[ 18 F]FDG Positron Emission Tomography for Initial Staging and Healing Assessment at the End of Therapy in Lymph Nodes and Bone Tuberculosis.

Objective: In extra-pulmonary tuberculosis, therapeutic management is difficult in the absence of reliable tool to affirm healing at the end of treatment. In this prospective multicenter study, we evaluated [18F]FDG-PET for this purpose. Methods: Forty-two patients out of 55 included patients could be analyzed. Additionally to usual biological, histological and morphological explorations, [18F]FDG-PET was performed at diagnosis (PET1), at the end of treatment (PET2), indeed 6 months later. Then patients were followed until 12 months after end of prescribed treatment. Results: PET1 was positive in 97.6% of patients and discovered unknown injured sites in 52.7% of cases. PET2 was positive in 83.3% of uncured patients, and in 82.3% of cured patients. The sum and mean value of SUVmax measured in PET/CT lesions decreased between PET1 and PET2 in all patients. Mean value of SUVmax (MSUV) and sum value of SUVmax on PET2 showed the highest AUC on ROC curves for the diagnosis of healing at the end of prescribed treatment; MSUV 3.5 on PET2 had a sensitivity of 76.5% and a specificity of 80.0% to affirm healing at the end of prescribed treatment. Conclusions: [18F]FDG-PET/CT was useful at diagnosis, discovering unknown lesions in 52.7% of cases. MSUV on PET2 was the best criteria to affirm healing at the end of prescribed treatment.

Metabolic syndrome and endocrine status in HIV-infected transwomen.

BACKGROUND: HIV-infected transwomen face multiple specific issues. Economic and social marginalization, sex work, substance abuse, hormonal consumption and silicone injection may affect the course of HIV infection and lead to metabolic and endocrine complications. METHODS: A matched case-control study was performed between 2013 and 2015 in a University Hospital and compared metabolic syndrome (MetS), thyroid and adrenal functions in HIV-infected transwomen (i.e. cases) and cisgender HIV-infected men (i.e. controls) matched for age and antiretroviral therapy. The interaction between hormonal consumption, the course of HIV infection and antiretroviral therapy was also studied. Clinical and biological data (CD4 cell count, HIV RNA load, antiretroviral plasma drug concentration, HDL, triglycerides, glucose, cortisol, thyroid stimulating hormone, free thyroxine, prolactine) were measured. RESULTS: A total of 292 HIV-infected patients (100 cases and 192 controls) were prospectively included. There was no difference between the two populations in terms of frequency of MetS, but subclinical hypothyroidism and adrenal insufficiency were more frequent in cases than in controls with, respectively, 12 vs. 3% (P < 0.002) for hypothyroidism and 20 vs. 8% (P < 0.001) for adrenal insufficiency. Prolactinemia, only performed in transwomen, was often elevated (21%) but rarely confirmed as true active hyperprolactinemia (monomeric form) (3%). Although hormonal intake was frequent among transwomen (31%), no impact on antiretroviral bioavailability and efficacy was detected. CONCLUSION: In this study, no increase in the prevalence of MetS was detected in HIV-infected transwomen patients. In contrast, adrenal and thyroid functions abnormalities were frequent and should be systematically assessed in this population. No impact of hormonal intake on antiretroviral bioavailability and efficacy was detected.

Dolutegravir and lamivudine maintenance therapy in HIV-1 virologically suppressed patients: results of the ANRS 167 trial (LAMIDOL).

OBJECTIVES: To evaluate the dolutegravir+lamivudine combination in virologically suppressed patients living with HIV. METHODS: The ANRS 167 LAMIDOL trial was an open-label, single arm, multicentre trial assessing once-daily dolutegravir (50 mg)+lamivudine (300 mg) in virologically suppressed HIV-1 patients on first-line triple-drug regimens. The main criteria for inclusion in the trial were plasma viral load (pVL) ≤50 copies/mL for ≥2 years, CD4 nadir >200 cells/mm3 and WT HIV prior to treatment initiation. From week -8 (W-8) to day 0 (D0) (Phase 1), the current third agent was switched to dolutegravir. From D0 to W48 (Phase 2), patients received once-daily dolutegravir+lamivudine, except if intolerant or if pVL >50 copies/mL during Phase 1. Virological failure was defined as pVL >50 copies/mL in two consecutive samples. The study was designed to show that the strategy had an efficacy of ≥80%, assuming a 90% success rate with a type I error of 5% and a power of 90%. RESULTS: In total, 104 of 110 patients enrolled in Phase 1 were included in Phase 2. These 104 patients were 86% male, 72% MSM and 87% CDC stage A. Their characteristics were (median): age 45 years, CD4 nadir 339 cells/mm3, baseline CD4 743 cells/mm3 and duration of viral suppression 4.5 years. The overall success rate at W48 was 97% (95% CI: 94%-100%), meeting the design expectation/assumption. Three therapeutic failures occurred: one virological failure at W4, one lost to follow-up at W32 and one interruption of therapeutic strategy at W40 after a blip (pVL 59 copies/mL but control pVL <50 copies/mL). Three viral blips occurred in two additional patients. Neither M184V nor integrase resistance mutations were detected after failure or blips. CONCLUSIONS: Dolutegravir+lamivudine is a promising maintenance therapy in HIV-1-infected patients with controlled virological suppression.

Assessement of Awareness of, Concerns and Attitudes Towards HIV-Related Court-Case Sentences in France in a Representative Sample of People Living with HIV (ANRS VESPA2 Survey).

Some of the 12 criminal trials and sentences in France for HIV transmission in 1998-2011 attracted substantial public attention, with a possible negative impact on people living with HIV (PLWH) through reinforced stigma and discrimination. This analysis aimed to characterize PLWH enrolled in the representative ANRS-VESPA2 survey, aware of and concerned about convictions for HIV transmission. Being a migrant from Sub-Saharan Africa, having difficult socio-economic conditions, having unprotected sex with one's main partner and concealing one's HIV status were all factors statistically associated with concern about the sentences. Participants tempted to press charges against someone for infecting them were more likely to be younger, women, not living in a couple, unemployed, and to report a major depressive disorder. Concern about HIV-related criminal proceedings among the most vulnerable PLWH do not reflect the actual risk of prosecution they are exposed to.

Budget impact of antiretroviral therapy in a French clinic cohort.

OBJECTIVES: In this study, we first assessed costs associated with the use of antiretroviral therapy (ART) in an infectious diseases University Hospital Clinic; second, we evaluated characteristics associated with these costs and finally simulated the impact on the overall ART budget of switching first-line and second-line regimens to less-costly regimens (as effective and well tolerated). DESIGN: Cohort analysis including persons living with HIV (PLHIV) aged at least 18 years on ART to estimate ART costs during 2014. METHODS: The current study was conducted in the Bichat-Claude Bernard University Hospital Clinic in Paris, France, where 4501 PLHIV consulted in 2014. We used the medical database Nadis to describe patients' ART, characteristics and estimated costs. When assessing the budgetary impact of potential switches, we considered patients' history of failure, CD4 cell count, plasma viral load, resistance mutations, hepatitis B surface antigen or HLAB5701 profile. RESULTS: A total of 4238 of 4501 patients were on ART (94%). The total annual cost of ART prescribed was estimated at &OV0556;48 280 200 in 2014; first/second (simplification)-line regimens represented 25% (1076/4238) of the treated PLHIV and 23% (&OV0556;11 209 000) of the annual cost. For these PLHIV, we considered switches from the most common ART regimens (protease inhibitor boosted by ritonavir or nonnucleoside reverse transcriptase inhibitor + two nucleoside reverse transcriptase inhibitors) to less-expensive regimens. We found savings ranging from &OV0556;36 100 to 1472 600/year. Savings were the highest when we considered switching to generic-based regimens or from protease inhibitor-based triple therapy to protease inhibitor monotherapy. CONCLUSION: Costs associated with ART prescriptions are very high. Switches to generic-based regimens are associated with large savings. However, those targeting protease inhibitor regimens are also associated with substantial savings and should be considered.

Impact of obesity on antiretroviral pharmacokinetics and immuno-virological response in HIV-infected patients: a case-control study.

Background: Obesity has high prevalence among HIV-infected patients. Increased adipose tissue mass affects the pharmacokinetics of numerous drugs, but few data are available for antiretroviral drugs. Objectives: In this study we aimed to explore the pharmacokinetics of antiretroviral drugs and the immuno-virological response in obese patients with HIV infection. Patients and methods: We examined data from 2009 to 2012 in our hospital's database for HIV-1-infected patients who received an antiretroviral drug (abacavir, emtricitabine, lamivudine, tenofovir, efavirenz, etravirine, nevirapine, atazanavir/ritonavir, darunavir/ritonavir, lopinavir/ritonavir or raltegravir). Obese patients were defined as those with BMI ≥30 kg/m 2 and normal-weight patients as those with BMI 19-25 kg/m 2 . Plasma concentrations ( C 12/24 ) were compared for each antiretroviral drug using a Mann-Whitney test. Suboptimal dosing and virological outcome were assessed by logistic regression, adjusting on covariates. Results: We enrolled 291 obese and 196 normal-weight patients. Among the 12 analysed antiretroviral drugs, tenofovir, efavirenz and lopinavir C 12 values were significantly lower in obese than normal-weight patients: 66 versus 86 ng/mL, 1498 versus 2034 ng/mL and 4595 versus 6420 ng/mL, respectively ( P < 0.001). Antiretroviral drug C 12/24 values were more frequently below efficacy thresholds for obese than for normal-weight patients after adjustment for other covariates ( P < 0.001). Although obese patients showed a higher CD4 count than normal-weight patients (510 versus 444 cells/mm 3 , P < 0.001), the groups did not differ in virological failure rate. Conclusions: This study highlights the impact of obesity on antiretroviral drug plasma exposure, but identifies no consequence of this suboptimal exposure on the immuno-virological control in this population.

Epidemiological Profile of Newly Diagnosed HIV-Infected Patients in Northern Paris: A Retrospective Study.

In attempt to identify the factors associated with delayed diagnosis during HIV infection, we studied retrospectively the epidemiological profile of HIV-infected patients diagnosed between January 1, 2012 and December 31, 2013 and followed in our clinical center in Paris. Data were compared to those obtained at the same site during the year 2003. One hundred eighty-six patients fulfilled the inclusion criteria: 49 (26%) had a CD4 count <200/mm3 at diagnosis. Compared to subjects with CD4 count ≥200/mm3, advanced patients were older, had a higher plasma viral load, had more often an AIDS-defining event at the time of HIV diagnosis (45% vs. 3%), had been infected more often through heterosexual contact (69% vs. 44%), had less frequently past HIV testing (23% vs. 63%), and tended to live in less favorable conditions. A higher proportion of these patients initiated antiretroviral therapy in the 3 months following diagnosis (93.9% vs. 48.1%). Compared to data obtained in 161 patients in 2003, the proportions of advanced patients were similar between the two periods (26% vs. 22%). There was a significant increase from year 2003 to the 2012-2013 period in the proportion of men who have sex with men (MSM) (50% vs. 27%) and in the percentage of patients infected with HIV-1 subtype B (48% vs. 27%) and with positive syphilis serology (22% vs. 8%). Our data show that (1) HIV screening should be extended to populations with the following characteristics: older age, heterosexuality, and low socioeconomic level, and (2) HIV transmission continues to progress in MSM, arguing for the value of preexposure prophylaxis.

Abacavir has no prothrombotic effect on platelets in vitro.

OBJECTIVES: HIV patients exposed to abacavir have an increased risk of myocardial infarction, with contradictory results in the literature. The aim of our study was to determine whether abacavir has a direct effect on platelet activation and aggregation using platelets from healthy donors and from HIV-infected patients under therapy with an undetectable viral load. METHODS: Platelet-rich plasma (PRP) or whole blood from healthy donors was treated with abacavir (5 or 10 µg/mL) or its active metabolite carbovir diphosphate. Experiments were also performed using blood of HIV-infected patients (n = 10) with an undetectable viral load. Platelet aggregation was performed on PRP by turbidimetry and under high shear conditions at 4000 s-1. Platelet procoagulant potential was analysed by measuring thrombin generation by thrombinography. RESULTS: Abacavir and carbovir diphosphate significantly increased the aggregation of platelets from healthy donors induced by collagen at 2 µg/mL (P = 0.002), but not at 0.5 µg/mL. No effect of abacavir or carbovir diphosphate was observed on platelet aggregation induced by other physiological agonists or by high shear stress, or on thrombin generation. Pretreatment of blood from HIV-infected patients with abacavir produced similar results. CONCLUSIONS: Our results suggest that abacavir does not significantly influence platelet activation in vitro when incubated with platelets from healthy donors or from HIV-infected patients. It is, however, not excluded that a synergistic effect with other drugs could promote platelet activation and thereby play a role in the pathogenesis of myocardial infarction.

Immunity, inflammation and reservoir in patients at an early stage of HIV infection on intermittent ART (ANRS 141 TIPI Trial).

OBJECTIVES: The objective of this study was to assess clinical and biological changes during intermittent ART (I-ART) started early, with significant time spent on versus off ART, which has never before been studied in ART-naive patients with high nadir and current CD4 cell count. PATIENTS AND METHODS: ART-naive HIV-1-infected patients with baseline CD4 ≥ 500/mm(3) and nadir CD4 ≥ 400/mm(3) received 2 years of I-ART (6 month periods on once-daily boosted-PI-based ART, alternating with 6 month periods without ART) in a 2 year, Phase II, non-comparative multicentre trial. The trial is registered with ClinicalTrials.gov, number NCT 00820118. RESULTS: The CD4 cell count remained ≥ 500/mm(3) at 2 years in all 44 patients included in the study. The mean 2 year count was higher than the mean count at baseline in 24 patients overall (55%; 95% CI 40%-69%) and in 20 (65%; 95% CI 48%-81%) of the 31 patients who fully adhered to the trial strategy. All but three of these latter patients had HIV-1 RNA concentrations below 50 copies/mL after each 6 month 'on' period. Only one strategy-related genotypic mutation (M184I) was detected. The HIV-1 DNA median load fluctuated, but it did not differ between month 0 and month 24 (2.8 versus 2.6 log10 copies/10(6) leucocytes, P = 0.29). Biomarkers of inflammation and endothelial activation remained stable between month 0 and month 24. Naive CD4, CD8+CCR5+ and CD8+CD38+ T cell numbers tended to decline. One patient developed Burkitt's lymphoma and 12 patients reported sexually transmitted infections. CONCLUSIONS: In patients with high nadir and current CD4 cell counts, 2 year I-ART maintained the CD4 cell count above 500/mm(3), with no increase in the viral reservoir. Immune activation seems related to HIV replication, while inflammation seems to evolve independently and require specific attention.

Use of PCR Signal and Therapeutic Drug Monitoring in a Switch Cohort Study to Tenofovir/Emtricitabine/Rilpivirine: A W96 Follow-Up.

OBJECTIVE: To assess, in a clinical cohort, the efficacy of switching treatment in virologically-suppressed patients to tenofovir/emtricitabine/rilpivirine as a single-tablet regimen (STR) using the PCR signal of the viral load (VL) assay and plasma drug determination (C24h). PATIENTS AND METHODS: An observational single-centre study enrolling patients with VL<50 copies/mL initiating rilpivirine-based STR. C24h and VL were performed until W48 and W96 of STR, respectively. PCRneg was defined as an undetected PCR signal. Medians (IQR) were presented. RESULTS: 116 patients were enrolled. At STR baseline, time since first antiretroviral therapy and time of virological suppression were 6 years (2-9) and 17 months (7-43), respectively. Before STR initiation, patients were receiving protease inhibitors and non-nucleoside reverse transcriptase inhibitors-based regimen in 44% and 47% of cases, respectively. Historical genotype showed virus resistant to one drug of the STR in 6 patients (5%). At W96, 17 (15%) discontinued STR due to adverse events. The proportion of patients maintaining VL <50 copies/mL on treatment was 98%, 99%, 100%, 100%, 100% and 100% at W12, W24, W36, W48, W72 and W96, respectively. Among them, 70%, 66%, 68%, 59%, 74%, 68% and 60% were PCRneg at baseline, W12, W24, W36, W48, W72 and W96, respectively. Median rilpivirine C24h was 91 ng/mL (57-141, n = 285), with 91% of rilpivirine C24h >50 ng/mL, the target effective concentration. CONCLUSIONS: In this clinical cohort of virologically-suppressed patients switching to a new STR, most subjects had adequate rilpivirine C24h and displayed a high level of virological suppression with no residual viremia until W96.

Patient-Reported Outcomes After a Switch to a Single-Tablet Regimen of Rilpivirine, Emtricitabine, and Tenofovir DF in HIV-1-Positive, Virologically Suppressed Individuals: Additional Findings From a Randomized, Open-Label, 48-Week Trial.

BACKGROUND: Patient-reported outcomes (PROs) can provide important information about treatment tolerability in HIV-1-infected patients. OBJECTIVE: The aim of this study was to evaluate PROs following switching from a boosted protease inhibitor-based regimen to the single-tablet regimen (STR) of rilpivirine/emtricitabine/tenofovir disoproxil fumarate (RPV/FTC/TDF) in the 48-week open-label Switching Boosted PI to Rilpivirine in Combination with Truvada as a Single-Tablet Regimen (SPIRIT) trial. METHODS: In the open-label SPIRIT trial, patients were randomized to receive an STR of RPV/FTC/TDF (n = 317) for 48 weeks or stay on their baseline regimen of a ritonavir-boosted protease inhibitor and two nucleoside/nucleotide analog reverse transcriptase inhibitors (PI + RTV + 2NRTIs, n = 159) for 24 weeks before switching to RPV/FTC/TDF for another 24 weeks. PRO assessments included the HIV Treatment Satisfaction Questionnaire (TSQ) and the HIV Symptom Index Questionnaire (SIQ). RESULTS: At week 24, the mean HIV TSQ improvement from baseline was significantly greater in the RPV/FTC/TDF group than the PI + RTV + 2NRTIs group (p < 0.001). On the HIV SIQ, the percentage of patients reporting a shift from 'symptom' to 'no symptom' was significantly greater with RPV/FTC/TDF treatment compared with PI + RTV + 2NRTIs for all items (all p ≤ 0.01), with total within-group occurrence of 13/20 symptoms significantly decreasing from baseline for RPV/FTC/TDF patients. In the delayed switch group, significantly fewer patients reported diarrhea and sleep problems at week 48 vs. week 24. CONCLUSIONS: These data suggest that switching to the STR RPV/FTC/TDF from a PI-based multi-pill regimen is associated with greater patient-reported treatment satisfaction and improved tolerability in HIV-1-infected, virologically suppressed individuals.

Intensive five-drug antiretroviral therapy regimen versus standard triple-drug therapy during primary HIV-1 infection (OPTIPRIM-ANRS 147): a randomised, open-label, phase 3 trial.

BACKGROUND: Early combination antiretroviral therapy (cART) initiation at the time of primary HIV-1 infection could restrict the establishment of HIV reservoirs. We aimed to assess the effect of a cART regimen intensified with raltegravir and maraviroc, compared with standard triple-drug cART, on HIV-DNA load. METHODS: In this randomised, open-label, phase 3 trial, we recruited patients from hospitals across France. Inclusion criteria were primary HIV-1 infection (an incomplete HIV-1 western blot and detectable plasma HIV-RNA), with either symptoms or a CD4+ cell count below 500 cells per µL. Patients were randomly assigned (1:1) to an intensive, five-drug cART regimen (raltegravir 400 mg and maraviroc 150 mg twice daily, and a fixed-dose combination of tenofovir disoproxil fumarate 300 g plus emtricitabine 200 g, darunavir 800 g, and ritonavir 100 g once daily) or a standard triple-drug cART regimen (tenofovir disoproxil fumarate 300 g plus emtricitabine 200 g, darunavir 800 g, and ritonavir 100 g once daily) using a predefined randomised list generated by randomly selected variable block sizes. The primary endpoint was the median number of HIV-DNA copies per 10(6) peripheral blood mononuclear cells (PBMC) at month 24, analysed in the modified intention-to-treat population, defined as all patients who started their assigned treatment. This study is registered with ClinicalTrials.gov, number NCT01033760. FINDINGS: Between April 26, 2010, and July 13, 2011, 110 patients were enrolled, of whom 92 were randomly assigned and 90 started treatment (45 in each treatment group). Six (13%) patients in the intensive cART group and two (4%) in the standard cART group discontinued before month 24. At month 24, HIV-DNA loads were similar between groups (2·35 [IQR 2·05-2·50] log10 per 10(6) PBMC in the intensive cART group vs 2·25 [1·71-2·55] in the standard cART group; p=0·21). Eight grade 3-4 clinical adverse events were reported in seven patients in the intensive cART group and seven grade 3-4 clinical adverse events were reported in seven patients in the standard cART group. Three serious clinical adverse events occurred: two (pancreatitis and lipodystrophy) in the standard cART group, which were regarded as treatment related, and one event (suicide attempt) in the intensive cART group that was unrelated to treatment. INTERPRETATION: After 24 months, cART intensified with raltegravir and maraviroc did not have a greater effect on HIV blood reservoirs than did standard cART. These results should help to design future trials of treatments aiming to decrease the HIV reservoir in patients with primary HIV-1 infection. FUNDING: Inserm-ANRS, Gilead Sciences, Janssen Pharmaceuticals, Merck, and ViiV Laboratories.

Plasma cholesterol efflux capacity from human THP-1 macrophages is reduced in HIV-infected patients: impact of HAART.

The capacity of HDL to remove cholesterol from macrophages is inversely associated with the severity of angiographic coronary artery disease. The effect of human immunodeficiency virus (HIV) infection or its treatment on the ability of HDL particles to stimulate cholesterol efflux from human macrophages has never been studied. We evaluated the capacity of whole plasma and isolated HDL particles from HIV-infected subjects (n = 231) and uninfected controls (n = 200), as well as in a subset of 41 HIV subjects receiving highly active antiretroviral therapy (HAART) to mediate cholesterol efflux from human macrophages. Plasma cholesterol efflux capacity was reduced (-12%; P = 0.001) in HIV patients as compared with controls. HIV infection reduced by 27% (P < 0.05) the capacity of HDL subfractions to promote cholesterol efflux from macrophages. We observed a reduced ABCA1-dependent efflux capacity of plasma (-27%; P < 0.0001) from HIV-infected subjects as a result of a reduction in the efflux capacity of HDL3 particles. HAART administration restored the capacity of plasma from HIV patients to stimulate cholesterol efflux from human macrophages (9.4%; P = 0.04). During HIV infection, the capacity of whole plasma to remove cholesterol from macrophages is reduced, thus potentially contributing to the increased coronary heart disease in the HIV population. HAART administration restored the removal of cholesterol from macrophages by increasing HDL functionality.

Association between first-year virological response to raltegravir and long-term outcomes in treatment-experienced patients with HIV-1 infection.

BACKGROUND: We explored the relationship between virological response in the first year of treatment and long-term outcomes in the BENCHMRK studies. METHODS: Patients failing antiretroviral treatment with 3-class resistant HIV-1 received double-blinded raltegravir (or placebo) with optimized background therapy (OBT) until week 156, followed by open-label raltegravir with OBT up to week 240. In this exploratory analysis of patients randomized to raltegravir, virological response over weeks 16-48 was categorized as continuous suppression (CS; viral RNA [vRNA] always <50 copies/ml), low-level viraemia (LLV; vRNA always <400 copies/ml, >50 copies/ml at least once), or not suppressed (NS; vRNA >400 copies/ml at least once). The association between these first-year vRNA response categories and baseline factors was analysed with univariate and multivariate models. Virological and immunological outcomes for years 2-5 were assessed by first-year vRNA response category (observed failure approach). RESULTS: Baseline vRNA, baseline CD4(+) T-cell count and rapid viral decay (vRNA <50 copies/ml between weeks 2-12) correlated with first-year vRNA response (P<0.001); only rapid viral decay remained significant by multiple regression. Virological response rates were similar in the LLV and CS groups and lowest in the NS group. CD4(+) T-cell count increased through week 240 in the CS and LLV groups. Time to loss of virological response (confirmed vRNA ≥400 copies/ml) through week 240 did not support as strong a difference between the LLV and CS groups (log-rank P=0.11) as previously reported through weeks 156 and 192 (P<0.05). CONCLUSIONS: Treatment-experienced patients on a raltegravir-based regimen with early LLV may have long-term virological and immunological benefit when their therapy is maintained.

[HIV infection and social condition: a disease which remains singular]. / Infection par le VIH et société: une maladie qui demeure singulière.

Increased efficacy of HIV therapy has resulted in a dramatic improvement in patient's health condition regarding life expectancy and life quality. However, such favorable evolution had no significant impact on the social condition of the population living with HIV, which remains more exposed to socio-economical difficulties and to different forms of stigmatization and discrimination. Public policies do address these issues. The national HIV/AIDS and STI strategic plan 2010-2014 provides a range of actions aimed at fighting against discriminations and improving social care for the most vulnerable people living with HIV. It notably tries to achieve equal access to programs and services developed for patients with chronic diseases and to improve their condition regarding access to care, employment, housing and income. Implementation of these measures, however, proves difficult. Addressing social and societal concerns that HIV infection still raises is part of the care and support that should be offered to patients. Providing this comprehensive approach remains critical for ensuring optimized individual therapeutic outcomes as well as an efficient collective response to the epidemic.

Virological outcome at week 48 of three recommended first-line regimens using ultrasensitive viral load and plasma drug assay.

OBJECTIVES: To describe the virological and pharmacological outcomes of three different recommended once-daily first-line regimens in a cross-sectional analysis within an observational cohort using ultra-sensitive HIV quantification. PATIENTS AND METHODS: We enrolled all HIV-1-infected patients who initiated tenofovir/emtricitabine with efavirenz, darunavir/ritonavir or atazanavir/ritonavir as a first-line regimen between 1 November 2010 and 30 June 2012. An ultrasensitive viral load (VL) assay was performed and plasma drug concentrations at 24 h (C24) were determined at Week (W) 4, W12, W24, W36 and W48. RESULTS: Sixty patients initiated efavirenz, 81 darunavir/ritonavir and 27 atazanavir/ritonavir. A higher proportion of patients with a VL >100 000 copies/mL received darunavir/ritonavir (P = 0.022). At W48, 89%, 85% and 88% of the patients had a VL <50 copies/mL, 69%, 73% and 79% had a VL <20 copies/mL and 45%, 48% and 54% had a VL <1 copy/mL using the ultrasensitive assay in the efavirenz, darunavir/ritonavir and atazanavir/ritonavir groups, respectively. Patients with a detectable VL signal at W48 had a higher baseline VL than those with no detectable VL signal (P = 0.0001). A total of 92%, 93% and 91% of the efavirenz, darunavir and atazanavir C24 values were above the respective effective cut-offs. CONCLUSIONS: In this observational cohort, the choice of the regimen was related to the physicians' preferences and the patients' characteristics. The proportion of patients reaching VL <1 copy/mL at W48 was similar in the three regimens and was not associated with drug concentrations.

Change in vitamin D levels and risk of severe vitamin D deficiency over 48 weeks among HIV-1-infected, treatment-naive adults receiving rilpivirine or efavirenz in a Phase III trial (ECHO).

BACKGROUND: This analysis assessed changes in serum 25-hydroxyvitamin D (25[OH]D; the precursor form of active vitamin D) in antiretroviral-naive adults receiving rilpivirine or efavirenz over 48 weeks in a randomized, double-blind, Phase III trial (ECHO). METHODS: ECHO included 690 patients randomized 1:1 to receive rilpivirine 25 mg once daily (n=346) or efavirenz 600 mg once daily (n=344), plus tenofovir disoproxil fumarate/emtricitabine. 25(OH)D was measured in stored serum samples collected at baseline, and weeks 24 and 48. Proportions of patients with optimal/sufficient (≥30 ng/ml), insufficient (21-29 ng/ml), deficient (10-20 ng/ml) and severely deficient (<10 ng/ml) 25(OH)D levels were determined. Data are presented for patients with paired baseline and week 48 25(OH)D data (rilpivirine, n=292; efavirenz, n=290). RESULTS: After 48 weeks, mean 25(OH)D levels remained largely unchanged from baseline with rilpivirine (-0.2 ng/ml; P=0.57 versus no change), but were significantly reduced with efavirenz (-2.5 ng/ml; P<0.0001 versus no change). When adjusting for season of randomization and the combined variable of race (Black/African American, White/Caucasian, Asian, other race) and ethnicity (Hispanic or Latino and not Hispanic or not Latino), the conclusion about the treatment difference between the rilpivirine and efavirenz treatment groups remained valid. At baseline the proportion of patients with severe 25(OH)D deficiency was similar in both groups (5%) but was significantly lower with rilpivirine than efavirenz at week 48 (5% versus 9%, respectively; P=0.032). Furthermore, of the patients with 25(OH)D insufficiency/deficiency at baseline, the proportion who developed severe 25(OH)D deficiency at week 48 was significantly lower with rilpivirine than efavirenz (2% versus 8%, respectively; P=0.0079). CONCLUSIONS: Rilpivirine had little effect on 25(OH)D, whereas efavirenz resulted in a significant reduction in 25(OH)D levels and an increase in the risk of severe 25(OH)D deficiency.

Is clinical practice concordant with the changes in guidelines for antiretroviral therapy initiation during primary and chronic HIV-1 infection? The ANRS PRIMO and COPANA cohorts.

OBJECTIVE: Guidelines for initiating HIV treatment are regularly revised. We explored how physicians in France have applied these evolving guidelines for ART initiation over the last decade in two different situations: chronic (CHI) and primary HIV-1 infection (PHI), since specific recommendations for PHI are also provided in France. METHODS: Data came from the ANRS PRIMO (1267 patients enrolled during PHI in 1996-2010) and COPANA (800 subjects enrolled at HIV diagnosis in 2004-2008) cohorts. We defined as guidelines-inconsistent during PHI and CHI, patients meeting criteria for ART initiation and not treated in the following month and during the next 6 months, respectively. RESULTS: ART initiation during PHI dramatically decreased from 91% of patients in 1996-99 to 22% in 2007 and increased to 60% in 2010, following changes in recommendations. In 2007, however, after the CD4 count threshold was raised to 350 cells/mm(3) in 2006, only 55% of the patients with CD4≤350 were treated and 66% in 2008. During CHI, ART was more frequently initiated in patients who met the criteria at entry (96%) than during follow-up: 83% when recommendation to treat was 200 and 73% when it was 350 cells/mm(3). Independent risk factors for not being treated during CHI despite meeting the criteria were lower viral load, lower educational level, and poorer living conditions. CONCLUSION: HIV ART initiation guidelines are largely followed by practitioners in France. What can still be improved, however, is time to treat when CD4 cell counts reach the threshold to treat. Risk factors for lack of timely treatment highlight the need to understand better how patients' living conditions and physicians' perceptions influence the decision to initiate treatment.