José A. Pérez-Molina

Safety and Tolerance of Efavirenz in Different Antiretroviral Regimens: Results from a National Multicenter Prospective Study in 1,033 HIV-Infected Patients

Abstract Purpose: To evaluate the incidence and severity of adverse events (AEs) and treatment interruption (TI) with efavirenz in a population with a high rate of intravenous drug use (IVDU). Method: This was a national, multicenter, and observational study of HIV-infected adult patients who were starting an efavirenz-containing regimen. Evaluations of AEs were made in routine clinical practice at baseline and at least 3 months later. A total of 1,033 patients were included from 60 participating hospitals; 20% were antiretroviral naive. The risk factor for HIV infection was IVDU in 62.3%, and 6.6% of participants were on methadone. Results: AEs affected 29.3% of participants, and treatment was interrupted in 8.23%. The most frequent AEs were CNS disturbances that affected 24.1% participants; these AEs were considered related to efavirenz in 18.5% patients. AEs were not severe, and treatment had to be interrupted in 6% of patients. Other AEs were cutaneous rash (incidence of 5.9%; 2.4% of TI), gastrointestinal disturbances (1.45%; no TI), and elevation of liver function test (0.68%; no TI). Patients taking methadone had more AEs (39.7%), mainly CNS disturbances, and TI (19.1%). Cutaneous rash was more frequent among women. Psychoactive drug consumption, previous history of psychiatric disorders, antiretroviral experience, or previous nevirapine intolerance were not associated with higher incidence of AEs. Conclusion: Safety and tolerance of efavirenz is good in most patients, even in a population with a high rate of IVDU. The most common AEs are CNS disturbances; they are not severe and rarely lead to TI.

Workload Due to Aspergillus fumigatus and Significance of the Organism in the Microbiology Laboratory of a General Hospital

ABSTRACT The increase in the immunocompromised population and the incidence of invasive aspergillosis (IA) are leading to an overinterpretation of the potential clinical significance of many isolates of Aspergillus fumigatus. Our work prospectively assesses the workload of the isolation of A. fumigatus and its clinical significance in the microbiology laboratory of a large teaching hospital. During a 3-year period, all patients from whom A. fumigatus was isolated were prospectively monitored and classified as having IA or “nonsignificant” disease. A point score based on the prediction of five easily obtained laboratory and clinical parameters was applied. We found 404 A. fumigatus isolates in 260 patients (1/1,000 microbiology laboratory samples; 2.1 patients/10,000 admissions). A total of 90 isolates (22.3%) were from patients with IA. Of the 260 patients, 31 (12%) had invasive disease (IA), and the remaining 229 had “nonsignificant” disease. A score based on points for five parameters was applied to our population. It was constructed as follows: “sample obtained by invasive procedures” (1 point), “presence of two or more positive samples from the same patient” (1 point), “leukemia” (2 points), “neutropenia” (5 points), and “corticosteroid treatment” (2 points). Patients with a score of 0 had only a 2.5% probability of IA. Those with a score of 1 or 2 had an increased probability of 10.3%. The probabilities rose to 40% and 70%, respectively, for patients with a score of 3 or 4 or a score of ≥5. A simple score based on five easily available parameters may be of help to microbiologists and clinicians to predict the risk of IA.

Guidelines on the Treatment of Chronic Coinfection by Trypanosoma cruzi and HIV Outside Endemic Areas

Abstract As a result of population migration, Chagas disease is no longer limited to the North and South American continents. In HIV-infected patients, chronic infection by Try-panosoma cruzi behaves as an opportunistic infection in severely immunosuppressed patients and is responsible for high morbidity and mortality. Unlike other opportunistic infections, information on the natural history, diagnosis, treatment, and prevention of Chagas disease is scarce. Spain has the highest number of cases of Chagas disease outside the North and South American continents, and coinfection with HIV is increasingly prevalent. In this article, the Spanish Society for Tropical Medicine and International Health (Sociedad Española de Medicina Tropical y Salud Interna-cional) reviews the current situation of coinfection with HIV and T. cruzi infection and provides guidelines on the diagnosis, treatment, and prevention in areas where Cha-gas disease is not endemic. It also identifies areas of uncertainty where additional research is necessary.

Didanosine, Lamivudine, and Efavirenz versus Zidovudine, Lamivudine, and Efavirenz for the Initial Treatment of HIV Type 1 Infection : Final Analysis (48 Weeks) of a Prospective, Randomized, Noninferiority Clinical Trial, GESIDA 3903

BACKGROUND The combination of didanosine, lamivudine, and efavirenz (ddI/3TC/EFV) for the initial treatment of human immunodeficiency virus type 1 (HIV-1) infection has been insufficiently analyzed in clinical trials. METHODS We conducted an open-label, randomized study to compare the noninferiority of ddI/3TC/EFV with the lamivudine-zidovudine tablet and EFV (COM/EFV), both administered with food to improve tolerability and convenience. Patients were stratified by HIV-1 RNA level of <5.0 log(10) or > or =5.0 log(10) copies/mL. The primary end point was the percentage of patients with an HIV-1 RNA level of <50 copies/mL at week 48, determined by intention-to-treat analysis. RESULTS Three hundred sixty-nine patients were randomized: 186 for ddI/3TC/EFV treatment and 183 for COM/EFV treatment. Both groups were well matched in terms of baseline characteristics; 19.3% of patients received a Centers for Disease Control and Prevention assessment of clinical category C, median HIV RNA level was 5.0 log(10) copies/mL, and median CD4(+) cell count was 208 cells/microL. At week 48, by intention-to-treat analysis, 70% of patients in the ddI/3TC/EFV group and 63% of patients in the COM/EFV group had an HIV-1 RNA level of <50 copies/mL (treatment difference, 7.1%; 95% confidence interval, -2.39% to 16.59%). Fourteen patients (8%) in the ddI/3TC/EFV arm (not the COM/EFV arm) and 26 patients (14%) in the COM/EFV arm (not the ddI/3TC/EFV arm) [corrected] discontinued the study medication because of adverse events (P = .046). One patient (1%) in the ddI/3TC/EFV arm and 11 patients (6%) in the COM/EFV arm discontinued medication because of hematological toxicity (P = .003). CONCLUSIONS At week 48, ddI/3TC/EFV administered once per day with food did not have results inferior to those of COM/EFV treatment. A statistically significantly higher proportion of patients in the COM/EFV arm than in the ddI/3TC/EFV arm discontinued therapy because of adverse events, mainly because of hematological toxicity. CLINICAL TRIALS REGISTRATION NCT00256828.

Cases of chikungunya virus infection in travellers returning to Spain from Haiti or Dominican Republic, April-June 2014.

Ten cases of chikungunya were diagnosed in Spanish travellers returning from Haiti (n=2), the Dominican Republic (n=7) or from both countries (n=1) between April and June 2014. These cases remind clinicians to consider chikungunya in European travellers presenting with febrile illness and arthralgia, who are returning from the Caribbean region and Central America, particularly from Haiti and the Dominican Republic. The presence of Aedes albopictus together with viraemic patients could potentially lead to autochthonous transmission of chikungunya virus in southern Europe.

Response to Combined Antiretroviral Therapy According to Gender and Origin in a Cohort of Naïve HIV-Infected Patients: GESIDA-5808 Study

Abstract Background: We analyzed differences in response to combined antiretroviral therapy (cART) according to sex and geographic origin in a retrospective comparative study of Spanish-born and immigrant patients initiating cART. Methods: The primary endpoint was time to treatment failure (TTF), defined as virological failure, death, opportunistic infection, interruption of cART, or loss to follow-up. Late diagnosis was defined as a CD4+ cell count ≤ 200 cells/mm3 and/or AIDS at initiation of cART. Survival was analyzed using Kaplan-Meier analysis and Cox regression. Results: We followed 1,090 patients, of whom 318 were women (45.6% immigrant women [IW]). At initiation of treatment, women had a higher CD4+ count than men (217 vs 190 cells/mm3), a lower viral load (4.7 vs 5 log), and fewer were late starters (49% vs 59%). The adjusted risk of TTF between women and men was not significantly different (hazard ratio [HR], 1.10; 95% CI, 0.79-1.53). TTF was shorter among IW than Spanish-born women (124 weeks [95% CI, 64-183] vs 151 [95% CI, 127-174]) and loss to follow-up was double that of Spanish-born women (25.5% vs 11.6%). Conclusions: Although response to cART was similar for both sexes, men started treatment later. IW were more frequently lost to follow-up and switched treatment. Measures to improve medical follow-up after initiation of cART should be promoted among this minority group.

Late Initiation of HAART Among HIV-Infected Patients in Spain Is Frequent and Related to a Higher Rate of Virological Failure but not to Immigrant Status

Abstract Purpose: To determine whether immigrant status is associated with late initiation of highly active antiretroviral treatment (HAART) and/or poor response to antiretrovirals. Methods: GESIDA 5808 is a multicenter, retrospective cohort study (inclusion period January 2005 through December 2006) of treatment-naïve patients initiating HAART that compares HIV-infected patients who are immigrants with Spanish-born patients. A late starter (LS) was defined as any patient starting HAART with a CD4+ lymphocyte count <200 cells/μL and/or diagnosis of an AIDS-defining illness before or at the start of therapy. The primary endpoint was time to treatment failure (TTF), defined as virological failure (VF), death, opportunistic infection, treatment discontinuation/switch (D/S), or missing patient. Secondary endpoints were time to treatment failure as observed data (TTO; censoring missing patients) and time to virological failure (TVF; censoring missing patients and D/S not due to VF). Results: LS accounted for 56% of the patients. Lower educational and socioeconomic level and intravenous drug use (IVDU) were associated with categorization as LS, but immigrant status was not. Cox regression analysis (hazard ratio [HR]; 95% CI) between LS and non-LS patients showed no differences in TTF (0.97; 0.78–1.20) or TTO (1.18; 0.88–1.58), although it did reveal a difference in TVF (1.97; 1.18–3.29). CD4+ lymphocyte recovery was equivalent for both LS and non-LS patients (159 vs 173). Conclusions: In our cohort, immigrant status was not shown to be related to late initiation of HAART. Although LS patients did not have a longer TTF for any reason, TVF was significantly shorter. Despite universal free access to HAART in Spain, measures to ensure early diagnosis and treatment of HIV infection are necessary.

Differential characteristics of HIV-infected penitentiary patients and HIV-infected community patients

Abstract PURPOSE: To identify particular characteristics of HIV+ patients from correctional facilities (CF) compared with an HIV+ population from the community to better detect variables for intervention. METHOD: In our hospital, HIV+ patients are admitted to an infectious diseases ward (IDW) when they come from the community or to a penitentiary unit (PU) when they are transferred from CF. We retrospectively reviewed admissions of those patients in both areas during 1999. RESULTS: Admissions of HIV+ patients to IDW and PU generate 2.3% and 53.4% of hospital and PU stays, respectively. Both populations were equivalent in terms of mean age, CD4 count, viral load, prophylaxis for opportunistic infections, average stay, and death during stay. Male sex (91% vs. 74%), previous or current intravenous drug use (88% vs. 77%), and hepatitis C virus (HCV) seropositivity (97% vs. 82.6%) were more frequent in the PU than in the IDW. Multivariate analysis identified three factors as being independently related to admission from prison: longer time of known HIV infection (average 3.3 years; 95% CI 1.9-4.6), no previous antiretroviral treatment (odds ratio [OR] 2.95; 95% CI 1.46-6.0), and admission due to tuberculosis (OR 2.5; 95% CI 1.03-6.0). CONCLUSION: HIV infection is still a serious medical problem in CF. Although imprisonment can provide access to health programs, HIV-infected prison patients suffer more frequently from tuberculosis and take less antiretroviral treatment.

Nelfinavir Plus Nevirapine Plus Two NRTIs As Salvage Therapy for HIV-Infected Patients Receiving Long-Term Antiretroviral Treatment

Abstract Purpose: To evaluate a rescue therapy involving nevirapine plus nelfinavir plus two nucleoside reverse transcriptase inhibitors (NRTIs) in patients with prior extensive antiretroviral therapy (AT) including protease inhibitors (PIs) but not nonnucleoside reverse transcriptase inhibitors (NNRTIs). Method: Patients with failing regimens were prospectively enrolled. According to genotypic profile at baseline, two groups were identified: a highly resistant (HR) group, which included strains resistant to PI and NRTI, and a moderate nonresistant group (MR), which showed resistance only to PI or NRTI or no resistance. Results: Twenty-two individuals were included. Average time of AT prior to enrollment was 3.7 years (range 1.4-7.6), median viral load 4.92 log10 (interquartile range [IQR] 1.63 log10), and median CD4 cell count 64 cells/μL (IQR 94). After 16 weeks of treatment, seven patients (31%) achieved virological response, five of them (22.7%) with <500 c/mL (bDNA). Fourteen patients were studied for resistance. The HR group showed a poorer response than the MR group (0 vs. 7 responses; p = .034). Conclusion: We found a virological response in 31% of our patients, and mainly in those of the MR group some presented previous intolerance. These two factors probably reflect the number of drugs included in the rescue therapy to which the patient is sensitive. Treatment history as well as genotypic resistance assays are useful in identifying patients with the best chance of responding.