Real-world effectiveness and durability of dual antiretroviral therapy in HIV-infected patients.

BACKGROUND AND OBJECTIVES: While randomised controlled trials in HIV-infected patients have shown that certain dual antiretroviral therapy (DAT) regimens are non-inferior in terms of efficacy compared with classical triple-drug regimens, few real clinical experiences have been described. The aim of the study was to investigate, in real clinical practice, DAT effectiveness, durability, and risk factors for treatment discontinuation. METHODS: This was a prospective cohort study that included HIV-infected patients treated with DAT (2015-2020). DAT was considered effective when patients achieved or maintained virological suppression and was assessed at 24 and 48 weeks. DAT durability was evaluated using the Kaplan-Meier method. Adherence and treatment cost were compared with patients' previous antiretroviral regimens. RESULTS: 51 patients were included, 27.5% with HIV-1 RNA ≥50 copies/mL at baseline, treated with a wide range of dual combinations. At 48 weeks follow-up, 83.8% and 50.0% of patients who started DAT with HIV-1 RNA <50 copies/mL and ≥50 copies/mL, respectively, were suppressed. 39 out of 51 patients (76.5%) maintained DAT for a mean treatment duration of 40.5±14.8 weeks. Full adherence was observed in 78.4% of patients compared with 70.2% in the previous regimen. Mean daily cost was €18.6±4.3 compared with €16.1±7.9 in the previous regimen (p=0.008). CONCLUSION: DAT effectiveness and durability were higher in patients who were virologically suppressed at baseline. DAT is a possible alternative for virologically non-suppressed patients who cannot be treated with a triple-drug regimen.

Sociodemographic, clinical, and immunological factors associated with SARS-CoV-2 diagnosis and severe COVID-19 outcomes in people living with HIV: a retrospective cohort study.

BACKGROUND: Factors affecting outcomes of SARS-CoV-2 infection in people living with HIV are unclear. We assessed the factors associated with SARS-CoV-2 diagnosis and severe outcomes among people living with HIV. METHODS: We did a retrospective cohort study using data from the PISCIS cohort of people with HIV in Catalonia (Spain) between March 1 and Dec 15, 2020. We linked PISCIS data with integrated health-care, clinical, and surveillance registries through the Public Data Analysis for Health Research and Innovation Program of Catalonia (PADRIS) to obtain data on SARS-CoV-2 diagnosis, chronic comorbidities, as well as clinical and mortality outcomes. Participants were aged at least 16 years in care at 16 hospitals in Catalonia. Factors associated with SARS-CoV-2 diagnoses and severe outcomes were assessed using univariable and multivariable Cox regression models. We estimated the effect of immunosuppression on severe outcomes (hospital admission for >24 h with dyspnoea, tachypnoea, hypoxaemia, asphyxia, or hyperventilation; or death) using Kaplan-Meier survival analysis. FINDINGS: We linked 20 847 (72·8%) of 28 666 participants in the PISCIS cohort with PADRIS data; 13 142 people had HIV. 749 (5·7%) people with HIV were diagnosed with SARS-CoV-2: their median age was 43·5 years (IQR 37·0-52·7), 131 (17·5%) were female, and 618 (82·5%) were male. 103 people with HIV (13·8%) were hospitalised, seven (0·9%) admitted to intensive care, and 13 (1·7%) died. SARS-CoV-2 diagnosis was more common among migrants (adjusted hazard ratio 1·55, 95% CI 1·31-1·83), men who have sex with men (1·42, 1·09-1·86), and those with four or more chronic comorbidities (1·46, 1·09-1·97). Age at least 75 years (5·2, 1·8-15·3), non-Spanish origin (2·1, 1·3-3·4), and neuropsychiatric (1·69, 1·07-2·69), autoimmune disease (1·92, 1·14-3·23), respiratory disease (1·84, 1·09-3·09), and metabolic disease (2·59, 1·59-4·23) chronic comorbidities were associated with increased risk of severe outcomes. A Kaplan-Meier estimator showed differences in the risk of severe outcomes according to CD4 cell count in patients with detectable HIV RNA (p=0·039) but no differences were observed in patients with undetectable HIV RNA (p=0·15). INTERPRETATION: People living with HIV with detectable HIV viraemia, chronic comorbidities, and some subpopulations could be at increased risk of severe outcomes from COVID-19. These groups should be prioritised in clinical management and SARS-CoV-2 vaccination programmes. FUNDING: Fundació "la Caixa". TRANSLATIONS: For the Catalan, Spanish and Russian translations of the Summary see Supplementary Materials section.

Estimating the HIV undiagnosed population in Catalonia, Spain: descriptive and comparative data analysis to identify differences in MSM stratified by migrant and Spanish-born population.

OBJECTIVE: Undiagnosed HIV continues to be a hindrance to efforts aimed at reducing incidence of HIV. The objective of this study was to provide an estimate of the HIV undiagnosed population in Catalonia and compare the HIV care cascade with this step included between high-risk populations. METHODS: To estimate HIV incidence, time between infection and diagnosis and the undiagnosed population stratified by CD4 count, we used the ECDC HIV Modelling Tool V.1.2.2. This model uses data on new HIV and AIDS diagnoses from the Catalan HIV/AIDS surveillance system from 2001 to 2013. Data used to estimate the proportion of people enrolled, on ART and virally suppressed in the HIV care cascade were derived from the PISCIS cohort. RESULTS: The total number of people living with HIV (PLHIV) in Catalonia in 2013 was 34 729 (32 740 to 36 827), with 12.3% (11.8 to 18.1) of whom were undiagnosed. By 2013, there were 8458 (8101 to 9079) Spanish-born men who have sex with men (MSM) and 2538 (2334 to 2918) migrant MSM living with HIV in Catalonia. A greater proportion of migrant MSM than local MSM was undiagnosed (32% vs 22%). In the subsequent steps of the HIV care cascade, migrants MSM experience greater losses than the Spanish-born MSM: in retention in care (74% vs 55%), in the proportion on combination antiretroviral treatment (70% vs 50%) and virally suppressed (65% vs 46%). CONCLUSIONS: By the end of 2013, there were an estimated 34 729 PLHIV in Catalonia, of whom 4271 were still undiagnosed. This study shows that the Catalan epidemic of HIV has continued to expand with the key group sustaining HIV transmission being MSM living with undiagnosed HIV.

Human Immunodeficiency Virus/Hepatits C Virus Coinfection in Spain: Elimination Is Feasible, but the Burden of Residual Cirrhosis Will Be Significant.

BACKGROUND: We assessed the prevalence of antibodies against hepatitis C virus (HCV-Abs) and active HCV infection in patients infected with human immunodeficiency virus (HIV) in Spain in 2016 and compared the results with those of similar studies performed in 2002, 2009, and 2015. METHODS: The study was performed in 43 centers during October-November 2016. The sample was estimated for an accuracy of 2% and selected by proportional allocation and simple random sampling. During 2016, criteria for therapy based on direct-acting antiviral agents (DAA) were at least significant liver fibrosis, severe extrahepatic manifestations of HCV, and high risk of HCV transmissibility. RESULTS: The reference population and the sample size were 38904 and 1588 patients, respectively. The prevalence of HCV-Abs in 2002, 2009, 2015, and 2016 was 60.8%, 50.2%, 37.7%, and 34.6%, respectively (P trend <.001, from 2002 to 2015). The prevalence of active HCV in 2002, 2009, 2015, and 2016 was 54.0%, 34.0%, 22.1%, and 11.7%, respectively (P trend <.001). The anti-HCV treatment uptake in 2002, 2009, 2015, and 2016 was 23.0%, 48.0%, 59.3%, and 74.7%, respectively (P trend <.001). In 2016, HCV-related cirrhosis was present in 7.6% of all HIV-infected individuals, 15.0% of patients with active HCV, and 31.5% of patients who cleared HCV after anti-HCV therapy. CONCLUSIONS: Our findings suggest that with universal access to DAA-based therapy and continued efforts in prevention and screening, it will be possible to eliminate active HCV among HIV-infected individuals in Spain in the short term. However, the burden of HCV-related cirrhosis will continue to be significant among HIV-infected individuals.

Safe Reduction in CD4 Cell Count Monitoring in Stable, Virally Suppressed Patients With HIV Infection or HIV/Hepatitis C Virus Coinfection.

BACKGROUND: It has been suggested that routine CD4 cell count monitoring in human immunodeficiency virus (HIV)-monoinfected patients with suppressed viral loads and CD4 cell counts >300 cell/µL could be reduced to annual. HIV/hepatitis C virus (HCV) coinfection is frequent, but evidence supporting similar reductions in CD4 cell count monitoring is lacking for this population. We determined whether CD4 cell count monitoring could be reduced in monoinfected and coinfected patients by estimating the probability of maintaining CD4 cell counts ≥200 cells/µL during continuous HIV suppression. METHODS: The PISCIS Cohort study included data from 14 539 patients aged ≥16 years from 10 hospitals in Catalonia and 2 in the Balearic Islands (Spain) since January 1998. All patients who had at least one period of 6 months of continuous HIV suppression were included in this analysis. Cumulative probabilities with 95% confidence intervals were calculated using the Kaplan-Meier estimator stratified by the initial CD4 cell count at the period of continuous suppression initiation. RESULTS: A total of 8695 patients were included. CD4 cell counts fell to <200 cells/µL in 7.4% patients, and the proportion was lower in patients with an initial count >350 cells/µL (1.8%) and higher in those with an initial count of 200-249 cells/µL (23.1%). CD4 cell counts fell to <200 cells/µL in 5.7% of monoinfected and 11.1% of coinfected patients. Of monoinfected patients with an initial CD4 cell count of 300-349 cells/µL, 95.6% maintained counts ≥200 cells/µL. In the coinfected group with the same initial count, this rate was lower, but 97.6% of coinfected patients with initial counts >350 cells/µL maintained counts ≥200 cells/µL. CONCLUSIONS: From our data, it can be inferred that CD4 cell count monitoring can be safely performed annually in HIV-monoinfected patients with CD4 cell counts >300 cells/µL and HIV/HCV-coinfected patients with counts >350 cells/µL.

Factors Associated with Influenza Vaccination of Hospitalized Elderly Patients in Spain.

Vaccination of the elderly is an important factor in limiting the impact of influenza in the community. The aim of this study was to investigate the factors associated with influenza vaccination coverage in hospitalized patients aged ≥ 65 years hospitalized due to causes unrelated to influenza in Spain. We carried out a cross-sectional study. Bivariate analysis was performed comparing vaccinated and unvaccinated patients, taking in to account sociodemographic variables and medical risk conditions. Multivariate analysis was performed using multilevel regression models. We included 1038 patients: 602 (58%) had received the influenza vaccine in the 2013-14 season. Three or more general practitioner visits (OR = 1.61; 95% CI 1.19-2.18); influenza vaccination in any of the 3 previous seasons (OR = 13.57; 95% CI 9.45-19.48); and 23-valent pneumococcal polysaccharide vaccination (OR = 1.97; 95% CI 1.38-2.80) were associated with receiving the influenza vaccine. Vaccination coverage of hospitalized elderly people is low in Spain and some predisposing characteristics influence vaccination coverage. Healthcare workers should take these characteristics into account and be encouraged to proactively propose influenza vaccination to all patients aged ≥ 65 years.

Effect of influenza vaccination on the prognosis of hospitalized influenza patients.

OBJECTIVES: This study aimed to assess whether influenza vaccination reduces the risk of severe and fatal outcomes in influenza inpatients aged ≥65 years. METHODS: During the 2013-2014 influenza season persons aged ≥65 years hospitalized with laboratory-confirmed influenza were selected in 19 Spanish hospitals. A severe influenza case was defined as admission to the intensive care unit, death in hospital or within 30 days after admission. Logistic regression was used to compare the influenza vaccination status between severe and non-severe influenza inpatients. RESULTS: Of 433 influenza confirmed patients, 81 (19%) were severe cases. Vaccination reduced the risk of severe illness (odds ratio: 0.57; 95%CI: 0.33-0.98). The cumulative number of influenza vaccine doses received since the 2010-2011 season was associated with a lower risk of severe influenza (odds ratio: 0.78; 95% CI 0.66-0.91). CONCLUSION: Adherence to seasonal influenza vaccination in the elderly may reduce the risk of severe influenza outcomes.

The continuum of HIV care in Catalonia.

The objective was to produce a cascade of care for Catalonia to gain a public health perspective on the overall quality of HIV services and allow comparison with other countries. It was constructed using the Integrated Epidemiological Surveillance System of HIV in Catalonia and data from the PISCIS Cohort. Estimates of the number of people living with HIV in Catalonia are modelled using Spectrum Projection Package 2011 (UNAIDS/WHO). Totals for each stage in the cascade are obtained by applying to the preceding stage a proportion estimated from available surveillance and cohort data. Undiagnosed HIV was estimated from the European literature. The proportions retained in care, on ART and virally suppressed were derived from the PISCIS cohort. Programmatic data on ART consumption was used to validate estimates. By the end of 2011 there were about 33,000 people living with HIV in Catalonia, 71% of which had been both diagnosed and linked to care. We estimate that 61% of all HIV infected persons were retained in care, 56% were on ART and 48% were virally suppressed. These figures data are comparable, although slightly lower, than that of France or the UK. The Cascade of HIV Care in Catalonia is similar to other western European countries such as France and the UK. Direct estimates of the undiagnosed HIV population and linkage to care are desirable but the contribution of cohort data to the cascade highlights their continued importance in HIV surveillance and design of evidence-based health strategies.

Virological failure to raltegravir in Spain: incidence, prevalence and clinical consequences.

OBJECTIVES: The objective of this study was to evaluate the incidence, prevalence and clinical consequences of virological failure (VF) to raltegravir-based regimens in Spain. METHODS: A multicentre, retrospective, observational study was performed in 10 tertiary hospitals (January 2006 to June 2013). The study included HIV-1-infected patients with loss of virological suppression (LVS; two consecutive HIV-1 RNA ≥50 copies/mL) while receiving raltegravir. VF and low-level viraemia (LLV) were defined as two consecutive HIV-1 RNA ≥200 copies/mL and 50 to <200 copies/mL, respectively. Integrase strand-transfer inhibitor resistance was investigated at LVS. During the 48 weeks following LVS, recorded data included clinical characteristics, treatment discontinuations, AIDS-associated events and deaths. Effectiveness of therapy following LVS was evaluated by ITT and PP. Multivariate regression was used to assess predictors of efficacy. RESULTS: Of the 15 009 HIV-infected patients in participating centres, 2782 (18.5%) had received raltegravir-based regimens. Of those, 192 (6.9%), 125 (4.5%) and 67 (2.4%) experienced LVS, VF and LLV, respectively. The incidence of VF was 1.8 (95% CI, 1.5-2.1) per 100 patients/year. The prevalence of VF was 4.5% (95% CI, 3.8%-5.3%). Integrase-associated mutations were found in 78.8% of patients with integrase genotyping results available. High-level resistance to dolutegravir was not observed. Salvage therapy failed in 34.1% of patients; progression to AIDS/death occurred in 8.3% during the first year following LVS. The latter was associated with intravenous drug use, time on raltegravir and lower CD4+ count nadir in patients who started raltegravir-based treatments as salvage regimens. CONCLUSIONS: VF with raltegravir is infrequent, but often associated with major clinical complications in treatment-experienced patients.

Long-term mortality in HIV-positive individuals virally suppressed for >3 years with incomplete CD4 recovery.

BACKGROUND: Some human immunodeficiency virus (HIV)-infected individuals initiating combination antiretroviral therapy (cART) with low CD4 counts achieve viral suppression but not CD4 cell recovery. We aimed to identify (1) risk factors for failure to achieve CD4 count >200 cells/µL after 3 years of sustained viral suppression and (2) the association of the achieved CD4 count with subsequent mortality. METHODS: We included treated HIV-infected adults from 2 large international HIV cohorts, who had viral suppression (≤500 HIV type 1 RNA copies/mL) for >3 years with CD4 count ≤200 cells/µL at start of the suppressed period. Logistic regression was used to identify risk factors for incomplete CD4 recovery (≤200 cells/µL) and Cox regression to identify associations with mortality. RESULTS: Of 5550 eligible individuals, 835 (15%) did not reach a CD4 count >200 cells/µL after 3 years of suppression. Increasing age, lower initial CD4 count, male heterosexual and injection drug use transmission, cART initiation after 1998, and longer time from initiation of cART to start of the virally suppressed period were risk factors for not achieving a CD4 count >200 cells/µL. Individuals with CD4 ≤200 cells/µL after 3 years of viral suppression had substantially increased mortality (adjusted hazard ratio, 2.60; 95% confidence interval, 1.86-3.61) compared with those who achieved CD4 count >200 cells/µL. The increased mortality was seen across different patient groups and for all causes of death. CONCLUSIONS: Virally suppressed HIV-positive individuals on cART who do not achieve a CD4 count >200 cells/µL have substantially increased long-term mortality.

Prognosis of patients treated with cART from 36 months after initiation, according to current and previous CD4 cell count and plasma HIV-1 RNA measurements.

OBJECTIVES: CD4 cell count and plasma viral load are well known predictors of AIDS and mortality in HIV-1-infected patients treated with combination antiretroviral therapy (cART). This study investigated, in patients treated for at least 3 years, the respective prognostic importance of values measured at cART initiation, and 6 and 36 months later, for AIDS and death. METHODS: Patients from 15 HIV cohorts included in the ART Cohort Collaboration, aged at least 16 years, antiretroviral-naive when they started cART and followed for at least 36 months after start of cART were eligible. RESULTS: Among 14 208 patients, the median CD4 cell counts at 0, 6 and 36 months were 210, 320 and 450 cells/microl, respectively, and 78% of patients achieved viral load less than 500 copies/ml at 6 months. In models adjusted for characteristics at cART initiation and for values at all time points, values at 36 months were the strongest predictors of subsequent rates of AIDS and death. Although CD4 cell count and viral load at cART initiation were no longer prognostic of AIDS or of death after 36 months, viral load at 6 months and change in CD4 cell count from 6 to 36 months were prognostic for rates of AIDS from 36 months. CONCLUSIONS: Although current values of CD4 cell count and HIV-1 RNA are the most important prognostic factors for subsequent AIDS and death rates in HIV-1-infected patients treated with cART, changes in CD4 cell count from 6 to 36 months and the value of 6-month HIV-1 RNA are also prognostic for AIDS.

Improvement of mitochondrial toxicity in patients receiving a nucleoside reverse-transcriptase inhibitor-sparing strategy: results from the Multicenter Study with Nevirapine and Kaletra (MULTINEKA).

BACKGROUND: Nucleoside reverse-transcriptase inhibitor (NRTI)-related mitochondrial toxicity has been suggested as a key factor in the induction of antiretroviral-related lipoatrophy. This study aimed to evaluate in vivo the effects of NRTI withdrawal on mitochondrial parameters and body fat distribution. METHODS: A multicenter, prospective, randomized trial assessed the efficacy and tolerability of switching to lopinavir-ritonavir plus nevirapine (nevirapine group; n = 34), compared with lopinavir-ritonavir plus 2 NRTIs (control group; n = 33) in a group of human immunodeficiency virus-infected adults with virological suppression. A subset of 35 individuals (20 from the nevirapine group and 15 from the control group) were evaluated for changes in the mitochondrial DNA (mtDNA) to nuclear DNA ratio and cytochrome c oxidase (COX) activity after NRTI withdrawal. Dual-energy X-ray absorptiometry (DEXA) scans were used to objectively quantify fat redistribution over time. RESULTS: The nevirapine group experienced a progressive increase in mtDNA content (a 40% increase at week 48; P = .039 for comparison between groups) and in the COX activity (26% and 32% at weeks 24 and 48, respectively; P = .01 and P = .09 for comparison between groups, respectively). There were no statistically significant between-group differences in DEXA scans at week 48, although a higher fat increase in extremities was observed in the nevirapine group. No virologic failures occurred in either treatment arm. CONCLUSIONS: Switching to a nucleoside-sparing regimen of nevirapine and lopinavir-ritonavir maintained full antiviral efficacy and led to an improvement in mitochondrial parameters, which suggests a reversion of nucleoside-associated mitochondrial toxicity. Although DEXA scans performed during the study only revealed slight changes in fat redistribution, a longer follow-up period may show a positive correlation between reduced mitochondrial toxicity and a clinical improvement of lipodystrophy.

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.

Functional status as a risk factor for mortality in very elderly patients with pneumonia.

BACKGROUND AND OBJECTIVE: The most commonly used prognostic mortality indexes for pneumonia take into account several variables including comorbidities, physical examination results, and laboratory test results, as well as age. Other factors such as functional status are not included. The objective of this study was to know whether the preadmission functional status was related to 30-day mortality in old or very old patients who were hospitalized for pneumonia. PATIENTS AND METHOD: This was a prospective study including all patients who were hospitalized for pneumonia in the Acute Geriatric Unit of Hospital de Mataró, Barcelona. We calculated the Pneumonia Severity Index (PSI), preadmission and admission Barthel Index (BI), Charlson Comorbidity Index and Mini Nutritional Assessment (MNA). Patients were assessed during hospitalisation and until death or 30 days after admission. RESULTS: We studied 117 patients, 69 (59%) were men. The mean age (standard deviation) was 84.7 (6.5) years. The 30-day mortality was 16.2%. The PSI score was 134.2 (31.8) on admission, and the BI scores on preadmission and admission were 60.3 (35.8) and 37.1 (33.5), respectively. In a multiple logistic regression model, using all variables statistically significant in the univariate analysis, those independently associated with 30-day mortality were: preadmission BI lower than 60 points (odds ratio = 4.89; 95% confidence interval, 1.27-18.9) and lymphopenia (odds ratio = 7.11; 95% confidence interval, 1.7-30.2). CONCLUSIONS: In very old patients who were hospitalized for pneumonia, preadmission functional status was an independent predictor of mortality. Functional status should be included in the severity indices of pneumonia in this population.

Determinants of HIV progression and assessment of the optimal time to initiate highly active antiretroviral therapy: PISCIS Cohort (Spain).

OBJECTIVE: We analyze the factors related to progression to AIDS or death in HIV-infected patients from the Proyecto para la Informatización del Seguimiento Clínico epidemiológico de los pacientes con Infección por VIH/SIDA (PISCIS) Cohort and we assess the optimal time to initiate highly active antiretroviral therapy (HAART) taking lead time into account. METHODS: We selected naive patients who were AIDS-free and initiated HAART after January 1998. Statistical analyses were performed using Cox proportional hazards models. Lead time was defined as the time it took the deferred group with an early disease stage to reach the later stage. The analysis accounting for lead time was performed using multiple imputation methods based on estimates from the pre-HAART period as described elsewhere. RESULTS: Multivariate analysis on 2035 patients (median follow-up = 34.3 months) showed significantly higher hazard ratios (HRs) for a CD4 count <200 cells/microL (HR = 3.79, 95% confidence interval [CI]: 2.18 to 6.57), HIV-1 RNA level >100,000 copies/mL (HR = 1.84, 95% CI: 1.26 to 2.69), and hepatitis C virus (HCV) coinfection (HR = 2.40, 95% CI: 1.65 to 3.49), whereas a lower risk was found for those who started HAART between January 2001 and June 2004 (HR = 0.55, 95% CI: 0.30 to 0.90). When lead time and unseen events were included, we found a higher risk of progression to AIDS among patients who deferred treatment when the CD4 count reached <200 cells/microL (HR = 2.97, 95% CI: 1.91 to 4.63) and 200 to 350 cells/microL (HR = 1.85, 95% CI: 1.03 to 3.33) compared with those who started treatment with CD4 counts from 200 to 350 cells/microL and >350 cells/microL, respectively. CONCLUSIONS: Advanced HIV disease, HCV coinfection, and early HAART period were determinants of AIDS progression or death. Lead-time analysis in asymptomatic HIV-infected patients suggests that the best time to start HAART is before the CD4 count falls to lower than 350 cells/microL.

Poor response to hepatitis C virus (HCV) therapy in HIV- and HCV-coinfected patients is not due to lower adherence to treatment.

The degree of adherence to anti-hepatitis C virus (HCV) therapy among HIV/HCV-coinfected patients is not known. A prospective cohort study was performed in two groups of patients: 79 HIV/HCV-coinfected patients (group 1) and 78-HCV-monoinfected patients (group 2). Patients were treated with interferon alpha-2a (3 million international units [MIU], three times per week) plus ribavirin (1000-1200 mg/day) for 48 weeks. Adherence to therapy was defined as having received +/-80% of both drug dosages for +/-80% of the expected duration of therapy. The degree of adherence to treatment was similar for patients with or without HIV coinfection (72.2 versus 80.8%). The overall sustained virological response (SVR) in patients with adherence to therapy was 41.7% as compared with only 8.1% (p = 0.0001) in patients without adherence. The difference in SVR rate according to adherence to treatment was also evident in patients of group 1 (29.8% versus 9.1%; p = 0.05) as well as in those of group 2 (52.4 versus 6.7%; p = 0.001). Adherence to anti-HCV therapy, which can be similar in mono- and coinfected patients, enhances the likelihood of achieving an increase in SVR rate. In addition to improved adherence, in coinfected patients more aggressive therapeutic strategies may be necessary to achieve SVR.

Long-term safety and efficacy of nevirapine-based approaches in HIV type 1-infected patients.

Using a multicenter, cross-sectional, observation study, the long-term safety, metabolic profile, and viral efficacy of nevirapine (NVP)-based approaches in HIV-1-infected patients treated for at least 2 years were assessed. For 4 months, all consecutive HIV-1-infected patients who had been receiving an NVP-containing regimen for at least 2 years were recruited. A total of 613 patients were included with a median follow-up period of 43 months (IQR: 31-51). At baseline, 24.5% (150 patients) were treatment naive, 41.5% (254 patients) switched for simplification purposes, and 34% (209 patients) were failing HAART. Increases by five times or more in AST/ALT values were observed in fewer than 2% of patients. Only 5.7% of all adverse events reported during the investigation were attributable to NVP. The percentage of patients with normal HDL cholesterol levels rose from 17.7% at baseline to 35.4% at the last visit. At the latest time point available for analysis, 76% of naive and 74% of those who had switched had HIV-1 RNA loads of <50 copies/ml, while 59% of salvage patients achieved this level of viral suppression. Factors associated with viral suppression at the latest visit were adequate adherence (OR: 2.58, 95% CI: 0.85-7.78, p < 0.001), first-line treatment (OR: 3.02, 95% CI: 1.52-6.00, p = 0.002), and baseline CD4 cells >400 cells/microl (OR: 2.34, 95% CI: 1.22-4.47, p = 0.010). Exposure to nevirapine for up to 4 years is safe. Liver toxicity is infrequent and generally mild. HDL cholesterol levels consistently increase over time and viral suppression is maintained.

Short communication. Baseline factors associated with haematological toxicity that leads to a dosage reduction of pegylated interferon-alpha2a and ribavirin in HIV- and HCV-coinfected patients on HCV antiviral therapy.

OBJECTIVE: To assess the baseline factors associated with haematological toxicity that lead to ribavirin or pegylated interferon (peginterferon) dosage reductions in hepatitis C and human immunodeficiency virus (HCV/HIV)-coinfected patients. DESIGN: Multicentre, prospective, observational study. SETTING: Eleven hospitals in Spain during the period 2002-2003. SUBJECTS AND METHODS: One-hundred and forty-two HIV/HCV-coinfected patients received peginterferon-alpha2a plus ribavirin. Baseline characteristics and haematological parameters were recorded at baseline, week 4, 8, 12, 24 and 48. Cox's regression model was used to study the factors associated with the appearance of a haemoglobin level below 10g/dl (haemoglobin-endpoint), a neutrophil count below 750/mm(3) (neutrophil-endpoint) and a platelet count below 50,000/mm(3) (platelet-endpoint). RESULTS: Nineteen patients (13.4%) reached the haemoglobin-endpoint, 22.5% the neutrophil-endpoint and 7% the platelet-endpoint. Mean time of follow-up was 8 months (+/-3.5). A baseline haemoglobin level below 14g/dl [hazard ratio (HR): 3.65; 95% confidence interval (CI): 1.46-9.06] and treatment with zidovudine (HR: 3.25; 95% CI: 1.31-8.11) were the independent factors associated with the appearance of the haemoglobin-endpoint. A baseline neutrophil below 2050/mm(3) (HR: 3.59; 95% CI: 1.77-7.28) and baseline weight <60 kg (HR: 2.21; 95% Cl: 1.04-4.56) were independently associated with the appearance of the neutrophil-endpoint. Baseline platelet count (x1000/mm(3) decrease) (HR: 1.074; 95% CI: 1.04-1.11) was independently associated with the appearance of the platelet-endpoint. CONCLUSIONS: Baseline factors allow the identification of a subset of HIV/HCV-coinfected patients who are prone to experience haematological toxicity during HCV antiviral therapy.

Cyanamide-induced aplastic anemia.

OBJECTIVE: To report a case of aplastic anemia in a patient treated with cyanamide, an alcohol-aversive drug. A 67-year-old man was admitted to hospital because of fever and pancytopenia. He had taken cyanamide for 6 months as an alcohol deterrent. No other risk factors for aplastic anemia were identified by interviewing the patient using a structured validated questionnaire. The results of bone-marrow biopsy showed severe aplastic anemia. Cyanamide was discontinued and the patient was treated according to a prespecified treatment protocol. One year after hospital admission, the patient was completely recovered with no need of immunosuppressive therapy. An objective causality assessment revealed that an adverse drug reaction was probable. DISCUSSION: As the efficacy of cyanamide has been questioned, due to the failure of various trials to show any benefit over placebo, its overall benefit/risk ratio should be reconsidered. The complete and rapid hematological recovery after discontinuation of the drug, and the absence of other factors that could explain the condition support the association of the present case of aplastic anemia with cyanamide. The mechanism remains unknown. Aplastic anemia is a rare but potentially serious adverse drug effect of cyanamide treatment. CONCLUSIONS: Given the poor evidence on the efficacy of cyanamide and the associated risk of aplastic anemia, its use in reducing alcohol consumption should be reconsidered.