Darunavir and ritonavir total and unbound plasmatic concentrations in HIV-HCV-coinfected patients with hepatic cirrhosis compared to those in HIV-monoinfected patients.

Our objective was to describe the pharmacokinetic (PK) parameters of total and unbound darunavir and ritonavir concentrations in HIV-hepatitis C virus (HCV)-coinfected patients with cirrhosis, as ritonavir-boosted darunavir is mainly metabolized in the liver, and hepatic cirrhosis might modify darunavir-ritonavir concentrations. This was a prospective, case-control, and unicenter study. HIV-HCV-coinfected patients with compensated cirrhosis (cases) and HIV-monoinfected patients with normal liver function (controls) were included. Darunavir-ritonavir was given at 800/100 mg once daily. Patients were followed for 24 weeks to assess safety and efficacy. A steady-state 12-h PK study was performed. Total and unbound concentrations were determined by liquid chromatography-tandem mass spectrometry. The unbound fraction was obtained by ultrafiltration. The plasma area under the concentration-time curve (AUC) and oral clearance (CL/F) were assessed by noncompartmental models. Thirty patients (20 cases and 10 controls) were included. Among cirrhotic patients, the Child-Pugh score was C in 4 cases, B in 1 case, and A in 15 cases; the median (interquartile range) transient elastography values were 20 kPa (14 to 26 kPa), and 5 patients had prior clinical decompensations. There were no significant differences in the darunavir PK parameters between cases and controls except for longer time to maximum plasma concentrations (Tmax) and half-lives in the cirrhotic patients. There were no significant differences in ritonavir total concentrations, but the unbound concentrations were higher in cirrhotic patients. There were significant correlations between the darunavir total and unbound concentrations in both cirrhotic patients and controls. There were no differences in PK parameters based on Child-Pugh score, liver elasticity, gender, or use of concomitant medications. In conclusion, in HIV-HCV-coinfected patients with clinically compensated cirrhosis receiving darunavir-ritonavir at 800/100 mg once daily, the darunavir total and unbound concentrations are similar to those observed in noncirrhotic patients, and dose adjustments are not necessary.

Epidemiology of infections by HIV, Syphilis, Gonorrhea and Lymphogranuloma Venereum in Barcelona City: a population-based incidence study.

BACKGROUND: The aim of this study was to determine the evolution of HIV infection, gonorrhea, syphilis and lymphogranuloma venereum (LGV), and their epidemiological characteristics in Barcelona city. METHODS: Population-based incidence study of all newly occurring diagnoses of HIV infection, syphilis, gonorrhea and LGV detected in Barcelona between January 2007 and December 2011. A descriptive analysis was performed. The annual incidence rates per 100,000 inhabitants were calculated by sex, sexual conduct and educational level. To estimate global sex-specific rates we used the Barcelona city census; for the calculation of rates by sexual conduct and educational level we used estimates of the Barcelona Health Interview Survey. Trends were analysed using the chi-squared test for linear trend. RESULTS: HIV. 66.8 % of the HIV cases were men who had sex with men (MSM). The incidence rates in MSM over the study period were from 692.67/100,000 to 909.88/100,000 inh. Syphilis. 74.2 % of the syphilis cases were MSM. The incidence rates in MSM were from 224.9/100,000 to 891.97/100,000 inh. and the MSM with a university education ranged from 196.3/100,000 to 1020.8/100,000. Gonorrhea. 45.5 % of the gonorrhea cases were MSM. The incidence rates in MSM were from 164.24/100,000 to 404.79/100,000 inh. and the MSM with university education ranged from 176.7/100,000 to 530.1/100,000 inh.. Lymphogranuloma venereum (LGV). 95.3 % of the LGV cases are MSM. The incidence rates in MSM were from 24.99/100,000 to 282.99/100,000 inh. and the MSM with university education ranged from 9.3/100,000 to 265/100,000 inh. CONCLUSION: An increase in cases of STI was observed. These STI mainly affected MSM with a university education. Continuing to monitor changes in the epidemiology of STI, and identifying the most affected groups should permit redesigning preventive programs, with the goal of finding the most efficient way to reach these population groups.

Epidemiological characteristics and predictors of late presentation of HIV infection in Barcelona (Spain) during the period 2001-2009.

BACKGROUND: Early diagnosis of HIV infection can prevent morbidity and mortality as well as reduce HIV transmission. The aim of the present study was to assess prevalence, describe trends and identify factors associated with late presentation of HIV infection in Barcelona (Spain) during the period 2001-09. METHODS: Demographic and epidemiological characteristics of cases reported to the Barcelona HIV surveillance system were analysed. Late presentation was defined for individuals with a CD4 count below 350 cells/ml upon HIV diagnosis or diagnosis of AIDS within 3 months of HIV diagnosis. Multivariate logistic regression were used to identify predictors of late presentation. RESULTS: Of the 2,938 newly diagnosed HIV-infected individuals, 2,507 (85,3%) had either a CD4 cell count or an AIDS diagnosis available. A total of 1,139 (55.6%) of the 2,507 studied cases over these nine years were late presenters varying from 48% among men who have sex with men to 70% among heterosexual men. The proportion of late presentation was 62.7% in 2001-2003, 51.9% in 2004-2005, 52.6% in 2006-2007 and 52.1% in 2008-2009. A decrease over time only was observed between 2001-2003 and 2004-2005 (p = 0.001) but remained constant thereafter (p = 0.9). Independent risk factors for late presentation were older age at diagnosis (p < 0.0001), use of injected drugs by men (p < 0.0001), being a heterosexual men (p < 0.0001), and being born in South America (p < 0.0001) or sub-Saharan Africa (p = 0.002). CONCLUSION: Late presentation of HIV is still too frequent in all transmission groups in spite of a strong commitment with HIV prevention in our city. It is necessary to develop interventions that increase HIV testing and facilitate earlier entry into HIV care.

Efficacy, safety and pharmacokinetics of 900/100 mg of darunavir/ritonavir once daily in treatment-experienced patients.

OBJECTIVES: To evaluate the virological efficacy, safety, tolerability and pharmacokinetics of a regimen containing 900/100 mg of ritonavir-boosted darunavir once daily in patients with antiretroviral experience but no darunavir resistance. PATIENTS AND METHODS: An observational, prospective, multicentre study was conducted. Patients were included if 900/100 mg of darunavir/ritonavir once daily and at least one other active drug had been started due to virological failure, simplification or toxicity. Minimum follow-up was 24 weeks, or less if there was premature discontinuation of any drug or loss to follow-up. In a subgroup of patients, a complete 24 h pharmacokinetic study was performed by HPLC. RESULTS: One hundred and three patients (47 switch strategies, 56 early salvage therapies) were included. After 6 months, 85/103 (83%; 95% CI: 74%-89%) and 85/93 (91%; 95% CI: 84%-97%) patients had <50 copies/mL HIV-RNA by intention-to-treat and on-treatment analyses, respectively. The respective values were 42/47 (89%; 95% CI: 72%-96%) and 42/43 (98%; 95% CI: 88%-100%) in switch therapy, and 43/56 (77%; 95% CI: 64%-87%) and 43/50 (86%; 95% CI: 73%-94%) in salvage therapy. There was a significant increase in CD4 cell counts [+73 cells/mm(3) (95% CI: 43%-102%), P<0.001]. There were no interruptions due to rash or liver toxicity. Significant decreases in cholesterol and triglycerides were seen in patients with abnormal lipids at baseline. Ten patients discontinued antiretrovirals (5 were lost to follow-up and 5 due to side effects). Twenty-five patients were included in the pharmacokinetic study. All patients had trough plasma concentrations >0.05 µg/mL. CONCLUSIONS: Darunavir/ritonavir at 900/100 mg once daily is highly effective, safe and well tolerated in treatment-experienced patients with no darunavir resistance, both in early salvage and switch strategies. Adequate drug plasma levels were achieved in all patients.

Response-guided therapy for chronic hepatitis C virus infection in patients coinfected with HIV: a pilot trial.

BACKGROUND: To study the feasibility of a response-guided therapy for chronic hepatitis C virus (HCV) infection in patients coinfected with human immunodeficiency virus (HIV) in a tertiary care hospital. METHODS: Treatment duration was individualized on the basis of week 4 and week 12 virologic response. Sixty patients were enrolled and received pegylated interferon alfa-2b (1.5 microg/kg per week) plus weight-based ribavirin (800-1400 mg/day). Patients who achieved a rapid virologic response, defined as viral load <50 IU/mL at treatment week 4, completed 24 weeks of therapy. Patients who did not achieve a rapid virologic response were reassessed at treatment week 12. Patients with a complete early virologic response, defined as an HCV RNA level <600 IU/mL, were treated for 48 weeks. Patients with a partial response, defined as a decrease in the viral load > or = 2 log10 and an HCV RNA level > or = 600 IU/mL, who attained an undetectable viral load at week 24 were treated for 60 weeks. The primary efficacy end point was sustained virologic response, defined as HCV RNA <50 IU/mL, 24 weeks after the end of treatment. RESULTS: Overall, 33 (55%) of 60 patients achieved a sustained virologic response: 11 (44%) of 25 patients with HCV genotype 1, 3 (27%) of 11 patients with genotype 4, and 19 (79%) of 24 patients with genotype 3. One-third of patients showed a rapid virologic response. Of patients with genotype 1, there was a rapid virologic response in 4 (16%) of 25; with genotype 4, in 1 (9%) of 11; and with genotype 3, in 14 (58%) of 24. Of the 19 patients with a rapid virologic response, 17 (89.5%) eradicated the virus after 24 weeks of therapy. The rate of sustained virologic response was significantly higher among patients with genotype 3 and low pretreatment HCV RNA levels. A high relapse rate (46%) after 48 weeks of therapy occurred among patients infected with genotypes 1 or 4 who first achieved undetectable viral load at treatment week 12. CONCLUSION: A response-guide therapy is feasible and may be useful to optimize the individual outcome of HCV treatment in patients coinfected with HIV.

Sexually transmitted infections in young people and factors associated with HIV coinfection: an observational study in a large city.

OBJECTIVES: Young people are a critical target group for sexually transmitted infections (STI) surveillance due to their particular behavioural and social related vulnerability. The aim of this study was to describe the epidemiological characteristics and trends in the incidence of gonorrhoea, syphilis, HIV and venereal lymphogranuloma (LGV) among 15-24-year-olds in Barcelona, and to determine factors associated with HIV coinfection. DESIGN: We performed a population-based incidence study covering the 2007-2015 period. PARTICIPANTS: All new cases of STI-HIV, gonorrhoea, infectious syphilis and LGV-notified to the epidemiological surveillance system in Barcelona between 2007 and 2015. 1218 cases were studied: 84.6% were men, 19.3% were 15-19 years old and 50.6% were born in Spain. Among men, 73.7% were men who have sex with men (MSM); among women, 85.6% were women that have sex with men. PRIMARY AND SECONDARY OUTCOMES: Incidence of HIV, gonorrhoea, infectious syphilis and LGV. HIV coinfection. RESULTS: There was an increase in the incidence of gonorrhoea, from 1.9 cases per 10 000 people in 2007 to 7.6/10 000 in 2015 (p<0.01), in MSM from 27.1 to 228.8/10 000 (p<0.01). The incidence of syphilis increased from 0.4/10 000 in 2007 to 3.1/10 000 in 2015 (significant in men only, p<0.01), in MSM from 18.1 to 116.9/10 000 (p<0.01). The incidence of HIV showed a non-significant increase in men (p=0.27), and that of LGV remained stable (p=0.59). Factors associated with increased risk of HIV coinfection included being MSM (adjusted OR[ORa]=14.14, 95% CI 3.34 to 59.91) and having >10 sexual partners (ORa=4.11, 95% CI 1.53 to 11.01) or STI diagnosis during the previous 12 months (ORa=2.06; 95% CI 1.13 to 3.77). CONCLUSIONS: The incidence of gonorrhoea and syphilis among 15-24-year-olds increased, while HIV infection remained stable but with a high incidence among MSM. Being MSM, having sex with multiple partners and having a diagnosis of an STI in the previous 12 months were factors associated with HIV coinfection.

Utility of week-4 viral response to tailor treatment duration in hepatitis C virus genotype 3/HIV co-infected patients.

OBJECTIVE: To investigate the utility of a week-4 virological response for sustained response prediction in hepatitis C virus (HCV) genotype 3/HIV-co-infected patients treated with interferon and ribavirin for 24 weeks. METHODS: Using a real-time polymerase chain reaction-based quantitative assay (COBAS AmpliPrep-COBAS-TaqMan 48; Roche Diagnostics) we retrospectively analysed samples obtained at baseline and weeks 4 and 12 from a subset of 35 HCV genotype 3-HIV co-infected patients enrolled in a randomized comparative trial of peginterferon alpha-2b versus interferon alpha-2b both in combination with ribavirin. RESULTS: In an intention-to-treat analysis, 78% of patients treated with peginterferon and 53% of those receiving standard interferon achieved a sustained virological response (SVR) Overall, at 4 weeks, 49% of patients had HCV RNA < 50 IU/ml and 63% had < 600 IU/ml. Of these rapid responders 88 and 86% achieved a SVR, respectively, with only one patient relapsing among end-of-treatment responders. In contrast, only 44 and 31% of patients with a week-4 HCV RNA >or= 50 or >or= 600 IU/ml achieved an SVR, respectively, with relapse rates of 33 and 50%, respectively. In multivariate logistic regression analysis a serum HCV RNA level below 600 IU/ml at week 4 was the strongest independent predictor of SVR (odds ratio, 11.3; 95% confidence interval, 1.7 to 75.0; P = 0.012). CONCLUSION: Monitoring early viral response may be useful to tailor the duration of treatment among patients with HCV genotype 3/HIV-co-infection. Patients whose HCV RNA falls below 600 IU/ml at 4 weeks are at low risk of relapse after 24 weeks of combination therapy.

Early monitoring of ribavirin serum concentration is not useful to optimize hepatitis C virus treatment in HIV-coinfected patients.

BACKGROUND: Emerging data suggest that higher ribavirin (RBV) exposure could improve early hepatitis C virus (HCV) response. Furthermore, interindividual RBV bioavailability shows high variation, and dose-limiting haemolytic anaemia is a common adverse event. Therefore, it has been suggested that monitoring RBV serum levels could be used to drive dose modification and to optimize management of HCV-infected patients receiving combination treatment. METHODS: To assess the effect of RBV serum levels on HCV RNA clearance at week 4 and 12 of treatment, and to determine the correlation between RBV serum concentration and haemoglobin decrease, RBV trough levels were measured by HPLC in stored serum samples obtained from 94 HCV-HIV-coinfected patients at week 4 and 12 of treatment with peginterferon-alpha2b (1.5 microg/kg/weekly) pIus ribavirin (800-1,200 mg/day). RESULTS: The median RBV levels increased from 1.70 microg/ml at week 4 to 1.97 microg/ml at week 12 of treatment (P = 0.001) and were independently predicted by weight-adjusted dose of RBV and co-administration of tenofovir. Haemoglobin drop was higher among patients who received zidovudine and weakly correlated with RBV level. Although RBV concentration was lower in genotype 1 or 4 HCV-infected patients who cleared the virus at treatment week 4, the ability of this parameter to discriminate between responders and non-responders at treatment week 4 and 12 was poor. CONCLUSION: Intracellular RBV accumulation early in treatment might improve the kinetics of HCV response in difficult to treat patients. Although this hypothesis and the potential interaction between RBV and tenofovir warrant further research, our data do not support RBV serum monitoring as a tool to optimize treatment in HCV-HIV-coinfected patients.

Acute leg ischaemia in an HIV-infected patient receiving antiretroviral treatment.

An HIV-infected patient treated with tenofovir disoproxil fumarate/emtricitabine/elvitegravir/cobicistat developed severe acute ischaemia of both legs during a migraine episode. After being interrogated he admitted taking an ergotamine-containing preparation. Ergotism due to interaction between ergotics and cobicistat was diagnosed. We describe the first reported case of this interaction.

Impact of low-level viraemia on virological failure in HIV-1-infected patients with stable antiretroviral treatment.

BACKGROUND: Low-level viraemia (LLV) occurs in 20-40% of patients achieving viral suppression with antiretroviral therapy (ART). The risk of virological failure (VF: confirmed HIV RNA >200 copies/ml) in these patients is still a matter of debate. METHODS: This is a prospective cohort study in HIV-infected adults attending the HIV clinic of a tertiary care hospital in Spain. Patients with HIV RNA <25 copies/ml and stable ART for at least 6 months presenting LLV (defined as HIV RNA between 25-1,000 copies/ml) from January 2011 to January 2013 were included and followed until VF or end of follow-up in June 2014. RESULTS: A total of 300 out of 1,733 (17.3%) patients with undetectable viraemia for 4.2 years showed LLV: 25-50 copies/ml in 167 (55.7%) patients, 51-200 copies/ml in 111 (37%) and 201-1,000 copies/ml in 22 (7.3%) cases. After a median follow-up of 2.6 years, 23 (7.7%) patients presented VF. No patient with a single or multiple unconfirmed LLV went on to develop VF. HIV RNA >200 copies/ml (HR 59.6; 95% CI 15.7, 227), ritonavir-boosted protease inhibtor (PI/r)-based dual therapy (HR 10.2; 95% CI 2.1, 49.8) and PI/r monotherapy (HR 7.9; 95% CI 1.4, 43.3) were associated with VF. Persistent LLV, defined as HIV RNA <200 copies/ml in at least three consecutive samples, for at least 12 weeks, was detected in 27 (1.6%) patients and 14 (51.9%) of those evolved to VF. CONCLUSIONS: Nearly one-fifth of patients on suppressive ART showed LLV and 8% of them developed VF. HIV RNA >200 copies/ml was the strongest predictor of VF. Over half of patients with persistent viraemia <200 copies/ml showed VF.

Epidemiology and long-term survival in HIV-infected patients with Pneumocystis jirovecii pneumonia in the HAART era: experience in a university hospital and review of the literature.

As highly active antiretroviral treatment (HAART) is widely available, the incidence of Pneumocystis jirovecii pneumonia (PJP) has decreased significantly but still represents a significant cause of morbidity and mortality in developed countries. We analyzed all the cases with PJP in human immunodeficiency virus (HIV)-infected patients from 2000 to 2013 in a university hospital in Barcelona, Spain, and conducted a systematic literature review to evaluate data regarding incidence, mortality, and long-term survival after PJP in developed settings. One hundred thirty-six episodes of PJP were analyzed. During the study period, the incidence decreased significantly (from 13.4 cases/1000 patients-year to 3.3 cases/1000 patients-year, P < 0.001). Oppositely, median age of the patients increased from 34 years in 2000 to 45 in 2013 (P = 0.024). PJP preceded HIV diagnosis in nearly 50% of the cases. Fifteen (11%) patients died during the PJP episode. The main risk factor for in-hospital mortality in our cohort was age >50 years (odds ratio 4.96, 95% confidence interval [CI] 1.45-15.14). Patients who survived were followed-up during a mean time of 44 months. Overall 5-year survival of patients after hospital discharge was 73%. Survival likelihood was 54% higher (88% [95% CI 81-96]) among HAART-adherent patients. Mean age and the proportion of patients with unknown HIV infection at the time of PJP diagnosis have increased in developed countries in the HAART era. Although the incidence has decreased, in-hospital mortality remains stable in this setting. Long-term survival is very high among HAART-adherent patients.

Mortality, Causes of Death and Associated Factors Relate to a Large HIV Population-Based Cohort.

INTRODUCTION: Antiretroviral therapy has led to a decrease in HIV-related mortality and to the emergence of non-AIDS defining diseases as competing causes of death. This study estimates the HIV mortality rate and their risk factors with regard to different causes in a large city from January 2001 to June 2013. MATERIALS AND METHODS: We followed-up 3137 newly diagnosed HIV non-AIDS cases. Causes of death were classified as HIV-related, non-HIV-related and external. We examined the effect of risk factors on survival using mortality rates, Kaplan-Meier plots and Cox models. Finally, we estimated survival for each main cause of death groups through Fine and Gray models. MORTALITY RESULTS: 182 deaths were found [14.0/1000 person-years of follow-up (py); 95% confidence interval (CI):12.0-16.1/1000 py], 81.3% of them had a known cause of death. Mortality rate by HIV-related causes and non-HIV-related causes was the same (4.9/1000 py; CI:3.7-6.1/1000 py), external was lower [1.7/1000 py; (1.0-2.4/1000 py)]. SURVIVAL RESULTS: Kaplan-Meier estimate showed worse survival in intravenous drug user (IDU) and heterosexuals than in men having sex with men (MSM). Factors associated with HIV-related causes of death include: IDU male (subHazard Ratio (sHR):3.2; CI:1.5-7.0) and <200 CD4 at diagnosis (sHR:2.7; CI:1.3-5.7) versus ≥500 CD4. Factors associated with non-HIV-related causes of death include: ageing (sHR:1.5; CI:1.4-1.7) and heterosexual female (sHR:2.8; CI:1.1-7.3) versus MSM. Factors associated with external causes of death were IDU male (sHR:28.7; CI:6.7-123.2) and heterosexual male (sHR:11.8; CI:2.5-56.4) versus MSM. CONCLUSION AND RECOMMENDATION: There are important differences in survival among transmission groups. Improved treatment is especially necessary in IDUs and heterosexual males.

Impact of an adherence program to antiretroviral treatment on virologic response in a cohort of multitreated and poorly adherent HIV-infected patients in Spain.

Several studies have shown the importance of adherence to highly active antiretroviral therapy (HAART) in achieving HIV-1 suppression. However, most have focused on naïve patients and do not assess the impact of HAART on viral load (VL). Our aim was to evaluate the effectiveness of an adherence program in a cohort of multitreated and poorly adherent patients. We performed a cohort study of all adult HIV-1 infected patients with detectable VL who were treatment experienced and poorly adherent to HAART, included in an adherence program since its introduction in 2009 (n=136). The adherence program consisted of a multidisciplinary team with a nurse who specialized in behavioral intervention, counselling on substance abuse, and motivational interviewing, as well as a social worker responsible for referring patients to local healthcare centers. Effectiveness was evaluated as percentage of patients with VL <50 copies/mL at week 48 by modified intent-to-treat (mITT) analysis. Initially, 76.6% of the patients had an adherence <30% according to the Simplified Medication Adherence Questionnaire (SMAQ). At 48 weeks, 48.1% of the patients had VL <50 copies/mL, and the adherence was >90% in 71% of the patients. In multivariate analysis, a ratio of bottle refill per month >0.9 during the study [odds ratio (OR) 14.3; 95% confidence interval (CI) 4.08-50.08, p<0.001] and being on a b.i.d. regimen (OR 12.5; 95% CI 1.81-86.4, p=0.010) were associated with an undetectable VL. In conclusion, the adherence program was successful in almost half of the patients, despite their long treatment experience and prior poor adherence. This strategy may help to prevent disease progression and the risk of HIV transmission in these patients.

Tropical diseases screening in immigrant patients with human immunodeficiency virus infection in Spain.

Latent parasitic infections can reactivate because of immunosuppression. We conducted a prospective observational study of all human immunodeficiency virus (HIV)-infected immigrants who visited the Infectious Diseases Department of the Hospital Universitari Vall d'Hebron, Barcelona, Spain, during June 2010-May 2011. Screening of the most prevalent tropical diseases (intestinal parasitosis, Chagas disease, leishmaniasis, malaria, schistosomiasis, and strongyloidiasis) was performed according to geographic origin. A total of 190 patients were included: 141 (74.2%) from Latin America, 41 (21.6%) from sub-Saharan Africa, and 8 (4.2%) from northern Africa. Overall, 36.8% (70 of 190) of the patients had at least one positive result for any parasitic disease: 5 patients with positive Trypanosoma cruzi serology, 11 patients with positive Schistosoma mansoni serology, 35 patients with positive Strongyloides stercoralis serology, 7 patients with positive Leishmania infantum serology, intestinal parasitosis were detected in 37 patients, malaria was diagnosed in one symptomatic patient. We propose a screening and management strategy of latent parasitic infections in immigrant patients infected with HIV.

Raltegravir, etravirine, and ritonavir-boosted darunavir: a safe and successful rescue regimen for multidrug-resistant HIV-1 infection.

BACKGROUND: Boosted darunavir (DRV/r) plus etravirine (ETR), in DUET trials, and raltegravir, in BENCHMRK trials, showed high rates of virologic response in patients with multidrug-resistant HIV-1 infection, particularly when associated with two more fully active antiretroviral drugs. No data from clinical trials, about this combination, are available. PATIENTS AND METHODS: Thirty-two consecutive heavily pretreated patients with multidrug-resistant HIV-1 infection who started a new salvage regimen with RAL (400 mg twice daily), ETR (200 mg twice daily), and DRV/r (600/100 mg twice daily) were studied. Clinical evaluation and immunologic, virologic, and biochemical parameters were collected at baseline and at Weeks 4, 12, and 24. RESULTS: Median baseline characteristics were age 44 years, 13 years on antiretroviral therapy, nine prior highly active antiretroviral therapy regimens, 261 CD4 cells/mL, and HIV-1 RNA 4.2 log10 copies/mL. Sixteen (50%) and 14 (44%) patients were enfuvirtide- and tipranavir-experienced, respectively. Three-class resistance mutations were present in all patients. Three patients (9%) had isolates with three ETR resistance mutations. All patients were DRV-naïve with a median of one DRV resistance mutation. At Weeks 4, 12, and 24, respectively, 63%, 81%, and 94% of patients achieved HIV1-RNA less than 50 copies/mL. Median CD4 cell count increased 30, 73, and 103 cells/mL at Weeks 4, 12, and 24, respectively. No patient had adverse events leading to discontinuation of the regimen. CONCLUSION: The combination of raltegravir, ETR, and DRV/r was a highly effective and well-tolerated antiretroviral salvage regimen in patients infected with multidrug-resistant HIV-1.

Serological response to pneumococcal vaccination in HAART-treated HIV-infected patients: one year follow-up study.

The aim of this study was to evaluate specific IgG responses against pneumococcal serotypes 1, 6B, 14, 19F, 23F at baseline, 1 and 12 months after vaccination with the 23-valent polysaccharide pneumococcal vaccine in 89 HAART-treated HIV-infected patients, 24 antiretroviral "naïve" HIV-infected and 30 non-HIV-infected healthy subjects. Levels of specific antipneumococcal IgG and the mean fold increase in IgG levels at 1 month as well as the kinetics of antibodies along the 12 months in all groups of HIV-infected patients and healthy subjects were similar. Neither CD4 cell count at baseline nor "nadir" CD4 cells correlated with the response to the vaccine. In conclusion, the immunogenicity conferred by the polysaccharide vaccine in HIV-infected patients under HAART is at least as good as that observed in healthy subjects.