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The SIMPL'HIV study investigated whether switching to dolutegravir (DTG) + emtricitabine (FTC) was noninferior to continuing combined antiretroviral therapy for maintaining HIV-1 suppression at 144 weeks. The study demonstrated that viral suppression, CD4 gains, adverse events, quality of life, and patient satisfaction were comparable between groups, confirming DTG + FTC's safety and efficacy for long-term management of HIV-1 infection. [ABSTRACT FROM AUTHOR]

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 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. Trial registration ClinicalTrials.gov NCT03160105., Author(s): Delphine Sculier 1,2,*, Gilles Wandeler 3,4, Sabine Yerly 5, Annalisa Marinosci 1, Marcel Stoeckle 6, Enos Bernasconi 7, Dominique L. Braun 8,9, Pietro Vernazza 10, Matthias Cavassini 11, Marta [...]

Bloodstream infections (BSIs) are a major cause of illness in HIV-infected persons. A series of studies, most of which were conducted in sub-Saharan Africa during the 1990s, demonstrated a high [...]

HIV-1 reservoir size and dynamics are promising parameters to ensure the safe prescription of simplified maintenance antiretroviral therapy in chronically HIV-1 infected patients. In the SIMPL'HIV trial, HIV-1 DNA was quantified in peripheral blood mononuclear cells obtained at baseline and week 48 to investigate changes over time and evidence of a predictive relationship to maintain HIV-1 RNA <20 copies/ml. Measurements were available for 175 patients, with no differences observed between treatment strategies. Findings showed that baseline HIV-1 DNA was lower in those with durable HIV-1 RNA <20 copies/ml compared with patients with incomplete viral suppression over 48 weeks. [ABSTRACT FROM AUTHOR]

This study aims to evaluate the association between dolutegravir (DTG) pharmacokinetic parameters and weight changes in treatment‐experienced people with HIV (PWHIV) from the Simpl'HIV study newly switched to a dual DTG‐based regimen. We used multivariable linear regressions to evaluate the association between DTG pharmacokinetic parameters at week 48 (derived using an established model) and weight change between week 0 and week 48. We adjusted our model for potential confounders including CD4 nadir, female sex, African origin, age, weight at week 0 and presence of a non‐nucleoside reverse transcriptase inhibitor‐based regimen before switch to DTG. The analysis included data from 39 PWHIV. An average significant weight gain of 2.4 kg was observed between baseline and week 48. DTG plasma exposure was not significantly associated with weight gain, even after adjusting for potential confounders (P =.9). We found no significant association between DTG pharmacokinetic parameters and weight gain amongst PWHIV newly switched to a DTG‐based dual regimen. [ABSTRACT FROM AUTHOR]

Introduction: 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. Materials and Methods: A 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. Results: We 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 Conclusions: Our case report and the review of literature suggest that physicians should be aware of the association between EBV infection/reactivation and Hodgkin lymphoma as a cause of HPS in HIV patients, even if successfully treated with HAART. The pathogenesis of these three interrelated conditions (viral infection, oncogenesis and immunologic reaction) remains unclear., Table 1: Reported cases of HPS associated with Hodgkin lymphoma and high EBV load in HIV patients Case report Number of cases Sex Age (years) CD4 count/µl Encoded EBV RNA [...]

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. Methods and Findings: PubMed, Embase, African Index Medicus, LILACS, and clinical trial registries were systematically searched. Randomised controlled trials, prospective cohort studies, and retrospective cohort studies were included if they compared tuberculosis incidence by antiretroviral therapy status in HIV-infected adults for a median of over 6 mo in developing countries. For the meta-analyses there were four categories based on CD4 counts at antiretroviral therapy initiation: (1) less than 200 cells/µl, (2) 200 to 350 cells/µl, (3) greater than 350 cells/µl, and (4) any CD4 count. Eleven studies met the inclusion criteria. Antiretroviral therapy is strongly associated with a reduction in the incidence of tuberculosis in all baseline CD4 count categories: (1) less than 200 cells/µl (hazard ratio [HR] 0.16, 95% confidence interval [CI] 0.07 to 0.36), (2) 200 to 350 cells/µl (HR 0.34, 95% CI 0.19 to 0.60), (3) greater than 350 cells/µl (HR 0.43, 95% CI 0.30 to 0.63), and (4) any CD4 count (HR 0.35, 95% CI 0.28 to 0.44). There was no evidence of hazard ratio modification with respect to baseline CD4 count category (p = 0.20). Conclusions: Antiretroviral therapy is strongly associated with a reduction in the incidence of tuberculosis across all CD4 count strata. Earlier initiation of antiretroviral therapy may be a key component of global and national strategies to control the HIV-associated tuberculosis syndemic. Review Registration: International Prospective Register of Systematic Reviews CRD42011001209 Please see later in the article for the Editors' Summary., Introduction Tuberculosis and human immunodeficiency virus (HIV) are major threats to global public health. HIV infection is the strongest risk factor for tuberculosis and has fuelled its resurgence [1]. In [...]

Background: Rilpivirine is safe and effective in HIV-naïve 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-naïve. At 24 months, viral suppression (HIV-RNA <50 copies/mL) was achieved in 100% and 96.7% of cART-naïve and cART-experienced patients respectively. The switch to RPV was mainly done for simplification (44.6%) and to overcome central nervous system toxicity symptoms due to efavirenz (24%). Six months after switch, 74.8% of patients reported an improvement of psycho-neurological symptoms with continued improvement at 12 months for almost 80%. However, one quarter of patients reported a discontinuation of RPV/TDF/FTC on October 30, 2015 after a median time of 18.4 months. Reasons for discontinuation included physician decision (5.3%) and side-effects (3.9%) mainly related to the central nervous system and to renal toxicity.Conclusion: The RPV/TDF/FTC co-formulation was safe and effective throughout 24 months of follow-up but barely prescribed for HIV-naïve patients. Despite excellent virological suppression among both treatment-naïve and -experienced patients, we observed a high rate of treatment discontinuation. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction 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. Materials and Methods The '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. Results A 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 <50 cp/ml in 87% of patients. Mean body mass index was 24.6 kg/m2. Mean waist to hip ratio (WHR) was 0.98 for males and 0.89 for females. A total of 9.8%, 29.5% and 35% of patients had abnormal levels of total cholesterol (≥6.5 mmol/L), triglycerides (≥2.0 mmol/L) and HDL cholesterol (≤1.0 mmol/L), respectively. Mean fasting glycaemia was 5.7 mmol/L and HbA1c 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). Conclusions Lipohypertrophy 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. Acknowledgments The 'Groupe Lipo & Metabolism' team. [ABSTRACT FROM AUTHOR]

Background: Clinical and laboratory monitoring of patients on antiretroviral therapy is an integral part of HIV care and determines whether treatment needs enhanced adherence or modification of the drug regimen. However, different monitoring and treatment strategies carry different costs and health consequences., Materials and Methods: The SIMPL'HIV study was a randomised trial that assessed the non-inferiority of dual maintenance therapy. The co-primary outcome was a comparison of costs over 48 weeks of dual therapy with standard antiretroviral therapy and the costs associated with a simplified HIV care approach (patient-centred monitoring [PCM]) versus standard, tri-monthly routine monitoring. Costs included outpatient medical consultations (HIV/non-HIV consultations), non-medical consultations, antiretroviral therapy, laboratory tests and hospitalisation costs. PCM participants had restricted immunological and blood safety monitoring at weeks 0 and 48, and they were offered the choice to complete their remaining study visits via a telephone call, have medications delivered to a specified address, and to have blood tests performed at a location of their choice. We analysed the costs of both strategies using invoices for medical consultations issued by the hospital where the patient was followed, as well as those obtained from health insurance companies. Secondary outcomes included differences between monitoring arms for renal function, lipids and glucose values, and weight over 48 weeks. Patient satisfaction with treatment and monitoring was also assessed using visual analogue scales., Results: Of 93 participants randomised to dolutegravir plus emtricitabine and 94 individuals to combination antiretroviral therapy (median nadir CD4 count, 246 cells/mm3; median age, 48 years; female, 17%),patient-centred monitoring generated no substantial reductions or increases in total costs (US$ -421 per year [95% CI -2292 to 1451]; p = 0.658). However, dual therapy was significantly less expensive (US$ -2620.4 [95% CI -2864.3 to -2331.4]) compared to standard triple-drug antiretroviral therapy costs. Approximately 50% of participants selected one monitoring option, one-third chose two, and a few opted for three. The preferred option was telephone calls, followed by drug delivery. The number of additional visits outside the study schedule did not differ by type of monitoring. Patient satisfaction related to treatment and monitoring was high at baseline, with no significant increase at week 48., Conclusions: Patient-centred monitoring did not reduce costs compared to standard monitoring in individuals switching to dual therapy or those continuing combined antiretroviral therapy. In this representative sample of patients with suppressed HIV, antiretroviral therapy was the primary factor driving costs, which may be reduced by using generic drugs to mitigate the high cost of lifelong HIV treatment., Trial Registration: ClinicalTrials.gov NCT03160105.

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., Competing Interests: Competing interests: We declare no competing interests. AC received unrestricted educational grants (to her Institution) in 2016 and 2017 from ViiV (DTG originator manufacturer).

The latest UNAIDS GAP report suggests the end of the HIV/AIDS epidemic by 2030 based on the progress in the fight against the disease during recent years. While the number of new infections and deaths related to HIV has decreased globally, more than half of people living with HIV do not know that they are infected with the virus. HIV testing and early initiation of antiretroviral therapy are both crucial elements in transmission prevention. Many treatment regimens are now available with new fixed dose combinations and new drugs that are better tolerated and with fewer drug interactions. A world without HIV will be possible only with an effective vaccine and cure--these are still hypothetical--and will require removal of societal, economical and political barriers.

Objective: This article reviews the antiretroviral therapy (ART)initiation criteria from national treatment guidelines for 70 countries and determines the extent of consistency with the current World Health Organization (WHO) recommendations., Methods: Published ART guidelines were collected from the Internet, databases, and WHO staff. ART eligibility criteria for asymptomatic people, pregnant women, people with HIV-associated tuberculosis, serodiscordant couples, injecting drug users, men who have sex with men, and sex workers were abstracted from them. Multiple regression analysis was used to determine the relation between ART eligibility criteria, ART coverage, and various population characteristics and policy interventions., Results: Of the 70 countries, 42 (60%) follow WHO’s ART guidelines for asymptomatic people and 31 (44%) for pregnant women,recommending ART at CD4 count of ≤350 cells/mm(3). Twenty-three(33%) countries recommend ART for people with HIV-associated tuberculosis irrespective of CD4 count. Nineteen countries are also recommending or considering earlier ART above CD4 count ≤350 cell/mm(3) for asymptomatic people, pregnant women, and/or serodiscordant couples. Multiple linear regression analysis shows that HIV prevalence, year of publication of guidelines, and HIV expenditure are significantly associated with published ART eligibility criteria. On average, the ART coverage is similar irrespective of published guidelines being consistent with the WHO recommendation(P , 0.53)., Conclusions: Published guidelines from a significant number of countries are not following WHO recommendations. Although published guidelines may not reflect practice, it is important to adapt recommendations and services quickly to reflect the emerging science on the health and prevention benefits of earlier access to ART.

Background: In resource-limited settings, abdominal ultrasound is often used to assist the diagnosis of tuberculosis (TB) in people with HIV (PLHIV), although data on performance characteristics are missing., Methods: Cross-sectional study of PLHIV in Cambodia receiving a standardized TB diagnostic evaluation, including history, physical examination, chest radiography, microscopy and culture of various specimens, and abdominal ultrasound. Patients with at least one specimen culture positive for Mycobacterium tuberculosis were classified as having TB., Results: TB was diagnosed in 37 (18%) of 212 PLHIV. Abdominal ultrasound was abnormal in 15 of 37 (41%) patients with TB compared with 14 of 175 (8%) without TB (P < 0.01). Predictors of TB disease included multiple enlarged (1.2 cm or greater) abdominal lymph nodes on ultrasound (adjusted odds ratio [OR], 6.4; 95% confidence interval [CI], 1.8-22.4), abnormal chest radiography (OR, 6.8; CI, 2.7-17.0), anorexia (OR, 4.6; CI, 1.8-11.7), and CD4 less than 200 cells/mm (OR, 3.3; CI, 1.2-9.1). Having multiple enlarged abdominal lymph nodes on ultrasound was 97.1% (CI, 93.5%-99.1%) specific for TB with a positive likelihood ratio of 11.4 (CI, 4.3-30.3)., Conclusions: Abdominal ultrasound is a useful diagnostic test for TB disease in PLHIV, increasing the posttest probability of TB when multiple enlarged abdominal lymph nodes are visualized. Its wider use may accelerate access to TB treatment, potentially reducing mortality in PLHIV.

Objective: To develop an algorithm for optimal use of viral load testing in patients with suspected first-line antiretroviral treatment (ART) failure., Methods: Data from a cohort of patients on first-line ART in Cambodia were analyzed in a cross-sectional way to detect markers for treatment failure. Markers with an adjusted likelihood ratio <0.67 or >1.5 were retained to calculate a predictor score. The accuracy of a 2-step algorithm based on this score followed by targeted viral load testing was compared with World Health Organization criteria for suspected treatment failure., Results: One thousand eight hundred three viral load measurements of 764 patients were available for analysis. Prior ART exposure, CD4 count below baseline, 25% and 50% drop from peak CD4 count, hemoglobin drop of > or =1 g/dL, CD4 count <100 cells per microliter after 12 months of treatment, new onset of papular pruritic eruption, and visual analog scale <95% were included in the predictor score. A score >or=2 had the best combination of sensitivity and specificity and required confirmatory viral load testing for only 9% of patients. World Health Organization criteria had a similar sensitivity but a lower specificity and required viral load testing for 24.9% of patients., Conclusion: An algorithm combining a predictor score with targeted viral load testing in patients with an intermediate probability of failure optimizes the use of scarce resources.