Comparison of HIV-Infected and Noninfected Patients Undergoing Bariatric Surgery: The ObeVIH Study.

OBJECTIVE: The aim of this study was to compare clinical characteristics and adipose/liver tissue histology analysis in HIV-infected and HIV-uninfected subjects undergoing bariatric surgery. DESIGN: This was a cross-sectional study of HIV-infected subjects undergoing single-port sleeve gastrectomy with prospective enrolment and frequency age (±5 years), sex, and body mass index (BMI, ± 5 kg/m2) matched on HIV-uninfected subjects. METHODS: This study was conducted at a single clinical site at Pitié-Salpêtrière hospital-Paris-France comprising 19 HIV-uninfected and 21 HIV-infected subjects with plasma VL < 20 copies/mL, all with a BMI > 40 kg/m2 or >35 kg/m2 with comorbidities. Histology of subcutaneous and visceral abdominal adipose tissue (SCAT/VAT) and liver biopsies was collected during single-port sleeve gastrectomy. Outcomes included anthropometric characteristics, comorbidities, cardiovascular parameters, adipose tissue, and liver histology. RESULTS: The age of HIV-infected participants was (median, interquartile range IQR) 48 y (42-51), with 76.2% females, a BMI of 41.4 kg/m2 (37.3-44.4), an antiretroviral duration of 16 y (8-21), current integrase strand transfer inhibitor (INSTI)-based regimen in 15 participants and non-INSTI regimen in 6 participants, and a CD4 count of 864/mm3 (560-1066). The age of controls was 43 y (37-51), with 78.9% females and a BMI of 39.2 kg/m2 (36.3-42.6). Anthropometric characteristics, comorbidities, and cardiovascular parameters did not differ according to HIV status and INSTI treatment. The number of macrophage crown-like structures in SCAT was lower in INSTI-treated participants than in HIV-uninfected participants (P = 0.02) and non-INSTI-treated HIV-infected subjects (P = 0.07). Hepatic steatosis and liver disease severity global score were lower in INSTI-treated participants than in non-INSTI-treated HIV-infected participants (P = 0.05 and P = 0.04, respectively). CONCLUSIONS: HIV-infected and HIV-uninfected subjects undergoing bariatric surgery presented a similar profile regarding anthropometric measures, cardiovascular parameters, and comorbidities. However, INSTI-treated participants presented milder SCAT and liver alterations than non-INSTI-treated participants.

Long COVID-19 symptoms: Clinical characteristics and recovery rate among non-severe outpatients over a six-month follow-up.

BACKGROUND: To describe persistent symptoms in long COVID-19 non-severe outpatients and report the 6-month clinical recovery (CR) rate. METHODS: Observational study enrolling outpatients (≥ 18 years) with confirmed non-severe COVID-19 (positive nasopharyngeal RT-PCR or presence of SARS-CoV-2 antibodies) who consulted for persistent symptoms after the first pandemic wave (March-May 2020). CR was assessed at the 6-month visit and defined as complete (no symptom), partial (persistent symptoms of lower intensity) or lack of recovery (no improvement). RESULTS: Sixty-three patients (79% women, mean age: 48 years) enrolled; main symptoms (mean 81 days after acute infection): asthenia/myalgia (77%), dyspnea (51%), headaches (35%), cough (33%). At 6 months (n=56), 30% had complete, 57% partial, and 13% lack of recovery. The proportion of patients with>2 persistent symptoms was 26% at 6 months (main symptoms: dyspnea [54%] and asthenia/myalgia [46%]). CONCLUSION: We observed a slow but high recovery rate at 6 months among these outpatients.

Prevalence and factors associated with symptom persistence: A prospective study of 429 mild COVID-19 outpatients.

INTRODUCTION: Persistent symptoms have recently emerged as a clinical issue in COVID-19. We aimed to assess the prevalence and risk factors in symptomatic non-hospitalized individuals with mild COVID-19. METHODS: We performed a prospective cohort study of symptomatic COVID-19 outpatients, from March to May 2020, with weekly phone calls from clinical onset until day 30 and up to day 60 in case of persistent symptoms. The main outcomes were the proportion of patients with complete recovery at day 30 and day 60 and factors associated with persistent symptoms. RESULTS: We enrolled 429 individuals mostly women (72.5%) and healthcare workers (72.5%), with a median age of 41.6 years [IQR 30-51.5]. Symptoms included: cough (69.7%), asthenia (68.8%), anosmia (64.8%), headaches (64.6%), myalgia (62.7%), gastrointestinal symptoms (61.8%), fever (61.5%), and ageusia (60.8%). Mean duration of disease was 27 days (95%CI: 25-29). The rate of persistent symptoms was 46.8% at day 30 and 6.5% at day 60 consisting in asthenia (32.6%), anosmia (32.6%), and ageusia (30.4%). The probability of complete recovery was 56.3% (95%CI: 51.7-61.1) at day 30 and 85.6% (95%CI: 81.2-89.4) at day 60. Factors associated with persistent symptoms were age>40 (HR 0.61), female sex (HR 0.70), low cycle threshold (HR 0.78), and ageusia (HR 0.59). CONCLUSIONS: COVID-19 - even in its mild presentation - led to persistent symptoms (up to one month) in nearly half of individuals. Identification of risk factors such as age, gender, ageusia and viral load is crucial for clinical management and argues for the development of antiviral agents.

Olfactory and gustatory dysfunctions in COVID-19 outpatients: A prospective cohort study.

OBJECTIVES: To describe the characteristics, evolution and risk factors for long-term persistence of olfactory and gustatory dysfunctions (OGD) in COVID-19 outpatients. PATIENTS AND METHODS: We conducted a prospective study in SARS-CoV-2 infected outpatients with OGD. Weekly phone interviews were set up starting from COVID-19 onset symptoms and over the course of 60 days, using standardized questionnaires that included a detailed description of general symptoms and OGD. The primary outcome was the proportion of patients with complete recovery of OGD at D30. Rate and time to recovery of OGD, as well as risk factors for late recovery (>30 days), were evaluated using Cox regression models. RESULTS: Ninety-eight outpatients were included. The median time to onset of OGD after first COVID-19 symptoms was 2 days (IQR 0-4). The 30-day recovery rate from OGD was 67.5% (95% CI 57.1-75.4) and the estimated median time of OGD recovery was 20 days (95% CI 13-26). Risk factors for late recovery of OGD were a complete loss of smell or taste at diagnosis (HR=0.26, 95% CI 0.12-0.56, P=0.0005) and age over 40 years (HR=0.56, 95% CI 0.36-0.89, P=0.01). CONCLUSIONS: COVID-19 patients with complete loss of smell or taste and over age 40 are more likely to develop persistent OGD and should rapidly receive sensorial rehabilitation.

Increased risk of IRIS-associated tuberculosis in HIV-infected patients receiving Integrase Inhibitors.

BACKGROUND: Tuberculosis is associated with a risk of immune reconstitution inflammatory syndrome (IRIS) after ART initiation. METHODS: Data from all patients with newly diagnosed tuberculosis disease and uncontrolled HIV infection from 1997 to 2017 in a French center were retrospectively collected. We evaluated the incidence of tuberculosis-IRIS in patients initiating ART with or without integrase inhibitors (INSTI) RESULTS: Fifty-five patients were included: 21 receiving an INSTI regimen and 34 a non-INSTI regimen. Except with regard to ART regimen, the two groups were comparable (median CD4 of 85/mm3). The overall percentage of IRIS was 34% (19/55), with 52% IRIS in INSTI regimen and 23% in non-INSTI regimen respectively (P=0.04). In a multivariate logistic model, we observed an increased risk of IRIS in the INSTI regimen compared to the non-INSTI, with an OR at 3.33 [95% CI, 1.01-11.1] (P=0.05) CONCLUSIONS: ART containing integrase inhibitors could be associated with increased incidence of TB-associated IRIS.

Low immune response rate of HIV-infected patients to a single injection of hepatitis A vaccine.

OBJECTIVES: We aimed to evaluate the immune response of HIV-1 positive patients to a single injection of HAV vaccine in a context of vaccine shortage during the 2017 European outbreak. METHODS: We retrospectively enrolled all HIV-1 positive patients vaccinated by a single injection of HAV vaccine Vaqta 50®. HAV serology was performed before and>30 days after the vaccine injection. RESULTS: Among the 73 patients, HIV-1 viral load was≤50 copies/mL in 93.2% of the cases. Medians of CD4 and median ratio of T CD4/CD8 cells were 658/mm3 and 0.9, respectively. A low immune response rate (59.7%) was observed among the patients. Responders had a significantly higher CD4/CD8 cell ratio than non-responders. CONCLUSIONS: A serologic control should be recommended in this population in the event of a single injection vaccination schedule. During routine follow-up, and prior to any untoward event, physicians should assess the vaccination coverage of HIV-infected patients.

Persistent low-level viraemia in antiretroviral treatment-experienced patients is not linked to viral resistance or inadequate drug concentrations.

OBJECTIVES: To assess genotypic sensitivity scores (GSSs), plasma antiretroviral concentrations (PACs) and immunovirological outcomes at Week 96 (W96) in patients with persistent low-level viraemia (LLV). METHODS: On 1 January 2017, we analysed data from patients on three-drug regimens with persistent LLV defined as at least two consecutive plasma viral loads (pVLs) between 21 and 200 copies/mL (including one pVL of ≥50 copies/mL), at the Pitié-Salpêtrière Hospital. Outcomes were: GSS, PACs and HIV-DNA load at study entry; and virological status and proportion of patients with resistance-associated mutations (RAMs) at W96. RESULTS: Fifty-seven patients were included, with median age of 52.6 years (IQR 45.2-57.9), last CD4 count of 658 cells/mm3 (IQR 462-909) and total ART duration of 10.2 years (IQR 5.7-15.2). LLV duration was 14.0 months (IQR 5.5-22.3). GSS was 3 in 46/57 (81%) patients and PACs were adequate in 53/57 (93%) patients. Median total HIV-DNA was 2.65 log10 copies/106 cells (IQR 2.44-2.86). During follow-up, 26/57 (46%) had experienced ART modifications. At W96, 38/57 (67%) patients remained with LLV, 15/60 (26%) had achieved confirmed pVL of <20 copies/mL and 4/57 (7%) had virological failure. The four virological failures were due to three ART interruptions and one incomplete adherence (selection of Y181C RAM). No factors (patient characteristics at study entry, GSS, PACs, total HIV-DNA load and ART modification) were associated with W96 viral outcome, except for time from HIV diagnosis and the LLV duration at study entry. CONCLUSIONS: A substantial number of patients harbouring LLV had no resistance to ART and adequate PACs. Two-thirds of these patients remained with this LLV status.

Long-term follow-up of HIV-infected patients on dolutegravir monotherapy.

BACKGROUND: In recent years, dolutegravir monotherapy has been explored as a drug-reduced regimen for HIV patients. METHODS: This was a retrospective observational study, including patients virologically suppressed for ≥6 months, without previous virological failure (VF) under integrase inhibitors (INIs), who had been switched to dolutegravir monotherapy (50 mg/day). The primary aim was to report the proportion of VF at week 48 (W48) and week 96 (W96) of dolutegravir monotherapy. The evolution from baseline to W48 of residual viraemia on ultra-deep sequencing and HIV DNA was also evaluated. RESULTS: Sixty-one patients were included. Prior to switching to dolutegravir monotherapy, they had a median (IQR) of 15.4 (6.5-19.9) years of antiretroviral exposure, 5.8 (3.2-10.3) years of viral suppression and 687 (461-848) CD4+ cells/mm3. They remained on dolutegravir monotherapy for a median (IQR) of 100 (29-148) weeks. Forty-two out of 61 patients (68.9%) reached W48 and 32 out of 61 patients (52.5%) reached W96. VF occurred in three patients, with the emergence of INI resistance. VF occurred before W24 and in patients pre-exposed to INIs. At W48, the probability of VF (Kaplan-Meier analysis) was 5.6% (95% CI = 1.8%-16.4%). The same result was obtained at W96. Detectable residual viraemia did not increase and median HIV DNA did not change significantly (2.4 log/106 cells at baseline and 2.3 log/106 cells at W48). Dolutegravir plasma concentration was above the IC90 in 41/41 samples, from 22 patients. CONCLUSIONS: Long-term follow-up showed a low risk of VF under dolutegravir monotherapy, in a selected population of patients with previous long-term virological suppression and low HIV reservoir.

Too fast to stay on track? Shorter time to first anti-retroviral regimen is not associated with better retention in care in the French Dat'AIDS cohort.

BACKGROUND: Rapid antiretroviral therapy (ART) initiation has been proven beneficial for patients and the community. We aimed to analyze recent changes in timing of ART initiation in France and consequences of early start. METHODS: We selected from a prospective nationwide cohort, on 12/31/2017, patients with HIV-1 infection diagnosed between 01/01/2010 and 12/31/2015. We described time from (1) diagnosis to first specialized medical encounter, (2) from this encounter to ART initiation, (3) from diagnosis to first undetectable HIV viral load (VL). We analyzed the determinants of measured temporal trends. A multivariate logistic regression was performed to assess characteristics related with 1-year retention in care. RESULTS: In the 7 245 included patients, median time (1) from HIV diagnosis to first medical encounter was 13 (IQR: 6-32) days, (2) to ART initiation was 27 (IQR: 9-91) days, decreasing from 42 (IQR: 13-272) days in 2010 to 18 (IQR: 7-42) in 2015 (p<0.0001), (3) to first undetectable VL was 257 (IQR: 151-496) days, decreasing from 378 (IQR: 201-810) days in 2010 to 169 (IQR: 97-281) in 2015. After one year, proportion of patients alive and still in care was significantly lower in those in the lower quartile of time from first encounter to ART (<9 days) than those in the higher quartile (>90 days), 79.9% and 85.2%, respectively (p<0.0001). CONCLUSIONS: In a country with unrestricted rapid access to ART, keeping recently diagnosed HIV infected patients in care remains challenging. Starting ART rapidly did not seem to be profitable for all and every patient.

Which antiretrovirals should be prescribed as first-line treatments? Changes over the past 10 years in France.

OBJECTIVE: To describe the changes in first-line antiretroviral (ART) regimens in France between 2005 and 2015 and patients' characteristics related to the use of protease inhibitors in 2015. METHODS: We extracted all patients starting ART between 2005 and 2015 from a large prospective cohort. Regimens were classified as three nucleoside reverse transcriptase inhibitors (NRTI), or two NRTIs with a boosted protease inhibitor (bPI), with a non-nucleoside reverse transcriptase inhibitor (NNRTI), or with an INSTI. Patients' characteristics at the time of initiation were collected. A multinomial logit model was fitted to analyze characteristics related to the choice of regimen in 2015. RESULTS: We analyzed data from 15,897 patients. The proportion of patients starting with (i) a bPI decreased from 60% before 2014 to 38.1% in 2015; (ii) an NNRTI decreased from 30% to 17.8% in 2015; (iii) an INSTI gradually increased to 39.4% in 2015. In 2015, patients with an initial viral load ˃5 log copies/mL were less likely to receive NNRTI (OR=0.08) or INSTI regimens (OR=0.69) than bPIs. Patients with initial CD4+ T cell count ˂200/mm3 were less likely to receive an NNRTI (OR=0.28) or an INSTI regimen (OR=0.52) than a bPI. Women were less likely to receive an NNRTI (OR=0.79) or an INSTI regimen (OR=0.71) than a bPI; although this depended on age. CONCLUSION: The use of bPI as first-line ART declined sharply in France from 2005 to 2015. bPI remained of preferential use in patients with high viral load, low CD4+ T cell count, and in women.

Factors associated with deaths from suicide in a French nationwide HIV-infected cohort.

OBJECTIVES: People living with HIV (PLHIV) are at a higher risk of dying by suicide than the general population. Epidemiological data regarding determinants of suicide in PLHIV are scarce. The aim of this study was thus to study demographic, socio-economic, psychiatric history and immunovirological characteristics associated with death from suicide in the French multicenter Dat'AIDS cohort, from January 2000 to July 2013. METHODS: This was a nested case-control study. All deceased PLHIV during the study period who died by suicide and whose medical files could be checked were included as cases. Controls were selected using incidence density sampling. For each case, up to four controls were selected among all actively followed PLHIV at the index date (date of death of cases). Controls were matched for time from HIV diagnosis (5-year periods) and clinical centre. RESULTS: Seventy cases and 279 controls were included in the study. By multivariable analysis, the factors significantly associated with death from suicide were: not having children, active or substituted drug consumption, alcohol intake > 20 g/day or history of alcohol abuse, history of depressive disorder and/or of attempted suicide, and psychotropic drug intake. Conversely, age, gender, country of birth, positive HCV serology and HIV-related factors, such as AIDS status, use of combination antiretroviral therapy (cART), nadir and current CD4 counts and HIV viral load, were not significantly associated with the risk of death from suicide. CONCLUSIONS: In the cART era, HIV-related factors are not associated with a higher risk of suicide mortality. Suicide prevention measures should target PLHIV with the psychological morbidities observed in our cohort.

Dynamics of drug resistance-associated mutations in HIV-1 DNA reverse transcriptase sequence during effective ART.

Objectives: To investigate the dynamics of HIV-1 variants archived in cells harbouring drug resistance-associated mutations (DRAMs) to lamivudine/emtricitabine, etravirine and rilpivirine in patients under effective ART free from selective pressure on these DRAMs, in order to assess the possibility of recycling molecules with resistance history. Patients and methods: We studied 25 patients with at least one DRAM to lamivudine/emtricitabine, etravirine and/or rilpivirine identified on an RNA sequence in their history and with virological control for at least 5 years under a regimen excluding all drugs from the resistant class. Longitudinal ultra-deep sequencing (UDS) and Sanger sequencing of the reverse transcriptase region were performed on cell-associated HIV-1 DNA samples taken over the 5 years of follow-up. Results: Viral variants harbouring the analysed DRAMs were no longer detected by UDS over the 5 years in 72% of patients, with viruses susceptible to the molecules of interest found after 5 years in 80% of patients with UDS and in 88% of patients with Sanger. Residual viraemia with <50 copies/mL was detected in 52% of patients. The median HIV DNA level remained stable (2.4 at baseline versus 2.1 log10 copies/106 cells 5 years later). Conclusions: These results show a clear trend towards clearance of archived DRAMs to reverse transcriptase inhibitors in cell-associated HIV-1 DNA after a long period of virological control, free from therapeutic selective pressure on these DRAMs, reflecting probable residual replication in some reservoirs of the fittest viruses and leading to persistent evolution of the archived HIV-1 DNA resistance profile.

Infectious complications in HIV-infected kidney transplant recipients.

Renal transplantation is now a viable alternative for dialysis in HIV-infected patients who achieve good immunovirological control with current antiretroviral therapy regimens available. However, there are few studies that analyze the incidence of post-transplant infections in this population. In this study, a retrospective analysis of data files of 24 HIV-infected kidney transplant (KT) recipients was undertaken, matched to 21 non-infected controls. All patients received induction with anti-interleukin-2 antibodies and were followed in the Pitié-Salpêtrière Hospital in Paris, France. The rate of incidence of post-transplant infections was 23.58 and 26.98/100 patient-years, in HIV-infected and HIV-negative groups (relative risk [RR]: 0.90; 95% confidence interval [CI]: 0.58-1.39; p = 0.63). In HIV-infected KT recipients, bacterial infections were the most frequent (67.7%), followed by viral (14.7%) and fungal and parasitic infections (8.8%). Similar trends were seen in the control group. Incidence of opportunistic infections was similar in HIV-infected KT recipients and controls (38.2 vs. 26.5%; p = 0.44). There were three post-transplant HIV reactivations in two patients, secondary to poor adherence to medication. HIV status did not influence survival, but infections increased the risk of unfavorable outcome. Incidence of post-transplant infections was similar in HIV-infected KT recipients and controls. Infections, but not HIV status, had adverse effects on patient and graft survival.

Efficacy, safety and patient-reported outcomes of ledipasvir/sofosbuvir in NS3/4A protease inhibitor-experienced individuals with hepatitis C virus genotype 1 and HIV coinfection with and without cirrhosis (ANRS HC31 SOFTRIH study).

OBJECTIVES: Studies evaluating the efficacy and safety of the fixed-dose combination ledipasvir (LDV)/sofosbuvir (SOF) in patients coinfected with HIV-1 and hepatitis C virus (HCV) have mainly included treatment-naïve patients without cirrhosis. We aimed to evaluate the efficacy and safety of this combination in treatment-experienced patients with and without cirrhosis. METHODS: We conducted a multicentre, open-label, double-arm, nonrandomized study in patients coinfected with HIV-1 and HCV genotype 1 with and without cirrhosis, who had good viral suppression on their antiretroviral regimens. All patients were pretreated with a first-generation NS3/4A protease inhibitor (PI) plus pegylated interferon/ribavirin. Patients received a fixed-dose combination of LDV/SOF for 12 weeks, or for 24 weeks if cirrhosis was present. The primary endpoint was a sustained virological response (SVR) 12 weeks after the end of therapy. Secondary endpoints included safety, pharmacokinetics and patient-reported outcomes. RESULTS: Of the 68 patients enrolled, 39.7% had cirrhosis. Sixty-five patients [95.6%; 95% confidence interval (CI): 87.6-99.1%; P < 0.0001] achieved an SVR, with similar rates of SVR in those with and without cirrhosis. Tolerance was satisfactory, with mainly grade 1 or 2 adverse events. Among patient-reported outcomes, only fatigue significantly decreased at the end of treatment compared with baseline [odds ratio (OR): 0.36; 95% CI: 0.14-0.96; P = 0.04]. Mean tenofovir area under the plasma concentration-time curve (AUC) at week 4 was high, with mean ± SD AUC variation between baseline and week 4 higher in cirrhotic than in noncirrhotic patients (3261.57 ± 1920.47 ng/mL vs. 1576.15 ± 911.97 ng/mL, respectively; P = 0.03). Mild proteinuria (54.4%), hypophosphataemia (50.0%), blood bicarbonate decrease (29.4%) and hypokalaemia (13.2%) were reported. The serum creatinine level was not modified. CONCLUSIONS: LDV/SOF provided a high SVR rate in PI-experienced subjects coinfected with HCV genotype 1 and HIV-1, including patients with cirrhosis.

Darunavir/ritonavir monotherapy at a low dose (600/100 mg/day) in HIV-1-infected individuals with suppressed HIV viraemia.

Background: Darunavir/ritonavir is a potent PI with a high genetic barrier and pharmacological robustness favourably investigated as monotherapy. Whether darunavir could be dose reduced in the context of monotherapy deserves investigation. Methods: Patients with HIV suppressed viraemia (plasma viral load <50 copies/mL for 12 months) under ART who had switched to darunavir/ritonavir monotherapy at 600/100 mg/day between 2013 and 2015 were included in this observational 48 week single-centre study. The primary outcome was the proportion of patients with virological success (defined as plasma viral load <50 copies/mL) at week 24. Secondary outcomes included treatment strategy success and resistance. Results: Thirty-one patients were included with the following baseline characteristics [median (IQR)]: age 52 years (47-57), CD4+ 649 cells/mm3 (463-813), ART duration 16.3 years (9.2-22.3), nadir CD4+ 195 cells/mm3 (144-261) and duration of HIV suppression 7.8 years (4.8-9.7). Prior to switch, ART consisted of PI monotherapy for 28 of 31 patients [darunavir/ritonavir 800/100 mg/day (n = 26), lopinavir/ritonavir (n = 1) and atazanavir/ritonavir (n = 1)] and a triple drug regimen for 3 of 31 patients. Within the 48 weeks of follow-up, no virological failure occurred and two patients discontinued 600/100 mg of darunavir/ritonavir due to side effects at week 16 and 40, leading to a virological suppression rate of 100% (95% CI = 89-100) at weeks 24 and 48. Strategy success rates were 96.8% (95% CI = 83.3-99.9) at week 24 and 93.5% (95% CI = 78.6-99.2) at week 48. Median (IQR) Ctrough values of 800/100 mg of darunavir/ritonavir and 600/100 mg of darunavir/ritonavir were 1537 ng/mL (1286-1724) and 1255 ng/mL (873-2161), respectively. Conclusions: A lower dose of darunavir/ritonavir used as monotherapy (600/100 mg/day) was highly effective in virologically suppressed HIV-infected patients. Further studies are needed to confirm these data.

Dolutegravir as monotherapy in HIV-1-infected individuals with suppressed HIV viraemia.

BACKGROUND: Reducing drug burden is a key challenge for achieving lifelong suppressive HIV therapy. Dolutegravir, with a high potency, long half-life and high genetic barrier, offers potential for monotherapy. METHODS: This observational single-centre study enrolled all patients with HIV RNA (viral load) <50 copies/mL for at least 12 months, with CD4 >350 cells/mm(3) and with no failure under integrase inhibitor therapy who had switched from suppressive ART to dolutegravir monotherapy (50 mg/day). Primary outcome was proportion of patients with viral load <50 copies/mL at week 24. RESULTS: Twenty-eight patients treated for a median ART duration of 17 years (IQR 11-20), virally suppressed for a median of 79 months (IQR 42-95) and with a median CD4 count of 624 cells/mm(3) (IQR 524-761), were enrolled. Baseline ART consisted of a three-drug (n = 10), two-drug (n = 10) or single-drug (n = 8) regimen with integrase inhibitor exposure in 13 patients. The proportion of patients maintaining viral load <50 copies/mL was 96% (95% CI 79%-100%) at week 4, 100% (95% CI = 85%-100%) at week 8, 93% (95% CI 76%-99%) at week 12 and 92% (75-99) at week 24. Three patients (3.70%; 95% CI 3.4%-10.8%) with prior integrase inhibitor experience had HIV RNA rebound with the presence of resistance mutations. Genotyping of HIV DNA using the Sanger method or ultradeep sequencing showed no integrase inhibitor resistance-associated mutations (RAMs) except for the mutation 74I in a patient on a suppressive elvitegravir regimen. The median within- and between-subject variability of dolutegravir C24 was 25% and 34%, respectively. Nine patients with a year of follow-up remained virally suppressed. CONCLUSIONS: Dolutegravir has the potency to be further investigated as a single ART in randomized studies, particularly in patients with no prior exposure to integrase inhibitors.

Psychiatric and substance use disorders in HIV/hepatitis C virus (HCV)-coinfected patients: does HCV clearance matter? [Agence Nationale de Recherche sur le SIDA et les Hépatites Virales (ANRS) HEPAVIH CO13 cohort].

OBJECTIVES: The objective of this nested study was to assess the prevalence of psychiatric disorders in a sample of HIV/hepatitis C virus (HCV)-coinfected patients according to their HCV status. METHODS: The nested cross-sectional study, untitled HEPAVIH-Psy survey, was performed in a subset of HIV/HCV-coinfected patients enrolled in the French Agence Nationale de Recherche sur le SIDA et les Hépatites Virales (ANRS) CO13 HEPAVIH cohort. Psychiatric disorders were screened for using the Mini International Neuropsychiatric Interview (MINI 5.0.0). RESULTS: Among the 286 patients enrolled in the study, 68 (24%) had never received HCV treatment, 87 (30%) were treatment nonresponders, 44 (15%) were currently being treated and 87 (30%) had a sustained virological response (SVR). Of the 286 patients enrolled, 121 patients (42%) screened positive for a psychiatric disorder other than suicidality and alcohol/drug abuse/dependence, 40 (14%) screened positive for alcohol abuse/dependence, 50 (18%) screened positive for drug abuse/dependence, 50 (17.5%) were receiving an antidepressant treatment and 69 (24%) were receiving an anxiolytic. Patients with an SVR did not significantly differ from the other groups in terms of psychiatric disorders. Patients receiving HCV treatment screened positive less often for an anxiety disorder. The highest rate of drug dependence/abuse was among HCV treatment-naïve patients. CONCLUSIONS: Psychiatric disorders were frequent in HIV/HCV-coinfected patients and their rates were comparable between groups, even for patients achieving an SVR. Our results emphasize the need for continuous assessment and care of coinfected patients, even after HCV clearance. Drug addiction remains an obstacle to access to HCV treatment. Despite the recent advent and continued development of directly acting antiviral agents (DAAs), it is still crucial to offer screening and comprehensive care for psychiatric and addictive disorders.

Impact of Age-related Comorbidities on Five-year Overall Mortality among Elderly HIV-Infected Patients in the Late HAART Era--Role of Chronic Renal Disease.

OBJECTIVES: To identify main prognostic factors for 5-year mortality among age-related comorbidities (ARCs) in older people living with HIV (PLHIV). DESIGN: A prospective, multicentre cohort study with a 5-year follow-up period in the late HAART era (from January 2008 to December 2012). SETTING: The Dat'AIDS cohort involving 12 French hospitals. PARTICIPANTS: All actively followed HIV-1 infected patients aged 60 or older. MEASUREMENTS: The study endpoint was all-cause five-year mortality. The following ARCs were considered: chronic renal disease, cardiovascular diseases, cancer, chronic pulmonary disease, cirrhosis, diabetes and nutritional status. Hepatitis C (HCV), hepatitis B (HBV) co-infection and sociodemographic characteristics were also evaluated. Cox's Proportional Hazards model was used for multivariate analysis. RESULTS: Among 1415 PLHIV aged 60 or more patients included, mean age was 66±5.5 years; 154 died (mortality rate 2.47/100 patient-years). The most prevalent ARCs were chronic renal disease (20.1%), diabetes (14.2%) and cardiovascular diseases (12.2%). By multivariate analysis, chronic renal disease (adjusted hazard ratio (aHR)=2.25; 95% confidence interval (CI) [1.58-2.21]; p<10-4), cardiovascular diseases (aHR=2.40; 95%CI[1.64-3.52]; p<10-4), non-HIV related cancer (aHR=1.91; 95%CI[1.20-3.05]; p=0.007), cirrhosis (aHR=2.99; 95%CI[1.68-5.33]; p<10-3), HCV co-infection (aHR=2.00; 95%CI[1.18-3.38]; p=0.009), low body mass index (aHR=2.42; 95%CI[1.46-4.01]; p<10-3) and CD4 cell count < 200 cells/µl (aHR=2.23; 95%CI[1.36-3.65]; p=0.002) were independently associated with 5 year mortality. CONCLUSION: Due to a high prevalence, chronic renal disease and cardiovascular disease are main prognostic factors for 5-year mortality among aged PLHIV.

Non-AIDS-related malignancies: expert consensus review and practical applications from the multidisciplinary CANCERVIH Working Group.

Malignancies represent a major cause of morbidity and mortality in human immunodeficiency virus (HIV)-infected patients. The introduction of combined antiretroviral therapy has modified the spectrum of malignancies in HIV infection with a decreased incidence of acquired immunodeficiency syndrome (AIDS) malignancies such as Kaposi's sarcoma and non-Hodgkin's lymphoma due to partial immune recovery and an increase in non-AIDS-defining malignancies due to prolonged survival. Management of HIV-infected patients with cancer requires a multidisciplinary approach, involving both oncologists and HIV physicians to optimally manage both diseases and drug interactions between anticancer and anti-HIV drugs. The French CANCERVIH group presents here a review and an experience of managing non-AIDS malignancies in HIV-infected individuals.