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Biomedical subjects

J González-Lahoz

Publications and source records attributed to J González-Lahoz.

At least 19 recordsLinked to original sources

Reduction in liver-related hospital admissions and deaths in HIV-infected patients since the year 2002.

Since the advent of highly active antiretroviral therapy (HAART), complications of chronic liver disease (CLD) have emerged as one of the leading causes of hospital admission and death among HIV-infected patients with chronic hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infections. The impact of CLD on hospital admissions and deaths in HIV-infected patients attended at one reference HIV hospital in Madrid during the last 9 years was analysed. All clinical charts from January 1996 to December 2004 were retrospectively examined. Demographics, discharge diagnosis, complications during inhospital stay and causes of death were recorded. A total of 2527 hospital admissions in 2008 distinct HIV-infected persons were recorded. Overall, 84% were iv drug users; mean age was 37 years and the mean CD4 count was 224 cells/muL. Both mean age and CD4 count significantly increased during the study period (P < 0.01). Overall, 42% of hospitalized patients were on antiretroviral therapy. Decompensated CLD was the cause of admission and/or developed during hospitalization in 345 patients (14%). Admissions caused by decompensated CLD increased significantly from 9.1% (30/329) in 1996 to 26% (78/294) in 2002. A significant steady decline occurred since then, being 11% (29/253) in the year 2004. Similarly, inhospital liver-related deaths were 9% (5/54) in 1996, peaked to 59% (10/17) in 2001 and declined to 20% (3/15) in the year 2004. Chronic hepatitis C was responsible for admissions and/or deaths in 73.5% of CLD cases. In conclusion, the rate of liver-related hospital admissions and deaths among HIV-infected patients peaked in the year 2002 and has steadily declined since then. A slower progression to liver cirrhosis in patients on HAART, avoidance of hepatotoxic antiretroviral drugs and more frequent use of anti-HCV therapy in HIV/HCV-coinfected patients could account for this benefit.

Adult↗

Clinical benefit of interventions driven by therapeutic drug monitoring.

BACKGROUND: Adequate plasma concentrations of antiretroviral drugs are key to achieving and maintaining long-term suppression of HIV replication. Multiple factors may influence drug levels, causing increases or reductions that may, respectively, result in toxicity or virological failure. Therapeutic drug monitoring (TDM) might help to detect and correct such abnormalities. OBJECTIVE: To evaluate the usefulness of TDM in the care of HIV-infected patients in an out-patient clinical setting. METHOD: S All the requests for TDM of protease inhibitors (PIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs) for patients attending our HIV out-patient clinic from October 2000 to August 2003 were analysed. Blood samples were collected before the morning dose. Drug concentrations were measured by high performance liquid chromatography by ultraviolet waves (HPLC-UV). R:A total of 151 requests from 137 patients were assessed. The reasons for requesting TDM were drug toxicity (59%), virological failure (39%) and possible drug interactions (2%). NNRTI levels were more often requested because of toxicity, while PI levels were more often requested because of virological failure. Elevated drug levels were confirmed in 36% of patients with suspected drug toxicity, while subtherapeutic levels were found in 37% of patients failing virologically. Based on the results of TDM, dose modifications were made in 37% of patients, allowing correction of such abnormalities in 80% of cases. Moreover, adequate plasma concentrations were confirmed in 79% of patients whose levels were assessed again. CONCLUSIONS: Therapeutic drug monitoring may be a useful tool to identify toxic levels of NNRTI and subtherapeutic concentrations of PI. Dose adjustments following TDM may ameliorate drug-related toxicities or improve virological response rates.

Adult↗

Consensus conference on chronic viral hepatitis and HIV infection: updated Spanish recommendations.

Chronic hepatitis B and C represent a leading cause of morbidity and mortality among human immunodeficiency virus (HIV)-infected patients worldwide. New treatment options against both hepatitis B (HBV) and C (HCV) viruses have prompted us to update previous recommendations for the management of coinfected individuals. Fifteen topics (nine related to HCV, five to HBV and one to both viruses) were selected for this purpose. A panel of Spanish experts in the field was invited to review these areas and propose specific recommendations, which were scored according to the Infectious Disease Society of America (IDSA) grading system. These guidelines represent a comprehensive and updated overview on the management of hepatitis B and C in HIV-infected patients.

Anti-HIV Agents↗

Human immunodeficiency virus type 1 recombinant B/G subtypes circulating in Coimbra, Portugal.

An increasing prevalence of HIV-1 non-B variants is being noticed in several European regions, particularly in countries such as Portugal, which have closer contacts with African endemic areas, where multiple HIV subtypes cocirculate. HIV-1 subtyping by phylogenetic analyses of reverse transcriptase, protease and env (C2-V3) genomic regions was carried out in plasma collected from 18 HIV-1-infected subjects living in Coimbra, Portugal, and suspected to be infected with non-B variants. Three (16.7%) subjects carried recombinant B/G viruses (BV3/BRT/Gpro; GV3/URT/Bpro; AV3/GRT/Bpro), whereas all the remaining individuals were infected with HIV-1 subtype B. This is the first report of recombinant B/G subtypes in Portugal.

Adult↗

Increasing impact of chronic viral hepatitis on hospital admissions and mortality among HIV-infected patients.

To assess the impact of chronic viral liver disease (CVLD) on hospital admissions and death in HIV-infected patients since the introduction of highly active antiretroviral therapy, all hospital charts, from January 1996 to December 2000, in a large HIV/AIDS reference center in Madrid were reviewed. Discharge diagnosis, complications during the inpatient period, and number and causes of death were recorded. A total of 1334 hospital admissions involving 875 HIV-infected individuals was recorded. Up to 82% of them were either active or former intravenous drug users. Overall, 158 (11.8%) were admitted because of complications of CVLD, or developed complications of CVLD during their admission for another reason. The absolute number and proportion of admissions caused by CVLD increased over time, from 9.4% (31 of 330) in 1996 to 16% (46 of 287) in 2000 (p < 0.05). Likewise, the total number and proportion of deaths due to CVLD increased from 9.3% (5 of 54) in 1996 to 45% (9 of 20) in 2000 (p < 0.05). Chronic hepatitis C was the only etiology in nearly three-quarters of patients who were admitted or died of CVLD. In conclusion, the proportion of hospital admissions caused by liver failure in HIV-infected patients has increased in the last 5 years, accounting for 16% of cases in 2000. End-stage liver disease currently represents 45% of causes of in-hospital death among HIV-infected individuals. Therefore, strategies to prevent infection by hepatitis viruses (hepatitis B vaccine) and specific treatment (interferon plus ribavirin for hepatitis C virus) should be encouraged among HIV-infected persons.

Adult↗

[Opportunistic episodes in patients infected with the human immunodeficiency virus during the first 6 months of HAART].

BACKGROUND: We aimed at analysing the incidence and characteristics of opportunistic events (OE) within a few months after starting highly active antiretroviral therapy (HAART) in HIV infected patients. PATIENTS AND METHOD: Retrospective study of HIV infected outclinic patients attended in a HIV/AIDS reference hospital in Madrid, who initiated HAART during the second semester of 1998, with a baseline CD4 cell count 250 x 10(6) cells/l. We recorded the incidence of OE within 6 months after beginning HAART and analysed virological and immunological parameters, sociodemographic variables and types of antiretroviral treatment. RESULTS: The study included 269 patients. Twenty-one (7.8%) OE were recorded. At the onset of HAART, the mean CD4 cell count in these 21 patients was 137 (92) x 10(6)/land the median viral load was 24,043 cop/ml. At the time of OE diagnosis, these parameters were 218 (114) x 10(6)/l (p = 0.012) and < 500 cop/ml, respectively. OE were distributed as follows: herpes zoster, 9 cases (43%), Pneumocystis carinii pneumonia, 5 cases (24%), Kaposi sarcoma,3 cases (14%) and tuberculosis, cerebral toxoplasmosis, cytomegalovirus retinitis, and non-Hodgkin lymphoma, 1 case each. Overall, 78% of OE occurred within first 4 months after beginning HAART. In addition, an OE was developed by 8% patients treated with NRTI and PI, 2% treated with NRTI and NNRTI, and 10% treated with NRTI,NNRTI and PI (p = 0.44). CONCLUSIONS: HIV-infected subjects with low CD4 counts are prone to develop OE within the first few moths after beginning HAART. An inflammatory response to latent antigens due to the immune recovery might explain this fact.

AIDS-Related Opportunistic Infections↗

Overall trends in CD4 counts and plasma viremia in an urban clinic since the introduction of highly active antiretroviral therapies.

OBJECTIVE: To assess whether the benefit of highly active antiretroviral therapies (HAART) is continuing, a longitudinal retrospective study of CD4 counts and viral load (VL) in a large group of human immunodeficiency virus (HIV)-infected subjects was undertaken in Madrid. METHODS: Consecutive plasma VL values and CD4+ T-lymphocyte counts were collected during a 3-month period yearly from 1996 to 2000 in one HIV/acquired immune deficiency syndrome (AIDS) reference institution, where currently around 1500 HIV-infected individuals are on regular follow-up. RESULTS: VL values and CD4+ counts were collected at each time-point from an average of 375 and 391 patients, respectively. The proportion of subjects receiving HAART among those on any kind of antiretroviral treatment increased between 1996 (61%) and 2000 (95.1%) (P < 0.01). The number of subjects with undetectable VL (<500 HIV-RNA copies/mL) increased from 12% in 1996 to 64% in 2000 (P < 0.01). Accordingly, the proportion of individuals with CD4+ counts >500 cells/microL increased from 16% in 1997 to 54% in 2000 (P < 0.01). Notably, the number of subjects with VL values >10 000 copies/mL has declined over time, and currently represents only 17% of the population. Despite this favorable trend, the proportion of subjects with low CD4+ counts (<200 cells/microL) seems to have reached a plateau, in the range of 10%. CONCLUSIONS: A dramatic virological and immunological benefit has followed the introduction of HAART in HIV-infected patients since 1996. This favorable trend seems to be maintained over time, despite the negative impact of drug-related toxicity and/or adherence issues. However, a subgroup of subjects seems to persist with low CD4 counts despite having good virological control. They should be managed with alternative treatment strategies, including immune stimulatory agents.

Anti-HIV Agents↗

Prevention of nevirapine-associated exanthema using slow dose escalation and/or corticosteroids.

OBJECTIVE: The appearance of rash is one of the most frequent and limiting side-effects during the first 4 weeks of treatment with nevirapine (NVP). We explored the efficacy and safety of four different strategies for reducing the incidence of this complication. PATIENTS AND METHODS: Four-hundred and sixty-nine patients were assigned randomly to accomplish the induction phase of NVP following either the standard recommendation of 200 mg daily during the first 2 weeks (n = 166), or any of three new strategies: adding prednisone 50 mg each other day during the first 2 weeks (n = 93); using a slowly escalating dose, beginning with 100 mg daily the first week, and increasing the dose by 100 mg/week up to the full daily dose of 400 mg (n = 107); and combining both the addition of prednisone with the slowly escalating dose (n = 103). A pharmacokinetic substudy was performed in seven patients receiving 100 mg of NVP during the first week. RESULTS: The incidence of rash diminished from 18.7% using the standard recommendation to 9.2% using the alternative approaches (P = 0.003). Rash appeared in 11.2%, 8.6%, and 7.7% of subjects assigned to receive the slowly escalating dose, prednisone, or both, respectively, without significant differences among them. The rate of drug discontinuation was also diminished by one-half using the new approaches (8.5% versus 4.3%; P = 0.06). NVP plasma concentrations within the first week of treatment using 100 mg daily were above the 90% inhibitory concentration for wild-type HIV-1 in all instances. CONCLUSION: The incidence of rash complicating the first few weeks of treatment with NVP can be diminished by adding corticosteroids for 2 weeks to the standard recommendation, or by using a slowly escalating dose. This second approach is proven to be pharmacokinetically safe.

Anti-HIV Agents↗