected in 39% of the patients and in 14% of the volunteer blood donors. HCV and HGV infections were detected in 42% and in 14% of the patients, and in 0% and 3% of the blood donors, respectively. Prevalences of TTV and HCV infection were higher among patients with parenteral (62% and 68%) than in those with sexual (17% and 16%) risk of exposure. A higher prevalence of TTV infection (but not of HCV or HGV infection) was observed among patients with hemophilia (76%) than IVDUs (47%), and among homosexuals (26%) than among heterosexuals (10%). Abnormal ALT levels were related with the presence of HCV infection, independently of the detection of TTV DNA. TTV infection did not seem to alter the levels of CD4+ T cells. CONCLUSIONS: Prevalence of current TTV infection is high among HIV-infected patients with parenteral risk of exposure, but TTV is also transmitted through sexual routes; detection of TTV does not seem to influence the clinical or immune status of HIV-infected patients.

Adolescent↗
PubMed2000

Thrice-weekly sulfadiazine-pyrimethamine for maintenance therapy of toxoplasmic encephalitis in HIV-infected patients. Spanish Toxoplasmosis Study Group.

An open, randomised, multicentre trial was conducted to evaluate the efficacy of thrice-weekly versus daily therapy with sulfadiazine-pyrimethamine in the prevention of relapses of toxoplasmic encephalitis in HIV-infected patients. Between February 1994 and July 1997, 124 patients with HIV infection were enrolled after resolution of the first acute episode of toxoplasmic encephalitis treated with sulfadiazine-pyrimethamine. Patients were randomly assigned to receive either a daily regimen consisting of sulfadiazine (1 g) twice a day plus 25 mg pyrimethamine and 15 mg folinic acid daily (n = 58), or a thrice-weekly regimen consisting of the same doses of sulfadiazine and folinic acid plus 50 mg pyrimethamine (n = 66). After a median follow-up period of 11 months (range 1-39 months), no differences were found in the incidence of toxoplasmic encephalitis relapses between the groups, there being 14.9 episodes per 100 patient-years (95% CI: 2.8-20.2) in the daily-regimen group versus 14.1 episodes (95% CI: 2.3-17.2) in the intermittent-regimen group. The estimated cumulative percentages of relapse at 12 months were 17% and 19%, respectively (P = 0.91). In a Cox multivariate analysis, not taking antiretroviral therapy was the only variable independently associated with relapse (adjusted risk ratio: 4.08; 95%CI: 1.32-12.66). Baseline CD4+ cell counts, prior AIDS, mental status, sequelae and allocated maintenance therapy regimen were not independent predictors of relapse. No differences were observed in the survival rate (P = 0.42), or in the incidence of severe adverse effects (P = 0.79). The efficacy of the thrice-weekly regimen was similar to that of the daily regimen in the prevention of relapses of toxoplasmic encephalitis. Administration of antiretroviral therapy was the only factor associated with a lower incidence of relapse.

AIDS-Related Opportunistic Infections↗
PubMed1999

High-dose saquinavir plus ritonavir: long-term efficacy in HIV-positive protease inhibitor-experienced patients and predictors of virologic response.

The year-long antiviral efficacy of a high-dose salvage regimen consisting of saquinavir (800 mg twice daily) plus ritonavir (400 mg twice daily) was evaluated in 58 HIV-positive patients who had seen no improvement under first-line protease inhibitor-containing regimens, nor in baseline predictors of virologic response. The efficacy of therapy was determined by CD4+/CD8+ and HIV-1 RNA values. The primary endpoint of our study was the percentage of patients with HIV-1 RNA levels <200 copies/ml (virologic success) at 6 and 12 months of of follow-up. Secondary endpoints were log10 reduction in HIV-1 RNA levels and CD4+ increases through follow-up. Surrogate markers related with a lower HIV-1 RNA area under the curve were identified at baseline. Kaplan-Meier analysis and Cox proportional hazards models were applied to identify baseline predictors of achieving viral suppression at <200 copies/ml. All analyses were intention to treat-last observation carried forward. Patients achieved a median HIV-1 RNA level reduction of >0.5 log through 1 year (-0.59 log10 at 12 months), as well as CD4+ counts increased significantly (89 cells/mm3 at 12 months). Overall, 53% of patients were likely to achieve HIV-1 RNA levels <200 copies/ml at 6 months. Seventy-six percent of patients who started therapy at HIV-1 RNA levels <5000 copies/ml but only 42% with baseline viral load of 5000 to 30,000 copies/ml and 18.7% with baseline viral load >30,000 copies/ml were likely to achieve viral suppression at 6 months (p < .001, log-rank test). Patients with baseline HIV-1 RNA levels between 5000 and 30,000 copies/ml (relative hazard [RH], 0.39; 95% confidence interval [CI], 0.01 to 0.98; p = .0396) and patients with baseline HIV-1 RNA levels >30,000 copies/ml (RH, 0.20; 95% CI, 0.07-0.61; p = .0040) were less likely to reach undetectable HIV-1 RNA levels than those with baseline HIV-1 RNA levels <5000 copies/ml. Salvage highly active antiretroviral therapy (HAART) strategies including saquinavir (SQV) at high doses plus ritonavir (RTV) exert a significant long-term efficacy in more than half of PI-experienced patients without significant additional toxicity. This therapeutic efficacy is strongly implemented by a switch at the lower HIV-1 RNA levels.

Adult↗
PubMed1999

[Mortality in a cohort of intravenous drug users before the introduction of potent HIV therapy].

BACKGROUND: The HIV/AIDS epidemics has contributed to an excess of morbidity and mortality in injecting drug users. The main goal of this study is to estimate incidence and factors associated with mortality from different causes among intravenous drug users. SUBJECTS AND METHODS: Prospective study of patients admitted to a detoxification unit between 1987 and 1990. At baseline they underwent interviews (drug injecting patterns) and venipuncture for HIV and other parameters including T-cell subsets. Viral status was determined for those who returned at least once. Cumulative incidence, overall and cause-specific mortality rates were calculated according to gender, HIV at admission and length of injecting drugs. RESULTS: 420 patients (334 men, 86 women), 69.6% HIV+, were admitted to treatment; the mean age of participants was 26 years and the mean duration of injecting drugs was 73 months. Three hundred and eighty seven patients were followed-up (92% of the initial cohort) for 2,029 persons-years and 101 deaths occurred. The overall mortality rate was 50/1000 persons-year (52/1000 for men and 40/1000 for women). The relative risk (RR) for death among women compared with men was 1.3 (95% CI = 0.8-2.2). The mortality rates for HIV+ was 60/1000 persons-year and 29/1000 persons-year for the seronegatives (RR: 2.1; 95% CI = 1.2-3.4). The HIV+ patients with CD4/microliter < or = 500 showed a threefold increase in mortality rates compared to HIV+ patients without immunosuppression (CI = 1.7-5.3). The cause-specific mortality rates were 27/1000 persons-year for HIV/AIDS, 15/1000 persons-year for drug overdose, 3/1000 persons-year for violence/trauma and 1/1000 persons-year for non-AIDS conditions. CONCLUSIONS: In this hospital cohort, HIV/AIDS and overdose have had a marked effect on mortality among intravenous drug users. Detoxification units may provide clinical services and extensive use of antiretroviral treatment for HIV infected drug users as a strategy to reduce the risk of death from AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1999

[Primary gastrointestinal lymphoma in patients infected with HIV: study of 15 cases in a series of 76 patients with non-Hodgkin's lymphoma and HIV infection].

BACKGROUND: To analyze the main clinical and biological data and the response to therapy in 15 patients with primary gastrointestinal lymphoma (PGIL) from a series of 76 patients with HIV related non-Hodgkin's lymphoma (NHL) diagnosed in a single institution in a 13 years period. PATIENTS AND METHODS: The main clinical, biological and evolutive data were recorded. Pathologic diagnosis of PGIL was made according to the REAL classification. Clinical stage was determined by the Ann Arbor system modified by Rohatiner et al. Response to therapy as well as overall survival (OS) were studied. Results were compared with non-PGIL HIV-related NHL patients. RESULTS: Mean age of the series was 38 years. Thirteen patients were male, and 8 intravenous drug abusers. Then had bad performance status (ECOG 2-4) and 11 B symptoms. All patients had a high grade malignant PGIL and the localization was gastric in 10 cases. The most frequent symptoms were abdominal pain (11 cases), gastrointestinal bleeding (4) and dysphagia (3). Ten patients had advanced stages (IIE2-IV). The median CD4 cell count was lower in PGIL patients (92 x 10(6)/l vs 148 x 10(6)/l; p < 0.05). Thirteen patients received intensive chemotherapy with CHOP regimen (in 5 surgical procedures were previously made). Complete response (CR) was obtained in 4 patients (31%) and 1 of them relapsed. Median OS was 10 months vs 16 months non-PGIL HIV-related lymphoma patients (p < 0.05). CONCLUSIONS: PGIL in HIV patients often presented advanced stages and high grade of malignancy. The most common localization is the stomach, and these patients usually have bad performance status and a low CD4 lymphocyte count. Response to therapy is poor. In our series OS was worse in PGIL patients than in the rest of HIV-related NHL, possibly due to the high degree of immunosuppression in the formers.

Adult↗
PubMed1999

Short-term risk for AIDS-indicator diseases predicted by plasma HIV-1 RNA and CD4+ lymphocytes.

The objective of this study was to assess the value of quantitative HIV-1 RNA as a predictor for the short-term risk of developing AIDS-defining events in comparison with CD4 cell counts. A total of 1,028 samples from 324 patients were analysed. Median initial CD4 cell counts and HIV-1 RNA were 249 x 10(6)/l (range 0-1400 x 10(6)/l) and 4.5 log copies/ml (range: 2.3-6.4 log copies/ml). CD4 cell counts and viral load (VL) values obtained the year before a single AIDS-indicator disease were selected to define the risk of developing that event. Cox regression models with CD4 cell counts and VL values treated as time-dependent covariates were performed to analyse the risk for developing certain events. Receiver operating characteristic (ROC) curves were used to compare CD4 cell counts and VL values as predictive markers for progression. During a median follow-up of 870 d (range 30-1381 d), 132 patients developed AIDS. Median log VL values during the year before the event were 3.6 for non-progressors and 5.2 for those who developed AIDS (p < 0.0001). Minimum log VL threshold values for developing diseases were 2.3 for tuberculosis, 3.8 for Candida esophagitis, 4.4 for wasting syndrome, 4.5 for CMV disease and 4.7 for PCP. VL values were not, however, a better predictive marker for developing specific events than were CD4 cell counts. Although we have identified VL thresholds for the risk of developing certain AIDS-indicator diseases, the indication for starting prophylactic regimens may still be based on CD4 cell counts.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Absence of Fas (CD95) and FasL (CD95L) immunohistochemical expression suggests Fas/FasL-mediated apoptotic signal is not relevant in cutaneous Kaposi's sarcoma lesions.

It has been suggested that Fas ligand (FasL), expressed by several neoplastic cell lines and some tumors in vivo, is able to trigger the apoptotic process in activated T-lymphocytes and may constitute a key element of the immunological escape mechanisms used by many types of neoplasia. In order to evaluate the possible role of Fas-mediated apoptosis in Kaposi's sarcoma (KS), we have studied the immunocytochemical expression of Fas and FasL in biopsy specimens showing different histopathological stages of classic KS (C-KS) and AIDS-associated KS (AIDS-KS), as well as in cultured cells derived from C-KS lesions. KS biopsy tissue failed to show Fas expression in all epidemiologic forms and histopathologic stages studied, while FasL positivity was present in a small number of cells in just a few cases. Double immunostaining ruled out the lymphocytic nature of these cells, whose morphology in adjacent sections stained with hematoxylin and eosin was consistent with KS cells. In contrast, cultured KS cells exhibited strong immunocytochemical cytoplasmic expression of both Fas and FasL. These findings indicate that the Fas-FasL system does not play a major role as a trigger of apoptosis in KS cells in vivo and that the upregulation of these molecules observed in KS cells in vitro probably is the result of cell stress induced by growth in culture.

Acquired Immunodeficiency Syndrome↗
PubMed1998

[Value of HIV-1 viral load and CD4 lymphocyte count as determinants of progression to AIDS and survival].

BACKGROUND: HIV-1 viral load is regarded as a better surrogate marker for progression and death than CD4+ cell counts. Both markers are analysed in a cohort of patients with unknown seroconversion date and advanced HIV infection. PATIENTS AND METHODS: Retrospective cohort analysis of 421 patients, most on antiretroviral therapy, with a median initial CD4+ cell count of 209 x 10(6)/l and a median initial viral load of 4.7 log copies/ml. One thousand two hundred and eighty-six samples were analysed. Univariate and bivariate analysis were performed with initial and sequential CD4+ cell counts and viral load values to estimate the risk of progression and death by Cox regression models. RESULTS: After a median follow up of 763 days, 124 patients developed AIDS and 117 died. Relative risks of progression related to the group that maintained viral load values always < 35,000 copies/ml were: 5-fold (95% CI: 1.4-17.0; p < 0.05) for patients with any viral load value > 35,000 copies/ml but always < 200,000 copies/ml; and 13.6 fold (95% CI: 5.4-34.2; p < 0.0001) for patients who could not maintain viral load < 200.000 copies/ml. CD4+ counts = 100 x 10(6)/l and viral load = 220,000 copies/ml were the threshold values that best fitted to estimate the probability of survival by a bivariate analysis. CONCLUSIONS: The maintenance of sequential viral load values < 35.000 copies/ml is associated with a lower risk of progression. The maintenance of sequential viral load values < 150,000 copies/ml is associated with higher short-term survival rates.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Prevalence and genotypes of GB virus C/hepatitis G virus (GBV-C/HGV) and hepatitis C virus among patients infected with human immunodeficiency virus: evidence of GBV-C/HGV sexual transmission.

The development of new antiretroviral agents may improve survival of HIV-infected individuals, and therefore chronic viral hepatitis may become more relevant in these patients. The presence of GBV-C/HGV and hepatitis C virus (HCV) RNA were investigated by reverse transcriptase-nested polymerase chain reaction in plasma from 168 Spanish HIV-infected patients belonging to four different risk groups: intravenous drug users (IVDUs), hemophiliacs, homosexuals, and heterosexuals. GBV-C/HGV-RNA and HCV-RNA were detected in 18% and 43% of the patients, respectively. The prevalence of current infection with these viruses was notably high, 19% for GBV-C/HGV and 69% for HCV, among individuals with parenteral risk of infection (intravenous drug abusers and hemophiliacs), but sexual transmission with GBV-C/HGV was also suggested because 16.5% of patients with sexual risk, either homosexual or heterosexual, had GBV-C/HGV-RNA in plasma. Although investigation of GBV-C/HGV-RNA possibly underestimates the actual prevalence of infection with GBV-C/HGV, the above data suggest that sexual contact may play a relevant role in the spread of this virus. Phylogenetic analysis showed no evidence for clustering of NS3 sequences into different genotypes or subtypes of GBV-C/HGV.

Adolescent↗