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Find video protocols related to scientific articles indexed in Pubmed.
Neighbourhood socio-economic position, late presentation and outcomes in people living with HIV in Switzerland.
AIDS
PUBLISHED: 11-15-2014
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Inequalities and inequities in health are an important public health concern. In Switzerland, mortality in the general population varies according to the socio-economic position (SEP) of neighbourhoods. We examined the influence of neighbourhood SEP on presentation and outcomes in HIV-positive individuals in the era of combination antiretroviral therapy (cART).
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Microstructural alterations of trabecular and cortical bone in long-term HIV-infected elderly men on successful antiretroviral therapy.
AIDS
PUBLISHED: 11-13-2014
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Progress in antiretroviral therapy (ART) has resulted in an almost normal life expectancy for HIV-infected individuals, but an increased risk of fragility fractures has been identified. We investigated the influence of long-term HIV infection on successful ART on bone microstructure in elderly men.
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Clinical significance of the CCR5delta32 allele in hepatitis C.
PLoS ONE
PUBLISHED: 09-05-2014
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The CCR5 receptor, expressed on Th1 cells, may influence clinical outcomes of HCV infection. We explored a possible link between a CCR5 32-base deletion (CCR5delta32), resulting in the expression of a non-functioning receptor, and clinical outcomes of HCV infection.
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Disentangling human tolerance and resistance against HIV.
PLoS Biol.
PUBLISHED: 09-01-2014
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In ecology, "disease tolerance" is defined as an evolutionary strategy of hosts against pathogens, characterized by reduced or absent pathogenesis despite high pathogen load. To our knowledge, tolerance has to date not been quantified and disentangled from host resistance to disease in any clinically relevant human infection. Using data from the Swiss HIV Cohort Study, we investigated if there is variation in tolerance to HIV in humans and if this variation is associated with polymorphisms in the human genome. In particular, we tested for associations between tolerance and alleles of the Human Leukocyte Antigen (HLA) genes, the CC chemokine receptor 5 (CCR5), the age at which individuals were infected, and their sex. We found that HLA-B alleles associated with better HIV control do not confer tolerance. The slower disease progression associated with these alleles can be fully attributed to the extent of viral load reduction in carriers. However, we observed that tolerance significantly varies across HLA-B genotypes with a relative standard deviation of 34%. Furthermore, we found that HLA-B homozygotes are less tolerant than heterozygotes. Lastly, tolerance was observed to decrease with age, resulting in a 1.7-fold difference in disease progression between 20 and 60-y-old individuals with the same viral load. Thus, disease tolerance is a feature of infection with HIV, and the identification of the mechanisms involved may pave the way to a better understanding of pathogenesis.
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[Antiretroviral therapy].
Ther Umsch
PUBLISHED: 08-06-2014
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Antiretroviral therapy to treat HIV, as we know it today, is nothing less than a huge success story in modern medical history. What used to be an almost certain death-sentence was transformed into a very manageable chronic disease by means of highly efficient und mostly well tolerated drugs. Today, HIV-infected patients treated according to international recommendations have a very good chance to outgo the negative effects of HIV-1 and are therefore able to reach an almost normal life expectancy. Furthermore, patients successfully treated with antiretroviral drugs are no longer infectious, which is an essential aspect of global strategies to overcome the pandemic. Nevertheless, due to the complexity of HIV, physicians treating patients with antiretroviral therapy require profound knowledge of aspects such as viral resistance mechanisms and immune reconstitution, as well as drug-toxicity und drug-drug-interactions. Many other aspects such as long-term side-effects of antiretroviral drugs are still unknown. Strict adherence to treatment is of utmost importance.
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Therapeutic drug monitoring of voriconazole: a case report of multiple drug interactions in a patient with an increased CYP2C19 activity.
AIDS Res Ther
PUBLISHED: 08-04-2014
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Voriconazole is metabolized by cytochrome P450 (CYP) 2C19 and CYP 3A4. Drug-drug interactions and genetic polymorphisms modulate their activities.
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Limited clinical benefit of minority K103N and Y181C-variant detection in addition to routine genotypic resistance testing in antiretroviral therapy-naive patients.
AIDS
PUBLISHED: 07-19-2014
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The presence of minority nonnucleoside reverse transcriptase inhibitor (NNRTI)-resistant HIV-1 variants prior to antiretroviral therapy (ART) has been linked to virologic failure in treatment-naive patients.
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Virologic and immunologic responses in treatment-naive patients to ritonavir-boosted atazanavir or efavirenz with a common backbone.
HIV Clin Trials
PUBLISHED: 06-21-2014
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Atazanavir boosted with ritonavir (ATV/r) and efavirenz (EFV) are both recommended as first-line therapies for HIV-infected patients. We compared the 2 therapies for virologic efficacy and immune recovery.
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Higher Risk of Incident Hepatitis C Virus Coinfection Among Men Who Have Sex With Men, in Whom the HIV Genetic Bottleneck at Transmission Was Wide.
J. Infect. Dis.
PUBLISHED: 06-18-2014
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High-risk sexual behaviors have been suggested as drivers of the recent dramatic increase of sexually transmitted hepatitis C virus (HCV) among human immunodeficiency virus (HIV)-infected men who have sex with men (MSM).
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Safety of efavirenz in the first trimester of pregnancy: an updated systematic review and meta-analysis.
AIDS
PUBLISHED: 05-23-2014
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Primate studies and some observational human data have raised concern regarding an association of first-trimester efavirenz exposure with central nervous system congenital anomalies. The objective of this review is to update evidence on efavirenz safety in HIV-infected pregnant women to inform revision of the 2013 WHO guidelines for antiretroviral therapy in low and middle-income countries.
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Systematic review and meta-analysis: Patient and programme impact of fixed-dose combination antiretroviral therapy.
Trop. Med. Int. Health
PUBLISHED: 03-17-2014
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To compare the advantages to patients and to programmes between fixed-dose combination (FDC) antiretroviral therapy and separate tablet regimens.
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Effect of baseline renal function on tenofovir-containing antiretroviral therapy outcomes in Zambia.
Clin. Infect. Dis.
PUBLISHED: 02-27-2014
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Although tenofovir disoproxil fumarate (TDF) use has increased as part of first-line antiretroviral therapy (ART) across sub-Saharan Africa, renal outcomes among patients receiving TDF remain poorly understood. We assessed changes in renal function and mortality in patients starting TDF- or non-TDF-containing ART in Lusaka, Zambia.
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Co-trimoxazole prophylaxis is associated with reduced risk of incident tuberculosis in participants in the Swiss HIV Cohort Study.
Antimicrob. Agents Chemother.
PUBLISHED: 02-10-2014
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Co-trimoxazole reduces mortality in HIV-infected adults with tuberculosis (TB), and in vitro data suggest potential antimycobacterial activity of co-trimoxazole. We aimed to evaluate whether prophylaxis with co-trimoxazole is associated with a decreased risk of incident TB in Swiss HIV Cohort Study (SHCS) participants. We determined the incidence of TB per 1,000 person-years from January 1992 to December 2012. Rates were analyzed separately in participants with current or no previous antiretroviral treatment (ART) using Poisson regression adjusted for CD4 cell count, sex, region of origin, injection drug use, and age. A total of 13,431 cohort participants contributed 107,549 person-years of follow-up: 182 patients had incident TB-132 (73%) before and 50 (27%) after ART initiation. The multivariable incidence rate ratios for cumulative co-trimoxazole exposure per year for persons with no previous ART and current ART were 0.70 (95% confidence interval [CI], 0.55 to 0.89) and 0.87 (95% CI, 0.74 to 1.0), respectively. Co-trimoxazole may prevent the development of TB among HIV-positive persons, especially among those with no previous ART.
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Clustering of HCV coinfections on HIV phylogeny indicates domestic and sexual transmission of HCV.
Int J Epidemiol
PUBLISHED: 01-22-2014
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HCV coinfection remains a major cause of morbidity and mortality among HIV-infected individuals and its incidence has increased dramatically in HIV-infected men who have sex with men(MSM).
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Haemophagocytic syndrome and elevated EBV load as initial manifestation of Hodgkin lymphoma in a HIV patient: case report and review of the literature.
J Int AIDS Soc
PUBLISHED: 01-01-2014
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In HIV patients, haemophagocytic syndrome (HPS) may occur in the presence of cancer, concomitant viral infection, HIV primo-infection or at the initiation of highly active antiretroviral therapy (HAART). Hodgkin lymphoma remains a rare cause of HPS. We describe a case of HPS with very high Epstein Barr virus (EBV) load in a HIV patient as initial manifestation of Hodgkin lymphoma.
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AIDS defining opportunistic infections in patients with high CD4 counts in the combination antiretroviral therapy (cART) era: things ain't what they used to be.
J Int AIDS Soc
PUBLISHED: 01-01-2014
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According to reports from observational databases, classic AIDS-defining opportunistic infections (ADOIs) occur in patients with CD4 counts above 500/µL on and off cART. Adjudication of these events is usually not performed. However, ADOIs are often used as endpoints, for example, in analyses on when to start cART.
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Lipohypertrophy and metabolic disorders in HIV patients on antiretroviral therapy: a systematic multidisciplinary clinical approach.
J Int AIDS Soc
PUBLISHED: 01-01-2014
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Morphological and metabolic complications in HIV patients on antiretroviral therapy remain a challenge. While new cases of lipoatrophy (LA) disappear, irreducible central lipohypertrophy (LH) and metabolic complications require highly specialized management. We described a day hospital dedicated to lipodystrophy (LD) and metabolic disorders in HIV patients on treatment in Geneva, Switzerland, with a focus on LH.
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HIV-infected women in Europe: gender-specific needs and challenges.
Antivir. Ther. (Lond.)
PUBLISHED: 11-13-2013
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In collaboration with the Strong, HIV positive, Empowered Women (SHE) programme, an industry-funded initiative aimed at improving the quality of life of HIV-positive women, Antiviral Therapy has taken the excellent step to dedicate a Supplement Issue addressing the needs and challenges related to the care of women living in Europe. Included articles present the multiple facets of gender-specific issues and research gaps, ranging from HIV testing strategies to antiretroviral combination therapy, including long-term challenges associated with chronic HIV infection.
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Evidence on the protective role of high-density lipoprotein (HDL) in HIV-infected individuals.
Curr Vasc Pharmacol
PUBLISHED: 11-06-2013
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During the last decades, the improvements in the assessment and management of cardiovascular risk have been successful in the reduction of acute cardiovascular outcomes. Among different prevention and therapeutic strategies, treatments targeting HDL increase have been indicated as promising interventions from both basic research and clinical studies. Although this therapeutic approach still requires confirmatory findings from large clinical trials, emerging evidence indicates that it would be particularly useful in some patient categories characterized by accelerated atherosclerotic diseases. In this regard, HIV-infected patients (under antiretroviral treatment or not) have been recently indicated as an appropriate target population. The present review will discuss the promising role of HDL in HIV-related cardiovascular pathophysiology and update novelties from clinical studies targeting HDL increase in HIV patients.
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Hepatitis B virus infection is associated with impaired immunological recovery during antiretroviral therapy in the Swiss HIV cohort study.
J. Infect. Dis.
PUBLISHED: 07-30-2013
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Hepatitis B virus (HBV) infection is a major cause of morbidity and mortality in human immunodeficiency virus (HIV)-infected patients worldwide. It is unclear whether HIV-related outcomes are affected by HBV coinfection. We compared virological suppression and immunological recovery during antiretroviral therapy (ART) of patients of different HBV serological status in the Swiss HIV Cohort Study. CD4 cell recovery during ART was significantly impaired in hepatitis B surface antigen-positive patients and in those with anti-hepatitis B core antigen alone compared with HBV-uninfected patients, despite similar virological efficacy of ART. CD4 increase in patients with resolved HBV infection was similar to that in HBV-uninfected individuals.
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Risk factors for anal cancer in persons infected with HIV: a nested case-control study in the Swiss HIV Cohort Study.
Am. J. Epidemiol.
PUBLISHED: 07-30-2013
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Although persons infected with human immunodeficiency virus (HIV), particularly men who have sex with men, are at excess risk for anal cancer, it has been difficult to disentangle the influences of anal exposure to human papillomavirus (HPV) infection, immunodeficiency, and combined antiretroviral therapy. A case-control study that included 59 anal cancer cases and 295 individually matched controls was nested in the Swiss HIV Cohort Study (1988-2011). In a subset of 41 cases and 114 controls, HPV antibodies were tested. A majority of anal cancer cases (73%) were men who have sex with men. Current smoking was significantly associated with anal cancer (odds ratio (OR) = 2.59, 95% confidence interval (CI): 1.25, 5.34), as were antibodies against L1 (OR = 4.52, 95% CI: 2.00, 10.20) and E6 (OR = ?, 95% CI: 4.64, ?) of HPV16, as well as low CD4+ cell counts, whether measured at nadir (OR per 100-cell/?L decrease = 1.53, 95% CI: 1.18, 2.00) or at cancer diagnosis (OR per 100-cell/?L decrease = 1.24, 95% CI: 1.08, 1.42). However, the influence of CD4+ cell counts appeared to be strongest 6-7 years prior to anal cancer diagnosis (OR for <200 vs. ?500 cells/?L = 14.0, 95% CI: 3.85, 50.9). Smoking cessation and avoidance of even moderate levels of immunosuppression appear to be important in reducing long-term anal cancer risks.
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Association of alcohol consumption and HIV surrogate markers in participants of the swiss HIV cohort study.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 07-30-2013
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Alcohol consumption may affect the course of HIV infection and/or antiretroviral therapy (ART). The authors investigated the association between self-reported alcohol consumption and HIV surrogate markers in both treated and untreated individuals.
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Origin of minority drug-resistant HIV-1 variants in primary HIV-1 infection.
J. Infect. Dis.
PUBLISHED: 07-11-2013
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Drug-resistant human immunodeficiency virus type 1 (HIV-1) minority variants (MVs) are present in some antiretroviral therapy (ART)-naive patients. They may result from de novo mutagenesis or transmission. To date, the latter has not been proven.
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Pharmacogenetics-based population pharmacokinetic analysis of etravirine in HIV-1 infected individuals.
Pharmacogenet. Genomics
PUBLISHED: 05-23-2013
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Etravirine (ETV) is metabolized by cytochrome P450 (CYP) 3A, 2C9, and 2C19. Metabolites are glucuronidated by uridine diphosphate glucuronosyltransferases (UGT). To identify the potential impact of genetic and non-genetic factors involved in ETV metabolism, we carried out a two-step pharmacogenetics-based population pharmacokinetic study in HIV-1 infected individuals.
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HIV infection disrupts the sympatric host-pathogen relationship in human tuberculosis.
PLoS Genet.
PUBLISHED: 03-07-2013
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The phylogeographic population structure of Mycobacterium tuberculosis suggests local adaptation to sympatric human populations. We hypothesized that HIV infection, which induces immunodeficiency, will alter the sympatric relationship between M. tuberculosis and its human host. To test this hypothesis, we performed a nine-year nation-wide molecular-epidemiological study of HIV-infected and HIV-negative patients with tuberculosis (TB) between 2000 and 2008 in Switzerland. We analyzed 518 TB patients of whom 112 (21.6%) were HIV-infected and 233 (45.0%) were born in Europe. We found that among European-born TB patients, recent transmission was more likely to occur in sympatric compared to allopatric host-pathogen combinations (adjusted odds ratio [OR] 7.5, 95% confidence interval [95% CI] 1.21-infinity, p = 0.03). HIV infection was significantly associated with TB caused by an allopatric (as opposed to sympatric) M. tuberculosis lineage (OR 7.0, 95% CI 2.5-19.1, p<0.0001). This association remained when adjusting for frequent travelling, contact with foreigners, age, sex, and country of birth (adjusted OR 5.6, 95% CI 1.5-20.8, p = 0.01). Moreover, it became stronger with greater immunosuppression as defined by CD4 T-cell depletion and was not the result of increased social mixing in HIV-infected patients. Our observation was replicated in a second independent panel of 440 M. tuberculosis strains collected during a population-based study in the Canton of Bern between 1991 and 2011. In summary, these findings support a model for TB in which the stable relationship between the human host and its locally adapted M. tuberculosis is disrupted by HIV infection.
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Nevirapine versus efavirenz for patients co-infected with HIV and tuberculosis: a randomised non-inferiority trial.
Lancet Infect Dis
PUBLISHED: 02-20-2013
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In countries with a high incidence of HIV and tuberculosis co-infection, nevirapine and efavirenz are widely used as antiretroviral therapy but both interact with antituberculosis drugs. We aimed to compare efficacy and safety of a nevirapine-based antiretroviral therapy (started at full dose) with an efavirenz-based regimen in co-infected patients.
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A validated assay by liquid chromatography-tandem mass spectrometry for the simultaneous quantification of elvitegravir and rilpivirine in HIV positive patients.
J Mass Spectrom
PUBLISHED: 02-08-2013
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Because of the large variability in the pharmacokinetics of anti-HIV drugs, therapeutic drug monitoring in patients may contribute to optimize the overall efficacy and safety of antiretroviral therapy. An LC-MS/MS method for the simultaneous assay in plasma of the novel antiretroviral agents rilpivirine (RPV) and elvitegravir (EVG) has been developed to that endeavor. Plasma samples (100??L) extraction is performed by protein precipitation with acetonitrile, and the supernatant is subsequently diluted 1:1 with 20-mM ammonium acetate/MeOH 50:50. After reverse-phase chromatography, quantification of RPV and EVG, using matrix-matched calibration samples, is performed by electrospray ionization-triple quadrupole mass spectrometry by selected reaction monitoring detection using the positive mode. The stable isotopic-labeled compounds RPV-(13) C6 and EVG-D6 were used as internal standards. The method was validated according to FDA recommendations, including assessment of extraction yield, matrix effects variability (<6.4%), as well as EVG and RPV short and long-term stability in plasma. Calibration curves were validated over the clinically relevant concentrations ranging from 5 to 2500?ng/ml for RPV and from 50 to 5000?ng/ml for EVG. The method is precise (inter-day CV%: 3-6.3%) and accurate (3.8-7.2%). Plasma samples were found to be stable (<15%) in all considered conditions (RT/48?h, +4°C/48?h, -20°C/3?months and 60°C/1?h). Selected metabolite profiles analysis in patients samples revealed the presence of EVG glucuronide, that was well separated from parent EVG, allowing to exclude potential interferences through the in-source dissociation of glucuronide to parent drug. This new, rapid and robust LCMS/MS assay for the simultaneous quantification of plasma concentrations of these two major new anti-HIV drugs EVG and RPV offers an efficient analytical tool for clinical pharmacokinetics studies and routine therapeutic drug monitoring service.
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Adverse events associated with nevirapine and efavirenz-based first-line antiretroviral therapy: a systematic review and meta-analysis.
AIDS
PUBLISHED: 01-25-2013
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Since 2002, the WHO has recommended either nevirapine (NVP) or efavirenz (EFV) as part of first-line antiretroviral therapy. These two drugs are known to have differing toxicity profiles, but the risk of these toxicities overall is not well established.
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Rivastigmine for HIV-associated neurocognitive disorders: a randomized crossover pilot study.
Neurology
PUBLISHED: 01-23-2013
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To assess the efficacy and safety of rivastigmine for the treatment of HIV-associated neurocognitive disorders (HAND) in a cohort of long-lasting aviremic HIV+ patients.
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Adverse events associated with nevirapine use in pregnancy: a systematic review and meta-analysis.
AIDS
PUBLISHED: 01-10-2013
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The risk of adverse drug events associated with nevirapine (NVP) is suggested to be greater in pregnant women. We conducted a systematic review and meta-analysis of severe adverse events in HIV-positive women who initiated NVP while pregnant.
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Risk of cardiovascular events and blood pressure control in hypertensive HIV-infected patients: Swiss HIV Cohort Study (SHCS).
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 01-05-2013
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Prevalence of hypertension in HIV infection is high, and information on blood pressure control in HIV-infected individuals is insufficient. We modeled blood pressure over time and the risk of cardiovascular events in hypertensive HIV-infected individuals.
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Persistent Difficulties in Switching to Second-Line ART in Sub-Saharan Africa - A Systematic Review and Meta-Analysis.
PLoS ONE
PUBLISHED: 01-01-2013
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Switching to second-line antiretroviral therapy (ART) largely depends on careful clinical assessment and access to biological measurements. We performed a systematic review and meta-analysis to estimate the incidence of switching to second-line ART in sub-Saharan Africa and its main programmatic determinants.
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Incidence of paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome and impact on patient outcome.
PLoS ONE
PUBLISHED: 01-01-2013
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We used data from a randomized trial of HIV-tuberculosis co-infected patients in Mozambique to determine the incidence and predictors of paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (IRIS) occurring within 12 weeks of starting antiretroviral therapy, and to evaluate its association with patient outcome at 48 weeks.
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Adherence as a predictor of the development of class-specific resistance mutations: the Swiss HIV Cohort Study.
PLoS ONE
PUBLISHED: 01-01-2013
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Non-adherence is one of the strongest predictors of therapeutic failure in HIV-positive patients. Virologic failure with subsequent emergence of resistance reduces future treatment options and long-term clinical success.
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Micro-structural brain alterations in aviremic HIV+ patients with minor neurocognitive disorders: a multi-contrast study at high field.
PLoS ONE
PUBLISHED: 01-01-2013
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Mild neurocognitive disorders (MND) affect a subset of HIV+ patients under effective combination antiretroviral therapy (cART). In this study, we used an innovative multi-contrast magnetic resonance imaging (MRI) approach at high-field to assess the presence of micro-structural brain alterations in MND+ patients.
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Mycobacterium tuberculosis transmission in a country with low tuberculosis incidence: role of immigration and HIV infection.
J. Clin. Microbiol.
PUBLISHED: 11-23-2011
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Immigrants from high-burden countries and HIV-coinfected individuals are risk groups for tuberculosis (TB) in countries with low TB incidence. Therefore, we studied their role in transmission of Mycobacterium tuberculosis in Switzerland. We included all TB patients from the Swiss HIV Cohort and a sample of patients from the national TB registry. We identified molecular clusters by spoligotyping and mycobacterial interspersed repetitive-unit-variable-number tandem-repeat (MIRU-VNTR) analysis and used weighted logistic regression adjusted for age and sex to identify risk factors for clustering, taking sampling proportions into account. In total, we analyzed 520 TB cases diagnosed between 2000 and 2008; 401 were foreign born, and 113 were HIV coinfected. The Euro-American M. tuberculosis lineage dominated throughout the study period (378 strains; 72.7%), with no evidence for another lineage, such as the Beijing genotype, emerging. We identified 35 molecular clusters with 90 patients, indicating recent transmission; 31 clusters involved foreign-born patients, and 15 involved HIV-infected patients. Birth origin was not associated with clustering (adjusted odds ratio [aOR], 1.58; 95% confidence interval [CI], 0.73 to 3.43; P = 0.25, comparing Swiss-born with foreign-born patients), but clustering was reduced in HIV-infected patients (aOR, 0.49; 95% CI, 0.26 to 0.93; P = 0.030). Cavitary disease, male sex, and younger age were all associated with molecular clustering. In conclusion, most TB patients in Switzerland were foreign born, but transmission of M. tuberculosis was not more common among immigrants and was reduced in HIV-infected patients followed up in the national HIV cohort study. Continued access to health services and clinical follow-up will be essential to control TB in this population.
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Impact of a nurse vaccination program on hepatitis B immunity in a Swiss HIV clinic.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 10-04-2011
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We evaluated the impact of a nurse program for hepatitis B virus vaccination in a center from the Swiss HIV Cohort Study. Immunity (anti-HBs >10 IU/mL) increased from 32% to 76% in the intervention center (n = 238) where vaccine management was endorsed by nurses, but only from 33% to 39% in control centers (n = 2712, P < 0.001) where management remained in charge of physicians. Immunity against HBV in the HIV population is insufficient in Switzerland. Specific nurse vaccination program may efficiently improve health care.
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Safety of efavirenz in the first trimester of pregnancy: an updated systematic review and meta-analysis.
AIDS
PUBLISHED: 09-16-2011
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Evidence of the risk of birth defects with efavirenz use is limited. We updated a meta-analysis of birth defects in infants with first trimester efavirenz exposure up to July 2011. In 21 studies, there were 39 defects among live births in 1437 women receiving first trimester efavirenz [2.0%, 95% confidence interval (CI) 0.82-3.18]. The relative risk of defects comparing women on efavirenz-based (1290 live births) and nonefavirenz-based regimens (8122 live births) was 0.85 (95% CI 0.61-1.20). One neural tube defect was observed (myelomeningocele), giving an incidence of 0.07% (95% CI 0.002-0.39).
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Squamous cell carcinoma of the anus-an opportunistic cancer in HIV-positive male homosexuals.
World J. Gastroenterol.
PUBLISHED: 07-30-2011
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Squamous cell carcinoma of the anus (SCCA) is a common cancer in the human immunodeficiency virus (HIV)-infected population, and its incidence continues to increase in male homosexuals. Combined chemoradiation with mitomycin C and 5-fluorouracil was poorly tolerated by severely immunocompromised patients in the early 1990s. In the era of highly active antiretroviral therapy (HAART), however, recent data indicate that: (1) most HIV patients with anal cancer can tolerate standard chemotherapy regimens; and (2) this approach is associated with survival rates similar to those of HIV-negative patients. However, HIV-positive patients with SCCA are much younger, more likely to develop local tumor recurrence, and ultimately die from anal cancer than immune competent patients. Taken together, these findings suggest that anal cancer is an often fatal neoplasia in middle-aged HIV-positive male homosexuals. In this population, SCCA is an opportunistic disease resulting in patients with suboptimal immune function from persistent infection and prolonged exposition to oncogenic human papillomaviruses (HPVs). Large-scale cancer-prevention strategies (routine anuscopy and anal papanicolaou testing) should be implemented in this population. In addition, definitive eradication of oncogenic HPVs within the anogenital mucosa of high-risk individuals might require a proactive approach with repeated vaccination.
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Ageing with HIV: medication use and risk for potential drug-drug interactions.
J. Antimicrob. Chemother.
PUBLISHED: 06-16-2011
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To compare the use of co-medication, the potential drug-drug interactions (PDDIs) and the effect on antiretroviral therapy (ART) tolerability and efficacy in HIV-infected individuals according to age, ? 50 years or <50 years.
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HIV treatment for prevention.
J Int AIDS Soc
PUBLISHED: 05-25-2011
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"No virus, no transmission." Studies have repeatedly shown that viral load (the quantity of virus present in blood and sexual secretions) is the strongest predictor of HIV transmission during unprotected sex or transmission from infected mother to child. Effective treatment lowers viral load to undetectable levels. If one could identify and treat all HIV-infected people immediately after infection, the HIV/AIDS epidemic would eventually disappear.Such a radical solution is currently unrealistic. In reality, not all people get tested, especially when they fear stigma and discrimination. Thus, not all HIV-infected individuals are known. Of those HIV-positive individuals for whom the diagnosis is known, not all of them have access to therapy, agree to be treated, or are taking therapy effectively. Some on effective treatment will stop, and in others, the development of resistance will lead to treatment failure. Furthermore, resources are limited: should we provide drugs to asymptomatic HIV-infected individuals without indication for treatment according to guidelines in order to prevent HIV transmission at the risk of diverting funding from sick patients in urgent need? In fact, the preventive potential of anti-HIV drugs is unknown. Modellers have tried to fill the gap, but models differ depending on assumptions that are strongly debated. Further, indications for antiretroviral treatments expand; in places like Vancouver and San Francisco, the majority of HIV-positive individuals are now under treatment, and the incidence of new HIV infections has recently fallen. However, correlation does not necessarily imply causation. Finally, studies in couples where one partner is HIV-infected also appear to show that treatment reduces the risk of transmission.More definite studies, where a number of communities are randomized to either receive the "test-and-treat" approach or continue as before, are now in evaluation by funding agencies. Repeated waves of testing would precisely measure the incidence of HIV infection. Such trials face formidable logistical, practical and ethical obstacles. However, without definitive data, the intuitive appeal of "test-and-treat" is unlikely to translate into action on a global scale. In the meantime, based on the available evidence, we must strive to provide treatment to all those in medical need under the current medical guidelines. This will lead to a decrease in HIV transmission while "test-and-treat" is fully explored in prospective clinical trials.
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A randomized cross-over study to compare raltegravir and efavirenz (SWITCH-ER study).
AIDS
PUBLISHED: 05-20-2011
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Efavirenz (EFV) causes neuropsychiatric side-effects and an unfavorable blood lipid profile. We investigated the effect of replacing EFV with raltegravir (RAL) on patient preference, daytime sleepiness, sleep quality, anxiety, and lipid levels.
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Safety, efficacy, and pharmacokinetics of rilpivirine: systematic review with an emphasis on resource-limited settings.
HIV AIDS (Auckl)
PUBLISHED: 04-28-2011
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The vast majority of people living with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome reside in the developing world, in settings characterized by limited health budgets, critical shortages of doctors, limited laboratory monitoring, a substantial burden of HIV in children, and high rates of coinfection, in particular tuberculosis. Therefore, the extent to which new antiretrovirals will contribute to improvements in the management of HIV globally will depend to a large extent on their affordability, ease of use, low toxicity profile, availability as pediatric formulations, and compatibility with tuberculosis and other common drugs. We undertook a systematic review of the available evidence regarding drug interactions, and the efficacy and safety of rilpivirine (also known as TMC-278), and assessed our findings in view of the needs and constraints of resource-limited settings. The main pharmacokinetic interactions relevant to HIV management reported to date include reduced bioavailability of rilpivirine when coadministered with rifampicin, rifabutin or acid suppressing agents, and reduced bioavailability of ketoconazole. Potential recommendations for dose adjustment to compensate for these interactions have not been elaborated. Trials comparing rilpivirine and efavirenz found similar outcomes up to 96 weeks in intent-to-treat analysis; failure of rilpivirine was mainly virological, whereas failure among those exposed to efavirenz was mainly related to the occurrence of adverse events. Around half of the patients who fail rilpivirine develop non-nucleoside reverse transcriptase inhibitor resistance mutations. The incidence of Grade 2-4 events was lower for rilpivirine compared with efavirenz. Grade 3-4 adverse events potentially related to the drugs were infrequent and statistically similar for both drugs. No dose-response relationship was observed for efficacy or safety, and the lowest dose (25 mg) was selected for further clinical development. The potential low cost and dose of the active pharmaceutical ingredient means that rilpivirine can potentially be manufactured at a low price. Moreover, its long half-life suggests the potential for monthly dosing via nonoral routes, with promising early results from studies of a long-acting injectable formulation. These characteristics make rilpivirine an attractive drug for resource-limited settings. Future research should assess the potential to improve robustness and assess the clinical significance of interaction with antituberculosis drugs.
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Immunovirological response to triple nucleotide reverse-transcriptase inhibitors and ritonavir-boosted protease inhibitors in treatment-naive HIV-2-infected patients: The ACHIEV2E Collaboration Study Group.
Clin. Infect. Dis.
PUBLISHED: 04-22-2011
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Triple nucleoside reverse-transcriptase inhibitors (NRTIs) are recommended by the World Health Organization as first-line regimen in treatment-naïve HIV-2-infected patients. However, ritonavir-boosted protease inhibitor (PI/r)-containing regimens are frequently prescribed. In the absence of previous randomized trials, we retrospectively compared these regimens in observational cohorts.
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Estimating loss to follow-up in HIV-infected patients on antiretroviral therapy: the effect of the competing risk of death in Zambia and Switzerland.
PLoS ONE
PUBLISHED: 04-13-2011
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Loss to follow-up (LTFU) is common in antiretroviral therapy (ART) programmes. Mortality is a competing risk (CR) for LTFU; however, it is often overlooked in cohort analyses. We examined how the CR of death affected LTFU estimates in Zambia and Switzerland.
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Successful efavirenz dose reduction guided by therapeutic drug monitoring.
Antivir. Ther. (Lond.)
PUBLISHED: 03-31-2011
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There are potential benefits to individualizing dosage in patients treated with efavirenz (EFV). We tested a simplified algorithm based on a Bayesian pharmacokinetic approach for guiding dose reduction in patients with EFV concentrations above the 75th percentile (P75) with documented virological efficacy.
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Driving a decade of change: HIV/AIDS, patents and access to medicines for all.
J Int AIDS Soc
PUBLISHED: 03-27-2011
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Since 2000, access to antiretroviral drugs to treat HIV infection has dramatically increased to reach more than five million people in developing countries. Essential to this achievement was the dramatic reduction in antiretroviral prices, a result of global political mobilization that cleared the way for competitive production of generic versions of widely patented medicines.Global trade rules agreed upon in 1994 required many developing countries to begin offering patents on medicines for the first time. Government and civil society reaction to expected increases in drug prices precipitated a series of events challenging these rules, culminating in the 2001 World Trade Organizations Doha Declaration on the Agreement on Trade-Related Aspects of Intellectual Property Rights and Public Health. The Declaration affirmed that patent rules should be interpreted and implemented to protect public health and to promote access to medicines for all. Since Doha, more than 60 low- and middle-income countries have procured generic versions of patented medicines on a large scale.Despite these changes, however, a "treatment timebomb" awaits. First, increasing numbers of people need access to newer antiretrovirals, but treatment costs are rising since new ARVs are likely to be more widely patented in developing countries. Second, policy space to produce or import generic versions of patented medicines is shrinking in some developing countries. Third, funding for medicines is falling far short of needs. Expanded use of the existing flexibilities in patent law and new models to address the second wave of the access to medicines crisis are required.One promising new mechanism is the UNITAID-supported Medicines Patent Pool, which seeks to facilitate access to patents to enable competitive generic medicines production and the development of improved products. Such innovative approaches are possible today due to the previous decade of AIDS activism. However, the Pool is just one of a broad set of policies needed to ensure access to medicines for all; other key measures include sufficient and reliable financing, research and development of new products targeted for use in resource-poor settings, and use of patent law flexibilities. Governments must live up to their obligations to protect access to medicines as a fundamental component of the human right to health.
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A randomized crossover study to compare efavirenz and etravirine treatment.
AIDS
PUBLISHED: 03-26-2011
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Efavirenz (EFV) causes neuropsychiatric side-effects and an unfavourable blood lipid profile. We investigated the effect of replacing EFV with etravirine (ETR) on patient preference, sleep, anxiety and lipid levels.
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[HIV and AIDS: whats new in 2010?].
Rev Med Suisse
PUBLISHED: 03-16-2011
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Antiretroviral therapy is now simpler than ever, with one tablet once daily being the gold standard for the development of new combinations. Indications for treatment initiation have now been extended before moderate immune suppression, taking in account not only the individual benefit, but also the public health aspect of preventing HIV transmission to a sexual partner. New preventing methods have been tested in 2010: microbicides as well as dual antiretroviral treatment in HIV-negative high risk population as a chemoprophylaxis have been published. If these last two tools offer some options for the future, their applicability at a large scale warrant further development.
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The first decade of antiretroviral therapy in Africa.
Global Health
PUBLISHED: 03-05-2011
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The past decade has seen remarkable progress in increasing access to antiretroviral therapy in resource-limited settings. Early concerns about the cost and complexity of treatment were overcome thanks to the efforts of a global coalition of health providers, activists, academics, and people living with HIV/AIDS, who argued that every effort must be made to ensure access to essential care when millions of lives depended on it. The high cost of treatment was reduced through advocacy to promote access to generic drugs; care provision was simplified through a public health approach to treatment provision; the lack of human resources was overcome through task-shifting to support the provision of care by non-physicians; and access was expanded through the development of models of care that could work at the primary care level. The challenge for the next decade is to further increase access to treatment and support sustained care for those on treatment, while at the same time ensuring that the package of care is continuously improved such that all patients can benefit from the latest improvements in drug development, clinical science, and public health.
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[Tuberculosis and HIV co-infection: a therapeutic challenge].
Rev Med Suisse
PUBLISHED: 01-22-2011
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Tuberculosis (TB) is the most frequent opportunistic infection in patients infected by the Human immunodeficiency virus (HIV). The mortality related to this co-infection can be reduced by the early introduction of an antiretroviral treatment. However, when treating subjects with TB and HIV, interactions between antiretroviral and tuberculostatic treatments can be problematic; also, these patients may develop, under treatment, an immune reconstitution inflammatory syndrome (IRIS). This review aims to summarize the necessary therapeutic adjustments which should be performed when treating patients co-infected with TB and HIV, the most important interactions between HIV and TB treatments, and the medical management of the IRIS.
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Pharmacokinetics and pharmacogenomics of once-daily raltegravir and atazanavir in healthy volunteers.
Antimicrob. Agents Chemother.
PUBLISHED: 09-07-2010
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Atazanavir inhibits UDP-glucuronyl-transferase-1A1 (UGT1A1), which metabolizes raltegravir, but the magnitude of steady-state inhibition and role of the UGT1A1 genotype are unknown. Sufficient inhibition could lead to reduced-dose and -cost raltegravir regimens. Nineteen healthy volunteers, age 24 to 51 years, took raltegravir 400 mg twice daily (arm A) and 400 mg plus atazanavir 400 mg once daily (arm B), separated by ?3 days, in a crossover design. After 1 week on each regimen, raltegravir and raltegravir-glucuronide plasma and urine concentrations were measured by liquid chromatography-tandem mass spectrometry in multiple samples obtained over 12 h (arm A) or 24 h (arm B) and analyzed by noncompartmental methods. UGT1A1 promoter variants were detected with a commercially available kit and published primers. The primary outcome was the ratio of plasma raltegravir C(tau), or concentration at the end of the dosing interval, for arm B (24 h) versus arm A (12 h). The arm B-to-arm A geometric mean ratios (95% confidence interval, P value) for plasma raltegravir C(tau), area under the concentration-time curve from 0 to 12 h (AUC(0-12)), and raltegravir-glucuronide/raltegravir AUC(0-12) were 0.38 (0.22 to 0.65, 0.001), 1.32 (0.62 to 2.81, 0.45), and 0.47 (0.38 to 0.59, <0.001), respectively. Nine volunteers were heterozygous and one was homozygous for a UGT1A1 reduction-of-function allele, but these were not associated with metabolite formation. Although atazanavir significantly reduced the formation of the glucuronide metabolite, its steady-state boosting of plasma raltegravir did not render the C(tau) with a once-daily raltegravir dose of 400 mg similar to the C(tau) with the standard twice-daily dose. UGT1A1 promoter variants did not significantly influence this interaction.
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Treatment failure and mortality factors in patients receiving second-line HIV therapy in resource-limited countries.
JAMA
PUBLISHED: 07-20-2010
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Long-term antiretroviral therapy (ART) use in resource-limited countries leads to increasing numbers of patients with HIV taking second-line therapy. Limited access to further therapeutic options makes essential the evaluation of second-line regimen efficacy in these settings.
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Reduction of missed appointments at an urban primary care clinic: a randomised controlled study.
BMC Fam Pract
PUBLISHED: 06-24-2010
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Missed appointments are known to interfere with appropriate care and to misspend medical and administrative resources. The aim of this study was to test the effectiveness of a sequential intervention reminding patients of their upcoming appointment and to identify the profile of patients missing their appointments.
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Prevalence of comedications and effect of potential drug-drug interactions in the Swiss HIV Cohort Study.
Antivir. Ther. (Lond.)
PUBLISHED: 06-03-2010
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Potential drug-drug interactions (PDDIs) might expand with new combination antiretroviral therapies (ART) and polypharmacy related to increasing age and comorbidities. We investigated the prevalence of comedications and PDDIs within a large HIV cohort, and their effect on ART efficacy and tolerability.
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Safety of efavirenz in first-trimester of pregnancy: a systematic review and meta-analysis of outcomes from observational cohorts.
AIDS
PUBLISHED: 05-19-2010
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Data on efavirenz safety in first trimester pregnancy are conflicting. We conducted a systematic review and meta-analysis of the available evidence from observational cohorts.
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Markers of inflammation, coagulation, and renal function are elevated in adults with HIV infection.
J. Infect. Dis.
PUBLISHED: 05-08-2010
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Human immunodeficiency virus (HIV) replication and immune activation may increase inflammation and coagulation biomarkers. Limited data exist comparing such biomarkers in persons with and without HIV infection.
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When to start antiretroviral therapy in resource-limited settings: a human rights analysis.
BMC Int Health Hum Rights
PUBLISHED: 03-31-2010
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Recent evidence from developed and developing countries shows clear clinical and public health benefit to starting antiretroviral therapy (ART) earlier. While discussions about when to start ART have often focused on the clinical risks and benefits, the main issue is one of fair limit-setting. We applied a human rights framework to assess a policy of early treatment initiation according to the following criteria: public-health purpose; likely effectiveness; specificity; human rights burdens and benefits; potential for less restrictive approaches; and fair administration.
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Patient needs and point-of-care requirements for HIV load testing in resource-limited settings.
J. Infect. Dis.
PUBLISHED: 03-16-2010
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Medecins Sans Frontieres (MSF) is an international, independent medical nongovernmental organization. One way in which MSF acts to improve patient care is to assist in the identification and development of adapted and appropriate tools for use in resource-limited settings. One strategy to achieve this goal is through active collaborations with scientists and developers, to make some of the field needs known and to help define the medical strategy behind the implementation of new diagnostic tests. Tests used in the field need to be effective in often extreme conditions and must also deliver high-quality, reliable results that can be used in the local context. In this article, we discuss some patient and health care provider needs for human immunodeficiency virus (HIV) load measurement in resource-limited settings. This is just one of the areas in which effective, quality tools are desperately needed, not only by MSF and other international nongovernmental organizations, but also by many other health service providers. We hope that, by clearly defining the needs of patients in MSF clinics-as well as we can assess this-and by explaining why these tools are needed, how they should perform, and how their results can be integrated into a program, we will encourage the development of such tools and hasten their implementation in areas where they are so urgently needed.
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Hepatotoxicity and effectiveness of a Nevirapine-based antiretroviral therapy in HIV-infected patients with or without viral hepatitis B or C infection in Cameroon.
BMC Public Health
PUBLISHED: 03-01-2010
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Coinfection with hepatitis B virus (HBV) or hepatitis C virus (HCV) in HIV-infected patients receiving a commonly used nevirapine-based antiretroviral therapy is a major concern for African clinicians owing to its high prevalence, the infrequent testing and treatment of viral hepatitis, and the impact of liver disease on the tolerability and effectiveness of anti-HIV treatment. We compared the hepatotoxicity and the immunological, virological and clinical effectiveness of a nevirapine-based antiretroviral therapy between patients infected with HIV only and patients coinfected with hepatitis B or C virus in Cameroon.
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High prevalence of severe vitamin D deficiency in combined antiretroviral therapy-naive and successfully treated Swiss HIV patients.
AIDS
PUBLISHED: 02-20-2010
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To evaluate the prevalence of 25-hydroxyvitamin D [25(OH)D] deficiency in HIV-positive patients, a population at risk for osteoporosis.
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ADME pharmacogenetics: investigation of the pharmacokinetics of the antiretroviral agent lopinavir coformulated with ritonavir.
Pharmacogenet. Genomics
PUBLISHED: 02-09-2010
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An ADME (absorption, distribution, metabolism and excretion)-pharmacogenetics association study may identify functional variants relevant to the pharmacokinetics of lopinavir co-formulated with ritonavir (LPV/r), a first-line anti-HIV agent.
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Improving first-line antiretroviral therapy in resource-limited settings.
Curr Opin HIV AIDS
PUBLISHED: 01-05-2010
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Access to first-line antiretroviral therapy in resource-limited settings has increased rapidly in the last 5 years. Newer medicines with greater potency and better safety profiles open the possibility for improving first-line antiretroviral therapy for developing countries.
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Safety and efficacy of once-daily nevirapine dosing: a multicohort study.
Antivir. Ther. (Lond.)
PUBLISHED: 11-18-2009
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Nevirapine (NVP) is often prescribed once daily in clinical practice in combination with a once daily nucleoside backbone. We investigated the relationship of NVP dosing with safety and efficacy.
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Low bone mineral density, renal dysfunction, and fracture risk in HIV infection: a cross-sectional study.
J. Infect. Dis.
PUBLISHED: 10-31-2009
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Reduced bone mineral density (BMD) is common in adults infected with human immunodeficiency virus (HIV). The role of proximal renal tubular dysfunction (PRTD) and alterations in bone metabolism in HIV-related low BMD are incompletely understood.
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Dried blood spots can expand access to virological monitoring of HIV treatment in resource-limited settings.
J. Antimicrob. Chemother.
PUBLISHED: 09-23-2009
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The global scale-up of antiretroviral treatment in past years has, unfortunately, not been accompanied by adequate strengthening of laboratory capacity. Monitoring of treatment with HIV viral load and resistance testing, as recommended in industrialized countries, is rarely available in resource-limited settings due to high costs and stringent requirements for storage and transport of plasma. Consequently, treatment failure usually passes unnoticed until severe symptoms occur, when resistance mutations have accumulated and second-line drug options are restricted. Dried blood spots (DBS) are easy to collect and store, and can be a convenient alternative to plasma. Recently, a number of studies have demonstrated the feasibility and reliability of using DBS to monitor viral load and genotypic resistance. Moreover, several African countries have already started to use DBS for paediatric HIV screening. In the absence of point-of-care assays, the WHO should encourage virological monitoring on DBS in antiretroviral treatment programmes in resource-limited settings.
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Association of noncirrhotic portal hypertension in HIV-infected persons and antiretroviral therapy with didanosine: a nested case-control study.
Clin. Infect. Dis.
PUBLISHED: 07-11-2009
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Noncirrhotic portal hypertension (NCPH) is a newly described life-threatening liver disease of unknown cause in human immunodeficiency virus (HIV)-infected persons. Postulated pathogenesis includes prolonged exposure to antiretroviral therapy, particularly didanosine.
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Switching to second-line antiretroviral therapy in resource-limited settings: comparison of programmes with and without viral load monitoring.
AIDS
PUBLISHED: 06-18-2009
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In high-income countries, viral load is routinely measured to detect failure of antiretroviral therapy (ART) and guide switching to second-line ART. Viral load monitoring is not generally available in resource-limited settings. We examined switching from nonnucleoside reverse transcriptase inhibitor (NNRTI)-based first-line regimens to protease inhibitor-based regimens in Africa, South America and Asia.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.