Participation, retention and uptake in a multicentre pre-exposure prophylaxis cohort using online, smartphone-compatible data collection.

OBJECTIVES: The aim of the study was to assess the feasibility of a national pre-exposure prophylaxis (PrEP) programme using smartphone-compatible data collection. METHODS: This was a multicentre cohort study (NCT03893188) enrolling individuals interested in PrEP in Switzerland. All centres participate in the SwissPrEPared programme, which uses smartphone-compatible data collection. Feasibility was assessed after centres had enrolled at least one participant. Participants were HIV-negative individuals presenting for PrEP counselling. Outcomes were participation (number enrolled/number eligible), enrolment rates (number enrolled per month), retention at first follow-up (number with first follow-up/number enrolled), and uptake (proportion attending first visit as scheduled). Participant characteristics were compared between those retained after baseline assessment and those who dropped out. RESULTS: Between April 2019 and January 2020, 987 individuals were assessed for eligibility, of whom 969 were enrolled (participation: 98.2%). The median enrolment rate was 86 per month [interquartile range (IQR) 52-137]. Retention at first follow-up and uptake were both 80.7% (782/969 and 532/659, respectively). At enrolment, the median age was 40 (IQR 33-47) years, 95% were men who have sex with men, 47% had a university degree, and 75.5% were already taking PrEP. Most reported multiple casual partners (89.2%), previous sexually transmitted infections (74%) and sexualized drug use (73.1%). At baseline, 25.5% tested positive for either syphilis, gonorrhoea or chlamydia. Participants who dropped out were at lower risk of HIV infection than those retained after baseline assessment. CONCLUSIONS: In a national PrEP programme using smartphone-compatible data collection, participation, retention and uptake were high. Participants retained after baseline assessment were at considerable risk of HIV infection. Younger, less educated individuals were underrepresented in the SwissPrEPared cohort.

Changes in alanine aminotransferase levels after switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) in HIV-positive people without viral hepatitis in the Swiss HIV Cohort Study.

OBJECTIVES: We previously demonstrated an association between tenofovir disoproxil fumarate (TDF) and chronic liver enzyme elevation in the D:A:D study. The objective of the study was to assess changes in alanine aminotransferase (ALT) levels after switching from TDF to tenofovir alafenamide (TAF). METHODS: We included Swiss HIV Cohort Study participants who switched from TDF to TAF with two or more ALT values in the 24 months before and two or more values in the 24 months after replacing TDF with TAF. Individuals with replicating viral hepatitis were excluded. Uni- and multivariable linear mixed models were used to explore changes in ALT values associated with switching from TDF to TAF, and to assess potential modifying effects. RESULTS: A total of 1712 participants were included, contributing 6169 ALT values before and 5482 after switching. Median (interquartile range, IQR) age was 50 (42-57) years, and 75% were male. Median (IQR) ALT was 28 (22-38) U/L before and 24 (19-32) U/L after replacing TDF with TAF. ALT values decreased by 3.7 U/L (95% confidence interval: 3.2-4.2) after the switch. The median drop was larger in patients with chronic ALT elevation (defined as two or more elevated values for ≥ 6 months) compared with patients with normal ALT values (17.8 vs. 3.3 U/L, P < 0.001). We did not identify any major effect modifications of the ALT change with any of the potential variables studied. CONCLUSIONS: Replacing TDF with TAF in HIV-monoinfected people led to a significant decrease in ALT values. Findings were not significantly affected by known risk factors for hepatotoxicity.

How helpful are the European AIDS Clinical Society cognitive screening questions in predicting cognitive impairment in an aging, well-treated HIV-positive population?

OBJECTIVES: Diagnosing neurocognitive impairment (NCI) in HIV infection requires time-consuming neuropsychological assessment. Screening tools are needed to identify when neuropsychological referral is indicated. We examined the positive and negative predictive values (PPVs and NPVs, respectively) of the three European AIDS Clinical Society (EACS) screening questions in identifying NCI. METHODS: The Neurocognitive Assessment in the Metabolic and Aging Cohort (NAMACO) study recruited patients aged ≥45 years enrolled in the Swiss HIV Cohort Study between 1 May 2013 and 30 November 2016. NAMACO participants (1) answered EACS screening questions, (2) underwent standardized neuropsychological assessment and (3) completed self-report forms [Center for Epidemiologic Studies Depression Scale (CES-D)] rating mood. NCI categories were defined using Frascati criteria. PPVs and NPVs of the EACS screening questions in identifying NCI categories were calculated. RESULTS: Of 974 NAMACO participants with complete EACS screening question data, 244 (25.1%) expressed cognitive complaints in answer to at least one EACS screening question, of whom 51.3% had NCI (26.1% HIV-associated and 25.2% related to confounding factors). The PPV and NPV of the EACS screening questions in identifying HIV-associated NCI were 0.35 and 0.7, respectively. Restricting analysis to NCI with functional impairment or related to confounding factors, notably depression, the NPV was 0.90. Expressing cognitive complaints for all three EACS screening questions was significantly associated with depression (P < 0.001). CONCLUSIONS: The EACS screening questions had an NPV of 0.7 for excluding patients with HIV-associated NCI as defined by Frascati criteria. The PPV and NPV may improve if NCI diagnoses are based on new criteria.

The Neurocognitive Assessment in the Metabolic and Aging Cohort (NAMACO) study: baseline participant profile.

OBJECTIVES: The aim of the study was to examine baseline neurocognitive impairment (NCI) prevalence and factors associated with NCI among patients enrolled in the Neurocognitive Assessment in the Metabolic and Aging Cohort (NAMACO) study. METHODS: The NAMACO study is an ongoing, prospective, longitudinal, multicentre and multilingual (German, French and Italian) study within the Swiss HIV Cohort Study. Between 1 May 2013 and 30 November 2016, 981 patients ≥ 45 years old were enrolled in the study. All underwent standardized neuropsychological (NP) assessment by neuropsychologists. NCI was diagnosed using Frascati criteria and classified as HIV-associated or as related to other factors. Dichotomized analysis (NCI versus no NCI) and continuous analyses (based on NP test z-score means) were performed. RESULTS: Most patients (942; 96.2%) had viral loads < 50 HIV-1 RNA copies/mL. NCI was identified in 390 patients (39.8%): 263 patients (26.8%) had HIV-associated NCI [249 patients (25.4%) had asymptomatic neurocognitive impairment (ANI)] and 127 patients (13%) had NCI attributable to other factors, mainly psychiatric disorders. There was good correlation between dichotomized and continuous analyses, with NCI associated with older age, non-Caucasian ethnicity, shorter duration of education, unemployment and longer antiretroviral therapy duration. CONCLUSIONS: In this large sample of aging people living with HIV with well-controlled infection in Switzerland, baseline HIV-associated NCI prevalence, as diagnosed after formal NP assessment, was 26.8%, with most cases being ANI. The NAMACO study data will enable longitudinal analyses within this population to examine factors affecting NCI development and course.

Why do sub-Saharan Africans present late for HIV care in Switzerland?

OBJECTIVES: Late presentation (LP) to HIV care disproportionally affects individuals from sub-Saharan Africa (SSA). We explored the reasons for late presentation to care among this group of patients in the Swiss HIV Cohort Study. METHODS: The prevalence of LP was compared between patients from Western Europe (WE) and those from SSA enrolled between 2009 and 2012. Patients were asked about HIV testing, including access to testing and reasons for deferring it, during face-to-face interviews. RESULTS: The proportion of LP was 45.8% (435/950) among patients from WE, and 64.6% (126/195) among those from SSA (P < 0.001). Women from WE were slightly more likely to present late than men (52.6% versus 44.5%, respectively; P = 0.06), whereas there was no sex difference in patients from SSA (65.6% versus 63.2%, respectively; P = 0.73). Compared with late presenters from WE, those from SSA were more likely to be diagnosed during pregnancy (9.1% versus 0%, respectively; P < 0.001), but less likely to be tested by general practitioners (25.0% versus 44.6%, respectively; P = 0.001). Late presenters from SSA more frequently reported 'not knowing about anonymous testing possibilities' (46.4% versus 27.3%, respectively; P = 0.04) and 'fear about negative reaction in relatives' (39.3% versus 21.7%, respectively; P = 0.05) as reasons for late testing. Fear of being expelled from Switzerland was reported by 26.1% of late presenters from SSA. CONCLUSIONS: The majority of patients from SSA were late presenters, independent of sex or education level. Difficulties in accessing testing facilities, lack of knowledge about HIV testing and fear-related issues are important drivers for LP in this population.

Relationship between enteric pathogens and acute gastroenteritis disease severity: a prospective cohort study.

OBJECTIVES: To evaluate the relationship between individual bacterial and viral pathogens and disease severity. METHODS: Children <18 years with three or more episodes of vomiting and/or diarrhoea were enrolled in two Canadian paediatric emergency departments between December 2014 and August 2016. Specimens were analysed employing molecular panels, and outcome data were collected 14 days after enrolment. The primary outcome was severe disease over the entire illness (symptom onset until 14-day follow-up), quantified employing the Modified Vesikari Scale (MVS) score. The score was additionally analysed in two other time periods: index (symptom onset until enrolment) and follow-up (enrolment until 14-day follow-up). RESULTS: Median participant age was 20.7 (IQR: 11.3, 44.2) months; 47.4% (518/1093) and 73.4% (802/1093) of participants had index and total MVS scores ≥11, respectively. The most commonly identified pathogens were rotavirus (289/1093; 26.4%) and norovirus (258/1093; 23.6%). In multivariable analysis, severe disease over the entire illness was associated with rotavirus (OR = 9.60; 95%CI: 5.69, 16.19), Salmonella (OR = 6.61; 95%CI: 1.50, 29.17), adenovirus (OR = 2.53; 95%CI: 1.62, 3.97), and norovirus (OR = 1.43; 95%CI: 1.01, 2.01). Pathogens associated with severe disease at the index visit were: rotavirus only (OR = 6.13; 95%CI: 4.29, 8.75), Salmonella (OR = 4.59; 95%CI: 1.71, 12.29), adenovirus only (OR = 2.06; 95%CI: 1.41, 3.00), rotavirus plus adenovirus (OR = 3.15; 95%CI: 1.35, 7.37), and norovirus (OR = 0.68; 95%CI: 0.49, 0.94). During the follow-up period, rotavirus (OR = 2.21; 95%CI: 1.50, 3.25) and adenovirus (OR = 2.10; 95%CI: 1.39, 3.18) were associated with severe disease. CONCLUSIONS: In children presenting for emergency department care with acute gastroenteritis, pathogens identified were predominantly viruses, and several of which were associated with severe disease. Salmonella was the sole bacterium independently associated with severe disease.

Gut Sphingolipid Composition as a Prelude to Necrotizing Enterocolitis.

Necrotizing enterocolitis (NEC) remains a major challenge in neonatology. Little is known about NEC pathophysiology apart from the presence of pre-event gut dysbiosis. Here, we applied broad range metabolomics to stools obtained 1-5 days before NEC developed from 9 cases (9 samples) and 19 (32 samples) controls matched for gestational age at birth and birth weight. The 764 identified metabolites identified six pathways that differ between cases and controls. We pursued sphingolipid metabolism because cases had decreased ceramides and increased sphingomyelins compared to controls, and because of the relevance of sphingolipids to human inflammatory disorders. Targeted analysis of samples from 23 cases and 46 controls confirmed the initial broad range observations. While metabolites provided only 73% accuracy of classification by machine learning, hierarchical clustering defined a sphingolipid associated grouping that contained 60% of the cases but only 13% of the controls, possibly identifying a pathophysiologically distinct subset of NEC. The clustering did not associate with any of the analyzed clinical and sample variables. We conclude that there are significant changes in sphingolipid metabolism components in pre-NEC stools compared to controls, but our data urge circumspection before using sphingolipids as broadly applicable predictive biomarkers.

Importance of case age in the purported association between phylogenetics and hemolytic uremic syndrome in Escherichia coli O157:H7 infections.

Escherichia coli O157:H7 is the largest cause of hemolytic uremic syndrome (HUS). Previous studies proposed that HUS risk varies across the E. coli O157:H7 phylogenetic tree (hypervirulent clade 8), but the role of age in the association is unknown. We determined phylogenetic lineage of E. coli O157:H7 isolates from 1160 culture-confirmed E. coli O157:H7 cases reported in Washington State, 2004-2015. Using generalised estimating equations, we tested the association between phylogenetic lineage and HUS. Age was evaluated as an effect modifier. Among 1082 E. coli O157:H7 cases with both phylogenetic lineage and HUS status (HUS n = 76), stratified analysis suggested effect modification by age. Lineages IIa and IIb, relative to Ib, did not appear associated with HUS in children 0-9-years-old. For cases 10-59-years-old, lineages IIa and IIb appeared to confer increased risk of HUS, relative to lineage Ib. The association reversed in ⩾60-year-olds. Results were similar for clade 8. Phylogenetic lineage appears to be associated with HUS risk only among those ⩾10-years-old. Among children <10, the age group most frequently affected, lineage does not explain progression to HUS. However, lineage frequency varied across age groups, suggesting differences in exposure and/or early disease manifestation.

Small bowel resection induces long-term changes in the enteric microbiota of mice.

PURPOSE: The enteric microbiome is known to play a major role in healthy gut homeostasis and several disease states. It may also contribute to both the intestinal recovery and complications that occur in patients with short bowel syndrome. The extent and nature of alterations to the gut microbiota following intestinal resection, however, are not well studied in a controlled setting. The purpose of this investigation is to characterize the effects of massive small bowel resection on the murine enteric microflora. METHODS: Wild-type C57BL6 mice, following a week of acclamation to a liquid rodent diet, underwent either 50% proximal small bowel resection (SBR) or a sham operation. Mice were sacrificed, and enteric contents from the small bowel, cecum, and stool were harvested at 7 and 90 days post-operatively. DNA was isolated, and the V3-V5 regions of the 16s rRNA gene amplified and pyrosequenced on a Roche 454 platform. Sequences were clustered into operation taxonomic units and classified. Communities were then analyzed for diversity and phylogenic composition. RESULTS: In the long-term group, the microbes inhabiting the ileum of mice undergoing SBR and sham operation differed significantly at the genus level (p < 0.001). Small bowel contents collected before and after SBR also differed significantly (p = 0.006). This was driven by an increase in Lactobacillus and decrease in Enterobacteriaceae species in mice undergoing SBR. No difference was seen in the long-term stool or in stool, cecal, or ileal contents in the short-term. No difference in microbial community diversity was found in any group. CONCLUSION: Bowel resection induces long-term changes in the microbial community of the murine ileum, but not at more distal sites of the gastrointestinal tract. The increase in Lactobacillus encountered small bowel of resected mice correlates with limited previous studies. These changes may reflect an adaptive response of the microbiota to maximize energy extraction, but further studies are needed to establish the role played by this altered community.

Transvaginal access for NOTES: a cohort study of microbiological colonization and contamination.

BACKGROUND AND STUDY AIMS: Animal data and limited clinical evidence suggest a low incidence of infection following transvaginal natural orifice transluminal endoscopic surgery (NOTES). However, a systematic microbiological evaluation has not yet been carried out. The aim of this prospective cohort study was to evaluate the extent of microbiological contamination of the peritoneal cavity caused by the transvaginal access for NOTES and the impact of preoperative vaginal disinfection on vaginal colonization. PATIENTS AND METHODS: Consecutive female patients with symptomatic cholecystolithiasis were offered either transvaginal rigid-hybrid cholecystectomy (tvCCE) or conventional laparoscopic cholecystectomy. Patients who opted for tvCCE were prospectively evaluated between February and June 2010. Disinfection in patients undergoing tvCCE included hexetidine tablets and octenidine applied vaginally. All patients received a single dose of perioperative cefuroxime. Swabs were obtained from the posterior fornix and the peritoneal cavity at different intervals. RESULTS: Of 32 patients, 27 (84 %) opted to undergo tvCCE. One patient (4 %; 95 % confidence interval [CI] 0.7 % - 18.3 %) had a positive bacterial culture in the Douglas pouch prior to transvaginal access compared with two patients (7 %; 95 %CI 2.1 % - 23.4 %) following colpotomy closure (P = 1.000). Vaginal disinfection significantly decreased vaginal bacterial load (P = 0.001) and bacterial growth in routine cultures (P < 0.001); in 16 patients (59 %; 95 %CI 40.7 % - 75.5 %) vaginal swabs were sterile after disinfection. No postoperative surgical site infections occurred (95 %CI 0 % - 12.5 %). CONCLUSIONS: In selected patients and following vaginal antisepsis, transvaginal access for NOTES is associated with microbiological contamination of the peritoneal cavity in a minority of patients, indicating a low risk of peritoneal contamination caused by the transvaginal access.

Longer prior exposure to zidovudine/lamivudine-containing combination antiretroviral therapy, age, and male gender are each associated with reduced subcutaneous adipose tissue.

OBJECTIVES: Whether zidovudine (AZT)-associated lipoatrophy occurrence differs by concomitant exposure to protease (PIs) or non-nucleoside reverse transcriptase inhibitors (NNRTIs) remains unclear. Baseline body composition data from a randomized trial in subjects stable on first-line AZT-based therapy were used to explore this issue. METHODS: In this substudy of the PREPARE trial, centrally read baseline whole-body dual energy x-ray aborptiometry (DXA) and single-slice abdominal CT scans were analyzed with respect to duration and type of prior AZT/lamivudine (3TC) combination antiretroviral therapy (cART), including by multivariate linear regression adjusted for age, gender, ethnicity, body mass index (BMI), and nadir CD4. RESULTS: DXA and CT, from 134 and 136 patients, respectively [87% male; 82% Caucasian; mean (SD) age, 45.6 years (10); BMI, 24.3 kg/m² (3.2)], were analyzed. Prior AZT/3TC cART exposure was 5.5 (2.2) years. Seventy-eight and 27 patients had concomitantly and exclusively used NNRTIs and PIs, respectively. AZT/3TC cART, AZT/3TC/NNRTI, and AZT/3TC/PI, respectively, were associated with the presence of a mean (95% CI) of 247 g (-438 to -56; P = .012), 267 g (-467 to -66; P = .010), and 216 g (-430 to -1.7; P = .048) less baseline limb fat per additional year of prior exposure. Although abdominal subcutaneous (SAT) adipose tissue was likewise less with longer AZT/3TC cART, this was only significant for AZT/3TC/ NNRTI but not AZT/3TC/PI. Visceral adipose tissue (VAT) amount was not clearly associated to prior treatment. Increased age and male gender were independently associated with lower limb fat and SAT, but more VAT. CONCLUSIONS: Longer exposure to AZT/3TC, regardless of whether in combination with PI or NNRTI, as well as increased age and male gender are independently associated with lower limb fat mass.

The age of necrotizing enterocolitis onset: an application of Sartwell's incubation period model.

OBJECTIVE: Model age of necrotizing enterocolitis (NEC) onset applying Sartwell's model of incubation periods, and examine its relationship to gestational age (GA). STUDY DESIGN: Retrospective chart review of St Louis Children's Hospital neonates diagnosed with NEC (≥Bell's stage II) from 2004 to 2008, inclusive. RESULT: The relationship between age of NEC (N=84 cases) onset and GA best fits a non-linear model, with infants ≤28 weeks having a disproportionately longer time to onset than older GA groups and explained 50.3% of the variability in age of NEC onset. Additional clinical variables provided no improvement in explaining age of NEC onset. Application of Sartwell's model to age of NEC onset proved a good fit, when birth is used as the common exposure episode, and age is equivalent of the incubation period. CONCLUSION: The relationship between day of NEC diagnosis and GA is non-linear, with lower GA infants having disproportionately longer time to onset. Despite these GA differences, the fit to Sartwell's model for incubation periods model is consistent with NEC being a consequence of an event that occurs at or soon after birth.

The ecology and pathobiology of Clostridium difficile infections: an interdisciplinary challenge.

Clostridium difficile is a well recognized pathogen of humans and animals. Although C. difficile was first identified over 70 years ago, much remains unknown in regards to the primary source of human acquisition and its pathobiology. These deficits in our knowledge have been intensified by dramatic increases in both the frequency and severity of disease in humans over the last decade. The changes in C. difficile epidemiology might be due to the emergence of a hypervirulent stain of C. difficile, ageing of the population, altered risk of developing infection with newer medications, and/or increased exposure to C. difficile outside of hospitals. In recent years, there have been numerous reports documenting C. difficile contamination of various foods, and reports of similarities between strains that infect animals and strains that infect humans as well. The purposes of this review are to highlight the many challenges to diagnosing, treating, and preventing C. difficile infection in humans, and to stress that collaboration between human and veterinary researchers is needed to control this pathogen.

Thymoma, immunodeficiency, and herpes simplex virus infections.

Hypogammaglobulinemia develops in 3 to 6% of patients with thymoma and this association is commonly referred to as thymoma with immunodeficiency (formerly Good syndrome). Recurrent infections with encapsulated bacteria and opportunistic infections associated with disorders of both humoral and cell mediated immunity frequently occur in this rare primary, adult-onset immunodeficiency. We report a case of thymoma with immunodeficiency complicated by disseminated herpes simplex virus (HSV) infection and review five additional cases of HSV-related infections reported since 1966 in patients presenting with thymoma with immunodeficiency. Patients presented with epiglottitis, keratitis, recurrent genital herpes, ulcerative dermatitis, and acute hepatitis. Four of the six cases had a fatal outcome, two of which were directly attributable to HSV infection. Since the risk of invasive opportunistic infections is high and the presentation atypical, lymphocyte count and total serum immunoglobulin should be measured regularly in all patients presenting with thymoma with immunodeficiency.

A glucagon-like endocrine pathway in Drosophila modulates both lipid and carbohydrate homeostasis.

The regulation of energy homeostasis is fundamental to all organisms. The Drosophila fat body serves as a repository for both triglycerides and glycogen, combining the energy storage functions of mammalian adipose and hepatic tissues, respectively. Here we show that mutation of the Drosophila adipokinetic hormone receptor (AKHR), a functional analog of the mammalian glucagon receptor, leads to abnormal accumulation of both lipid and carbohydrate. As a consequence of their obese phenotypes, AKHR mutants are markedly starvation resistant. We show that AKHR is expressed in the fat body, and, intriguingly, in a subset of gustatory neurons that mediate sweet taste. Genetic rescue experiments establish that the metabolic phenotypes arise exclusively from the fat body AKHR expression. Behavioral experiments demonstrate that AKHR mutants are neither sedentary nor hyperphagic, suggesting the metabolic abnormalities derive from a genetic propensity to retain energy stores. Taken together, our results indicate that a single endocrine pathway contributes to both lipid and carbohydrate catabolism in the Drosophila fat body.

Associations between bovine, human, and raw milk, and beef isolates of non-O157 Shiga toxigenic Escherichia coli within a restricted geographic area of the United States.

A survey for Shiga toxigenic Escherichia coli in raw milk and beef was conducted within a defined geographic region of the United States. Prevalence rates based on detection of Shiga toxin gene (stx) were 36% for retail beef, 23% for beef carcasses, and 21% for raw milk samples, which were significantly higher than were Shiga toxigenic E. coli isolation rates of 7.5, 5.8, and 3.2%, respectively. Seasonal prevalence differences were significant for stx positivity among ground beef and milk samples. Distribution of stx subtypes among isolates varied according to sample type, with stx1 predominating in milk, stx2 on carcasses, and the combination of both stx1 and stx2 in beef. Ancillary virulence markers eae and ehx were evident in 23 and 15% of isolates, respectively. Pulsed-field gel electrophoresis demonstrated associations between food isolates and sympatric bovine fecal, and human clinical isolates. These data demonstrate that non-O157 Shiga toxigenic E. coli is present in the food chain in the Pacific Northwest, and its risk to health warrants critical assessment.

Lipodystrophy and weight changes: data from the Swiss HIV Cohort Study, 2000-2006.

BACKGROUND AND OBJECTIVES: Combination antiretroviral therapy (cART) is changing, and this may affect the type and occurrence of side effects. We examined the frequency of lipodystrophy (LD) and weight changes in relation to the use of specific drugs in the Swiss HIV Cohort Study (SHCS). METHODS: In the SHCS, patients are followed twice a year and scored by the treating physician as having 'fat accumulation', 'fat loss', or neither. Treatments, and reasons for change thereof, are recorded. Our study sample included all patients treated with cART between 2003 and 2006 and, in addition, all patients who started cART between 2000 and 2003. RESULTS: From 2003 to 2006, the percentage of patients taking stavudine, didanosine and nelfinavir decreased, the percentage taking lopinavir, nevirapine and efavirenz remained stable, and the percentage taking atazanavir and tenofovir increased by 18.7 and 22.2%, respectively. In life-table Kaplan-Meier analysis, patients starting cART in 2003-2006 were less likely to develop LD than those starting cART from 2000 to 2002 (P<0.02). LD was quoted as the reason for treatment change or discontinuation for 4% of patients on cART in 2003, and for 1% of patients treated in 2006 (P for trend <0.001). In univariate and multivariate regression analysis, patients with a weight gain of >or=5 kg were more likely to take lopinavir or atazanavir than patients without such a weight gain [odds ratio (OR) 2, 95% confidence interval (CI) 1.3-2.9, and OR 1.7, 95% CI 1.3-2.1, respectively]. CONCLUSIONS: LD has become less frequent in the SHCS from 2000 to 2006. A weight gain of more than 5 kg was associated with the use of atazanavir and lopinavir.