Association of Patients' Geographic Origins with Viral Hepatitis Co-infection Patterns, Spain.

To determine if hepatitis C virus seropositivity and active hepatitis B virus infection in HIV-positive patients vary with patients' geographic origins, we studied co-infections in HIV-seropositive adults. Active hepatitis B infection was more prevalent in persons from Africa, and hepatitis C seropositivity was more common in persons from eastern Europe.

Delayed diagnosis of HIV infection in a multicenter cohort: prevalence, risk factors, response to HAART and impact on mortality.

To study the prevalence of Delayed HIV Diagnosis (DHD) and its associated risk factors, to evaluate the effect of DHD on virological and immunological responses to HAART and to estimate the impact of DHD on all-causes mortality. Prospective cohort of 2, 564 HIV-positive HAART-naïve subjects attending 19 hospitals in Spain, 2004-2006. Estimations were made by logistic regression and survival analyses by Cox regression models. Prevalence of DHD was 37.3% (35.0-39.6). DHD was related to low educational level (OR:1.31, 95% CI:1.0-1.7). Compared to men who have sex with men (MSM), DHD was more frequent in heterosexuals (OR:1.9 95% CI:1.5-2.5) and injection drug users (IDUs) (OR:2.0 95% CI:1.5-2.8). An interaction between age and sex was found. Although risk of having DHD did not increase after age 30 in women, it increased linearly with age in men. No differences in virological (OR 1.2 95% CI: 0.8-1.8) and CD4 T cell (OR 1.1 95% CI: 0.7-1.8) responses to HAART were seen. The adjusted hazard ratio for death in patients with DHD was 5.2, (95% CI: 1.9-14.5). DHD is very common, especially in older men, heterosexuals and IDUs. Although we did not find differences in virological and immunological responses to HAART, we did observe higher mortality in people with DHD. Increased efforts to early diagnose HIV infection are urgently needed.

Safety of Switching Nevirapine Twice Daily to Nevirapine Once Daily in Virologically Suppressed Patients.

BACKGROUND: The strategy of switching nevirapine (NVP) twice daily to once daily was evaluated. METHODS: Forty-eight-week randomized, open, multicenter trial. Stable HIV-infected patients on NVP twice daily for >12-18 weeks with alanine aminotransferase (ALT) <2.5, the upper normal limit were randomized to continue their regimen or switch to NVP 400 mg once daily. Primary end point was the proportion of ALT/aspartate transaminase (AST) > or =grade 3. RESULTS: Two hundred eighty-nine patients were included, mean CD4 620 cells per microliter. Noninferiority was demonstrated in the per protocol analysis, with 97.9% (once daily) and 99.3% (twice daily) of patients event free (difference, 1.4%; 95% confidence interval, -1.95% to 5.4%), whereas 81.8% vs. 93.8% were event free by intent-to-treat switch = toxicity analysis (difference, 12%; 95% confidence interval, 4.6% to 19.4%). Only 4 patients (3 once daily, 1 twice daily) had NVP-related grade 3/4 ALT/AST increases, but in 2 of them (once daily), transaminases decreased despite continuation with NVP. Two other once daily patients presented grade 3/4 ALT/AST increase due to well-documented acute hepatitis A virus or hepatitis C virus infection. Grade 2 ALT/AST increases occurred in 11.2% (once daily) vs. 10.3% (twice daily) of patients (P = 0.80). A larger number of once daily patients were lost to follow-up/violated protocol (15% vs. 5%). CONCLUSIONS: In patients on standard twice daily NVP-containing regimens for at least 12-18 weeks, per protocol analysis showed that switching to once daily NVP was not inferior to continued twice daily NVP in terms of the predefined noninferiority margin of 10% for hepatotoxicity.

[Current infectious disease care in Spain]. / La asistencia infectológica actual en España.

Despite the specialist activity of Infectious Diseases not being officially recognised, the majority of the hospitals in the autonomous communities of Spain are equipped with structures, with significant heterogeneity among them, to be able to offer high quality care in these diseases. The main characteristics of and Infectious Diseases Department is its important healthcare activity, more than in other officially recognised medical specialities, and also its important interrelationship with other services in the hospital which is clearly horizontal healthcare. Furthermore, the aforementioned infectious disease care units have developed important activities in the arena of community and public health and, in collaboration with health authorities, contribute to the rational use of antimicrobials and the relationship with Primary Care. The future of specialists in infectious diseases, when they are officially recognised, will be the creation of clinical management units in every health institution with the objective of coordinating all the specialised health care, both in the hospital environment and in its health area of influence.

Efficacy and safety of a once daily regimen with efavirenz, lamivudine, and didanosine, with and without food, as initial therapy for HIV Infection: the ELADI study.

The combination of didanosine (ddI) and lamivudine (3TC) is attractive considering its low cost, potency, tolerability, and convenience (once daily administration), but it is not recommended as first-line therapy for HIV infection. A prospective, multicenter, open, comparative trial was conducted in HIV-infected, antiretroviral-naive persons in Spain who begun a QD regimen with efavirenz (EFV), 3TC, plus ddI, the latter with or without food. A total of 103 patients were recruited in the study. Median baseline CD4 count was 229 cells/microl and plasma HIV-RNA was 4.9 logs copies/ml. In an intent-to-treat analysis, 78 (75.8%) had undetectable viremia at week 48 of therapy, without significant differences when comparing patients on and without fasting ddI (75% vs. 76.6%, respectively). The mean CD4 increase was of 199 cells/microl, with no significant differences between groups. Overall, 29 adverse events were recorded in 23 patients, the majority associated with neuropsychiatric symptoms of EFV. Treatment was discontinued in 10 (9.7%) patients due to adverse events. Virological failure was recognized in only six patients, four taking ddI with and two without food (p = 0.3). Drug resistance mutations were recognised in four of them. Plasma ddI concentrations did not differ significantly between groups. Mitochondrial DNA within peripheral blood mononuclear cells tended to increase in most subjects over 48 weeks of therapy regardless of treatment group. A QD regimen with ddI, 3TC, and EFV shows potency and tolerance similar to that reported using other currently recommended regimens in drug-naive HIV-infected patients. Its efficacy does not seem to be compromised when ddI is administered with food. Therefore, this regimen merits further investigation in larger comparative trials.

Premature treatment discontinuation in HIV/HCV-coinfected patients receiving pegylated interferon plus weight-based ribavirin.

BACKGROUND: Chronic hepatitis C therapy in HIV patients is often penalized by more frequent premature treatment discontinuations. It is unclear what the relative contribution of more adverse events and/or early virological failures are. METHODS: PRESCO was a prospective, multicentre, comparative trial, in which 389 HIV/HCV-coinfected patients with CD4+ T-cell counts >300 cells/ml and elevated aminotransferases received pegylated interferon-alpha2a (peg IFN-alpha2a) 180 mg per week plus ribavirin (RBV) 1,000-1,200 mg daily. Patients with HCV genotypes 1 or 4 were treated for 48 or 72 weeks while HCV genotypes 2 or 3 carriers were treated for 24 or 48 weeks. Use of didanosine was not allowed. RESULTS: Sustained virological response (SVR) was achieved by 193 (49.6%), and was significantly greater in HCV-2/3 than in HCV-1/4 patients (72.4% versus 35%; P<0.0001). Premature treatment discontinuations occurred in 174 patients (44.7%). This was due to early virological failure in 66 (17%), serious adverse events in 32 (8.2%), loss-to-follow-up in 12 (3.1%) and voluntary withdrawal in 64 (16.4%). Only 10 patients (2.6%) stopped HCV therapy due to severe anaemia. Two patients stopped HCV medication due to symptomatic mitochondrial toxicity. There were no episodes of hepatic decompensation. CONCLUSIONS: Treatment with RBV 1,000-1,200 mg/day plus peg IFN-alpha2a is relatively safe and provided SVR in nearly half of the HIV/HCV-coinfected patients, twice as many amongst the HCV-2/3 than HCV-1/4 carriers. Avoidance of didanosine, limited use of zidovudine and therapy restricted to patients with CD4+ T-cell counts >300 cells/ml most probably explains the lower and different spectrum of serious adverse events in PRESCO compared with prior trials conducted in coinfected patients.

Role of weight-based ribavirin dosing and extended duration of therapy in chronic hepatitis C in HIV-infected patients: the PRESCO trial.

The response to pegylated interferon (pegIFN) plus ribavirin (RBV) as treatment of chronic hepatitis C virus (HCV) infection is lower in HIV-coinfected than in HCV-monoinfected patients and could be due to suboptimal RBV dosing and/or insufficient duration of therapy in prior trials. In a prospective, multicenter, open, comparative trial, HCV/HIV-coinfected patients received pegIFN plus weight-based RBV for 48 or 72 weeks (HCV genotypes 1 and 4) and 24 or 48 weeks (HCV genotypes 2 and 3). Use of didanosine was not allowed. Out of 389 patients included in the trial, 61% were infected by HCV-1/4 and 67% had serum HCV-RNA >500,000 IU/ml. Sustained virological response (SVR) was achieved by 49.6%, significantly higher in HCV-2/3 than HCV-1/4 (72.4% vs. 35%; p < 0.0001). A high drop-out rate in the longer treatment arms precluded obtaining definitive conclusions about the efficacy of prolonging therapy. Premature treatment discontinuations due to serious adverse events occurred in 8.2%. Infection with HCV-2/3, lower baseline HCV-RNA, and negative HCV-RNA at week 12 were all independent predictors of SVR in the multivariate analysis. The use of RBV 1000-1200 mg/day plus pegIFN is relatively safe and provides SVR in nearly half of coinfected patients, twice as high in HCV-2/3 than HCV-1/4.

Baseline serum hepatitis C virus (HCV) RNA level and response at week 4 are the best predictors of relapse after treatment with pegylated interferon plus ribavirin in HIV/HCV-coinfected patients.

BACKGROUND: Relapse after achieving virologic response to anti-hepatitis C virus (HCV) treatment considerably reduces sustained virologic response rates. It is unclear what the main predictors of relapse in HCV/HIV-coinfected patients are. PATIENTS AND METHODS: The Pegasys Ribavirina España Coinfección (PRESCO) study evaluated short and extended duration of treatment for chronic hepatitis C using pegylated interferon (peg-IFN)-alpha2a at a dose of 180 microg/wk plus weight-based ribavirin (RBV) at a dose of 1000 to 1200 mg/d in HIV-infected subjects. Patients with HCV-2/3 were treated for 6 or 12 months, and patients with HCV-1/4 were treated for 12 or 18 months. RESULTS: Of 389 patients included in the trial, end-of-treatment response was achieved by 262 (67.3%): 106 with HCV-1 (55%), 137 with HCV-2/3 (90%), and 19 with HCV-4 (41%). Six patients were lost to follow-up after completing therapy. Of the remaining 256 patients, 62 (24%) relapsed: 33% of HCV-1 patients, 18% of HCV-2/3 patients, and 21% of HCV-4 patients. In multivariate logistic regression analysis, baseline serum HCV RNA level > or =500,000 IU/mL (relative risk [RR] = 4.81, 95% confidence interval [CI]: 1.52 to 15.22; P = 0.008) and lack of rapid virologic response, defined as undetectable HCV RNA level at week 4 (RR = 2.94, 95% CI: 1.22 to 7.09; P = 0.02) were the best independent predictors of HCV relapse. Use of concomitant antiretroviral therapy also predicted relapse (P = 0.04), and a trend toward a higher relapse rate was recognized for HCV genotypes 1 and 4 versus genotypes 2 and 3 (P = 0.08). Extended treatment did not result in a lower incidence of relapse, at least for HCV genotypes 2 and 3. CONCLUSION: High baseline serum HCV RNA level and lack of undetectable viremia at week 4 are the most significant predictors of relapse in HCV/HIV-coinfected patients treated with peg-IFN plus weight-based RBV.