Wireless capsule endoscopy for the detection of small bowel diseases in HIV-1-infected patients

<p>Abstract</p> <p>Background and Aims</p> <p>In HIV-infected patients, manifestations of the disease are common in the gastrointestinal tract. The objective of our study was to evaluate the diagnostic yield of the Given^®Video Capsule System (Given Imaging, Yoqneam, Israel) in these patients.</p> <p>Methods</p> <p>After exclusion of GI-tract stenosis by anamnestic exploration, 49 patients were included into the study. Stratification: Group A (n = 19): HIV-positive, CD₄cell count < 200/μl, gastrointestinal symptoms present. Group B: HIV-positive, CD₄< 200/μl, without gastrointestinal symptoms (n = 19 Group) C: healthy volunteers (n = 11).</p> <p>Results</p> <p>In group A there was a total of 30 pathological findings, 15 of which with therapeutic implications. In group B, there was a total of 22 pathological findings, 5 relevant for therapy. In group C there was a total of 13 pathological findings, 3 with therapeutic relevance. In 89% (group A) vs. 26% (group B), pathological findings were detected distal the ligament of Treitz (p = 0.001). All capsules were recovered without complications after 12 to 96 h from the stool.</p> <p>Conclusion</p> <p>Wireless capsule endoscopy of the small intestine should be considered for HIV-infected patients with marked immunosuppression and gastrointestinal symptoms.</p

Maraviroc in treatment-experienced patients with HIV-1 infection - experience from routine clinical practice

<p>Abstract</p> <p>Objective</p> <p>Few data are available about the efficacy of maraviroc (MVC) during routine use. We characterized indications for MVC use and the efficacy of MVC in clinical practice.</p> <p>Methods</p> <p>Thirty-two patients treated with MVC at our institution between 2006 and 2009 were included. Genotypic (n = 31) and phenotypic (n = 13) tropism analysis was performed. We determined indications for MVC use, characteristics of antiretroviral combination partners and treatment outcome.</p> <p>Results</p> <p>Complete suppression of viral replication was achieved in 78% after 6 months. A median increase of 124 CD4⁺cells/μl after 6 months was observed. Concordance between phenotypic and genotypic tropism was found in 75%. Indications for MVC treatment included treatment failure (n = 15), intolerance to previous antiretrovirals (n = 6) and add-on MVC for intensification without changing the current regimen (n = 11). The add-on strategy was used in patients with a relatively low viremia in order to achieve complete viral load suppression or in situations with suppressed viral load but judged as unstable due to an extensive resistance pattern. Salvage drugs most frequently combined with MVC were darunavir (n = 14) and raltegravir (n = 14).</p> <p>The genotypic assay had predicted CXCR4 tropism in 5 patients, using a false positive rate (FPR) of 20%. Lowering the FPR to 5% predicted CCR5 tropism in 4 cases, still resulting in sustained complete viral response under MVC use.</p> <p>Conclusions</p> <p>MVC containing salvage regimens achieve relevant CD4 cell increases and high viral response rates. In patients with few remaining treatment options it may be justified to lower the FPR-cutoff to 5% when predicting the coreceptor usage. Hereby, MVC could still be applied in selected patients with otherwise limited treatment options.</p

Gender Differences in HIV Disease Progression and Treatment Outcomes among HIV Patients One Year after Starting Antiretroviral Treatment (ART) in Dar es Salaam, Tanzania.

We investigated gender differences in treatment outcome during first line antiretroviral treatment (ART) in a hospital setting in Tanzania, assessing clinical, social demographic, virological and immunological factors. We conducted a cohort study involving HIV infected patients scheduled to start ART and followed up to 1 year on ART. Structured questionnaires and patients file review were used to collect information and blood was collected for CD4 and viral load testing. Gender differences were assessed using Kruskal-Wallis test and chi-square test for continuous and categorical data respectively. Survival distributions for male and female patients were estimated using the Kaplan-Meier method and compared using Cox proportional hazards models. Of 234 patients recruited in this study, 70% were females. At baseline, women had significantly lower education level; lower monthly income, lower knowledge on ARV, less advanced HIV disease (33% women; 47% men started ART at WHO stage IV, p = 0.04), higher CD4 cell count (median 149 for women, 102 for men, p = 0.02) and higher BMI (p = 0.002). After 1 year of standard ART, a higher proportion of females survived although this was not significant, a significantly higher proportion of females had undetectable plasma viral load (69% women, 45% men, p = 0.003), however females ended at a comparable CD4 cell count (median CD4, 312 women; 321 men) signifying a worse CD4 cell increase (p = 0.05), even though they still had a higher BMI (p = 0.02). The unadjusted relative hazard for death for men compared to women was 1.94. After correcting for confounding factors, the Cox proportional hazards showed no significant difference in the survival rate (relative hazard 1.02). We observed women were starting treatment at a less advanced disease stage, but they had a lower socioeconomical status. After one year, both men and women had similar clinical and immunological conditions. It is not clear why women lose their immunological advantage over men despite a better virological treatment response. We recommend continuous follow up of this and more cohorts of patients to better understand the underlying causes for these differences and whether this will translate also in longer term differences

Prevalence of Transmitted Drug Resistance and Impact of Transmitted Resistance on Treatment Success in the German HIV-1 Seroconverter Cohort

BACKGROUND: The aim of this study is to analyse the prevalence of transmitted drug resistance, TDR, and the impact of TDR on treatment success in the German HIV-1 Seroconverter Cohort. METHODS: Genotypic resistance analysis was performed in treatment-naïve study patients whose sample was available 1,312/1,564 (83.9% October 2008). A genotypic resistance result was obtained for 1,276/1,312 (97.3%). The resistance associated mutations were identified according to the surveillance drug resistance mutations list recommended for drug-naïve patients. Treatment success was determined as viral suppression below 500 copies/ml. RESULTS: Prevalence of TDR was stable at a high level between 1996 and 2007 in the German HIV-1 Seroconverter Cohort (N = 158/1,276; 12.4%; CI(wilson) 10.7-14.3; p(for trend) = 0.25). NRTI resistance was predominant (7.5%) but decreased significantly over time (CI(Wilson): 6.2-9.1, p(for trend) = 0.02). NNRTI resistance tended to increase over time (NNRTI: 3.5%; CI(Wilson): 2.6-4.6; p(for trend)= 0.07), whereas PI resistance remained stable (PI: 3.0%; CI(Wilson): 2.1-4.0; p(for trend) = 0.24). Resistance to all drug classes was frequently caused by singleton resistance mutations (NRTI 55.6%, PI 68.4%, NNRTI 99.1%). The majority of NRTI-resistant strains (79.8%) carried resistance-associated mutations selected by the thymidine analogues zidovudine and stavudine. Preferably 2NRTI/1PIr combinations were prescribed as first line regimen in patients with resistant HIV as well as in patients with susceptible strains (susceptible 45.3%; 173/382 vs. resistant 65.5%; 40/61). The majority of patients in both groups were treated successfully within the first year after ART-initiation (susceptible: 89.9%; 62/69; resistant: 7/9; 77.8%). CONCLUSION: Overall prevalence of TDR remained stable at a high level but trends of resistance against drug classes differed over time. The significant decrease of NRTI-resistance in patients newly infected with HIV might be related to the introduction of novel antiretroviral drugs and a wider use of genotypic resistance analysis prior to treatment initiation

Characterization of Novel HIV Drug Resistance Mutations Using Clustering, Multidimensional Scaling and SVM-Based Feature Ranking

We present a case study on the discovery of clinically relevant domain knowledge in the field of HIV drug resistance. Novel mutations in the HIV genome associated with treatment failure were identified by mining a relational clinical database. Hierarchical cluster analysis suggests that two of these mutations form a novel mutational complex, while all others are involved in known resistance-conferring evolutionary pathways. The clustering is shown to be highly stable in a bootstrap procedure. Multidimensional scaling in mutation space indicates that certain mutations can occur within multiple pathways. Feature ranking based on support vector machines and matched genotype-phenotype pairs comprehensively reproduces current domain knowledge. Moreover, it indicates a prominent role of novel mutations in determining phenotypic resistance and in resensitization effects. These effects may be exploited deliberately to reopen lost treatment options. Together, these findings provide valuable insight into the interpretation of genotypic resistance tests