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Background: Sparing of antiretroviral drug classes could reduce the toxicity and cost of maintenance treatment for HIV infection.Objectives: To evaluate the non-inferiority of efficacy and the safety of lopinavir/ritonavir (r) monotherapy versus a single-tablet regimen of efavirenz, emtricitabine and tenofovir (EFV/FTC/TDF) over 2 years.Methods: Adults on stable ART with plasma HIV-1 RNA viral load <50 copies/mL for the past 12 months and no documented treatment failure were randomized to receive either lopinavir/r or EFV/FTC/TDF for 2 years. The primary endpoint was the proportion of patients without treatment failure at week 96 (viral load <50 copies/mL at week 96, confirmed at week 98), without study treatment discontinuation, a new AIDS-defining illness, or death.Results: In the ITT analysis, the primary endpoint was reached by, respectively, 64% and 71% of patients in the lopinavir/r (n = 98) and EFV/FTC/TDF arms (n = 97), yielding a difference of -6.8% (lower limit of the 95% two-sided CI: -19.9%). Sanger and UltraDeep sequencing showed the occurrence of PI mutations in the lopinavir/r arm (n = 4) and of NNRTI and/or NRTI mutations in the EFV/FTC/TDF arm (n = 2). No unexpected serious clinical events occurred.Conclusions: Lopinavir/r monotherapy cannot be considered non-inferior to EFV/FTC/TDF. PI resistance rarely emerged in the lopinavir/r arm and did not undermine future PI options. Two years of lopinavir/r monotherapy had no deleterious clinical impact when compared with EFV/FTC/TDF. [ABSTRACT FROM AUTHOR]

Background: Intermittent treatment could improve the convenience, tolerability and cost of ART, as well as patients' quality of life. We conducted a 48 week multicentre study of a 4-days-a-week antiretroviral regimen in adults with controlled HIV-1-RNA plasma viral load (VL).Methods: Eligible patients were adults with VL < 50 copies/mL for at least 1 year on triple therapy with a ritonavir-boosted PI (PI/r) or an NNRTI. The study protocol consisted of the same regimen taken on four consecutive days per week followed by a 3 day drug interruption. The primary outcome was the proportion of participants remaining in the strategy with VL < 50 copies/mL up to week 48. The study was designed to show an observed success rate of > 90%, with a power of 87% and a 5% type 1 error. The study was registered with ClinicalTrials.gov (NCT02157311) and EudraCT (2014-000146-29).Results: One hundred patients (82 men), median age 47 years (IQR 40-53), were included. They had been receiving ART for a median of 5.1 (IQR 2.9-9.3) years and had a median CD4 cell count of 665 (IQR 543-829) cells/mm3. The ongoing regimen included PI/r in 29 cases and NNRTI in 71 cases. At 48 weeks, 96% of participants (95% CI 90%-98%) had no failure while remaining on the 4-days-a-week regimen. Virological failure occurred in three participants, who all resumed daily treatment and became resuppressed. One participant stopped the strategy. No severe treatment-related events occurred.Conclusions: Antiretroviral maintenance therapy 4 days a week was effective for 48 weeks in 96% of patients, leading to potential reduction of long-term toxicities, high adherence to the antiretroviral regimen and drug cost saving. [ABSTRACT FROM AUTHOR]

Background: The preferred regimen for HIV post-exposure prophylaxis (PEP) is based mainly on safety and tolerability because it is given to immunocompetent people without HIV infection for a limited time (28 days). The frequency of adverse events (AEs) may be > 60%. Although AEs are generally not severe, they can lead to lack of adherence and failure to complete the regimen. We evaluated the co-formulation elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate (Stribild®) prescribed as one pill taken once daily for HIV PEP in terms of tolerability and adherence. Methods: This was a prospective cohort study conducted in one hospital in Paris (April to December 2015. Each participant receiving the PEP treatment (FTC-150 mg/TDF-245 mg/elvitegravir-200 mg/cobicistat 150 mg once daily) at the pharmacy of the hospital were recruited consecutively. A clinical visit was planned at 8 weeks after sexual exposure. Reminders were sent to participants who missed the appointment. A standardized questionnaire was administered to evaluate completeness and tolerability at week 8. Results: Overall, 284 participants (86% men; 80% MSM; median age 30 years) were prescribed Stribild®; 50 stopped after reassessment of risk. Among 234 participants who effectively received PEP, 215 (92%) completed 28 days of PEP with only three who switched from Stribild® to another PEP because of side effects. More than 60% of participants reported at least one AE, which were mild to moderate. Fatigue, central neurological and abdominal side effects were the most frequently reported. Conclusions: Stribild® seems to be a good option for HIV PEP due to the easiness of use, the side effects profile and the high completion rate. [ABSTRACT FROM AUTHOR]

Purpose: Prospective data on potential factors associated with severity of imported Plasmodium falciparum malaria are lacking. We evaluated whether several host- and parasite-related biomarkers may improve early severity evaluation.Methods: Prospective multicenter observational study comparing uncomplicated and severe imported falciparum malaria in adults conducted in France in 52 units, from 2007 to 2010. Association of several host- and parasite-related biomarkers with severity of malaria was tested using univariate and multivariate analyses.Results: Of 295 patients, 140 had uncomplicated malaria and 155 severe malaria (including very severe and less severe cases according to predefined criteria). Curative intravenous quinine treatment was used in 154/155 patients with severe malaria and atovaquone/proguanil in 74 % of patients with uncomplicated malaria. Hospital mortality was 5.2 % (8 patients), all in the severe malaria group. Among host-related biomarkers, CRP, procalcitonin, and sTREM-1 were significantly higher and albumin was significantly lower in severe versus uncomplicated malaria; only the last three biomarkers also differed significantly between the very and less severe malaria groups. Among parasite-related biomarkers, only plasma PfHRP2 was significantly higher in severe versus uncomplicated malaria and in very severe versus less severe malaria; parasitemia did not differ between very and less severe malaria. By multivariate analysis, only lower plasma albumin and higher sTREM-1 were associated with greater severity, with intermediate accuracies.Conclusions: During imported malaria, the most useful biomarkers associated with severity seem to be plasma albumin and sTREM-1; and among parasite-related parameters, PfHRP2 was more strongly associated with severity than parasitemia was. [ABSTRACT FROM AUTHOR]

Early events during primary HIV infection (PHI) are thought to influence disease outcome. Although a growing body of evidence suggests a beneficial role of HIV-specific CD4 help in HIV infection, it is unclear how early viral replication, systemic immune activation, and antiretroviral therapy (ART) may shape CD4 T-cell responses during PHI, and whether HIV-specific CD4 responses contribute to the high immune activation observed in PHI. Twenty-seven patients with early PHI were included in a prospective longitudinal study and 12 of them received ART after enrollment. Fresh peripheral blood mononuclear cells were used for measurement of ex vivo T-cell activation and of cytokine-producing CD4 T-cells following stimulation with PMA/ionomycin or HIV-1-gag-p24 antigen. Patients were segregated based on CD8 T-cell activation level (i.e., % HLA-DR+CD38+ CD8 T-cells) at baseline (BL). Patients with lower immune activation exhibited higher frequency of bulk CD4 T-cells producing IFN-γ or IL-17 and higher effector-to-regulatory cell ratios. No differences were found in HIV-specific CD4 T-cell frequencies. In contrast, segregation of patients based on plasma viral load (pVL) revealed that patients with higher pVL showed higher cytokine-producing HIV-specific CD4 responses. Of note, the frequency of IFN-γ+ HIV-specific CD4 T cells significantly diminished between BL and month 6 only in ART-treated patients. However, early treatment initiation was associated with better maintenance of HIV-specific IFN-γ+ CD4 T-cells. These data suggest that HIV-specific CD4 responses do not fuel systemic T-cell activation and are driven by viral replication but not able to contribute to its control in the early phase of infection. Moreover, our data also suggest a benefit of early treatment for the maintenance of HIV-specific CD4 T-cell help. [ABSTRACT FROM AUTHOR]

Objectives: Boosted PIs are commonly prescribed in patients presenting with advanced HIV infection. We assessed the efficacy and tolerability of once-daily ritonavir-boosted atazanavir or darunavir plus two NRTIs in HIV-1-infected ART-naive patients with severe immunosuppression, targeting at least an 85% success rate at week 48.Methods: This 48 week, open-label, non-comparative, randomized, multicentre trial included ART-naive patients with CD4 cell counts <200 cells/mm(3), with plasma HIV-1 RNA >1000 copies/mL and without genotypic mutations conferring resistance to the study drugs. Patients were randomized (1:1) to receive once-daily atazanavir/ritonavir (300/100 mg) or darunavir/ritonavir (800/100 mg) plus tenofovir disoproxil fumarate/emtricitabine or abacavir/lamivudine. The primary endpoint was treatment success, defined as plasma HIV-1 RNA ≤50 copies/mL at week 48 and no permanent PI/ritonavir discontinuation. The study was registered with ClinicalTrials.gov (NCT01928407).Results: One hundred and twenty patients were enrolled: 77% were men, 30% were born in Africa and 39% had AIDS. The median baseline CD4 and plasma HIV-RNA values were 69 cells/mm(3) and 5.4 log10 copies/mL. All but four patients received tenofovir disoproxil fumarate/emtricitabine. The week 48 treatment success rate was 66% (95% CI 54%-78%) with atazanavir/ritonavir and 80% (95% CI 68%-89%) with darunavir/ritonavir. The median CD4 cell count increased similarly in the two groups (Δweek 48 to week 0: +194 cells/mm(3)). Adverse events occurred in 23 and 18 patients, respectively.Conclusions: Despite good adherence, neither study regimen reached the predefined objective, suggesting a need for more potent regimens for patients with advanced HIV infection. [ABSTRACT FROM AUTHOR]

Background and Aim In Sub-Saharan Africa, seroclearance of hepatitis B surface antigen (HBsAg) and hepatitis B 'e' antigen (HBeAg), including their quantifiable markers, have rarely been evaluated during long-term antiviral treatment among patients coinfected with HIV and hepatitis B virus (HBV). Methods In this prospective cohort study from two randomized-control trials in Côte d'Ivoire, 161 antiretroviral-naïve HIV-HBV coinfected patients starting lamivudine ( n = 76) or tenofovir/emtricitabine ( n = 85) containing antiretroviral therapy were included. HBV DNA was quantified using an in-house assay (detection limit = 12 copies/mL) and HBsAg quantification (qHBsAg) using the Elecsys assay. Results Overall, 33 (20.5%) patients were HBeAg positive, 121 (75.2%) had detectable HBV DNA, and 92/93 (98.9%) harbored HBV genotype E. Median treatment duration was 35.5 months (interquartile range: 24.3-36.4). Among HBeAg-positive patients, cumulative proportion with HBeAg seroclearance was 46.3% ( n = 14). Overall, cumulative proportion of HBsAg seroclearance was 6.6% ( n = 10). Lower baseline qHBsAg levels and strong 12-month declines in qHBsAg were significantly associated with HBsAg seroclearance for both HBeAg-negative and HBeAg-positive patients. When taken at certain levels, these determinants provided moderate sensitivity (Se) and specificity (Sp) in predicting HBsAg seroclearance at month 36 (≤ 1000 IU/mL at baseline, Se = 0.80, Sp = 0.80; ≥ 1.0 log10 IU/mL drop at month 12, Se = 0.57, Sp = 1.00). Instead, qHBsAg levels ≤ 100 or ≤ 10 IU/mL at month 12 were optimal (both Se = 0.90 and Sp = 1.00). Detectable HBV-DNA provided fairly high Se and Sp when evaluated at baseline (Se = 1.00, Sp = 0.80), but not at month 12 (Se = 0.80, Sp = 0.40). Conclusions HBsAg seroclearance rates are not common in patients from Sub-Saharan Africa treated with anti-HBV containing antiretroviral therapy. qHBsAg levels at 12 months of treatment may accurately predict HBsAg seroclearance. [ABSTRACT FROM AUTHOR]

Objectives: To relate socio-demographic and virological information to phylogenetic clustering in HIV infected patients in a limited geographical area and to evaluate the role of recently infected individuals in the spread of HIV. Methods: HIV-1 pol sequences from newly diagnosed and treatment-naive patients receiving follow-up between 2008 and 2011 by physicians belonging to a health network in Paris were used to build a phylogenetic tree using neighbour-joining analysis. Time since infection was estimated by immunoassay to define recently infected patients (very early infected presenters, VEP). Data on socio-demographic, clinical and biological features in clustered and non-clustered patients were compared. Chains of infection structure was also analysed. Results: 547 patients were included, 49 chains of infection containing 108 (20%) patients were identified by phylogenetic analysis. analysis. Eighty individuals formed pairs and 28 individuals were belonging to larger clusters. The median time between two successive HIV diagnoses in the same chain of infection was 248 days [CI = 176–320]. 34.7% of individuals were considered as VEP, and 27% of them were included in chains of infection. Multivariable analysis showed that belonging to a cluster was more frequent in VEP and those under 30 years old (OR: 3.65, 95 CI 1.49–8.95, p = 0.005 and OR: 2.42, 95% CI 1.05–5.85, p = 0.04 respectively). The prevalence of drug resistance was not associated with belonging to a pair or a cluster. Within chains, VEP were not grouped together more than chance predicted (p = 0.97). Conclusions: Most newly diagnosed patients did not belong to a chain of infection, confirming the importance of undiagnosed or untreated HIV infected individuals in transmission. Furthermore, clusters involving both recently infected individuals and longstanding infected individuals support a substantial role in transmission of the latter before diagnosis. [ABSTRACT FROM AUTHOR]

Summary Background Our objective was to assess therapeutic non-inferiority of dual treatment with lopinavir–ritonavir and lamivudine to triple treatment with lopinavir–ritonavir plus two nucleos(t)ides for maintenance of HIV-1 viral suppression. Methods In this randomised, open-label, non-inferiority trial, we recruited patients from 32 HIV units in hospitals in Spain and France. Eligible patients were HIV-infected adults (aged ≥18 years) with HIV-1 RNA of less than 50 copies per mL, for at least 6 months on triple treatment with lopinavir–ritonavir (twice daily) plus lamivudine or emtricitabine and a second nucleos(t)ide, with no resistance or virological failure to these drugs, and no positive hepatitis B serum surface antigen. Investigators at each centre randomly assigned patients (1:1; block size of four; stratified by time to suppression [<1 year or >1 year] and nadir CD4 cell count [<100 cells per μL or >100 cells per μL]; computer-generated random sequence) to continue triple treatment or switch to dual treatment (oral lopinavir 400 mg and oral ritonavir 100 mg twice daily plus oral lamivudine 300 mg once daily). The primary endpoint was response to treatment in the intention-to-treat population (all randomised patients) at 48 weeks. The non-inferiority margin was 12%. This study is registered with ClinicalTrials.gov , number NCT01471821 . Findings Between Oct 1, 2011, and April 1, 2013, we randomly assigned 250 participants to continue triple treatment (127 [51%] patients) or switch to dual treatment (123 [49%] patients). In the intention-to-treat population, 110 (86·6%) of 127 patients in the triple-treatment group responded to treatment versus 108 (87·8%) of 123 in the dual-treatment group (difference −1·2% [95% CI −9·6 to 7·3]; p=0·92), meeting the criteria for non-inferiority. Serious adverse events occurred in eight (7%) patients in the triple-treatment group and five (4%) in the dual-treatment group (p=0·515), and study drug discontinuations due to adverse events occurred in four (3%) in the triple-treatment group and one (1%) in the dual-treatment group (p=0·223). Interpretation Dual treatment with lopinavir–ritonavir plus lamivudine has non-inferior therapeutic efficacy and is similarly tolerated to triple treatment. Funding AbbVie and Red Temática Cooperativa de Investigación en Sida. [ABSTRACT FROM AUTHOR]

Background. Combined antiretroviral therapy (cART) initiation during primary human immunodeficiency virus (HIV) infection (PHI) yields a larger decrease in cell-associated HIV-DNA (CA-HIV-DNA) than initiation during the chronic phase. Our objective was to model the short and long-term decay of CA-HIV-DNA blood reservoir in patients initiating cART during PHI and to assess the impact of the timing of cART initiation on CA-HIV-DNA decay. Methods. We included patients enrolled during PHI in the Agence Nationale de Recherche sur le Sida PRIMO cohort, treated within the month following enrollment and achieving sustained virologic response. The decay of CA-HIV-DNA over time while on successful cART was modeled with a 3-slope linear mixed-effects model according to the delay between estimated date of infection and cART initiation. Results. Three hundred twenty-seven patients were included, accounting for 1305 CA-HIV-DNA quantifications. Median time between infection and cART initiation was 41 days (interquartile range, 33-54 days). Median follow-up under cART was 2.3 years (range, 0.4-16.6 years). The timing of cART initiation had significant impact on the first slope of decrease: The earlier cART was initiated after HIV infection, the faster CA-HIV-DNA level decreased during the first 8 months of cART: -0.171, -0.131, and -0.068 log10 copies/106 peripheral blood mononuclear cells (PBMCs) per month when cART was initiated 15 days, 1 month, and 3 months after infection, respectively (P < .0001). The predicted mean CA-HIV-DNA level achieved after 5 years of successful cART was 1.62 and 2.24 log10 copies/106 PBMCs when cART was initiated 15 days and 3 months after infection, respectively (P = .0006). Conclusions. This study provides strong arguments in favor of cART initiation at the earliest possible time point after HIV infection. [ABSTRACT FROM AUTHOR]

Objectives: An open-label randomized trial (DAYANA) was conducted in sub-Saharan settings to evaluate four different regimens containing tenofovir disoproxil fumarate as first-line treatment for HIV infection. The objectives of the present substudy were to assess the relationship between trough concentrations of tenofovir in plasma collected after 24 h (C24) and estimated glomerular filtration rates (eGFR) calculated by the different formulae that are available. Methods: The criteria for eligibility were those of the DAYANA trial, recruiting naive patients. The four tenofovir regimens were: Group 1, tenofovir/emtricitabine/nevirapine; Group 2, tenofovir/lopinavir/ritonavir; Group 3, tenofovir/emtricitabine/zidovudine; and Group 4, tenofovir/emtricitabine/efavirenz. The C24 of tenofovir was determined using LC-MS/MS. The eGFR was calculated using the Cockcroft-Gault, Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formulae. Results: The median C24 of tenofovir was 42 ng/mL. The C24 of tenofovir was higher with lopinavir/ritonavir than with the other three regimens: at Week 4, 84 ng/mL versus 25 ng/mL; and at Week 48, 81 ng/mL versus 52 ng/mL. The baseline merged eGFR was 98.2 mL/min/1.73 m2 with the CKD-EPI equation. Only the mean changes in eGFR in Group 2 differed from the absolute value of zero (-8.2 mL/min/1.73 m2) with the CKD-EPI equation between baseline and Week 48. The Cockcroft-Gault formula is inappropriate for these African patients because it underestimated the baseline eGFR and overestimated the changes in eGFR between baseline and Week 48. Conclusions: In this population of mostly female HIV-1-infected African patients, tenofovir plasma overexposure was associated with PI/ritonavir and a time-dependent decrease in eGFR, probably via an inhibition of MRP2/MRP4 efflux transporters. The close monitoring over time of the eGFR using MDRD or CKD-EPI calculations and by using other biomarkers of renal disorder should be proposed as an alternative to therapeutic drug monitoring in resource-limited countries. [ABSTRACT FROM AUTHOR]

Background: While residual plasma viremia is commonly observed in HIV-infected patients undergoing antiretroviral treatment (ART), little is known about its subclinical consequences. Methods: This cross-sectional study included 47 male, never-smoking, non-diabetic patients with ≥4 years of ART and controlled HIV-replication (HIV-viral load, VL <20 copies/mL for ≥1 year). Residual HIV-VL was measured using an ultrasensitive assay (quantification limit: 1 copy/ml). Patients were categorized as having detectable (D; 1-20 copies/mL, n = 14) or undetectable (UD; <1 copies/mL, n = 33) HIV-VL. Linear regression was used to model the difference in total carotid intima-media thickness [c-IMT, measures averaged across common carotid artery (cca), bifurcation, and internal carotid artery] and cca-IMT alone across detection groups. Multivariable models were constructed for each endpoint in a forward-stepwise approach. Results: No significant differences were observed between viremia groups with respect to median ART-duration (9.6 years, IQR = 6.8–10.9), nadir CD4+T-cell (208/mm3, IQR = 143–378), and CD4+T-cell count (555/mm3, IQR = 458–707). Median adjusted inflammatory markers tended to be higher in patients with D- than UD-viremia, with differences in IL-10 being significant (p = 0.03). After adjustment on age, systolic blood pressure, and insulin resistance, mean cca-IMT was significantly lower in patients with undetectable (0.668 mm±0.010) versus detectable viremia (0.727 mm±0.015, p = 0.002). Cca-IMT was also independently associated with age and insulin resistance. Mean adjusted total c-IMT was no different between viremia groups (p = 0.2), however there was large variability in bifurcation c-IMT measurements. Conclusions: Higher cca-IMT was observed in patients with detectable, compared to undetectable, HIV-VL in never-smoking ART-controlled patients, suggesting that residual HIV viremia may be linked to atherosclerosis. [ABSTRACT FROM AUTHOR]

Objectives To investigate the best conditions of raltegravir use to avoid the selection of resistance mutations in the three main genetic pathways: 148, 155 and 143. Methods A total of 161 patients failing on raltegravir with two consecutive HIV-1 viral loads >20 copies/mL were studied. Ten parameters [HIV-1 RNA and CD4 at baseline and failure, genotypic sensitivity score (GSS) of treatment associated with raltegravir, protease inhibitors used, time spent on raltegravir, subtype, sex and age] were tested in univariate and multivariate logistic regression analyses and compared with the emergence of resistance mutations to raltegravir at failure. Phenotypic susceptibility to raltegravir was studied in 16 patients without the main resistance mutations to raltegravir at failure. Results At raltegravir failure, 46/161 patients (28.6%) had integrase resistance mutations, whereas 115/161 (71.4%) had no resistance mutations. High HIV-1 viral load level at failure (OR = 2.81, 95% CI 1.8–4.6, P < 0.001) and low GSS of treatment associated with raltegravir (OR = 11.6, 95% CI 4.5–36.4, P < 0.001) were independently associated with the selection of raltegravir mutations. The percentages of patients with integrase resistance mutations were 7.7% (6/78) versus 48.1% (40/83) when viral load is ≤200 or >200 copies/mL and 47.5% (39/82) versus 8.9% (7/79) when GSS is <2 or ≥2. Among patients without main resistance mutations, two patients showed raltegravir phenotypic resistance, one naturally with F121Y at baseline and the other acquiring G118R at failure. Conclusions Our results show that to avoid the selection of raltegravir resistance mutations, patients have to be treated with at least two active drugs in combination with raltegravir and to maintain a viral load ≤200 copies/mL. [ABSTRACT FROM PUBLISHER]

Objectives: To examine how treatment adherence differences in ARTEMIS (96 week analysis) affected clinical outcome, and to assess factors impacting adherence. [ABSTRACT FROM PUBLISHER]

Background. Treatment strategies that would induce durable virological control of human immunodeficiency virus (HIV)-1 in the absence of continued antiretroviral therapy (ART) are highly desirable. Methods. We assessed, in a randomized, double-blind, placebo-controlled trial, whether the addition of therapeutic vaccines (ALVAC-HIV [vCP1452] or ALVAC-HIV and Remune) to ART initiated during acute infection could increase the probability of having a plasma viral load ⩽1000 HIV-1 RNA copies/mL 24 weeks after planned discontinuation of ART. Results. All 79 randomized subjects completed the immunization schedule, and 78 discontinued ART with no major safety concerns. After immunization, subjects in the vaccine study arms had significantly increased HIV-1-specific CD4+ and CD8+ T cell responses, by interferon-γ enzyme-linked immunospot assay, compared with those in the placebo study arm. Overall, 17.7% of subjects had ⩽1000 HIV-1 RNA copies/mL 24 weeks after discontinuation of ART, with no significant difference between the vaccine study arms and the placebo study arm (15.4% vs. 22.2%; difference, -6.8% [95% confidence interval, -26.8% to 10.0%]; P = .54). Conclusion. Therapeutic immunization and ART, compared with ART alone, generated HIV-1-specific cellular immunity but did not lead to better virological control of HIV-1 24 weeks after discontinuation of ART. Our trial design appears to be feasible and safe for testing future immune-boosting strategies. [ABSTRACT FROM AUTHOR]

Background: Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg is a once-daily, single-tablet regimen for treatment of HIV-1 infection. The efficacy/safety of switching to D/C/F/TAF versus continuing boosted protease inhibitor (bPI) + emtricitabine/tenofovir disoproxil fumarate (control) were demonstrated in a phase 3, randomized study (EMERALD) of treatment-experienced, virologically suppressed adults through week 48. The objective of this analysis was to evaluate EMERALD outcomes across subgroups of patients based on demographic characteristics, prior treatment experience, and baseline antiretroviral regimen. Methods: EMERALD patients were virologically suppressed (viral load [VL] < 50 copies/mL for ≥ 2 months at screening). Prior non-darunavir virologic failure (VF) was allowed. Primary endpoint was proportion of patients with virologic rebound (confirmed VL ≥ 50 copies/mL) cumulative through week 48. Virologic response was VL < 50 copies/mL (FDA snapshot). Safety was assessed by adverse events, renal proteinuria markers, and bone mineral density. Outcomes were examined for prespecified subgroups by age (≤/> 50 years), gender, race (black/non-black), prior number of antiretrovirals used (4/5/6/7/> 7), prior VF (0/≥ 1), baseline bPI (darunavir/atazanavir or lopinavir), and baseline boosting agent (ritonavir/cobicistat). Results: Among 1141 patients in the D/C/F/TAF (n = 763) and control (n = 378) arms, virologic rebound rates (2.5% and 2.1%, respectively) were similar, and this was consistent across all subgroups. Virologic response rates ranged from 91 to 97% (D/C/F/TAF) and 89 to 99% (control) across all subgroups, with differences between treatment arms of 0 and 6%. Adverse event rates were low in both arms and across subgroups. Improvements in renal and bone parameters were observed with D/C/F/TAF across demographic subgroups. Conclusions: For treatment-experienced, virologically suppressed patients, switching to D/C/F/TAF was highly effective and safe, regardless of demographic characteristics, prior treatment experience, or pre-switch bPI. Trial registration ClinicalTrials.gov Identifier: NCT02269917. Registered 21 October 2014. https://clinicaltrials.gov/ct2/show/NCT02269917 [ABSTRACT FROM AUTHOR]

Introduction In high-income countries, ≥30% of HIV-infected patients are ≥50 years (yrs) old (UNAIDS 2013). In two phases, three clinical trials (Studies 102 and 103) elvitegravir/cobicistat/emtricitabine/tenofovir DF (E/C/F/TDF; STB) had non-inferior efficacy and favourable safety vs efavirenz/emtricitabine/tenofovir DF (EFV/FTC/TDF; ATR) or ritonavir-boosted atazanavir (ATV+RTV)+FTC/TDF (TVD) in HIV-infected, treatment-naïve subjects at Week 144. The efficacy and safety of STB in subjects < or ≥50 yrs is described. Materials and Methods Post hoc analysis of efficacy, tolerability and safety in subjects < or ≥50 yrs at Week 144. Results Subjects ≥50 yrs in Study 102: STB: 14% (49/348), ATR: 16% (56/352); in Study 103: STB: 14% (48/353), ATV+RTV+TVD: 14% (48/355). Efficacy, safety and tolerability by age and study endpoint are shown in Table 1. Regardless of age, STB had robust efficacy at Week 144 with similar virologic outcomes vs ATR or ATV+RTV+TVD. Discontinuations (DC) due to AE on STB were similar to the comparators, most occurred by Week 48. Median changes in eGFR on STB were similar by age; DC with renal PRT was rare [STB: 4 (0.6%); ATV: 3 (0.8%); ATR: 0], 2 and 1 in ≥50 yrs old strata, respectively. Conclusions STB compared to ATR or ATV+RTV+TVD, is an efficacious, well-tolerated and safe regimen for HIV-1-infected, treatment-naïve subjects

Introduction The efficacy of protease inhibitor monotherapy has been analyzed with different endpoints: initial HIV-1 RNA rebound, long-term HIV-1 RNA suppression after re-intensification, treatment-emergent drug resistance, neurocognitive testing and HIV-1 RNA in the cerebrospinal fluid (CSF). Methods A PUBMED search identified nine randomised trials of PI monotherapy versus triple therapy in patients with HIV RNA<50 copies/mL at baseline. Results from the recently completed PROTEA trial were also included. The percentage of patients with HIV RNA suppression <50 copies/mL was analyzed using switch equals failure and intensification included endpoints (ITT). The number of patients with new drug resistance mutations, HIV RNA in the CSF or change in neurocognitive function was analyzed by treatment arm. Results Four trials evaluated darunavir/r monotherapy (n=785: MONET, MONOI, MONARCH, PROTEA), five evaluated lopinavir/r monotherapy (n=592: OK-04, KalMo, KALESOLO, KRETA, MOST) and one evaluated both (MRC PIVOT, n=587). HIV-1 RNA suppression rates tended to be lower on PI monotherapy than triple therapy in 'switch equals failure' analysis (76% vs 82%), but not when the outcome of intensification was included (87% vs 85%). There were small numbers of patients taking PI monotherapy with detectable HIV-1 RNA in the CSF, in three trials: PROTEA (n=2), MONOI (n=2) and MOST (n=5), but only two cases of CSF viral escape (MONOI). In two trials, there was no difference in neurocognitive test results between PI monotherapy and triple therapy, based on z-scores from five domains (in PROTEA, mean change in NPZ-5 score=0.0 for DRV/r monotherapy vs −0.10 for triple therapy); similar results were observed in the MRC PIVOT trial. The risk of treatment emergent NRTI or PI resistance (Table 1) was 11/973 (1.1%) for patients on PI monotherapy, versus 7/991 (0.7%) for patients on triple therapy. Conclusions In 10 randomised trials of 1964 patients with HIV-1 RNA suppression at baseline, PI monotherapy showed a higher risk of HIV RNA elevations, and small numbers with HIV RNA detectable in CSF and concomitantly in the plasma. However there was no increased risk of treatment-emergent drug resistance, neurocognitive endpoints were not different between the arms and HIV-1 RNA suppression rates after intensification were similar between PI monotherapy and triple therapy. [ABSTRACT FROM AUTHOR]

Introduction We report the SVR12 final analysis of a phase 3 study of telaprevir in combination with peginterferon (P)/ribavirin (R) in HCV-genotype 1, treatment-naïve and -experienced patients with HCV/HIV co-infection (INSIGHT). Materials and Methods Patients receiving stable, suppressive HIV antiretroviral (ARV) therapy, containing atazanavir/ritonavir, efavirenz, darunavir/ritonavir, raltegravir, etravirine or rilpivirine, received telaprevir 750 mg q8h (1125 mg q8h if on efavirenz) plus P (180 µg once-weekly) and R (800 mg/day) for 12 weeks, followed by an additional 12 weeks (non-cirrhotic HCV treatment-naïve and relapse patients with extended rapid viral response [eRVR]) or 36 weeks (all others) of PR alone. Analysis was performed when all patients had completed the follow-up visit of 12 weeks after last planned dose. Results One hundred sixty-two patients were enrolled and treated (65 efavirenz, 59 atazanavir/ritonavir, 17 darunavir/ritonavir, 17 raltegravir, 4 etravirine). Mean age was 45 years, 78% were male, 92% were Caucasian; mean CD4 count was 687 cells/mm3. Sixty four patients (40%) were HCV treatment-naïve and 98 (60%) were treatment experienced (29 relapsers, 18 partial responders and 51 null responders). 64% were subtype 1a. 30% had bridging fibrosis (17%) or cirrhosis (13%). 19% of patients discontinued telaprevir, including 9% due to an adverse event (AE), 8% reaching a virologic endpoint and 2% for other reasons (non compliance or not defined). Treatment responses are shown in Table 1. There were no HIV RNA breakthroughs. Most frequently reported (≥20% patients) AEs were pruritus 43%; fatigue 27%; rash 34%, anorectal events 30% and influenza-like illness (25%). Anemia was reported in 15% of patients; grade ≥3 haemoglobin decrease occurred in 2.5% of patients. 6% of patients experienced serious AEs. Conclusions In this phase 3 study of HIV-infected, HCV treatment-naïve and -experienced patients, 49% achieved eRVR and 57% reached SVR12. In patients with an eRVR, SVR12 rates were >80%, irrespective of prior treatment history. [ABSTRACT FROM AUTHOR]

Introduction In previous studies, protease inhibitor (PI) monotherapy has shown trends for higher low-level elevations in HIV-1 RNA compared to triple therapy, but no increase in the risk of drug resistance. Methods A total of 273 patients with HIV-1 RNA <50 copies/mL for over 24 weeks on current antiretrovirals switched to DRV/r (darunavir/ritonavir) 800/100 mg once-daily, either as monotherapy ( n=137) or with 2NRTIs (nucleoside reverse-transcriptase inhibitors) ( n=136), after a 4 week run-in phase with DRV/r + 2NRTI. Treatment failure was defined as HIV-1 RNA levels above 50 copies/mL (FDA Snapshot method) by Week 48, or switches off study treatment. Patients with elevations in HIV-1 RNA on DRV/r monotherapy could be re-intensified with NRTIs. The trial had 80% power to show non-inferiority for the monotherapy arm (delta = − 12%). Results Patients were 83% male and 87% Caucasian, with mean age 42 years; 10% were HCV antibody positive. In the DRV/r monotherapy arm, there were more patients with nadir CD4 count below 200 cells/µL (30% versus 22%). In the primary efficacy analysis, HIV-1 RNA <50 copies/mL by Week 48 (intent-to-treat (ITT)) was 118/137 (86.1%) in the DRV/r monotherapy arm versus 129/136 (94.9%) in the triple therapy arm; DRV/r monotherapy did not show non-inferiority versus triple therapy in the primary analysis (difference=− 8.7%, 95% CI −15.5 to −1.8%). In the multivariate analysis, the main predictor of treatment failure was nadir CD4 count. For patients with nadir CD4 counts <200 cells/µL, HIV-1 RNA suppression rates at Week 48 were 27/41 (66%) in the DRV/r monotherapy arm and 29/30 (97%) in the triple therapy arm; for patients with CD4 nadir at least 200 cells/µL, HIV-1 RNA suppression rates were 91/96 (95%) in the DRV/r monotherapy arm and 100/106 (94%) in the triple therapy arm. In the overall population, by a switch included analysis, efficacy was 92.0% versus 96.3%, showing non-inferiority (difference=− 4.3%, 95% CI=−9.7 to +1.2%). No treatment-emergent primary PI mutations were detected in three patients with sustained elevations in HIV-1 RNA at least 400 copies/mL (two on PI monotherapy, one on triple therapy). CD4 counts remained stable during the trial in both arms. Conclusions In this study for patients with HIV-1 RNA < 50 copies/mL at baseline, switching to DRV/r monotherapy showed lower efficacy versus triple antiretroviral therapy at Week 48 in the primary switch equals failure analysis (86% versus 95%). However, this lower efficacy was seen mainly in patients with CD4 nadir levels below 200 cells/µL. There was no development of PI resistance. [ABSTRACT FROM AUTHOR]

Introduction Etravirine (ETR), a non-nucleoside reverse transcriptase inhibitor available in France since 2006, is indicated for the treatment of HIV-1 infection in combination with a ritonavir boosted protease inhibitor (PI) in antiretroviral treatment-experienced adult patients. To assess its impact in routine clinical care, our objective was to compare hospitalization rates in highly pre-treated failing HIV-1 infected individuals between 2005 and 2011 depending on whether or not they received ETR+PI. Methods From the French Hospital Database on HIV (ANRS CO4), we selected highly pre-treated individuals (prior exposure to at least 2NRTI, 2PI and 1 NNRTI) with a viral load (VL)>50 copies/mL initiating a new regimen between 2005 and 2011. Hospitalization rates were calculated for each calendar month and depending on whether patients never received ETR+PI at any time or during months before initiating ETR+PI (no ETR+PI) or during months after initiating ETR+PI (ETR+PI), using an intention to continue treatment approach. Poisson regression models were used to compare incidence between the two groups, after adjustment for potential confounders (age, transmission group, origin, AIDS, PCP prophylaxis, viral load, CD4, nb of previous ARV). Results Overall 3884 patients fulfilled inclusion criteria. Among them 838 (21.6%) received ETR+PI at least once. Among all enrolled patients, 35.8% had CD4 <200/mm3, 17.5% had VL >100,000 copies/ml, 42.8% had had an AIDS event and 47.8% had received more than 10 different antiretroviral drugs. There were 2484 hospitalizations in 808 individuals over 13,986 patient-years. The hospitalization rates for 1000 P-Y were 169.0 for the ETR+PI group and 179.3 for the no ETR+PI group. After adjustment, the corresponding figures were 144.8 for 1000 P-Y and 192.7 for 1000 P-Y respectively, with a relative risk estimated as 0.75 (95% CI 0.67-0.84). Conclusions Access to ETR+PI between 2005 and 2011 was associated with a 25% reduction in the hospitalization rate among highly pre-treated failing HIV-1 infected individuals. [ABSTRACT FROM AUTHOR]

Background: Effective two-drug regimens could decrease long-term drug exposure and toxicity with HIV-1 antiretroviral therapy (ART). We therefore aimed to evaluate the efficacy and safety of a two-drug regimen compared with a three-drug regimen for the treatment of HIV-1 infection in ART-naive adults.Methods: We conducted two identically designed, multicentre, double-blind, randomised, non-inferiority, phase 3 trials: GEMINI-1 and GEMINI-2. Both studies were done at 192 centres in 21 countries. We included participants (≥18 years) with HIV-1 infection and a screening HIV-1 RNA of 500 000 copies per mL or less, and who were naive to ART. We randomly assigned participants (1:1) to receive a once-daily two-drug regimen of dolutegravir (50 mg) plus lamivudine (300 mg) or a once-daily three-drug regimen of dolutegravir (50 mg) plus tenofovir disoproxil fumarate (300 mg) and emtricitabine (200 mg). Both drug regimens were administered orally. We masked participants and investigators to treatment assignment: dolutegravir was administered as single-entity tablets (similar to its commercial formulation, except with a different film colour), and lamivudine tablets and tenofovir disoproxil fumarate and emtricitabine tablets were over-encapsulated to visually match each other. Primary endpoint was the proportion of participants with HIV-1 RNA of less than 50 copies per mL at week 48 in the intention-to-treat-exposed population, using the Snapshot algorithm and a non-inferiority margin of -10%. Safety analyses were done on the safety population. GEMINI-1 and GEMINI-2 are registered with ClinicalTrials.gov, numbers NCT02831673 and NCT02831764, respectively.Findings: Between July 18, 2016, and March 31, 2017, 1441 participants across both studies were randomly assigned to receive either the two-drug regimen (n=719) or three-drug regimen (n=722). At week 48 in the GEMINI-1 intention-to-treat-exposed population, 320 (90%) of 356 participants receiving the two-drug regimen and 332 (93%) of 358 receiving the three-drug regimen achieved plasma HIV-1 RNA of less than 50 copies per mL (adjusted treatment difference -2·6%, 95% CI -6·7 to 1·5); in GEMINI-2, 335 (93%) of 360 in the two-drug regimen and 337 (94%) of 359 in the three-drug regimen achieved HIV-1 RNA of less than 50 copies per mL (adjusted treatment difference -0·7%, 95% CI -4·3 to 2·9), showing non-inferiority at a -10% margin in both studies (pooled analysis: 655 [91%] of 716 in the two-drug regimen vs 669 [93%] of 717 in the three-drug regimen; adjusted treatment difference -1·7%, 95% CI -4·4 to 1·1). Numerically, more drug-related adverse events occurred with the three-drug regimen than with the two-drug regimen (169 [24%] of 717 vs 126 [18%] of 716); few participants discontinued because of adverse events (16 [2%] in the three-drug regimen and 15 [2%] in the two-drug regimen). Two deaths were reported in the two-drug regimen group of GEMINI-2, but neither was considered to be related to the study medication.Interpretation: The non-inferior efficacy and similar tolerability profile of dolutegravir plus lamivudine to a guideline-recommended three-drug regimen at 48 weeks in ART-naive adults supports its use as initial therapy for patients with HIV-1 infection.Funding: ViiV Healthcare. [ABSTRACT FROM AUTHOR]

Background Lifelong HIV antiretroviral therapy (ART) has prompted an interest in two-drug regimens to minimise cumulative drug exposure and toxicities. The safety, tolerability, and efficacy of dolutegravir and rilpivirine suggest potential compatibility and effectiveness as a two-drug regimen. We aimed to investigate this two-drug regimen in a phase 3 study. Methods We identically designed SWORD-1 and SWORD-2, which were open-label, parallel-group, multicentre, phase 3, randomised, non-inferiority studies in 12 countries evaluating efficacy and safety of once-daily elvitegravir 50 mg plus rilpivirine 25 mg versus current ART regimen (CAR). We included participants aged 18 years or older who were on first or second ART with stable plasma HIV-1 RNA (viral load <50 copies per mL) for 6 months or longer at screening. We randomly assigned participants (1:1) with stratification by third-agent class, age, and planned participation in a bone mineral density substudy. The primary endpoint was proportion of participants with viral load lower than 50 copies per mL at week 48 among those individuals who received one or more doses of study medication. Investigators monitored adverse events to assess safety. These trials are registered with ClinicalTrials.gov, numbers NCT02429791 (SWORD-1) and NCT02422797 (SWORD-2). Findings We screened for participants from April 14, 2015, to Oct 15, 2015, for SWORD-1 and from April 21, 2015, to Sept 25, 2015, for SWORD-2. We randomly assigned 516 participants to dolutegravir-rilpivirine and 512 to continue with CAR. At week 48 (last patient visit was Nov 22, 2016), in the pooled analysis of the intention-to-treat population, 95% of participants had viral loads lower than 50 copies per mL in each group (486 of 513 in the dolutegravir-rilpivirine group vs 485 of 511 in the CAR group), with an adjusted treatment difference of −0·2% (95% CI −3·0 to 2·5) and showed non-inferiority with a predefined margin of −8%. 395 (77%) of 513 participants in the dolutegravir-rilpivirine group and 364 (71%) of 511 participants in the CAR group reported adverse events. The most common adverse events were nasopharyngitis (49 [10%] for dolutegravir-rilpivirine vs 50 [10%] for CAR) and headache (41 [8%] vs 23 [5%]). More participants taking dolutegravir-rilpivirine (17 [3%]) reported adverse events leading to withdrawal than did participants taking CAR (three [<1%]). Interpretation Dolutegravir-rilpivirine was non-inferior to CAR over 48 weeks in participants with HIV suppression and showed a safety profile consistent with its components. Results support the use of this two-drug regimen to maintain HIV suppression. Funding ViiV Healthcare and Janssen Pharmaceutica NV. [ABSTRACT FROM AUTHOR]

Background Hepatitis B surface antigen (HBsAg)-seroconversion, or loss of HBsAg and acquisition of anti-hepatitis B surface (HBs) antibodies, defines functional cure of chronic hepatitis B virus (HBV) infection. After HBsAg-loss, little is known regarding the development of anti-HBs antibodies and even less so in individuals co-infected with HIV. Objectives To determine anti-HBs antibody kinetics after HBsAg-loss and explore determinants of HBsAg-seroconversion in HIV-HBV co-infected patients. Study design Patients enrolled in the French HIV-HBV cohort were included if they had >1 study visit after HBsAg-loss. Individual patient kinetics of anti-HBs antibody levels were modeled over time using mixed-effect non-linear regression, whereby maximum specific growth rate and maximal level of antibody production were estimated from a Gompertz growth equation. Results Fourteen (4.6%) of 308 co-infected patients followed in the cohort exhibited HBsAg-loss, all of whom were undergoing antiretroviral therapy. Nine (64.3%) of these patients achieved HBsAg-seroconversion during a median 3.0 years (IQR = 1.1–5.1) after HBsAg-loss. Across individuals with HBsAg-seroconversion, the fastest rates of antibody growth ranged between 0.57–1.93 year −1 (population maximum growth rate = 1.02) and antibody production plateaued between 2.09–3.66 log 10 mIU/mL at the end of follow-up (population maximal antibody levels = 2.66). Patients with HBsAg-seroconversion had substantial decreases in HBV DNA viral loads ( P = 0.03) and proportion with elevated ALT levels ( P = 0.02) and HBeAg-positive serology ( P = 0.08). No such differences were observed in those without HBsAg-seroconversion. Conclusions Most co-infected patients with HBsAg-seroconversion produced and maintained stable antibody levels, yet kinetics of anti-HBs production were much slower compared to those observed post-vaccination or after clearance of acute HBV-infection. [ABSTRACT FROM AUTHOR]

Background: Antiretroviral regimens containing tenofovir disoproxil fumarate have been associated with renal toxicity and reduced bone mineral density. Tenofovir alafenamide is a novel tenofovir prodrug that reduces tenofovir plasma concentrations by 90%, thereby decreasing off-target side-effects. We aimed to assess whether efficacy, safety, and tolerability were non-inferior in patients switched to a regimen containing tenofovir alafenamide versus in those remaining on one containing tenofovir disoproxil fumarate.Methods: In this randomised, actively controlled, multicentre, open-label, non-inferiority trial, we recruited HIV-1-infected adults from Gilead clinical studies at 168 sites in 19 countries. Patients were virologically suppressed (HIV-1 RNA <50 copies per mL) with an estimated glomerular filtration rate of 50 mL per min or greater, and were taking one of four tenofovir disoproxil fumarate-containing regimens for at least 96 weeks before enrolment. With use of a third-party computer-generated sequence, patients were randomly assigned (2:1) to receive a once-a-day single-tablet containing elvitegravir 150 mg, cobicistat 150 mg, emtricitabine 200 mg, and tenofovir alafenamide 10 mg (tenofovir alafenamide group) or to carry on taking one of four previous tenofovir disoproxil fumarate-containing regimens (tenofovir disoproxil fumarate group) for 96 weeks. Randomisation was stratified by previous treatment regimen in blocks of six. Patients and treating physicians were not masked to the assigned study regimen; outcome assessors were masked until database lock. The primary endpoint was the proportion of patients who received at least one dose of study drug who had undetectable viral load (HIV-1 RNA <50 copies per mL) at week 48. The non-inferiority margin was 12%. This study was registered with ClinicalTrials.gov, number NCT01815736.Findings: Between April 12, 2013 and April 3, 2014, we enrolled 1443 patients. 959 patients were randomly assigned to the tenofovir alafenamide group and 477 to the tenofovir disoproxil fumarate group. Viral suppression at week 48 was noted in 932 (97%) patients assigned to the tenofovir alafenamide group and in 444 (93%) assigned to the tenofovir disoproxil fumarate group (adjusted difference 4·1%, 95% CI 1·6-6·7), with virological failure noted in ten and six patients, respectively. The number of adverse events was similar between the two groups, but study drug-related adverse events were more common in the tenofovir alafenamide group (204 patients [21%] vs 76 [16%]). Hip and spine bone mineral density and glomerular filtration were each significantly improved in patients in the tenofovir alafenamide group compared with those in the tenofovir disoproxil fumarate group.Interpretation: Switching to a tenofovir alafenamide-containing regimen from one containing tenofovir disoproxil fumarate was non-inferior for maintenance of viral suppression and led to improved bone mineral density and renal function. Longer term follow-up is needed to better understand the clinical impact of these changes.Funding: Gilead Sciences. [ABSTRACT FROM AUTHOR]

Summary: Background: Coformulated elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate (tenofovir) might be a safe and efficacious switch option for virologically suppressed patients with HIV who have neuropsychiatric side-effects on a non-nucleoside reverse transcriptase inhibitor (NNRTI) or who are on a multitablet NNRTI-containing regimen and want a regimen simplification. We assessed the non-inferiority of such a switch compared with continuation of an NNRTI-containing regimen. Methods: STRATEGY-NNRTI is a 96 week, international, multicentre, randomised, open-label, phase 3b, non-inferiority trial enrolling adults (≥18 years) with HIV-1 and plasma HIV RNA viral load below 50 copies per mL for at least 6 months on an NNRTI plus emtricitabine and tenofovir regimen. With a computer-generated randomisation sequence, we randomly allocated participants (2:1; blocks of six, stratified by efavirenz use at screening) to switch to coformulated elvitegravir, cobicistat, emtricitabine, and tenofovir (switch group) or continue the NNRTI plus emtricitabine and tenofovir regimen (no-switch group). Key eligibility criteria included no history of virological failure and an estimated glomerular filtration rate of 70 mL per min or greater. The primary endpoint was the proportion of participants with plasma viral loads below 50 copies per mL at week 48 based on a snapshot algorithm with a non-inferiority margin of 12% (assessed by modified intention to treat). This trial is ongoing and is registered at ClinicalTrials.gov, number NCT01495702. Findings: Between Dec 29, 2011, and Dec 13, 2012, we randomly allocated 439 participants to treatment: 290 participants in the switch group and 143 participants in the no-switch group received treatment and were included in the modified intention-to-treat population. At week 48, 271 (93%) of 290 participants in the switch group and 126 (88%) of 143 participants in the no-switch group maintained plasma viral loads below 50 copies per mL (difference 5·3%, 95% CI −0·5 to 12·0; p=0·066). We detected no treatment-emergent resistance in either group. Safety events leading to discontinuation were uncommon in both groups: six (2%) of 291 participants in the switch group and one (1%) of 143 in the no-switch group. Interpretation: Coformulated elvitegravir, cobicistat, emtricitabine, and tenofovir seems to be efficacious and well tolerated in virologically suppressed adults with HIV and might be a suitable alternative for patients on an NNRTI with emtricitabine and tenofovir regimen considering a regimen modification or simplification. Funding: Gilead Sciences. [ABSTRACT FROM AUTHOR]

Multiple hepatitis co-infections are frequent in HIV-infected patients, often resulting in severe liver diseases that are difficult to treat. We report here the complete resolution of a chronic hepatitis B and D co-infection in a patient who was also infected with HCV and HIV. This cure was observed after 24weeks of combination therapy associating pegylated-IFN and ribavirin, which was initially given to treat HCV. An unexpected and extensive HDV replication was observed in this patient after HBs Ag had cleared from the serum, which was followed by a stable halt in HDV replication. Implications of this unusual observation will be discussed. [Copyright &y& Elsevier]