Perspectives of people with HIV and HIV clinicians on characteristics of antiretroviral treatment and HIV-related symptoms.

OBJECTIVES: We aimed to assess HIV symptoms from the perspective of both patients and HIV specialists and the impact of discontinuing antiretroviral treatment (ART) on symptomology. We gathered opinions from HIV specialists and people living with HIV about ideal ART parameters and treatment satisfaction. METHODS: Ex post-facto cross-sectional surveys were administered to 502 people living with HIV and 101 HIV clinicians in Spain (18 sites). RESULTS: The median age of participants with HIV was 43.2 years, 74.5% were male, and 91.6% had an undetectable viral load. The mean time since initiation of ART was 10.2 years. Between 54% and 67% of people living with HIV reported experiencing nervousness or anxiety, sadness, fatigue, sleep problems, or muscle/joint pain during the preceding 4 weeks. However, only 22%-27% of specialists acknowledged the presence of these symptoms. The most bothersome symptoms were related to mental health or the central nervous system. There were significant differences between the burden of symptoms reported by people living with HIV and those acknowledged by specialists. The symptoms that more frequently caused ART discontinuation were depression, dizziness, and sleep problems. Both people living with HIV and specialists prioritized ART efficacy and low toxicity, but their importance ratings differed for 5 of the 11 ART characteristics assessed. People living with HIV rated their satisfaction with ART at a mean (± standard deviation) of 8.9 ± 1.5 out of 10, whereas HIV specialists rated it lower, at 8.3 ± 0.7 (p < 0.001). CONCLUSIONS: Despite advances in HIV care and treatment, a large proportion of patients still experience symptoms. HIV specialists may not be fully aware of these. People living with HIV and HIV specialists are, overall, satisfied with ART. However, the importance they place on different ART characteristics may vary.

Individual patient data meta-analysis of randomized controlled trials of dual therapy with a boosted PI plus lamivudine for maintenance of virological suppression: GeSIDA study 9717.

Background: Dual therapy (DT) with a ritonavir-boosted PI (PI/r) plus lamivudine has proven non-inferior (12% margin) to triple therapy (TT) with PI/r plus two nucleos(t)ide reverse transcriptase inhibitors [N(t)RTIs] in four clinical trials. It remains unclear whether DT is non-inferior based on the US FDA endpoint (virological failure with a margin of 4%) or in specific subgroups. Methods: We performed a systematic search (January 1990 to March 2017) of randomized controlled trials that compared switching of maintenance ART from TT to DT. The principal investigators were contacted and agreed to share study databases. The primary endpoint was non-inferiority of DT to TT based on the current FDA endpoint (4% non-inferiority margin for virological failure at week 48). We also analysed whether efficacy was modified by gender, active HCV infection and type of PI. Effect estimates and 95% CIs were calculated using generalized estimating equation-based models. Results: We found 881 references that yielded eight articles corresponding to four clinical trials (1051 patients). At week 48, 4% of patients on DT versus 3.04% on TT had experienced virological failure (difference 0.9%; 95% CI -1.2% to 3.1%), and 84.7% of patients on DT versus 83.2% on TT had <50 copies of HIV RNA/mL (FDA snapshot algorithm) (difference 1.4%; 95% CI -2.8% to 5.8%). Gender, active HCV infection and type of PI had no effect on differences in treatment efficacy between DT and TT. Conclusions: DT was non-inferior to TT using both current and past FDA endpoints. The efficacy of DT was not influenced by gender, active HCV infection status, or type of PI.

Simplification to dual therapy (atazanavir/ritonavir + lamivudine) versus standard triple therapy [atazanavir/ritonavir + two nucleos(t)ides] in virologically stable patients on antiretroviral therapy: 96 week results from an open-label, non-inferiority, randomized clinical trial (SALT study).

OBJECTIVES: We evaluated whether maintenance therapy with atazanavir/ritonavir plus lamivudine (ATV/r + 3TC) was non-inferior to ATV/r plus two nucleosides (ATV/r + 2NUCs) at 96 weeks of follow-up. METHODS: SALT is a multicentre, open-label, non-inferiority clinical trial in HIV-1-infected virologically suppressed patients. Hepatitis B virus surface antigen-negative subjects with no previous treatment failure/resistance mutations and HIV-1-RNA <50 copies/mL for ≥6 months were randomized (1 : 1) to ATV/r + 3TC or ATV/r + 2NUCs. The primary endpoint was HIV-1-RNA <50 copies/mL in the PP population. Non-inferiority was demonstrated if the lower bound of the 95% CI for the difference was not below -12%. RESULTS: Some 286 patients were analysed. At week 96, 74.4% had HIV-1-RNA <50 copies/mL in the ATV/r + 3TC arm versus 73.9% in the ATV/r + 2NUCs arm (95% CI for the difference, -9.9%-11.0%). In both groups, similar values were observed for patients with confirmed virological failure in ATV/r + 3TC versus ATV/r + 2NUCs (9 versus 5), death (1 versus 0), discontinuation due to ART-related toxicity (7 versus 11), withdrawal from the study (7 versus 9) and loss to follow-up (6 versus 6). One patient taking ATV/r + 2NUCs developed resistance mutations (M184V and L63P). Similar values were obtained for change in mean CD4 count [19 versus 18 cells/mm3 (95% CI for the difference, -49.3-50.7), grade 3-4 adverse events (70.7% versus 70.2%) and changes in the global deficit score, -0.3 (95% CI, -0.5 to -0.1) for ATV/r + 3TC, versus -0.2 (95% CI, -0.4 to -0.1) for ATV/r + 2NUCs]. CONCLUSIONS: The long-term results of switching to ATV/r + 3TC show that this strategy is effective, safe and non-inferior to ATV + 2NUCs in virologically suppressed HIV-infected patients.

Opt-out screening strategy for HIV infection among patients attending emergency departments: systematic review and meta-analysis.

OBJECTIVES: International health agencies have promoted nontargeted universal (opt-out) HIV screening tests in different settings, including emergency departments (EDs). We performed a systematic review and meta-analysis to assess the testing uptake of strategies (opt-in targeted, opt-in nontargeted and opt-out) to detect new cases of HIV infection in EDs. METHODS: We searched the Pubmed and Embase databases, from 1984 to April 2015, for opt-in and opt-out HIV diagnostic strategies used in EDs. Randomized controlled or quasi experimental studies were included. We assessed the percentage of positive individuals tested for HIV infection in each programme (opt-in and opt-out strategies). The mean percentage was estimated by combining studies in a random-effect meta-analysis. The percentages of individuals tested in the programmes were compared in a random-effect meta-regression model. Data were analysed using stata version 12. Quality assessments were performed using the Newcastle-Ottawa Scale. RESULTS: Of the 90 papers identified, 28 were eligible for inclusion. Eight trials used opt-out, 18 trials used opt-in, and two trials used both to detect new cases of HIV infection. The test was accepted and taken by 75 155 of 172 237 patients (44%) in the opt-out strategy, and 73 581 of 382 992 patients (19%) in the opt-in strategy. The prevalence of HIV infection detected by the opt-out strategy was 0.40% (373 cases), that detected by the opt-in nontargeted strategy was 0.52% (419 cases), and that detected by the opt-in targeted strategy was 1.06% (52 cases). CONCLUSIONS: In this meta-analysis, the testing uptake of the opt-out strategy was not different from that of the opt-in strategy to detect new cases of HIV infection in EDs.

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.

Clinical, epidemiological characteristics and indications for liver biopsy and treatment in immigrants with chronic hepatitis B at a referral hospital in Madrid.

The increase in immigration from less developed countries to Europe has led to an increase in the incidence of hepatitis B infection. The objective of this study was to describe the clinical, epidemiological characteristics and indications for treatment of chronic hepatitis B in a cohort of immigrants, given the relative lack of current evidence. We performed a noninterventional retrospective chart review; different characteristics depending on geographical origin were compared. A case-control study was also performed to describe factors potentially associated with chronic or past hepatitis B virus (HBV) infection. We selected a random sample of 436 patients out of the 2989 immigrants attending during the study period (1989-2008). Hepatitis B serology was performed in 74% (322/436): 10.6% had chronic HBV infection (95% CI: 7.4-13.7%), and 46.9% had evidence of past infection (95% CI: 41.7-52.0%). The average age was 31 years, 60% were men, and 70% were sub-Saharan Africans. Chronic infection was related to being men (OR 2.03; 95%CI: 1.29-3.18), younger (OR 0.98; 0.96-0.99) and sub-Saharan African (OR 5.41; 2.71-10.83). Past or current infection was related to male sex (OR 2.80; 1.81-4.30), longer time elapsed until first seen at the unit (OR 0.998; 0.997-1.000), HIV infection (OR 4.99; 1.15-21.60) and being sub-Saharan African (OR 15.46; 8.97-27.18). These associations were not confirmed after adjustment for geographical origin. In 27% and 29.5% of patients, liver biopsy and treatment, respectively, would have been indicated. Prevalence of chronic HBV infection amongst immigrants is high, especially in sub-Saharan Africans. Almost a third could be considered for liver biopsy or antiviral therapy.

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.

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.

Gastro-intestinal Chagas disease in migrants to Spain: prevalence and methods for early diagnosis.

Each year in Spain, the number of Latin American immigrants who present with chronic Trypanosoma cruzi infection increases. Although gastro-intestinal abnormalities are not as common as cardiomyopathy in such infection, they can still lead to an impaired quality of life. In a recent study based in Madrid, the frequencies of gastro-intestinal involvement in a cohort of Latin American immigrants infected with T. cruzi, and the role of early diagnostic techniques in the detection of such involvement, were explored. Between January 2003 and April 2009, all Latin Americans who attended the Tropical Medicine Unit of the Hospital Universitario Ramón y Cajal were tested for T. cruzi infection, in IFAT and ELISA. Each subject found both IFAT- and ELISA-positive was considered to be infected (chronically) and checked for symptoms indicative of Chagas disease. Each infected subject giving informed consent was investigated further, using an electrocardiogram, an echocardiogram and oesophageal manometry. Between January 2003 and June 2008, every infected subject who consented was also explored using a barium swallow and barium enema. After July 2008, however, only subjects showing oesophageal and/or colonic symptoms were investigated in this manner. Of the 248 patients found infected with T. cruzi, 118 underwent oesophageal manometry, 75 a barium enema and 48 a barium swallow. Thirteen (11%) showed evidence of oesophageal involvement (incomplete relaxation of the lower oesophageal sphincter; three cases) or bowel involvement (five cases of dolichosigma, three of dolichocolon and two of megacolon). Only six of these 13 had any gastro-intestinal symptoms (all six were suffering from constipation). None of the barium swallows revealed any pathology. It appears that oesophageal manometry can reveal mild abnormalities not detected by barium swallow, even in asymptomatic patients, while barium enemas are useful in the detection of colonic involvement.

Lack of association between blood-based detection of Trypanosoma cruzi DNA and cardiac involvement in a non-endemic area.

Cases of chronic Chagas disease have been increasing in non-endemic areas due to the growth in immigration. This study examined the association between positive Trypanosoma cruzi-DNA detection in blood by PCR and presence of chagasic cardiac involvement in a cohort of immigrants in a European city. No association was found in this study between the positive T. cruzi blood PCR and cardiac involvement.

EuroTravNet: imported Chagas disease in nine European countries, 2008 to 2009.

In recent years, Chagas disease has emerged as a disease of importance outside of endemic areas, largely as a result of migration. In Europe, clinicians may have to treat infected migrants from endemic areas as well as people with acute infections transmitted congenitally,through organ donation or blood transfusion.We describe here the characteristics of patients diagnosed with chronic Chagas disease at the core clinical sites of the EuroTravNet network during 2008 and 2009. Of the 13,349 people who attended the sites, 124 had chronic Chagas disease. Most (96%) were born in Bolivia and the median number of months in the country of residence before visiting a EuroTravNet core site was 38 months (quartile (Q1)­Q3: 26­55). The median age of the patients was 35 years (Q1­Q3: 29­45) and 65% were female. All but one were seen as outpatients and the most frequent reason for consultation was routine screening. Considering that Chagas disease can be transmitted outside endemic regions and that there is effective treatment for some stages of the infection, all migrants from Latin America (excluding the Caribbean) should be questioned about past exposure to the parasite and should undergo serological testing if infection is suspected.

Targeted screening and health education for Chagas disease tailored to at-risk migrants in Spain, 2007 to 2010.

Chagas disease is endemic in Latin America, but migration has expanded the disease's geographical limits. Spain is the most affected country in Europe. From 2007, a specific Chagas disease programme aimed at at-risk migrants was developed in three Spanish cities (Madrid, Jerez de la Frontera and Alicante). The objectives of the programme were to increase participants' knowledge and decrease their fears about the disease and to encourage them to undergo screening for Trypanosoma cruzi infection. The programme was specially focused on migrants from Bolivia and Latin American women of childbearing age. Culturally tailored interventions were carried out in non-clinical settings. A total of 276 migrants were screened using a rapid immunochromatographic test following talks on the disease: the results were then later confirmed by standard serological tests. Of those tested, 44 (15.9%) were confirmed cases of Chagas disease. All of them came from Bolivia and a quarter were pregnant women. Of the 44 cases, 31 were later followed up at a specialised Chagas disease clinic. We consider that the adaptation of the programme to the target population's needs and collaboration with non-governmental organisations and migrants' associations contributed to the acceptance of the programme and the increasing number of patients seen at a specialised clinic.

Comparison of antiviral activity of regimens containing nucleos(t)ide (NUC) Pairs in HIV-Infected Patients Initiating REScue therapy (The NUCREST Study).

BACKGROUND: recycling nucleos(t)ides (NUCs) is useful in regions where new antiretrovirals are not available. This study compares the effectiveness of NUC-containing regimens as rescue therapy in routine care. METHODS: retrospective, multicentre cohort study (January 2001 to June 2006) of patients with ≥ 1 virological failure who started therapy with 2 NUCs and 1 non-nucleoside reverse transcriptase inhibitor (NNRTI) or a protease inhibitor (PI). The primary endpoint was the rate of treatment response at 6 months (intention-to-treat [ITT] analysis). RESULTS: we included 719 patients (average of 4 prior regimens over a median 6.1 years). The most frequent NUC pairs were tenofovir plus lamivudine (TDF+3TC; 25%), tenofovir plus stavudine (TDF+d4T; 23%), and stavudine plus didanosine (d4T+ddI; 15%). A boosted PI was used in 68% of total cases. Resistance to both NUCs was more frequent in zidovudine plus lamivudine (AZT+3TC; 22.0%), abacavir plus lamivudine (ABC+3TC; 35.5%), and stavudine plus lamivudine (d4T+3TC; 31.2%). No significant differences were observed in treatment response (overall 65%, P = .67); ddI+3TC (71%) and d4T+3TC (53%) had the highest and lowest response rates, respectively. Median time to failure was shorter with d4T+3TC, d4T+ddI, and ABC+3TC (48, 51, and 58 weeks, respectively; P = .0012). Lower response rates associated with an increasing number of thymidine analog mutations (TAMs) were observed for ABC+3TC (P = .027). CONCLUSION: the clinical utility of NUCs for rescue therapy is limited and selection should be individualized. Specific combinations (d4T+3TC and d4T+ddI) might be less efficacious.

Update on the major imported helminth infections in travelers and migrants.

Helminth infections cause considerable morbidity worldwide and may be frequently underdiagnosed especially in areas of lower endemicity. Patients may harbor latent infections that may become symptomatic years or decades after the initial exposure and timely diagnosis may be critical to prevent complications and improve outcomes. In this context, disease in special populations, such as immunosuppressed patients, may be of particular concern. Heightened awareness and recent diagnostic developments may contribute to the correct management of helminth infections in nonendemic regions. A review of the main helminth infections in travelers and migrants (strongyloidiasis, taeniasis-neurocysticercosis and schistosomiasis) is presented, focusing on epidemiology, developments in diagnosis, treatment and prevention.

Comparison of the toxicity of two treatment schemes with benznidazole for chronic Chagas disease: a prospective cohort study in two Spanish referral centres.

OBJECTIVES: Chagas disease (CD) treatment is limited to two therapeutic options: benznidazole (generally the first option in Spain) and nifurtimox. Both drugs present high rates of adverse reactions and treatment discontinuation and there is no consensus regarding the most effective administration schedule for benznidazole or how to prevent and manage treatment toxicity. We aim to compare the tolerability and treatment discontinuation rate between two different treatment schemes with benznidazole. METHODS: This was a prospective observational study of adult patients with CD, enrolled from January 2014 to March 2018 in two referral centres in Madrid (Spain). Participants were treated either with benznidazole 5 mg/kg/day (full dose) over 60 days (benznidazole standard dose scheme (BSD)), or with an escalating dose lasting 5 days up to a maximum of 300 mg/day (benznidazole increasing dose scheme (BID)). RESULTS: 471 patients were analysed: 201 in the BSD group and 270 in the BID group. There were no significant differences regarding age (40.4 (SD 8.7) vs 41 (SD 8.2) years), sex (74.1% (149/201) vs 68.5% (185/270) women), weight (69.4 (SD 12.8) vs 68.9 (SD 11) kg) or nationality (97.5% (196/201) vs 96.7% (261/270) Bolivians) between groups. There were also no differences in adverse reactions rate (55.2% (111/201) vs 55.6% (150/270)), number of adverse reactions per patient, adverse reactions type (except for arthralgias and myalgias which occurred more frequently in the BID group (0% (0/111) BSD vs 8% (12/150) BID; p 0.002)) and degree and time to first adverse reactions. There was significantly more treatment discontinuation (49.8% (100/201) vs 33.0% (89/270); p <0.001) in the BSD group, but not during the first 30 days of treatment (32.3% (65/201) vs 25.6% (69/270); p 0.08). CONCLUSION: The use of increasing doses of benznidazole for 5 days and a maximum dose of 300 mg, does not significantly improve drug tolerability. However, while the treatment discontinuation rates were similar during the first 30 days of treatment, it may improve the treatment completion rate at 60 days.

Toxicity of nifurtimox as second-line treatment after benznidazole intolerance in patients with chronic Chagas disease: when available options fail.

OBJECTIVE: To describe the tolerability and rate of nifurtimox discontinuation when administered as a second-line treatment to patients with previous treatment interruptions due to adverse reactions with benznidazole. METHODS: We studied a prospective cohort study of adult patients with chronic Chagas disease in a referral centre in Spain treated from July 2007 to July 2017. We analysed the tolerability profile and treatment interruption rate due to adverse reactions (ARs) to nifurtimox in patients previously incompletely treated (less than 30 days) with benznidazole due to ARs. RESULTS: A total of 472 patients initiated treatment with benznidazole during the study period. Of these, 118 (25%) developed ARs that led to treatment discontinuation before 30 days of therapy. Fifty-three (44.9%) of 118 initiated nifurtimox as second-line treatment; most were women (79.3%), were of Bolivian origin (98.1%) and had a median age of 37.3 years (interquartile range, 29.8-43.2). The most common ARs with nifurtimox were cutaneous hypersensitivity (24.1%), digestive disorders (22.2%), fever (12.9%), neurologic disturbances (11.1%), depression, anxiety or insomnia (9.2%), dyspnoea (7.4%), myalgia (5.5%), and dizziness, asthenia or malaise (7.4%). Twenty-six (49.1%) of 53 patients discontinued nifurtimox due to ARs, all of them before the required minimal therapy duration of 60 days. There were no deaths. CONCLUSIONS: Treatment of chronic Chagas disease relies on two drugs with a poor tolerability profile. In our cohort, 12.3% of the patients who initiated benznidazole and subsequently nifurtimox in case of nontolerance developed ARs that led to permanent treatment discontinuation. Most were women of childbearing age, a group for whom therapy has the added benefit of interrupting vertical transmission.

CTX-M-15-non-ST131 Escherichia coli isolates are mainly responsible of faecal carriage with ESBL-producing Enterobacteriaceae in travellers, immigrants and those visiting friends and relatives.

Prevalence of extended-spectrum ß-lactamases (ESBL) and/or carbapenemase-producing Enterobacteriaceae (EPE and CPE) in stool samples from 75 travellers, 8 people visiting friends and relatives and 3 immigrants who had travelled or came from tropical or subtropical areas was determined. Thirty-one per cent (27/86) of the subjects were faecal carriers of EPE, and 37 EPE isolates were recovered (36 Escherichia coli, 1 Klebsiella pneumoniae). CTX-M-15 was the most prevalent enzyme (64.8%) mainly associated with E. coli belonging to phylogroup A and sequence type complex 10. Most of the ESBL-positive travellers (50%) had visited countries from Asia.

Clinicoepidemiologic characteristics, prognostic factors, and survival analysis of patients coinfected with human immunodeficiency virus and Leishmania in an area of Madrid, Spain.

From 1987 to 1995, a retrospective case study was conducted at the Ramon y Cajal Hospital in Madrid, Spain, a public teaching hospital with 1,100 beds, to determine the clinicoepidemiologic characteristics, survival, and prognostic factors of patients with visceral leishmaniasis (VL) and human immunodeficiency virus (HIV) infection. The prevalence of VL in HIV+ patients compared with HIV- patients was studied. Epidemiologic, clinical, and parasitologic characteristics, as well as the effects of treatment, prognosis, and survival in 54 HIV+ patients (90 episodes) with VL were defined. Comparative survival studies among patients with and without acquired immunodeficiency syndrome (AIDS)-defining criteria and multivariate analysis of survival risk factors were performed. The prevalence of VL in patients with AIDS was much higher than in immunocompetent individuals. In spite of a good initial response to treatment for VL, 60.6% of the patients had relapsed by the end of one year. Mortality from the first episode was 18.5%, and 24% died in the first month after diagnosis of any VL episode. The mean survival of the 29 patients who died was 10.27 months. Survival in patients with and without AIDS at the time of the first episode of VL was compared at 30 months: 53.7% versus 20.5% (P = 0.00149). We found no significant difference (P = 0.24) in the survival of HIV+ patients who had died of VL without AIDS at the time of the first episode of VL compared with those of a control group of 413 dead patients with AIDS without VL. A diagnosis of AIDS at the time of the first episode of VL and thrombocytopenia were the only risk factors found related to survival. We conclude that in AIDS patients, VL is a recurrent disease that is highly prevalent and whose clinical course is modified by HIV.

Nelfinavir plus nevirapine plus two NRTIS as salvage therapy for HIV-infected patients receiving long-term antiretroviral treatment.

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 log(10) (interquartile range [IQR] 1.63 log(10)), and median CD4 cell count 64 cells/microL (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.

Semiquantitative culture of subcutaneous segment for conservative diagnosis of intravascular catheter-related infection.

BACKGROUND: Sensitivity and negative predictive values of combined surface cultures (skin and hub) are high in the presumptive diagnosis of catheter-related infection, but specificity and PPVs are poor. The purpose of the study was to evaluate the yield of the semiquantitative culture of the subcutaneous segment in the diagnosis of colonization of the catheter tip without removal of the catheter. METHODS: A prospective study was performed in 124 nontunneled central venous catheters that were removed because of suspected infection or the end of therapy. Catheter colonization was considered if >15 colony-forming units (CFU) in the roll procedure or > 1,000 CFU in the quantitative Cleri procedure were recovered from the tip cultures ("gold standard"). Before removing the catheter, a semiquantitative culture of skin surrounding the point of insertion, a semiquantitative culture of the subcutaneous segment (after removing the catheter only 2 cm), a semiquantitative cultures of the hub, and a pareated quantitative blood culture were performed. Receiver operating characteristic curves were calculated to estimate the cutoff points, and a culture was considered positive when CFUs were > or =15, > or =15, and > or =5 for skin, hub, and subcutaneous segment cultures, respectively. RESULTS: Catheter colonization was detected in 51 catheters. The mean duration of catheterization was 14 +/- 8 days, and the rates of incidence of tip colonization and bacteremia were 2.9 per 100 catheter days and 1.2 per 100 catheter days, respectively. Sensitivity of skin, subcutaneous, and hub cultures analyzed individually were < or =61%; however, specificity and positive predictive values (PPVs) of subcutaneous segment cultures were significantly higher than skin cultures (94% and 88.5% vs 71.6% (p = .001) and 62% (p = .014), respectively). Sensitivity of the combined skin and hub cultures and of the combined subcutaneous segment and hub cultures were similar: 86.2% and 84.3%, respectively; however, specificity and PPVs of this latter combination were significantly higher than former: 82% and 78.1% vs 59.7% (p = .008) and 61.9% (p = .07), respectively. The likelihood ratio of a positive test for the combined subcutaneous segment and hub culture was 4.68, and only 2.13 for the combined skin and hub culture. CONCLUSIONS: These results indicate that the combined subcutaneous segment and hub culture constitutes an easy, effective procedure for the conservative diagnosis of catheter colonization.

Travelers visiting friends and relatives (VFR) and imported infectious disease: travelers, immigrants or both? A comparative analysis.

INTRODUCTION: Immigrants are increasingly traveling back to their countries of origin to visit friends and relatives (VFRs). They account for an important proportion of all international travelers and have a high risk for certain travel-related infectious diseases. METHODS: We describe the spectrum of infectious diseases diagnosed in a cohort of 351 VFRs and compare them with two previously published cohorts: of immigrants and travelers attended at our centre. RESULTS: The most frequent diagnoses observed among VFRs were typical travel-associated infections such as malaria (75 [21.4%]), traveler's diarrhea 17 [4.8%]), intestinal parasites (16 [4.6%]) and dengue (11 [3.1%]). Asymptomatic chronic infectious diseases, such as latent tuberculosis (56 [16%]), chronic viral hepatitis (18 [5.1%]) and filariasis (18 [5.1%]), probably acquired before migration, were also observed. CONCLUSIONS: VFRs should thus be approached from two perspectives as concerns imported infectious diseases: as travelers and as immigrants. Etiological studies focusing on the presenting complaint as well as systematic screening for other latent infectious diseases should be performed.