Maintenance darunavir/ritonavir monotherapy to prevent perinatal HIV transmission, ANRS-MIE 168 MONOGEST study.

OBJECTIVES: Because NRTIs can have fetal toxicities, we evaluated a perinatal NRTI-sparing strategy to prevent perinatal HIV transmission. Our primary objective was to determine the proportion maintaining a viral load (VL) of <50 copies/mL up to delivery on darunavir/ritonavir monotherapy, without requiring treatment intensification. METHODS: In a one-arm, multicentre Phase 2 clinical trial, eligible patients in the first trimester of pregnancy on ART with plasma VL < 50 copies/mL received maintenance monotherapy with darunavir/ritonavir, 600/100 mg twice daily. VL was monitored monthly. ART was intensified in the case of VL > 50 copies/mL. Neonates received nevirapine prophylaxis for 14 days. RESULTS: Of 89 patients switching to darunavir/ritonavir monotherapy, 4 miscarried before 22 weeks' gestation, 2 changed treatment for elevated liver enzymes without virological failure, and 83 were evaluable for the main outcome. Six had virological failure confirmed on a repeat sample (median VL = 193 copies/mL; range 78-644), including two before switching to monotherapy. In these six cases, ART was intensified with tenofovir disoproxil fumarate/emtricitabine. The success rate was 75/83, 90.4% (95% CI, 81.9%-95.7%) considering two patients with VL missing at delivery as failures, and 77/83, 92.8% (95% CI, 84.9%-97.3%) when considering them as successes since both had undetectable VL on darunavir/ritonavir throughout pregnancy. In ITT, the last available VL before delivery was <50 copies/mL in all of the patients. There was no case of perinatal HIV transmission. CONCLUSIONS: Darunavir/ritonavir maintenance monotherapy required intensification in nearly 10% of cases. This limits its widespread use, thus other regimens should be evaluated in order to limit exposure to antiretrovirals, particularly NRTIs, during pregnancy.

Use of rilpivirine in HIV-1-infected individuals in routine clinical practice from 2012 to 2017 in France.

OBJECTIVES: We assessed virological outcomes of rilpivirine use in France from 2012 to 2017, in three groups of people living with HIV (PLHIV): (i) antiretroviral (ARV)-naive PLHIV; (ii) ARV-experienced PLHIV switching to rilpivirine while failing therapy; and (iii) ARV-experienced PLHIV switching to rilpivirine while virologically controlled. METHODS: Virological success (VS) was defined as a plasma HIV-1 viral load (VL) <50 copies/mL and virological failure (VF) as two consecutive VL >50 copies/mL or one VL >50 copies/mL followed by a treatment switch prior to the next VL measurement. The cumulative incidence of VS was assessed considering rilpivirine discontinuation, loss to follow-up and death as competing risks, while estimates of cumulative incidence of VF accounted for loss to follow-up and death. RESULTS: Among the 2166 ARV-naive PLHIV initiating rilpivirine, the 4 year cumulative incidence of VS was 91.0% and was associated with baseline VL. Among the 2125 ARV-experienced PLHIV switching to rilpivirine while failing therapy, the 4 year cumulative incidence of VS was 82.5% and was associated with lower VL, higher CD4 and less than three prior ARVs. Among the 11 828 ARV-experienced PLHIV switching to rilpivirine while virologically controlled, the 4 year cumulative incidence of VF was 9.6%. The risk of VF was lower among MSM, for PLHIV with CD4 ≥ 500 cell/mm3, without a prior AIDS event, or with a longer VL suppression at baseline. CONCLUSIONS: Rilpivirine-containing regimens yielded high rates of viral suppression in most participants, while it was ineffective when used outside the marketing authorization in naive participants.

New Kaposi's sarcoma-associated herpesvirus variant in men who have sex with men associated with severe pathologies.

BACKGROUND: Kaposi sarcoma (KS)-associated herpesvirus (KSHV) subtype depends mostly on patient origin. The current study aimed to assess KSHV diversity in a population of men who have sex with men (MSM) living in France. METHODS: The study included 264 patients. In 65 MSM, including 57 human immunodeficiency virus (HIV)-infected men with KS, multicentric Castleman disease, or primary effusion lymphoma and 8 HIV-uninfected men receiving HIV preexposure prophylaxis (PrEP), we performed KSHV typing with K1 open reading frame Sanger and KSHV whole-genome sequencing. In 199 other patients, we performed real-time polymerase chain reaction screening for the new variant. RESULTS: We found that 51% of KSHV-strains were subtype C (85% C3), and 33% were subtype A. Four patients with severe KSHV disease (2 with visceral KS, 1 with multicentric Castleman disease, and 1 with primary effusion lymphoma) and 1 asymptomatic PrEP user had a new variant resembling the Ugandan subtype F, but with different K1 open reading frame and KSHV whole-genome sequences and a different epidemiological context (MSM vs African population). Its prevalence was 4.5% in Caucasian MSM, and it was absent in other epidemiological groups. CONCLUSIONS: Subtype C predominated among MSM living in France. The new F variant was identified in Caucasian MSM and associated with severe KSHV disease, suggesting that subtype F could be split into F1 and F2 variants. Careful screening for this variant may be required in MSM, given the severe clinical presentation of associated diseases.

Incidence and Clearance of Anal Human Papillomavirus (HPV)-16 and HPV-18 Infection, and Their Determinants, Among Human Immunodeficiency Virus-Infected Men Who Have Sex With Men in France.

BACKGROUND: Prospective data on the natural history of anal human papillomavirus (HPV) infection are scarce in human immunodeficiency virus (HIV)-infected men who have sex with men (MSM). METHODS: We analyzed incidence and clearance of HPV-16 and HPV-18 in a French cohort of HIV-infected MSM, aged ≥35 years, followed-up annually (n = 438, 2014-2018). RESULTS: Human papillomavirus-16 and HPV-18 incidence were similar (~10% incident infections at 24 months). Human papillomavirus-16 incidence was higher among high-grade versus no lesion at baseline (adjusted incidence rate ratio = 3.0; 95% confidence interval, 1.07-8.18). Human papillomavirus-16 cleared significantly slower than HPV-18 (32% versus 54% by 24 months). CONCLUSIONS: In conclusion, anal HPV-16 is more persistent than HPV-18, and its incidence correlates with a prior detection of high-grade lesions.

Rilpivirine in HIV-1-positive women initiating pregnancy: to switch or not to switch?

BACKGROUND: Safety data about rilpivirine use during pregnancy remain scarce, and rilpivirine plasma concentrations are reduced during second/third trimesters, with a potential risk of viral breakthroughs. Thus, French guidelines recommend switching to rilpivirine-free combinations (RFCs) during pregnancy. OBJECTIVES: To describe the characteristics of women initiating pregnancy while on rilpivirine and to compare the outcomes for virologically suppressed subjects continuing rilpivirine until delivery versus switching to an RFC. METHODS: In the ANRS-EPF French Perinatal cohort, we included women on rilpivirine at conception in 2010-18. Pregnancy outcomes were compared between patients continuing versus interrupting rilpivirine. In women with documented viral suppression (<50 copies/mL) before 14 weeks of gestation (WG) while on rilpivirine, we compared the probability of viral rebound (≥50 copies/mL) during pregnancy between subjects continuing rilpivirine versus those switching to RFC. RESULTS: Among 247 women included, 88.7% had viral suppression at the beginning of pregnancy. Overall, 184 women (74.5%) switched to an RFC (mostly PI/ritonavir-based regimens) at a median gestational age of 8.0 WG. Plasma HIV-1 RNA nearest delivery was <50 copies/mL in 95.6% of women. Among 69 women with documented viral suppression before 14 WG, the risk of viral rebound was higher when switching to RFCs than when continuing rilpivirine (20.0% versus 0.0%, P = 0.046). Delivery outcomes were similar between groups (overall birth defects, 3.8/100 live births; pregnancy losses, 2.0%; preterm deliveries, 10.6%). No HIV transmission occurred. CONCLUSIONS: In virologically suppressed women initiating pregnancy, continuing rilpivirine was associated with better virological outcome than changing regimen. We did not observe a higher risk of adverse pregnancy outcomes.

Use of darunavir in HIV-1-infected individuals in routine clinical practice from 2012 to 2016 in France.

OBJECTIVES: We assessed virological outcomes of darunavir use in France from 2012 to 2016, in three groups of people living with HIV (PLHIV): (i) antiretroviral (ARV)-naive PLHIV; (ii) ARV-experienced PLHIV switching to darunavir while failing therapy; and (iii) ARV-experienced PLHIV switching to darunavir while virologically controlled. METHODS: Virological success (VS) was defined as a plasma HIV-1 viral load (VL) <50 copies/mL and virological failure (VF) as two consecutive VL >50 copies/mL or one VL >50 copies/mL followed by a treatment switch prior to the next VL measurement. The cumulative incidence of VS was assessed considering darunavir discontinuation, loss to follow-up and death as competing risks, while estimates of cumulative incidence of VF accounted for loss to follow-up and death. RESULTS: Among the 3235 ARV-naive PLHIV initiating darunavir, the 4 year cumulative incidence of VS was 80.9% and was associated with lower VL and higher CD4 cell counts. Among the 3485 ARV-experienced PLHIV switching to darunavir while failing therapy, the 4 year cumulative incidence of VS was 82.2% and was associated with lower VL. Among the 3005 ARV-experienced PLHIV switching to darunavir while virologically controlled, the 4 year cumulative incidence of VF was 12.6%. The risk of VF was higher with darunavir monotherapy [subdistribution hazard ratio (sHR)=1.67, 95% CI 1.15-2.42] while no difference was observed with dual therapy (sHR = 1.00, 95% CI 0.71-1.42) relative to triple therapy or more. CONCLUSIONS: Darunavir-containing regimens yielded similarly high rates of viral suppression in PLHIV whether they were ARV naive or ARV experienced switching to darunavir while failing therapy, or of maintaining VS in ARV-experienced PLHIV switching to darunavir while virologically controlled.

Hepatitis B virus reactivation during belatacept treatment after kidney transplantation.

We report a case of HBV reactivation following belatacept treatment in a patient who underwent kidney transplantation in 2015 for HIV-associated nephropathy (HIVAN). Human immunodeficiency virus viral load was undetectable prior to transplantation, and CD4+ lymphocyte count was greater than 300/mL. Baseline HBV serology at transplantation was HBsAg negative, anti-HBcAb positive, anti-HBsAb 312 UI/L, and HBeAg negative/anti-HBeAb positive. Liver function tests were normal, and viral DNA was undetectable. Two years later, the patient presented with severe acute hepatitis after a progressive disappearance of anti-HbsAb, quickly followed by HBV reactivation. Immunosuppressive treatment was drastically reduced, and treatment with entecavir was started. The outcome was favorable, and HBV DNA became undetectable after 9 weeks of treatment. This is the first report of acute hepatitis related to HBV reactivation in a kidney transplant recipient treated with belatacept. The risk for HBV reactivation in patients treated with belatacept should not be underestimated, especially in those with resolved HBV infection.

Prevalence and Risk Factors for Anal Human Papillomavirus Infection in Human Immunodeficiency Virus-Positive Men Who Have Sex with Men.

Background: We assessed prevalence and risk factors for anal human papillomavirus (HPV) in human immunodeficiency virus (HIV)-positive men who have sex with men (MSM), who are at high-risk of HPV-related anal cancer. Methods: APACHES is a multicentric, prospective study of anal HPV infection and lesions in HIV-positive MSM aged ≥35 years. At baseline, participants underwent anal swabs for HPV and cytology, plus high-resolution anoscopy. High-risk HPV (HR-HPV) was tested by Cobas4800, with genotyping of HR-HPV positives by PapilloCheck. Results: Among 490 participants, prevalence of HPV16 and HR-HPV was 29% and 70%, respectively, and did not differ significantly by age, sexual behavior, or markers of HIV or immune deficiency. Smoking was the only, albeit weak (odds ratio, 1.8; 95% confidence interval, 1.2-2.7), predictor of HR-HPV. High-risk HPV and HPV16 prevalence increased strongly with anal diagnosis severity, both by worse cytological/histological (composite) diagnosis at APACHES baseline and worse historical diagnosis. HPV16 rose from 19% among participants who were negative for lesions to 63% among participants with high-grade lesions. In contrast, non-HPV16 HR-HPVs were less prevalent in high-grade (37%) than negative (64%) composite diagnosis, and their causal attribution was further challenged by multiple HPV infections. Conclusions: Human papillomavirus 16 is ubiquitously frequent among human immunodeficiency virus -positive men having sex with men, and more strongly associated with high-grade anal lesions than other high-risk types, confirming it as a target for anal cancer prevention.

Silent Cerebral Small-Vessel Disease Is Twice as Prevalent in Middle-Aged Individuals With Well-Controlled, Combination Antiretroviral Therapy-Treated Human Immunodeficiency Virus (HIV) Than in HIV-Uninfected Individuals.

Background: Silent cerebral small-vessel disease (CSVD) is defined as white matter hyperintensities, silent brain infarction, or microbleeds. CSVD is responsible for future vascular events, cognitive impairment, frailty, and shorter survival. CSVD prevalence among middle-aged people living with well-controlled human immunodeficiency virus (HIV) infection (PLHIV) is unknown. Methods: The French National Agency for Research on AIDS and Viral Hepatitis (ANRS) EP51 Microvascular Brain Retina and Kidney Study (MicroBREAK; NCT02082574) is a cross-sectional study with prospective enrollment of treated PLHIV, ≥50 years old with viral load controlled for ≥12 months, and frequency age- and sex-matched HIV-uninfected controls (HUCs). It was designed to estimate CSVD prevalence on 3T magnetic resonance imaging (3D fluid-attenuated inversion recovery, transversal T2-weighted gradient-echo imaging and diffusion-weighted imaging), as diagnosed by 2 blinded neuroradiologists. A logistic regression model was used to assess the impact of HIV on CSVD after adjustment for traditional risk factors. Results: Between June 2013 and May 2016, 456 PLHIV and 154 HUCs were recruited. Median age was 56 and 58 years, respectively (P = .001), among whom 84.9% and 77.3%, respectively (P = .030), were men. CSVD was detected in 51.5% of PLHIV and 36.4% of HUCs with an adjusted odds ratio (aOR) of 2.3. The HIV impact differed according to age, with aOR values of 5.3, 3.7, and 1.0 for age groups <54, 54-60, and >60 years, respectively (P = .022). Older age, hypertension, and lower CD4 cell count nadir were independently associated with a higher risk of CSVD among PLHIV. Conclusions: HIV is an independent risk factor for CSVD. Despite sustained immunovirological control, the CSVD prevalence was twice as high among middle-aged PLHIV than HUCs. Clinical Trials Registration: NCT02082574.

Virological factors associated with outcome of dual maraviroc/raltegravir therapy (ANRS-157 trial).

OBJECTIVES: ROCnRAL ANRS-157 was a single-arm study designed to evaluate a switch to a maraviroc (300 mg twice a day) plus raltegravir (400 mg twice a day) regimen in virologically suppressed HIV-1-infected patients (ClinicalTrials.gov: NCT01420523). The aim of this work was to investigate the factors associated with virological failure (VF) (5/44 patients) or virological rebound defined as one viral load (VL) >50 copies/mL or VL >1 copy/mL. METHODS: At baseline (BL), ultradeep sequencing (UDS) of DNA gp120 V3 and integrase regions and quantification of HIV DNA were performed in PBMCs. Tropism, VL, BL ultrasensitive HIV RNA VL, BL HIV DNA VL, subtype, age, ethnicity, transmission group, AIDS status, nadir CD4 and BL CD4 cell count, time since HIV diagnosis, duration of ART and suppressed viraemia, VL zenith, CD4/CD8 ratio and BL CD8 cell count were investigated as potential factors associated with virological rebound. RESULTS: The proportion of patients with VL <1 copy/mL did not evolve over time. Among the 44 included patients, 3 had minority X4-tropic viruses determined by UDS at BL and one of them presented VF. Minority resistant variants in the integrase gene were detected at BL at two positions (E138 and G140) for three patients who did not have VF. Among all studied factors, none was associated with virological rebound. CONCLUSIONS: Maraviroc plus raltegravir failed to maintain virological suppression in virologically suppressed HIV-1-infected patients. However, neither minority viral variants nor ultrasensitive viraemia was found to be a predictive factor of VF or virological rebound in this context.

HIV-1 DNA levels in peripheral blood mononuclear cells and cannabis use are associated with intermittent HIV shedding in semen of men who have sex with men on successful antiretroviral regimens.

BACKGROUND: Few data exist on the efficacy of combined antiretroviral therapy (cART) in semen of human immunodeficiency virus type 1 (HIV-1) infected men who have sex with men (MSM) with sustained control of HIV replication in blood. METHODS: HIV-1 infected MSM on successful cART for >6 months were enrolled. HIV-RNA was quantified in seminal plasma (spVL) and in blood plasma (bpVL) from 2 paired samples collected 4 weeks apart. Relationship between spVL and bpVL (measured by an ultrasensitive assay, LOQ 10 copies/mL), total peripheral blood mononuclear cells (PBMC)-associated HIV-DNA, sexually transmitted infections (STIs), and self-reported socio-behavioral characteristics was assessed using GEE logistic regression. RESULTS: In total, 157 patients were included. Median time with bpVL <50 copies/mL was 3.3 years. spVL was detectable in 23/304 samples (prevalence 7.6%). Median spVL was 145 cp/mL (100-1475). spVL was detectable on the first, on the second, and on both samples in 5, 14, and 2 men, respectively. In sum, 33 individuals (21%) had STIs (asymptomatic in 24/33). Residual bpVL was undetectable by ultrasensitive assay in 225/300 samples (75%). After multivariable adjustments, PBMC-associated HIV-DNA (OR 2.6[1.2; 6.0], for HIV-DNA > 2.5 log10 cp/10(6) PBMC, P = .02), and cannabis use during sexual intercourse (OR 2.8[1.2; 6.7], P = .02) were the only factors associated significantly with spVL. CONCLUSION: We show that HIV-RNA can be detected intermittently in semen of HIV-1 infected MSM despite successful cART. The size of blood HIV-1 reservoir predicted spVL detection. Our results indicated also that the possible effect of cannabis should be taken into account when developing prevention interventions targeted toward HIV-infected MSM on successful cART.

Comparison of in vitro fertilization cycles in couples with human immunodeficiency virus type 1 infection versus noninfected couples through a retrospective matched case-control study.

OBJECTIVE: To compare in vitro fertilization (IVF) outcomes in couples in which at least one partner is human immunodeficiency virus (HIV) positive with that of couples in which neither partner is HIV-positive. DESIGN: Retrospective matched case-control study. SETTING: Fertility center at Tenon Hospital, Paris, France. PATIENTS: A total of 179 IVF cycles in couples infected with HIV-1 and 179 IVF cycles in control couples. INTERVENTIONS: Ovarian stimulation, oocytes retrieval, IVF (standard and microinjection), embryo transfer, pregnancy, and live birth follow-up. MAIN OUTCOME MEASURES: Live birth rate and IVF outcomes. RESULTS: The first comparison between HIV and non-HIV couples showed poorer outcomes in the HIV group (higher administered gonadotropin doses and longer stimulation periods, lower cumulative pregnancy and live birth rates, among other things). A subgroup analysis was performed in addition. No differences were found in the "men HIV" group compared with the controls. In contrast, poorer outcomes in the "women HIV" and "women and men HIV" groups were shown in terms of administered doses, duration of stimulation, and number of oocytes retrieved. For the "women HIV" group, lower cumulative clinical pregnancy and live birth rates were found. CONCLUSION: The data suggested that couples with HIV-positive women have poorer medically assisted procreation outcomes than couples with non-HIV-infected women. Therefore, physicians should pay particular attention to couples with HIV-positive women.

A case of tuberculosis and black-grain eumycetoma co-infection in a non-endemic country: clinical presentation and therapeutic management.

We report a case of black-grain eumycetoma co-localized with Mycobacterium tuberculosis infection, presenting as a painless leg abscess and associated with vertebral tuberculosis. The rare association of these two pathogens raises several challenges regarding foreseeable drug interactions, side effects, the most appropriate management, and the potential link between these two diseases.

Pyogenic lung abscess in an infectious disease unit: a 20-year retrospective study.

BACKGROUND: Pyogenic lung abscesses are rare and poorly described infections. This study aimed to describe their prognostic factors. METHODS: We retrospectively included all patients hospitalized between 1 January 1998 and 1 June 2018, with an International Classification of Diseases, version 10 (IDC-10) diagnosis of pyogenic lung abscess, from the Diamm based medical records (Micro6, Nancy, France). Parasitic, fungal, or mycobacterial lung abscesses were excluded. RESULTS: A total of 64 patients were included. Abscesses were associated with immunosuppression in 28 patients, including HIV infection and immunosuppressive therapy for eight and 12 patients, respectively. Bacterial identification was obtained for 36 patients. Nine patients (14%) developed lung abscesses after hematogenous dissemination. They differed from bronchogenic abscesses by their younger age (p = 0.03), the absence of smoking or emphysema (p = 0.05), Staphylococcus aureus (p = 0.001) or Streptococcus spp. (p = 0.05) isolation, and the smaller size of their abscess (p = 0.02). Overall, evolution was marked by radiological sequelae (46.9%), relapse (12.5%), and death (4.8%). Radiological sequelae occurred more frequently during the course of bronchogenic abscesses (p = 0.02), particularly when they spontaneously discharged (p = 0.04). Relapses were more frequent in patients with emphysema (p = 0.04) and when Haemophilus influenzae was isolated (p = 0.04). In multivariate analysis, poor outcomes, including death, sequelae, and relapse occurred more frequently in patients who had bronchogenic abscess (p = 0.02), and in those who received antibiotics during less than 6 weeks (p = 0.05). CONCLUSION: A duration of antibiotic treatment of less than 6 weeks and bronchogenic presentation were globally associated with poor outcome of pyogenic lung abscesses. These data should be considered when proposing guidelines for the care of pyogenic lung abscesses.The reviews of this paper are available via the supplemental material section.

Discordance between cerebral spinal fluid and plasma HIV replication in patients with neurological symptoms who are receiving suppressive antiretroviral therapy.

OBJECTIVE: We report data on 11 patients with neurological symptoms and human immunodeficiency virus (HIV) cerebrospinal fluid (CSF) viremia contrasting with suppressed plasma HIV RNA during receipt of combined antiretroviral therapy. DESIGN: We retrospectively identified instances of central nervous system (CNS) symptoms in patients who had been receiving stable combination antiretroviral therapy. Discordance between plasma and CSF HIV RNA levels was defined by any detectable CSF HIV RNA level >200 copies/mL while plasma levels were <50 copies/mL or by a CSF HIV RNA level that was 1 log greater than the plasma HIV RNA level. RESULTS: Eleven patients had experienced acute or subacute neurological symptoms. All but one patient had CSF pleocytosis and/or elevated protein levels. The median CSF HIV RNA level was 880 copies/mL (range, 558-12,885 copies/mL). Patients had been receiving stable combination antiretroviral therapy for a median of 13 months (range, 10-32 months). Eight of 11 patients had a plasma HIV RNA level <50 copies/mL, and 3 had plasma HIV RNA blips with their CSF HIV RNA level >1 log higher than their plasma HIV RNA level. Resistance-associated mutations were detected in 7 of 8 CSF HIV RNA genotypic strains. The median number of resistance-associated mutations was 6 (range, 2-8) to nucleoside reverse-transcriptase inhibitors and 3 (range, 1-9) to protease inhibitors. One patient had a virus harboring nonnucleoside reverse-transcriptase inhibitor mutations. The median central nervous system penetration-effectiveness (CPE) rank was 2 (range, 1-3), and 5 patients had a CPE 1.5. After antiretroviral therapy optimization based on genotypes and CPE, all patients clinically improved, with normalization of CSF. CONCLUSIONS: Despite successful suppression of plasma viremia with antiretroviral therapy, HIV may replicate in CSF, with development of CSF HIV resistance resulting in acute or subacute neurological manifestations.

Raltegravir as functional monotherapy leads to virological failure and drug resistance in highly treatment-experienced HIV-infected patients.

The objective of this study was to evaluate the development of resistance to raltegravir (RAL) in patients with viraemia between 40 and 400 copies/ml. All HIV-1-infected patients with multidrug-resistant virus, plasma HIV-1 RNA >1000 copies/ml and starting RAL were enrolled in this observational study and followed up until week 48. Sixty-seven patients with median plasma HIV-1 RNA at 4.3 log(10) copies/ml and CD4 at 177 cells/mm(3) were included. At week 24, 43 achieved full viral suppression (FVS; plasma HIV-1 RNA <40 copies/ml), 18 had incomplete viral suppression (IVS; plasma HIV-1 RNA 40-400 copies/ml). At week 48, all the FVS were sustained, 16 of the IVS patients retained a plasma HIV-1 RNA <400 copies/ml and only 2 of the IVS at week 24 experienced VF. No RAL resistance was detected in the persistent low viraemia. In contrast, integrase mutation was detected in 6 of the patients with VF. A genotypic sensitivity score equal to 0 was associated with plasma HIV-1 RNA >40 copies/ml at week 24 (OR 20.9, 95% CI 2.0-215.1) and with RAL resistance (OR 14.2, 95% CI 2.1-94.7). This study confirmed the high efficacy of a RAL-containing regimen under routine clinical conditions in infections caused by multidrug-resistant virus. If persistent low viraemia is observed over more than 48 weeks without the emergence of resistance, RAL should never be given as functional monotherapy, as it is associated with a maximal risk of VF and the emergence of RAL resistance.

Brief Report: Impact of ART Classes on the Increasing Risk of Cerebral Small-Vessel Disease in Middle-Aged, Well-Controlled, cART-Treated, HIV-Infected Individuals.

BACKGROUND: Cerebral small-vessel disease (CSVD) is a chronic disease accounting for one-third of strokes and the second etiology of dementia. Despite sustained immunovirological control, CSVD prevalence is doubled in middle-aged persons living with HIV (PLHIVs), even after adjustment for traditional cardiovascular risk factors. We aimed to investigate whether exposure to any antiretroviral drug class could be associated with an increasing risk of CSVD. METHODS: The MicroBREAK-2 case-control study (NCT02210130) enrolled PLHIVs aged 50 years and older, treated with combined antiretroviral therapy for ≥5 years, with plasma HIV load controlled for ≥12 months. Cases were PLHIVs with radiologically defined CSVD, and controls were CSVD-free PLHIVs matched for age (±5 years), sex, and year of HIV diagnosis (±5 years). Multivariable conditional logistic regression analyses focused on cumulative exposure to nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors and/or exposure to integrase inhibitors (yes or no), adjusted for hypertension, CD4 nadir, current CD4/CD8 ratio, and HIV transmission group. RESULTS: Between May 2014 and April 2017, 77 cases and 77 controls (85.7% males) were recruited. PLHIVs' median age was 57.6 years, and median HIV diagnosis year was 1992. The increasing risk of CSVD was not associated with exposure to any ART class. CONCLUSION: No deleterious effect of ART class exposure on the risk of CSVD was found for middle-aged treated PLHIVs.

"Real life" use of raltegravir during pregnancy in France: The Coferal-IMEA048 cohort study.

INTRODUCTION: Limited "real life" data on raltegravir (RAL) use during pregnancy are available. Thus, we aimed at describing effectiveness and safety of RAL-based combined antiretroviral therapy (cART) in this setting. METHODS: HIV-1-infected women receiving RAL during pregnancy between 2008 and 2014 in ten French centers were retrospectively analysed for: (1) proportion of women receiving RAL anytime during pregnancy who achieved a plasma HIV-RNA (pVL) < 50 copies/mL at delivery, and (2) description of demographics, immuno-virological parameters and safety in women and new-borns. RESULTS: We included 94 women (median age, 33 years) of which 85% originated from Sub-Saharan Africa and 16% did not have regular health insurance coverage. Sixteen women were cART-naïve (median HIV diagnosis at 30 weeks of gestation), whereas 78 were already on cART before pregnancy (40% with pVL < 50 copies/mL). RAL was initiated before pregnancy (n = 33), during the second trimester (n = 11) and the third trimester of pregnancy (n = 50). No RAL discontinuations due to adverse events were observed. Overall, at the time of delivery, pVL was < 50 copies/mL in 70% and < 400 copies/mL in 84% of women. Specifically, pVL at delivery was < 50 copies/mL in 82%, 55% and 56% of cases when RAL was started before pregnancy, during the second or third trimester of pregnancy, respectively. Median term was 38 weeks of gestation, no defect was reported and all new-borns were HIV non-infected at Month 6. CONCLUSIONS: RAL appears safe and effective in this "real-life" study. No defect and no HIV transmission was reported in new-borns.

Chagas disease, France.

Chagas disease (CD) is endemic to Latin America; its prevalence is highest in Bolivia. CD is sometimes seen in the United States and Canada among migrants from Latin America, whereas it is rare in Europe. We report 9 cases of imported CD in France from 2004 to 2006.