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1.
Sex Transm Dis ; 39(10): 792-3, 2012 Oct.
Article in English | MEDLINE | ID: mdl-23007707

ABSTRACT

Primary cutaneous cryptococcosis is characterized by skin lesions confined to one body region, without evidence of simultaneous dissemination. Skin lesions frequently occur in immunocompromised patients. We report a case of primary cutaneous cryptococcosis in an immunocompetent patient affecting genital area successfully treated with oral itraconazole.


Subject(s)
Antifungal Agents/therapeutic use , Cryptococcosis/pathology , Cryptococcus neoformans/isolation & purification , Itraconazole/therapeutic use , Penile Diseases/pathology , Skin/pathology , Aged , Cryptococcosis/drug therapy , Humans , Male , Penile Diseases/drug therapy , Penis/pathology , Sexual Behavior , Sexual Partners , Skin/microbiology , Travel , Treatment Outcome
2.
Gastroenterol. hepatol. (Ed. impr.) ; 32(6): 387-394, jun.-jul. 2009. tab, graf
Article in Spanish | IBECS | ID: ibc-60808

ABSTRACT

Objetivo.Evaluar la utilidad de 2 modelos bioquímicos (APRI y FIB-4) para la predicción del grado de fibrosis hepática (FH) en la población penitenciaria con hepatitis C crónica (HCC). Método: Estudio observacional para evaluación de pruebas diagnósticas. Se incluyeron 165 internos de 2 centros penitenciarios españoles con HCC y biopsia hepática. Los grados de FH se definieron según el Índice Metavir y posteriormente clasificados como FH ausente o leve (FH } 1), fibrosis significativa (FH ~ 2) y fibrosis grave (FH ~ 3). Se calculó el índice APRI y FIB-4 en todos los casos. La capacidad predictiva de FH se calculó mediante el área bajo la curva y se obtuvo el punto de corte óptimo en base al mejor valor de la especificidad para el diagnóstico del grado de FH. Posteriormente se calculó la sensibilidad (S), el valor predictivo positivo (VPP) y el valor predictivo negativo (VPN). Resultados: Ciento dieciséis pacientes (80,3%) presentaban una FH inferior o igual a 1, 49 pacientes (29,3%) presentaban FH significativa y 24 pacientes (14,5%) presentaban FH grave. Un valor de APRI superior o igual a 0,55 o de FIB-4 superior o igual a 1,0 mostraba un VPP del 91% y del 92% para diagnosticar la presencia de FH (~1), aunque con una S diagnóstica baja (el 61,8 y el 61,1%, respectivamente). Un valor de APRI superior o igual a 0,86 o de FIB-4 superior o igual a 1,3 presentaba un VPN para el diagnóstico de FH avanzada del 92,5 y del 88,4%, respectivamente. Conclusiones: Ambos índices muestran una elevada capacidad predictiva para detectar la presencia de FH en reclusos con HCC, aunque su validez para identificar los grados intermedios de FH es baja. Además, un número importante de reclusos con FH no se identificaron (AU)


Objective: To evaluate the utility of two biochemical tests (APRI and FIB-4) to predict liver fibrosis (LF) in prison inmates with chronic hepatitis C. Method:We performed a cross-sectional study in 165 inmates with chronic hepatitis C and liver biopsy from two Spanish prisons. LF was staged according to the Metavir Index and was subsequently reclassified as mild or absent (LF}1), significant (LF~2) or serious (LF~3). APRI and FIB-4 were calculated in all patients. The predictive value was calculated by the area under the curve and the optimal cut-off was obtained based on the best specificity value for each LF stage. Then, we analyzed the sensitivity, positive predictive value (PPV) and negative predictive value (NPV) for each cut-off point. Results: LF}1 was found in 116 inmates (80.3%), significant LF in 49 (29.3%) and serious LF in 24 (14.5%). An APRI value ~0.55 or FIB-4 ~1.0 showed a PPV of 91% and 92%, respectively, for the presence of any grade of LF (~1), but both tests had low diagnostic sensitivity: 61.8% and 61.1%, respectively. An APRI value ~0.86 or FIB-4 ~1.3 showed a high NPV for serious LF (92.5% and 88.4% respectively). Conclusions: Both tests have a high predictive capacity to detect the presence of LF in inmates with chronic hepatitis C, but their predictive value in detecting intermediate stages of LF is low. Moreover, a significant number of inmates with LF are not identified (AU)


Subject(s)
Humans , Adult , Hepatitis C, Chronic/complications , Liver Cirrhosis/epidemiology , Biomarkers/analysis , Prisoners/statistics & numerical data , Biopsy , Risk Factors , Risk Adjustment/methods
3.
Gastroenterol Hepatol ; 32(6): 387-94, 2009.
Article in Spanish | MEDLINE | ID: mdl-19477553

ABSTRACT

OBJECTIVE: To evaluate the utility of two biochemical tests (APRI and FIB-4) to predict liver fibrosis (LF) in prison inmates with chronic hepatitis C. METHOD: We performed a cross-sectional study in 165 inmates with chronic hepatitis C and liver biopsy from two Spanish prisons. LF was staged according to the Metavir Index and was subsequently reclassified as mild or absent (LFor=2) or serious (LF>or=3). APRI and FIB-4 were calculated in all patients. The predictive value was calculated by the area under the curve and the optimal cut-off was obtained based on the best specificity value for each LF stage. Then, we analyzed the sensitivity, positive predictive value (PPV) and negative predictive value (NPV) for each cut-off point. RESULTS: LFor=0.55 or FIB-4 >or=1.0 showed a PPV of 91% and 92%, respectively, for the presence of any grade of LF (>or=1), but both tests had low diagnostic sensitivity: 61.8% and 61.1%, respectively. An APRI value >or=0.86 or FIB-4 >or=1.3 showed a high NPV for serious LF (92.5% and 88.4% respectively). CONCLUSIONS: Both tests have a high predictive capacity to detect the presence of LF in inmates with chronic hepatitis C, but their predictive value in detecting intermediate stages of LF is low. Moreover, a significant number of inmates with LF are not identified.


Subject(s)
Hepatitis C, Chronic/complications , Liver Cirrhosis/pathology , Models, Biological , Prisoners , Severity of Illness Index , Adult , Alanine Transaminase/blood , Area Under Curve , Aspartate Aminotransferases/blood , Biopsy , Cross-Sectional Studies , Female , Genotype , HIV Infections/epidemiology , Hepacivirus/genetics , Hepatitis C, Chronic/epidemiology , Humans , Liver Cirrhosis/epidemiology , Liver Cirrhosis/etiology , Male , Middle Aged , Predictive Value of Tests , Prospective Studies , Sensitivity and Specificity , Spain/epidemiology , Substance Abuse, Intravenous/epidemiology
4.
J Hepatol ; 48(5): 756-64, 2008 May.
Article in English | MEDLINE | ID: mdl-18314217

ABSTRACT

BACKGROUND/AIMS: Hepatic steatosis is caused by the complex interaction of host and viral factors, such as metabolic syndrome (MS), alcoholism and HCV genotype, and in HIV-HCV co-infected patients, antiretroviral therapy may also play a role. A large population of patients from the AIDS Pegasys Ribavirin International Co-infection Trial (APRICOT) had paired liver biopsies interpreted and graded for steatosis along with lipid measurements and anthropometric data. METHODS: We analyzed these patients to determine the prevalence of steatosis, baseline factors associated with steatosis, effect of steatosis in HCV therapy efficacy and the impact of anti-HCV treatment on steatosis. RESULTS: A total of 65/283 (23%) patients with paired biopsies were positive for steatosis. Patients with steatosis were significantly more likely to have HCV genotype 3, bridging fibrosis/cirrhosis, higher HCV RNA levels, increased triglycerides and lower cholesterol levels. The only different body measurement was neck circumference which was greater in patients with steatosis and significantly decreased from baseline during the study. Hip circumference was predictive of steatosis at baseline. CONCLUSIONS: Factors associated to the metabolic syndrome are important in co-infected patients. Treatment outcome affected steatosis in that viral eradication reduced steatosis in genotype 3 patients, but altogether steatosis did not affect efficacy of treatment in any genotype.


Subject(s)
Fatty Liver/etiology , HIV Infections/complications , Hepatitis C/complications , Hepatitis C/drug therapy , Liver/pathology , Adult , Biopsy , Body Composition , Fatty Liver/epidemiology , Female , Genotype , HIV Infections/pathology , Hepacivirus/classification , Hepacivirus/genetics , Hepatitis C/pathology , Humans , Male , Middle Aged , Treatment Outcome
5.
AIDS ; 21(12): 1555-9, 2007 Jul 31.
Article in English | MEDLINE | ID: mdl-17630550

ABSTRACT

OBJECTIVE: To identify baseline characteristics predictive of a sustained virological response (SVR) in patients with HIV-hepatitis C virus (HCV) co-infection treated with interferon-based therapy. DESIGN/METHODS: A stepwise multiple logistic regression analysis was used to explore the prognostic factors associated with SVR [undetectable HCV-RNA (< 50 IU/ml) at the end of untreated follow-up in week 72]. RESULTS: In all patients (n = 853), in addition to the HCV therapy received, the factors most predictive of SVR were baseline HCV-RNA [< or = versus > 400 000 IU/ml; odds ratio (OR) 4.77; 95% confidence interval (CI) 3.15-7.22; P < 0.0001] and HCV genotype (OR 2.87; 95% CI 2.00-4.12; P < 0.0001). HIV treatment (with a protease inhibitor or non-nucleoside reverse transcriptase inhibitor; P = 0.034), race (P = 0.027), and body mass index (P = 0.039) were also weak predictors of HCV treatment response. CONCLUSIONS: In the AIDS PEGASYS Ribavirin International Co-infection Trial (APRICOT), the predictors of SVR among HIV-HCV co-infected patients treated with peginterferon alfa-2a plus ribavirin were similar to those in patients with HCV mono-infection. The HCV genotype and pretreatment HCV-RNA level had the greatest influence on SVR.


Subject(s)
Antiviral Agents/therapeutic use , HIV Infections/complications , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/drug therapy , Adult , Anti-HIV Agents/therapeutic use , Drug Therapy, Combination , Female , Genotype , HIV Infections/drug therapy , Hepacivirus/genetics , Hepacivirus/isolation & purification , Hepatitis C, Chronic/virology , Humans , Interferon alpha-2 , Interferon-alpha/therapeutic use , Logistic Models , Male , Middle Aged , Polyethylene Glycols/therapeutic use , Prognosis , RNA, Viral/blood , Recombinant Proteins , Ribavirin/therapeutic use , Treatment Outcome , Viral Load
6.
AIDS ; 20(17): 2175-81, 2006 Nov 14.
Article in English | MEDLINE | ID: mdl-17086057

ABSTRACT

OBJECTIVE: Paired liver biopsies from patients enrolled in the multinational AIDS PEGASYS Ribavirin International Co-infection Trial were analysed to investigate a possible correlation between virological and histological responses. DESIGN AND METHODS: A total of 860 HIV-hepatitis C virus (HCV)-co-infected patients were randomly assigned to receive pegIFNalpha-2a (40KD) 180 microg/week plus 800 mg daily ribavirin, pegIFNalpha-2a (40KD) plus placebo or conventional IFNalpha-2a 3 MIU three times a week plus ribavirin for 48 weeks. Paired biopsies were obtained from 401 patients and scored locally using the Ishak-modified histological activity index (HAI). The second biopsy was obtained, on average, 26 weeks or more after the end of treatment. Histological response was defined as a 2-point or greater reduction in the HAI score. RESULTS: The histological response rate was significantly higher in patients receiving pegIFNalpha-2a (40KD) plus ribavirin (57%) than in patients receiving pegIFNalpha-2a (40KD) plus placebo (39%; P < 0.017) or IFNalpha-2a plus ribavirin (41%; P = 0.04). Histological response was correlated with virological response, with the histological response rate ranging from 62 to 74% in patients who achieved a sustained virological response (SVR). Histological response was also seen in 32-43% of patients not achieving an SVR. A higher total HAI score was the only prognostic factor for achieving histological response. CONCLUSION: The histological response rate was significantly higher in HIV-HCV-co-infected patients who received pegIFNalpha-2a (40KD) plus ribavirin than in those receiving pegIFNalpha-2a (40KD) plus placebo or IFNalpha-2a plus ribavirin. Histological response was correlated with virological response, although a substantial proportion of patients who did not achieve an SVR experienced histological improvement.


Subject(s)
Antiviral Agents/administration & dosage , HIV Infections/complications , Hepatitis C, Chronic/drug therapy , Interferon-alpha/administration & dosage , Liver/pathology , Polyethylene Glycols/administration & dosage , Ribavirin/administration & dosage , Administration, Cutaneous , Administration, Oral , Adult , Aged , Biopsy , Drug Therapy, Combination , HIV Infections/pathology , Hepatitis C, Chronic/pathology , Humans , Interferon alpha-2 , Middle Aged , Recombinant Proteins , Treatment Outcome
7.
Enferm Infecc Microbiol Clin ; 24(7): 453-61; quiz 462, 2006.
Article in Spanish | MEDLINE | ID: mdl-16956535

ABSTRACT

In the past 25 years remarkable progress has been made in our understanding of the natural history of chronic HBV. The infection is now perceived as having three consecutive phases: immune tolerance, immune clearance, and inactive carrier status, with possible reactivation episodes. Accumulating evidence indicates that antiviral therapy can prevent progression of HBV-related liver disease, particularly among patients with sustained response. Five agents are now approved for therapy of chronic hepatitis B: interferon-alpha (standard and pegylated), lamivudine, adefovir and entecavir. All five drugs are effective in suppressing HBV DNA levels and improving serum alanineaminotransferase levels and hepatic histology, but it is still unclear who should be treated, with which agent (or combination of agents), for how long, and what endpoints measure the success or failure of treatment. Until a drug therapy results in lasting virological remission in most patients after a reasonably short period of treatment, individualized treatment decisions will remain key to maximizing efficacy, and chronic HBV infection will continue to be treated as a liver disease rather than as an infectious disease.


Subject(s)
Antiviral Agents/therapeutic use , Hepatitis B, Chronic/drug therapy , Clinical Trials as Topic , Guidelines as Topic , Humans
8.
Enferm. infecc. microbiol. clín. (Ed. impr.) ; 24(7): 453-462, ago. 2006. tab
Article in Es | IBECS | ID: ibc-048536

ABSTRACT

Nuestro conocimiento acerca de la historia natural de la infección crónica por el virus de la hepatitis B (VHB) ha progresado de manera muy importante en los últimos 25 años. La infección se entiende ahora como la sucesión de 3 fases: inmunotolerancia, inmunoaclaramiento y estado de portador inactivo en el que pueden existir episodios de reactivación. Cada vez es mayor la evidencia de que el tratamiento antiviral puede prevenir la progresión a estadios finales de la enfermedad hepática, especialmente en los pacientes que logran una respuesta sostenida. Son cinco los fármacos que están disponibles para el tratamiento de la hepatitis crónica B. Interferón alfa (convencional o pegilado), lamivudina, adefovir y entecavir. Los cinco han demostrado ser capaces de reducir la concentración de ADN del VHB y de las transaminasas y mejorar la histología hepática, pero hasta el momento no está claro quién debe recibir tratamiento, con qué fármacos o combinación de fármacos, durante cuánto tiempo y cuáles son los objetivos que se persiguen. Mientras no dispongamos de fármacos capaces de inducir una remisión duradera en la mayoría de los pacientes tras un razonablemente corto período de tratamiento, la hepatitis crónica B deberá seguir siendo tratada más como una enfermedad hepática que como una enfermedad infecciosa (AU)


In the past 25 years remarkable progress has been made in our understanding of the natural history of chronic HBV. The infection is now perceived as having three consecutive phases: immune tolerance, immune clearance, and inactive carrier status, with possible reactivation episodes. Accumulating evidence indicates that antiviral therapy can prevent progression of HBV-related liver disease, particularly among patients with sustained response. Five agents are now approved for therapy of chronic hepatitis B: interferon-alpha (standard and pegylated), lamivudine, adefovir and entecavir. All five drugs are effective in suppressing HBV DNA levels and improving serum alanineaminotransferase levels and hepatic histology, but it is still unclear who should be treated, with which agent (or combination of agents), for how long, and what endpoints measure the success or failure of treatment. Until a drug therapy results in lasting virological remission in most patients after a reasonably short period of treatment, individualized treatment decisions will remain key to maximizing efficacy, and chronic HBV infection will continue to be treated as a liver disease rather than as an infectious disease (AU)


Subject(s)
Humans , Antiviral Agents/therapeutic use , Hepatitis B, Chronic/drug therapy
9.
Hepatology ; 43(6): 1317-25, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16729309

ABSTRACT

Liver biopsy remains the gold standard in the assessment of severity of liver disease. Noninvasive tests have gained popularity to predict histology in view of the associated risks of biopsy. However, many models include tests not readily available, and there are limited data from patients with HIV/hepatitis C virus (HCV) coinfection. We aimed to develop a model using routine tests to predict liver fibrosis in patients with HIV/HCV coinfection. A retrospective analysis of liver histology was performed in 832 patients. Liver fibrosis was assessed via Ishak score; patients were categorized as 0-1, 2-3, or 4-6 and were randomly assigned to training (n = 555) or validation (n = 277) sets. Multivariate logistic regression analysis revealed that platelet count (PLT), age, AST, and INR were significantly associated with fibrosis. Additional analysis revealed PLT, age, AST, and ALT as an alternative model. Based on this, a simple index (FIB-4) was developed: age ([yr] x AST [U/L]) / ((PLT [10(9)/L]) x (ALT [U/L])(1/2)). The AUROC of the index was 0.765 for differentiation between Ishak stage 0-3 and 4-6. At a cutoff of <1.45 in the validation set, the negative predictive value to exclude advanced fibrosis (stage 4-6) was 90% with a sensitivity of 70%. A cutoff of >3.25 had a positive predictive value of 65% and a specificity of 97%. Using these cutoffs, 87% of the 198 patients with FIB-4 values outside 1.45-3.25 would be correctly classified, and liver biopsy could be avoided in 71% of the validation group. In conclusion, noninvasive tests can accurately predict hepatic fibrosis and may reduce the need for liver biopsy in the majority of HIV/HCV-coinfected patients.


Subject(s)
Diagnostic Tests, Routine/methods , HIV Infections/diagnosis , Hepatitis C, Chronic/diagnosis , Liver Cirrhosis/diagnosis , Age Factors , Biopsy, Needle , Blood Chemical Analysis , Cohort Studies , Disease Progression , Female , HIV Infections/epidemiology , Hepatitis C, Chronic/epidemiology , Humans , Immunohistochemistry , Liver Cirrhosis/epidemiology , Liver Cirrhosis/virology , Liver Function Tests , Logistic Models , Male , Predictive Value of Tests , Probability , Prognosis , ROC Curve , Reproducibility of Results , Retrospective Studies , Risk Assessment , Sensitivity and Specificity , Severity of Illness Index , Sex Factors
11.
Viral Immunol ; 19(4): 759-67, 2006.
Article in English | MEDLINE | ID: mdl-17201671

ABSTRACT

Immunovirologic parameters of 24 heavily antiretroviral drug-pretreated patients with prolonged virologic treatment failure under highly active antiretroviral therapy, and who harbored highly resistant human immunodeficiency virus (HIV) isolates, were studied in this retrospective cross-sectional study. Most of the patients were injecting drug users (71%) and male (88%). All patients were studied for CD4(+) cell count, HIV viral load, resistance mutations, and viral phenotype. The patients showed a high accumulation of resistance-associated mutations, their CD4(+) cell count and viral load directly correlated with their respective values at initiation of therapy, and the presence of K103N was inversely associated with lower viral load. On the other hand, patients with K103N had the same level of CD4(+) cell count compared with patients without this mutation. Among the patients, a majority with a specific viral phenotype was not present. Rather, a dual-tropic virus was found most frequently, suggesting a preferential suppression of X4-specific strains and less cytopathogenicity during antiretroviral therapy and a greater proportion of R5X4 viruses due to an adaptation to that pressure.


Subject(s)
Anti-HIV Agents/therapeutic use , HIV Infections/drug therapy , HIV-1 , Adult , Amino Acid Sequence , Antiretroviral Therapy, Highly Active , CD4 Lymphocyte Count , Cross-Sectional Studies , Female , HIV Envelope Protein gp120/genetics , HIV Infections/immunology , HIV Infections/virology , HIV-1/genetics , Humans , Male , Middle Aged , Molecular Sequence Data , Peptide Fragments/genetics , Retrospective Studies , Substance Abuse, Intravenous , Treatment Failure , Viral Load
12.
Viral Immunol ; 18(4): 740-6, 2005.
Article in English | MEDLINE | ID: mdl-16359240

ABSTRACT

One of the strategies that has been investigated to reduce antiretroviral treatment toxicity in patients infected with human immunodeficiency virus (HIV) is structured treatment interruption (STI). Our aim was to analyze early viral and immune dynamics after interruption of highly active antiretroviral therapy (HAART) and to determine whether thymic function-related markers play a role in preventing CD4 count decline caused by increased viral replication. This was a prospective study of an open cohort of 47 HIV-infected patients with a median 969 CD4 count and prolonged viral suppression. They were followed every 4 weeks though week 24. Thymic volume and TREC level were analyzed at baseline. Increased thymic volume was associated with higher plasma viral load and greater CD4 count decline early after interruption. Three virologic patterns were observed: rapid/high (RH), delayed/high (DH), and low/slow (LS) viral replication. RH correlated with higher thymic volume at baseline and with higher CD4 count decline at week 4. Patients with greater thymic volume was associated with an immune and virologic impairment only early after interruption, probably because of infection of the increased number of available target cells. As the long-term consequences of these observations are unknown, the safety of treatment interruption must be further studied.


Subject(s)
Anti-HIV Agents/administration & dosage , Antiretroviral Therapy, Highly Active , HIV Infections/immunology , HIV Infections/virology , HIV-1/physiology , Thymus Gland/immunology , Adult , CD4 Lymphocyte Count , Drug Administration Schedule , Female , HIV Infections/drug therapy , HIV Infections/pathology , Humans , Male , Middle Aged , Prospective Studies , Thymus Gland/pathology , Viral Load , Virus Replication
13.
J Clin Immunol ; 25(3): 296-302, 2005 May.
Article in English | MEDLINE | ID: mdl-15981096

ABSTRACT

Whether HAART allows complete recovery of humoral immune function in HIV-infected individuals is still controversial. Our objective was to study the effect of HAART on both B cell repopulation and hypergammaglobulinemia in 72 naïve patients, including 35 HCV-coinfected individuals, during 156 weeks on HAART. The possible role of HCV coinfection on the recovery of the humoral immune system was also investigated. At baseline, HCV-coinfected patients had greater circulant IgG levels than HIV-only-infected patients, while B cell count and CD21(low) B cell subpopulation were similar in both groups. During HAART, HIV-only-infected patients reached normal B cell counts and circulant IgG levels, while HCV-coinfected individuals did not. CD21(low) B cell subpopulation significantly decreased in both groups of patients at week 48 after the initiation of HAART compared to baseline. Thus, B cells remained continuously stimulated in HCV-coinfected patients and this stimulation seemed to be through a CD21-independent pathway.


Subject(s)
Antibody Formation/drug effects , Antiretroviral Therapy, Highly Active , HIV Infections/complications , Hepatitis C/complications , Adult , B-Lymphocytes/drug effects , B-Lymphocytes/pathology , B-Lymphocytes/physiology , Case-Control Studies , Female , Follow-Up Studies , HIV Infections/drug therapy , HIV Infections/immunology , Hepatitis C/drug therapy , Hepatitis C/immunology , Humans , Hypergammaglobulinemia/drug therapy , Male , Receptors, Complement 3d , Regeneration
14.
J Clin Virol ; 33(2): 110-115, 2005 Jun.
Article in English | MEDLINE | ID: mdl-15952251

ABSTRACT

The prevalence and the factors involved in discordant responses to highly active antiretroviral therapy were analysed in a closely followed cohort of 51 naïve HIV-infected patients at 48 weeks. A complete treatment response was considered as an increase in CD4 cell count of >or=50 cells/mm3 with a >or=1 log10 decrease in viral load or viral suppression. Virologic response (<50 CD4+ cells/mm3 increase) and immune response (<1 log10 decrease in viral load) were observed in 15.7% and 5.8% of the patients, respectively. We demonstrated that the prevalence of virologic response decreased at week 72 and disappeared after 96 weeks of treatment. This slower response did not correlate with protease inhibitor-based (PI-based) regimens or HCV coinfection. On the other hand, immune response in our cohort could be easily attributable to a simple mechanism, i.e. irregular treatment compliance.


Subject(s)
Anti-HIV Agents/therapeutic use , Antiretroviral Therapy, Highly Active , HIV Infections/drug therapy , Adult , CD4 Lymphocyte Count , Cohort Studies , Female , HIV , HIV Infections/immunology , HIV Infections/virology , Humans , Male , Patient Compliance , Retrospective Studies , Spain , Thymus Gland/anatomy & histology , Time Factors , Treatment Outcome , Viral Load
15.
N Engl J Med ; 351(5): 438-50, 2004 Jul 29.
Article in English | MEDLINE | ID: mdl-15282351

ABSTRACT

BACKGROUND: Hepatitis C virus (HCV) infection is highly prevalent and is associated with substantial morbidity and mortality among persons infected with the human immunodeficiency virus (HIV). We compared the efficacy and safety of pegylated interferon alfa-2a (peginterferon alfa-2a) plus either ribavirin or placebo with those of interferon alfa-2a plus ribavirin for the treatment of chronic HCV infection in patients who were also infected with HIV. METHODS: A total of 868 persons who were infected with both HIV and HCV and who had not previously been treated with interferon or ribavirin were randomly assigned to receive one of three regimens: peginterferon alfa-2a (180 microg per week) plus ribavirin (800 mg per day), peginterferon alfa-2a plus placebo, or interferon alfa-2a (3 million IU three times a week) plus ribavirin. Patients were treated for 48 weeks and followed for an additional 24 weeks. The primary end point was a sustained virologic response (defined as a serum HCV RNA level below 50 IU per milliliter at the end of follow-up, at week 72). RESULTS: The overall rate of sustained virologic response was significantly higher among the recipients of peginterferon alfa-2a plus ribavirin than among those assigned to interferon alfa-2a plus ribavirin (40 percent vs. 12 percent, P<0.001), or peginterferon alfa-2a plus placebo (40 percent vs. 20 percent, P<0.001). Among patients infected with HCV genotype 1, the rates of sustained virologic response were 29 percent with peginterferon alfa-2a plus ribavirin, 14 percent with peginterferon alfa-2a plus placebo, and 7 percent with interferon alfa-2a plus ribavirin. The corresponding rates among patients infected with HCV genotype 2 or 3 were 62 percent, 36 percent, and 20 percent. Neutropenia and thrombocytopenia were more common among patients treated with regimens that contained peginterferon alfa-2a, and anemia was more common among patients treated with regimens containing ribavirin. CONCLUSIONS: Among patients infected with both HIV and HCV, the combination of peginterferon alfa-2a plus ribavirin was significantly more effective than either interferon alfa-2a plus ribavirin or peginterferon alfa-2a monotherapy.


Subject(s)
Antiviral Agents/therapeutic use , HIV Infections/complications , Hepatitis C, Chronic/drug therapy , Interferon-alpha , Interferon-alpha/therapeutic use , Polyethylene Glycols , Ribavirin/therapeutic use , Adult , Antiviral Agents/adverse effects , Drug Therapy, Combination , Female , Genotype , Hepacivirus/drug effects , Hepacivirus/genetics , Hepatitis C Antibodies/blood , Hepatitis C, Chronic/complications , Humans , Interferon alpha-2 , Interferon-alpha/adverse effects , Male , RNA, Viral/blood , Recombinant Proteins , Ribavirin/adverse effects
16.
J Antimicrob Chemother ; 53(1): 95-101, 2004 Jan.
Article in English | MEDLINE | ID: mdl-14657091

ABSTRACT

OBJECTIVE: To assess the durability of the undetectability of HIV plasma viraemia (pV) and to determine the factors associated with virological rebound (VR) in HIV-infected adults on protease inhibitor (PI)-sparing highly active antiretroviral therapy (HAART). The development of resistance mutations during virologically successful therapy and VR was also analysed. MATERIALS AND METHODS: One hundred and twenty-six HIV-infected adults on PI-sparing HAART were prospectively followed from April 1998 to December 2002: Group 1, naive for antiretroviral drugs (n = 26); Group 2, previously PI-HAART-exposed patients (n = 19); Group 3, previously exposed to suboptimal therapy (n = 81). Genotypic resistance tests on peripheral blood mononuclear cells or on plasma RNA (when feasible) were carried out when undetectable HIV pV was demonstrated for at least 48 weeks. Additionally, patients showing a therapy adherence >95% developing VR were also tested at rebound, at simplification and during previous suboptimal therapy exposure. RESULTS: The median follow-up time was 630 [329-903] days. VR was considered as two consecutive pV levels >50 copies/mL. Twenty-two (17.5%) patients developed VR. Only therapy adherence <95% was independently associated with VR (adjusted hazard ratio: 8.42; 95% CI: 3.33-21.27). Twenty (40%) of the 50 patients with pV < 50 copies/mL for at least 48 weeks showed at least one thymidine-associated mutation (TAM) but none had NNRTI-resistance mutations. Ten (83.3%) of 12 available adherent patients showing VR harboured NNRTI-resistance-associated mutations; 50% of them were considered as wild-type strains at simplification time. However, the TAM number and resistance mutations profile found on suboptimal exposure were very similar to those found at VR on simplification therapy. CONCLUSIONS: PI-sparing HAART allows maintenance of successful long-term control of HIV replication, adherence to therapy being the main factor associated with VR. However, a small proportion of patients on simplification regimen may develop VR regardless of therapy compliance. VR on PI-sparing HAART is characterized by the emergence of NNRTI cross-resistance mutations. Finally, TAMs 'archived' during previous suboptimal exposures are partially involved in subsequent VR on simplification HAART.


Subject(s)
Drug Resistance, Multiple, Viral/genetics , HIV Infections/drug therapy , HIV Protease Inhibitors/therapeutic use , HIV-1/drug effects , Viral Load , Adult , Antiretroviral Therapy, Highly Active , Female , Follow-Up Studies , HIV Infections/virology , HIV Protease/genetics , HIV-1/enzymology , HIV-1/genetics , Humans , Male , Mutation , Prospective Studies , Time Factors , Treatment Outcome
17.
Antiviral Res ; 61(2): 129-32, 2004 Feb.
Article in English | MEDLINE | ID: mdl-14670587

ABSTRACT

Once highly active antiretroviral therapy (HAART) fails to suppress HIV replication and resistant viruses emerge, it is difficult to find a salvage regimen since cross-resistance is high among the available classes of antiretroviral drugs. In this retrospective analysis, genotypic resistance profiles were analysed in 24 patients who switched treatment to abacavir (ABV), efavirenz (EFV), and either a NRTI or a PI at baseline and after 24 weeks of treatment. At baseline, 71% of patients harboured at least one resistance mutation in the protease gene. In the RT gene, 87.5% of the patients showed nucleoside analogue resistance mutations, and an equal 87.5% showed resistance mutations to non-nucleoside analogues. After 24 weeks of treatment, only mutations to nucleoside analogues raised in 95.8% of the patients, while resistance mutations to the other drug classes remained constant. Substitutions conferring cross-resistance within each drug family were very common among this treatment-experienced population. These data also indicate that salvage therapy is likely to remain one of the most important issues in the treatment of HIV infections.


Subject(s)
Anti-HIV Agents/therapeutic use , Dideoxynucleosides/therapeutic use , HIV Infections/drug therapy , HIV Infections/virology , HIV-1/drug effects , HIV-1/genetics , Oxazines/therapeutic use , Alkynes , Antiretroviral Therapy, Highly Active , Benzoxazines , Cyclopropanes , Drug Resistance, Viral/genetics , Genotype , HIV Protease/genetics , HIV Reverse Transcriptase/genetics , HIV-1/enzymology , Humans , Mutation , Salvage Therapy , Time Factors
19.
Antivir Ther ; 8(4): 289-94, 2003 Aug.
Article in English | MEDLINE | ID: mdl-14518697

ABSTRACT

The aim of this work was to compare thymic function-related markers for predicting early CD4 T-cell repopulation in adult HIV-infected patients under HAART. Forty-three consecutive antiretroviral-naive patients were prospectively analysed for clinical, biochemical, immunological and virological parameters at starting HAART, and followed for 4 weeks and every 12 weeks thereafter. At baseline, all patients underwent a thoracic computer tomography scan, in order to measure thymic volume, as well, T-cell phenotype (naive CD4 and CD8 T cells) and the number of TREC-bearing cells were obtained. CD4 cell repopulation was considered as an increase > or = 200 cells/mm3 above baseline count. Twenty-seven patients (62.8%) increased > or = 200 cells/mm3 above baseline levels during the follow-up. The median time to event was 182 days (84-537 days). On the univariate analysis, to be younger than 36 years, showing a CD4 cell count > or = 272 cells/mm3, a total naive T-cell count > or = 128 cells/mm3, a TREC-bearing cell count > or = 0.74 cells/mm3, and a thymic volume > or =3.07 cc at baseline were statistically associated to the event studied. However, when the multivariate analysis was performed, only thymic volume at baseline was independently associated (P=0.002) to CD4 cell recovery. This co-variable was identified as a positive predictor [hazard ratio, 1.22 (95% confidence interval: 1.16-1.28)]. In summary, data presented herewith show that thymic volume is the best thymic function-related marker for predicting early CD4 T-cell recovery in adult HIV-infected patients under HAART.


Subject(s)
Antiretroviral Therapy, Highly Active , CD4-Positive T-Lymphocytes/immunology , HIV Infections/drug therapy , Thymus Gland/diagnostic imaging , Thymus Gland/immunology , Adult , Biomarkers , CD4 Lymphocyte Count , Female , HIV Infections/immunology , HIV-1/immunology , Humans , Male , Predictive Value of Tests , Prospective Studies , Receptors, Antigen, T-Cell , T-Lymphocyte Subsets/immunology , Tomography, X-Ray Computed
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