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Background: Dolutegravir-containing maintenance therapy is a promising simplification strategy for virologically suppressed HIV-infected individuals. However, most of the available data to inform this strategy come from small, unc...
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Background: Dolutegravir-containing maintenance therapy is a promising simplification strategy for virologically suppressed HIV-infected individuals. However, most of the available data to inform this strategy come from small, uncontrolled studies. We estimated the proportion of HIV-infected patients experiencing virological failure (VF) and developing drug resistance on dolutegravir (DTG)-based maintenance therapy. Methods: We searched Medline, Embase, Cochrane Central, Web of Science, and conference abstracts for studies assessing VF on DTG-based maintenance therapy. Studies including ≥5 adults with an undetectable viral load on antiretroviral therapy (ART) who switched to a DTG-based mono- or dual therapy were included. Pooled proportions of VF were estimated using random-intercept logistic meta-regression and acquired drug resistance mutations described for each strategy. Results : Of 1719 studies considered, 21 met our selection criteria, including seven interventional and 14 observational studies. Eight studies including 251 patients assessed VF on DTG monotherapy and fourteen studies including 1670 participants VF on dual therapy. The participant’s median age ranged from 43 to 63 years, their median nadir CD4 count from 90 to 399 cells/μl, and 27.6% were female. The proportion of participants experiencing VF on DTG-monotherapy was 3.6% (95% confidence interval [CI] 1.9-6.7) at 24 weeks and 8.9% (95% CI 4.7-16.2) at 48 weeks. Resistance mutations developed in seven (3.6%) participants on DTG-monotherapy. Among patients on dual therapy, ten (0.7%, 95% CI 0.4-1.3) experienced VF by 48 weeks and none developed resistance to DTG. In adjusted analyses, VF at 24 weeks was less likely on dual therapy than on monotherapy (adjusted odds ratio: 0.10, 95% CI 0.03-0.30). Conclusions: Whereas VF is relatively common on DTG maintenance monotherapy, DTG-based dual therapy appears to be a promising simplification strategy for individuals with a suppressed HIV viral load on triple-ART.
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Background Dolutegravir (DTG)–based dual therapy is becoming a new paradigm for both the initiation and maintenance of HIV treatment. The SIMPL’HIV study investigated the outcomes of virologically suppressed patients on standard...
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Background Dolutegravir (DTG)–based dual therapy is becoming a new paradigm for both the initiation and maintenance of HIV treatment. The SIMPL’HIV study investigated the outcomes of virologically suppressed patients on standard combination antiretroviral therapy (cART) switching to DTG + emtricitabine (FTC). We present the 48-week efficacy and safety data on DTG + FTC versus cART. Methods and findings SIMPL’HIV was a multicenter, open-label, non-inferiority randomized trial with a factorial design among treatment-experienced people with HIV in Switzerland. Participants were enrolled between 12 May 2017 and 30 May 2018. Patients virologically suppressed for at least 24 weeks on standard cART were randomized 1:1 to switching to DTG + FTC or to continuing cART, and 1:1 to simplified patient-centered monitoring versus standard monitoring. The primary endpoint was the proportion of patients virologically suppressed with <100 copies/ml through 48 weeks. The secondary endpoints included virological suppression at 48 weeks according to the US Food and Drug Administration (FDA) snapshot analysis. Non-inferiority of DTG + FTC versus cART for viral suppression was assessed using a stratified Mantel–Haenszel risk difference, with non-inferiority declared if the lower bound of the 95% confidence interval was greater than ?12%. Adverse events were monitored to assess safety. Quality of life was evaluated using the PROQOL-HIV questionnaire. Ninety-three participants were randomized to DTG + FTC, and 94 individuals to cART. Median nadir CD4 count was 246 cells/mm3; median age was 48 years; 17% of participants were female. DTG + FTC was non-inferior to cART. The proportion of patients with viral suppression (<100 copies/ml) through 48 weeks was 93.5% in the DTG + FTC arm and 94.7% in the cART arm in the intention-to-treat population (risk difference ?1.2%; 95% CI ?7.8% to 5.6%). Per-protocol analysis showed similar results, with viral suppression in 96.5% of patients in both arms (risk difference 0.0%; 95% CI ?5.6% to 5.5%). There was no relevant interaction between the type of treatment and monitoring (interaction ratio 0.98; 95% CI 0.85 to 1.13; p = 0.81). Using the FDA snapshot algorithm, 84/93 (90.3%) participants in the DTG + FTC arm had an HIV-1 RNA viral load of <50 copies/ml compared to 86/94 (91.5%) participants on standard cART (risk difference ?1.1%; 95% CI ?9.3% to 7.1%; p = 0.791). The overall proportion of patients with adverse events and discontinuations did not differ by randomization arm. The proportion of patients with serious adverse events was higher in the cART arm (16%) compared to the DTG + FTC arm (6.5%) (p = 0.041), but none was considered to be related to the study medication. Quality of life improved more between baseline and week 48 in the DTG + FTC compared to the cART arm (adjusted difference +2.6; 95% CI +0.4 to +4.7). The study’s main limitations included a rather small proportion of women included, the open label design, and its short duration. Conclusions In this study, DTG + FTC as maintenance therapy was non-inferior to cART in terms of efficacy, with a similar safety profile and a greater improvement in quality of life, thus expanding the offer of 2-drug simplification options among virologically suppressed individuals.
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Background Human immunodeficiency virus (HIV) infection is the strongest risk factor for developing tuberculosis and has fuelled its resurgence, especially in sub-Saharan Africa. In 2010, there were an estimated 1.1 million incide...
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Background Human immunodeficiency virus (HIV) infection is the strongest risk factor for developing tuberculosis and has fuelled its resurgence, especially in sub-Saharan Africa. In 2010, there were an estimated 1.1 million incident cases of tuberculosis among the 34 million people living with HIV worldwide. Antiretroviral therapy has substantial potential to prevent HIV-associated tuberculosis. We conducted a systematic review of studies that analysed the impact of antiretroviral therapy on the incidence of tuberculosis in adults with HIV infection.
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Human Immunodeficiency Virus (HIV) is the strongest risk factor for developing tuberculosis (TB) disease in people with latent or new Mycobacterium tuberculosis infection. The risk of developing TB is between 21 and 34 times great...
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Human Immunodeficiency Virus (HIV) is the strongest risk factor for developing tuberculosis (TB) disease in people with latent or new Mycobacterium tuberculosis infection. The risk of developing TB is between 21 and 34 times greater in people living with HIV than among individuals who do not have HIV infection. At least one-third of the estimated 34 million people living with HIV worldwide are infected with M tuberculosis. Yet, only 178000 were receiving IPT at the end of 2010 and TB was responsible for a quarter of deaths in people living with HIV.
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Human Immunodeficiency Virus (HIV) is the strongest risk factor for developing tuberculosis (TB) disease in people with latent or new Mycobacterium tuberculosis infection. The risk of developing TB is between 21 and 34 times great...
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Human Immunodeficiency Virus (HIV) is the strongest risk factor for developing tuberculosis (TB) disease in people with latent or new Mycobacterium tuberculosis infection. The risk of developing TB is between 21 and 34 times greater in people living with HIV than among individuals who do not have HIV infection. At least one-third of the estimated 34 million people living with HIV worldwide are infected with M tuberculosis. Yet, only 178000 were receiving IPT at the end of 2010 and TB was responsible for a quarter of deaths in people living with HIV.To reduce the morbidity and mortality from TB in people living with HIV, the World Health Organization (WHO) recommends the following interventions: early provision of antiretroviral therapy (ART) at CD4 count <35O cells/mm and the Three I's for HIV/TB: intensified case-finding of TB (ICF), isoniazid preventive therapy (IPT), and infection control forTB (1C). ICF and treatment of TB interrupts transmission of disease by infectious cases, decreases morbidity and delays mortality. Most importantly, active TB screening offers the opportunity to provide preventive therapy for people who do not have symptoms and signs of TB. The WHO 'Guidelines for intensified TB case-finding and isoniazid preventive therapy for people living with HIV in resource-constrained settings' provide guidance to national HIV and TB programmes and to HIV service providers to scale-up the implementation of TB screening and IPT.
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Bloodstream infections (BSIs) are a major cause of illness in HIV-infected persons. To evaluate prevalence of and risk factors for BSIs in 2,009 HIV-infected outpatients in Cambodia, Thailand, and Vietnam, we performed a single My...
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Bloodstream infections (BSIs) are a major cause of illness in HIV-infected persons. To evaluate prevalence of and risk factors for BSIs in 2,009 HIV-infected outpatients in Cambodia, Thailand, and Vietnam, we performed a single Myco/F Lytic blood culture. Fifty-eight (2.9%) had a clinically signifi cant BSI (i.e., a blood culture positive for an organism known to be a pathogen). Mycobacterium tuberculosis accounted for 31 (54%) of all BSIs, followed by fungi (13 [22%]) and bacteria (9 [16%]). Of patients for whom data were recorded about antiretroviral therapy, 0 of 119 whohad received antiretroviral therapy for >14 days had a BSI, compared with 3% of 1,801 patients who had not. In multivariate analysis, factors consistently associated with BSI were fever, low CD4+ T-lymphocyte count, abnormalities on chest radiograph, and signs or symptoms of abdominal illness. For HIV-infected outpatients with these risk factors, clinicians should place their highest priority on diagnosing tuberculosis.
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Background Rilpivirine is safe and effective in HIV-na?ve patients with low baseline HIV-RNA or in switch strategy. It offers the advantages of few drug-drug interactions and a favourable toxicity profile. We aimed to determine th...
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Background Rilpivirine is safe and effective in HIV-na?ve patients with low baseline HIV-RNA or in switch strategy. It offers the advantages of few drug-drug interactions and a favourable toxicity profile. We aimed to determine the reasons for prescribing the rilpivirine (RPV)/tenofovir disoproxil (TDF)/emtricitabine (FTC) co-formulation within the Swiss HIV Cohort Study and to assess its effectiveness and safety over a 24 months period. Methods All individuals enrolled in the Swiss HIV Cohort Study who initiated a RPV/TDF/FTC co-formulation between April 2013 and March 2014 were included. Primary outcomes were the HIV-RNA viral load (copies/mL) and CD4 cell count (cells/mm3) at 6, 12 and 24 months. Reasons for a switch to RPV/TDF/FTC were evaluated through a standardized questionnaire. We also assessed discontinuation and reasons for discontinuation of RPV/TDF/FTC until October 30, 2015. Results Of 644 individuals who started the RPV/TDF/FTC co-formulation, only 7.5% were treatment-na?ve. At 24 months, viral suppression (HIV-RNA Conclusion The RPV/TDF/FTC co-formulation was safe and effective throughout 24 months of follow-up but barely prescribed for HIV-na?ve patients. Despite excellent virological suppression among both treatment-na?ve and -experienced patients, we observed a high rate of treatment discontinuation.
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IntroductionMorphological 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 complication...
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IntroductionMorphological 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.Materials and MethodsThe “Groupe Lipo & Metabolism” is a multidisciplinary consultation where patients undergo a standard evaluation including questionnaire, physical examination, dual-energy x-ray absorptiometry (DEXA) and L5-level CT scans, blood tests and consultations with various specialists. Based on prospectively maintained data, we describe clinical, biological and radiological characteristics of patients ≥18 years who attended the consultation between 2008 and 2013. We defined LH by CT scan, the gold standard method, as abdominal visceral adipose tissue (VAT) ≥130 cm2, value associated with increased risk of cardiovascular event.ResultsA total of 195 patients attended the consultation during study period. Reasons for referral included LH in 28.3%, LA in 25% and mixed syndrome in 15.5% of cases. Metabolic disorders accounted for 19% of referrals with or without LD features. Among patients with a CT scan performed (n=183), 46 (25%) had LH with a VAT ≥130 cm2. In this population, mean age was 49.1 years and 53.6% were male. HIV viral load was 6% in 10.5% of patients. Vitamin-D level was <75 nmol/L in 70.7% of patients. Respectively 31.2% and 12.1% of patients had osteopenia and osteoporosis on the spine and 44.8% and 6.6% on the hip neck. Factors associated with a VAT≥130 cm2 included male gender (OR 3.7 [95% CI 1.7–8.2] p<0.001), triglycerides ≥2 mmol/L (OR 2.6 [95% CI 1.3–5.4] P<0.01) and increase in BMI category (OR 1.8 [95% CI 1.2–2.8] p<0.01).ConclusionsLipohypertrophy is a prevalent feature of fat redistribution among HIV patients on treatment. Risk factors for LH include male gender, dyslipidemia and overweight. Glucose impairment and bone disorders are also common. A multidisciplinary approach is important to identify and promptly address these disorders.AcknowledgmentsThe “Groupe Lipo & Metabolism” team.
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IntroductionIn 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 lympho...
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IntroductionIn 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.Materials and MethodsA 29-year-old HIV positive man, successfully treated with HAART with an undetectable viral load and CD4 cells count of 438/μl, was admitted for high fever of unknown origin. Laboratory results showed a pancytopenia with haemoglobin at 82 g/l, lymphocyte count at 0.36G/l and platelets count at 47G/l; a highly elevated ferritine >7500 μg/l; increased lactate dehydrogenase at 885U/l and soluble IL2 receptor (CD25) >60 ng/ml. EBV load was measured and confirmed at 2,600,000 copies/ml. A PET-CT imaging showed diffuse elevated metabolic activity in the bone marrow and in two lesions in the spleen without lymphadenopathy. Bone marrow and liver biopsies revealed images of haemophagocytosis and lymphocyte depleted Hodgkin lymphoma. Treatment consisted in etoposid, steroids, and R-ABVD (rituximab, doxorubicin, bleomycin, vinblastine, dacarbazine) chemotherapy. The patient completed six cycles of chemotherapy. We reviewed the literature in PubMed with the following keywords: HPS, HIV, EBV, Hodgkin lymphoma.ResultsWe identified four publications and two reviews reporting cases of HPS associated with Hodgkin lymphoma in HIV patients with either a positive EBV load either the presence of encoded EBV RNA in tumour cells. Twenty-two cases (including one pediatric case) were described. Among adults, mostly men, the median age was <50 years and immune suppression was marked with a median CD4 cell count<100 cells/μl, even in patients receiving HAART. When measured, EBV load in the serum was high. Prognosis was poor with a high mortality despite adequate treatment consisting in steroids and chemotherapy, with or without etoposide (Table 1).Table 1Reported cases of HPS associated with Hodgkin lymphoma and high EBV load in HIV patients
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Operational research is necessary to improve the access to and delivery of tuberculosis prevention, diagnosis and treatment interventions for people living with HIV. We conducted an extensive review of the literature and reports f...
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Operational research is necessary to improve the access to and delivery of tuberculosis prevention, diagnosis and treatment interventions for people living with HIV. We conducted an extensive review of the literature and reports from recent expert consultations and research-related meetings organized by the World Health Organization and the Stop TB Partnership to identify a TB/HIV operational research agenda. We present critical operational research questions in a series of key areas: optimizing TB prevention by enhancing the uptake of isoniazid preventive therapy and the implementation of infection control measures; assessing the effectiveness of existing diagnostic tools and scaling up new technologies; improving service delivery models; and reducing risk factors for mortality among TB patients living with HIV. We discuss the potential impact that addressing the operational research questions may have on improving programmes’ performance, assessing new strategies or interventions for TB control, or informing global or national policy formulation. Financial resources to implement these operational research questions should be mobilized from existing and new funding mechanisms. National TB and HIV/AIDS programmes should develop their operational research agendas based on these questions, and conduct the research that they consider crucial for improving TB and HIV control in their settings in collaboration with research stakeholders.
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