Celestino Rey-Joly

Clinical utility of HIV-1 genotyping and expert advice: the Havana trial.

Objective To determine whether HIV-1 genotyping and expert advice add additional short-term virologic benefit in guiding antiretroviral changes in HIV+ drug-experienced patients. Design A two factorial (genotyping and expert advice), randomized, open label, multi-center trial. The patients were stratified according to the number of treatment failures. Patients and methods HIV-1 infected patients on stable antiretroviral therapy who presented virological failure were included into the study. Genotypic testing was performed by using TrueGene HIV Genotyping kit and the results were interpreted by a software package (RetroGram®, version 1.0). An expert advisory committee suggested the new therapeutic approach based on clinical information alone or on clinical information plus HIV-1 genotyping results. Plasma HIV-1 RNA load, CD4+ cell count and adverse events were recorded at baseline and every 12 weeks. Results A total of 326 patients were included. The baseline CD4+ cell count and plasma HIV-1 RNA were 387 (± 224) × 106 cells/l and 4 (± 1) log10 respectively. The proportion of patients with plasma HIV-1 RNA < 400 copies/ml at 24 weeks differed between genotyping and no genotyping arms (48.5 and 36.2%, P < 0.05). Factors associated with a higher probability of plasma HIV-1 RNA < 400 copies/ml were HIV-1 genotyping [odds ratio (OR), 1.7; 95% confidence interval (CI), 1.1–2.8;P = 0.016] and the expert advice in patients failing to a second-line antiretroviral therapy (OR, 3.2; 95% CI, 1.2–8.3;P = 0.016). Conclusions HIV-1 genotyping interpreted by a software package improves the virological outcome when it is added to the clinical information as a basis for decisions on changing antiretroviral therapy. The expert advice also showed virologic benefit in the second failure group.

Ezetimibe, a promising lipid-lowering agent for the treatment of dyslipidaemia in HIV-infected patients with poor response to statins.

Objective:To assess the efficacy, safety, and pharmacokinetic interactions of ezetimibe in HIV-infected patients with poorly controlled antiretroviral-associated dyslipidaemia while taking pravastatin alone. Design:A prospective, open-label, one-arm study of 24 weeks duration. Patients and setting:Nineteen patients (18 on stable HAART), with low density lipoprotein (LDL)-cholesterol values of ≥ 130 mg/dl despite the use of pravastatin. Methods:Ezetimibe, 10 mg/day, was added to pravastatin 20 mg/day, while patients maintained the same antiretroviral regimen. Determinations of total, LDL-, and high density lipoprotein (HDL)-cholesterol, triglycerides, apoproteins, and inflammatory factors (homocystein and C-reactive protein) were performed at baseline, and at weeks 6, 12, and 24. Liver enzymes and creatinine phosphokinase were also assessed. Protease inhibitor (PI) or non-nucleoside reverse transcriptase inhibitor (NNRTI) Cmin was determined just before and 12 weeks after ezetimibe introduction. Results:At week 24, 61.5% of patients achieved the endpoint of the study (LDL-cholesterol < 130 mg/dl). Significant declines in mean total and LDL-cholesterol levels were observed between baseline and weeks 6, 12, and 24, irrespective of antiretroviral type (PI or NNRTI). Mean HDL-cholesterol and apoprotein A increased significantly. No patients discontinued therapy due to intolerance or presented toxicity of grade 2 or more. No differences were observed in lopinavir or nevirapine Cmin measured just before and 12 weeks after ezetimibe introduction. Conclusion:The addition of ezetimibe to ongoing pravastatin seems to be an effective and safe option for HIV-infected patients not achieving the NCEP ATPIII LDL-cholesterol goals while receiving a statin alone. Its high tolerability and the lack of interactions with the cytochrome CYP3A4 indicate that ezetimibe will not increase the risk of toxicity or pharmacokinetic interactions with antiretrovirals.

High prevalence of human papillomavirus infection in the anus, penis and mouth in HIV-positive men.

Human papillomavirus (HPV) types are associated with squamous cell cancers. HIV infection is linked with a higher prevalence of anal HPV infection. It is important to assess whether HPV is present in other body parts involved in sexual practices to establish a cancer prevention program. A high prevalence of high-risk HPV types was present in the anus, penis and mouth (78, 36 and 30%, respectively) in a cohort of HIV-infected males (men who have sex with men and heterosexual), without evidence of pathology in these areas.

Efavirenz induces a striking and generalized increase of HDL-cholesterol in HIV-infected patients

This study analyses in depth lipid and lipoprotein changes in 20 HIV-infected patients on an efavirenz-containing regimen, either as initial therapy or as a substitute for a protease inhibitor. Total plasma lipids and the distribution of subclasses of lipoproteins were analysed at baseline and after 48 weeks by nuclear magnetic resonance spectroscopy, and showed a mean increase of 20% in HDL-cholesterol in both regimens. Up to 85% of patients significantly improved their atherogenic index (LDL/HDL ratio).

Early HCV dynamics on Peg-interferon and ribavirin in HIV/HCV co-infection: indications for the investigation of new treatment approaches

Objectives: To describe the 28-day hepatitis C virus (HCV) kinetics under Pegylated-interferon (Peg-IFN) + ribavirin (RBV) therapy in HIV/HCV co-infected patients. To evaluate the predictive value of early virological response (EVR) of achieving a sustained virological response (SVR). To investigate the baseline mutations in the interferon sensitivity determining region (ISDR)2209–2248 in the non-structural 5A protein of HCV according to genotype. Methods: Open, prospective trial including 28 co-infected patients with directly observed treatment with Peg-IFN + RBV. We assessed the predictive values of EVR (⩾ 2 log10 of HCV decay or a negative qualitative test) at days 1, 7, 28 and in week 12 of the SVR. Results: The SVR in an intention-to-treat analysis was 28.6% (genotype 1, 1/13; genotype 3, 6/10; genotype 4, 1/5). Patients who reached SVR presented a significantly faster HCV plasma viral load reduction compared to non-responders from the first 24 h [−1.06 log10 (interquartile range, −1.7 to −0.4) versus –0.05 log10 (interquartile range, −0.4 to +0.14) respectively; P = 0.002]. The median HCV viral load at week 12 was significantly different from that at baseline in responder and transient responders but not in non-responder patients. The positive predictive value was 100% within the first month and the best negative predictive value was 92% and 88.8% at weeks 4 and 12 respectively. The only genotype 1 responder patient had eight mutations in ISDR2209–2248. Conclusions: A very early HCV viral decay is observed in responder patients. An early virological response assessment at week 4 and 12 might be a useful tool in the clinical management of the co-infected population.

Significant reductions of HIV prevalence but not of hepatitis C virus infections in injection drug users from metropolitan Barcelona: 1987–2001

OBJECTIVES To characterize trends from 1987 to 2001 in the prevalence of HIV and HCV infections among 2219 injection drug users (IDUs) starting treatment for substance abuse in two large hospitals in metropolitan Barcelona. METHODS The study population comprised IDUs with HIV tests completed from 1987 to 2001 and admitted for detoxification. Testing for HCV started in 1991 (n=1132). Characterization of temporal trends was carried out using logistic regression methods. Stratification was used to describe possible heterogeneities of the temporal trends. RESULTS The overall prevalence of HIV, HCV, and HBV (HBsAg+) was 55%, 88%, and 7%, respectively. Adjusted by duration of IDU, sex, and age at initiation, the prevalence of HIV infection declined significantly (p<0.001) from 1989 to 2004. The substantially higher prevalence of HCV showed a decline (p=0.065) of lesser magnitude. The decline of HIV infection was consistently observed among those with duration of IDU of less than 10 years. In turn, the decline of HCV was restricted to those with short duration of IDU (<4 years) because the prevalence of HCV infection was close to 100% for durations longer than 4 years in all calendar periods. CONCLUSIONS Preventive interventions and treatment for substance abuse might have contributed to the waning of the HIV epidemic in Spain. However, the extremely high levels of HCV infection and the underlying prevalence of HIV might lead to a large health burden of liver disease.

Significado pronóstico de los valores de hemoglobina en pacientes con insuficiencia cardíaca

Introduccion y objetivos Evaluar el valor pronostico de las concentraciones de hemoglobina (Hb) en relacion con la mortalidad y con los ingresos hospitalarios por insuficiencia cardiaca (IC) al ano de la primera visita a la Unidad de IC. Pacientes y metodo Conocemos la situacion vital y los ingresos por IC al ano en 337 pacientes admitidos entre agosto de 2001 y marzo de 2003. Las concentraciones de Hb se recogieron en la primera visita. Resultados Fallecieron 28 (8%) pacientes y hubo 158 ingresos por IC en 66 pacientes. Los valores de Hb se asociaron con la mortalidad a 1 ano (pacientes vivos, 13,0 ± 1,7 g/dl; pacientes fallecidos, 11,6 ± 1,7 g/dl; p Conclusiones Los valores de Hb se asocian inversamente con la mortalidad y los ingresos por IC en el primer ano de seguimiento. La prevalencia de anemia en nuestra poblacion con IC es elevada y tiene valor pronostico independiente.

Presence and chromosomal subtyping of Legionella species in potable water systems in 20 hospitals of Catalonia, Spain.

OBJECTIVE To investigate the presence and clonal distribution of Legionella species in the water supply of 20 hospitals in Catalonia, Spain. SETTING 20 hospitals in Catalonia, an area of 32,000 km2, located in northeast Spain. METHODS Environmental cultures of 186 points of potable water supply and 10 cooling towers were performed for the presence of Legionella species. Following filtration and acid treatment, the samples were seeded in selective MWY (modified Wadowsky Yee)-buffered charcoal yeast extract-alpha agar. All isolates obtained were characterized microbiologically and genotyped by SfiI pulsed-field gel electrophoresis (PFGE). RESULTS 73 of 196 water samples, representing 17 of the 20 hospitals included in the study, were positive for Legionella pneumophila (serogroups 1, 2-14, or both). The degree of contamination ranged from 200 to 74,250 colony-forming units/L. Twenty-five chromosomal DNA subtypes were detected by PFGE. A single DNA subtype was identified in 10 hospitals, 2 DNA subtypes were observed in 6 hospitals, and 1 hospital exhibited 3 different DNA subtypes. Each hospital had its own Legionella DNA subtype, which was not shared with any other hospitals. CONCLUSIONS Legionella was present in the water of most of the hospitals studied; each such hospital had a unique, dominant chromosomal DNA subtype. The verification of several genomic DNA restriction profiles in such a small geographic area demonstrates the great genetic diversity of Legionella in the aquatic environment.

Lopinavir/ritonavir plus nevirapine as a nucleoside-sparing approach in antiretroviral-experienced patients (NEKA study).

Objectives: To compare the efficacy and safety of a nucleoside-sparing approach with a conventional highly active antiretroviral therapy (HAART) regimen in antiretroviral-experienced patients with prolonged viral suppression. Methods: Pilot study including 31 antiretroviral-experienced patients with HIV RNA <80 copies/mL. Subjects were randomly assigned to lopinavir/ritonavir (LPV/rtv) 400/100 mg BID plus nevirapine (NVP) 200 mg BID (NVP group, n = 16) or LPV/rtv plus the 2 previous NRTIs (NRTI group, n = 15). The primary endpoint was the percentage of subjects who maintained viral suppression at week 48. Changes in lipid metabolism, mitochondrial parameters, and LPV trough levels were also assessed. Results: All patients maintained viral suppression after 48 weeks. No subject discontinued therapy because of adverse events. HDL cholesterol increased by 28% at week 24 (P < 0.0001) and 10% after 48 weeks of follow-up (P = 0.319) in the NVP group. In the NRTI group, LDL cholesterol increased by 14% at week 48 (P = 0.076). Mitochondrial DNA/nuclear DNA ratio and mitochondrial respiratory chain complex IV activity showed a trend toward increasing in the NVP group. Mean (SD) LPV trough levels were 6340 (2129) ng/mL in the NRTI group and 5161 (2703) ng/mL in the NVP group (P = 0.140). Conclusions: In antiretroviral-experienced subjects with sustained viral suppression, dual therapy with NVP plus LPV/rtv at standard dosage was as potent and safe as standard-of-care HAART at 48 weeks of follow-up. This approach may reduce mitochondrial toxicity and improve LPV/rtv-associated lipid abnormalities. The results of this pilot study support the study of this approach in a larger, randomized trial.

Survival of HIV-Infected Injection Drug Users (IDUs) in the Highly Active Antiretroviral Therapy Era, Relative to Sex- and Age-Specific Survival of HIV-Uninfected IDUs

BACKGROUND In the era of highly active antiretroviral therapy (HAART), it remains unclear whether human immunodeficiency virus (HIV)-infected injection drug users (IDUs) have durations of survival similar to those for comparable HIV-uninfected IDUs. The goal of this study was to compare survival durations of HIV-infected and HIV-uninfected IDUs for the period 1987-2004.Methods. Demographic data, drug use characteristics, and biological markers were obtained at the time of admission to a substance abuse treatment program. The outcome of interest was the duration of survival after admission, and the primary exposure was HIV infection. Vital status was ascertained by means of the mortality register by the end of 2004. Three calendar periods, which were defined on the basis of use of specific therapies, were considered: 1987-1991 (the antiretroviral monotherapy era), 1992-1996 (the dual combination therapy era and the era when methadone was introduced in Spain), and 1997-2004 (the era of HAART and of established methadone programs). We used Cox regression methods allowing for late entries to handle the contribution of persons who survived a given period and entered the following period with nonzero time. We compared HIV-uninfected and HIV-infected IDUs with adjustments for age, sex, and duration of follow-up after admission. RESULTS A total of 1209 IDUs were admitted to the hospital during the period from January 1987 through December 2004, and 1181 were eligible for the study. The majority (81.3%) of patients were men. The mean age (+/- standard deviation) at admission was 27.8+/-5.6 years, and the mean duration of injection drug use (+/- standard deviation) was 7.6+/-5.0 years. The prevalences of HIV and hepatitis C virus infections were 59.0% and 92.3%, respectively, and the total duration of follow-up was 10.116 person-years. Although survival duration for HIV-uninfected IDUs in 1997-2004 was similar to the duration in earlier periods, the duration for HIV-infected IDUs improved significantly since 1997 (P<.01). Furthermore, among patients admitted in the last period, the survival durations for HIV-uninfected and HIV-infected IDUs was virtually the same (relative hazard, 0.89; 95% confidence interval, 0.44-1.81). CONCLUSIONS The duration of survival of HIV-infected IDUs has improved substantially since 1997, reaching rates similar to the rates for HIV-seronegative IDUs who accessed the health care system in the era of HAART.