Sexually Transmitted Trichophyton mentagrophytes Genotype VII Infection among Men Who Have Sex with Men.

Transmission of dermatophytes, especially Trichophyton mentagrophytes genotype VII, during sexual intercourse has been recently reported. We report 13 such cases in France. All patients were male; 12 were men who have sex with men. Our findings suggest sexual transmission of this pathogen within a specific population, men who have sex with men.

Kinetics of Archived M184V Mutation in Treatment-Experienced Virally Suppressed HIV-Infected Patients.

BACKGROUND: We aimed to assess the kinetics of drug-resistant viral variants (DRVs) harboring the M184V mutation in proviral DNA of long-term virally suppressed patients, and factors associated with DRV persistence. METHODS: Human immunodeficiency virus (HIV) DNA from blood cells stored in 2016 and 2019 was sequenced using Sanger and ultradeep sequencing (SS and UDS; detection threshold 1%) in antiretroviral therapy (ART)-treated patients with HIV RNA < 50 copies/mL for at least 5 years, with past M184V mutation documented in HIV RNA. RESULTS: Among 79 patients, by combining SS and UDS, M184V was found to be absent in 26/79 (33%) patients and persistent in 53/79 (67%). M184V-positive patients had a longer history of ART, lower CD4 nadir, and higher pretherapeutic HIV RNA. Among 37 patients with viral sequences assessed by UDS, the proportion of M184V-positive DRVs significantly decreased between 2016 and 2019 (40% vs 14%, P = .005). The persistence of M184V was associated with duration and level of HIV RNA replication under lamivudine/emtricitabine (3TC/FTC; P = .0009 and P = .009, respectively). CONCLUSIONS: While it decreased over time in HIV DNA, M184V mutation was more frequently persistent in HIV DNA of more treatment-experienced patients with longer past replication under 3TC/FTC.

More HIV-1 RNA detected and quantified with the Cobas 6800 system in patients on antiretroviral therapy.

BACKGROUND: Target-detected (TD) results or low-level viraemia (LLV) can be observed in HIV-1 patients on ART, which regularly raises questions. OBJECTIVES: We describe here the impact on HIV-1 RNA quantification of switching from the COBAS AmpliPrep/COBAS TaqMan (CAP/CTM) to the Cobas 6800 system (C6800), based on analyses of viraemia close to the lower limit of quantification (LLoQ). PATIENTS AND METHODS: We retrospectively selected two groups of patients: 200 individuals whose viral loads (VLs) were consistently <50 copies/mL with CAP/CTM for at least 3 years before switching to C6800 (group 1), and 35 other patients with confirmed LLV when C6800 was in use (group 2). In both groups, we compared several consecutive VL results performed before and after the change of quantification assay. Analyses were performed with McNemar's paired tests or Fisher's exact tests. RESULTS: In group 1, the frequency of TD results (below or above the LLoQ) increased significantly after the switch to C6800 for patients with <25% of results being TD for VLs performed with CAP/CTM (P < 0.0001). Significantly more patients had at least one VL ≥20 or ≥50 copies/mL with C6800, in both group 1 (37.0% versus 18.5%; P < 0.0001 and 6.5% versus 0%; P = 0.0009, respectively) and group 2 (100% versus 66%; P = 0.0015 and 97% versus 40%; P < 0.0001, respectively). CONCLUSIONS: C6800 revealed residual or low-level HIV-1 RNA that was not detected with CAP/CTM, resulting in twice as many patients being found to have a VL ≥20 copies/mL. Physicians and patients should be aware of possible differences in results between assays, and it is crucial to specify the quantitative assay used in studies.

Household transmission of SARS-CoV-2 infection in the Paris/Ile-de-France area.

This st udy aims to evaluate the prevalence of SARS-CoV-2 antibodies in locked-down family households to determine viral dynamics and immunity acquisition. COVID-19 individuals and their households in lockdown under the same roof during early spring 2020 were interviewed and tested using rapid immunochromatographic lateral flow antibodies assays (LFA) between July and September 2020. Outcomes were secondary infection rate (SIR) among contacts, household infection rate, and predictors of transmission. We enrolled 87 households including 87 COVID-19 index cases (female 78.2%; median age: 47.0 years, IQR: 42.0-51.5) and 255 contacts (males: 52.9%; median age: 19.0 years, IQR: 11.0-43.5) consisting of their children (42%) or spouses/partners (28.2%). A total of 95/255 contacts were SARS-CoV-2 antibody positive leading to a SIR of 37.3% (95% confidence interval (CI): 31.3-43.5%). Viral transmission was observed in 54 households (62%). SARS-CoV-2 infection was asymptomatic in 33/95 (34.7%) of SARS-CoV-2-positive contacts. Independent predictors of virus transmission from index to contacts were housing surface area < 60 m2 (OR: 5.6 [1.1; 28.2] and a four-member family compared to five (OR: 3.6 [1.2; 10.3]). Households represent a high-risk setting for SARS-CoV-2 transmission through close contact within the family amplified by the number of family members and the housing surface area.

Intermittent two-drug antiretroviral therapies maintain long-term viral suppression in real life in highly experienced HIV-infected patients.

OBJECTIVES: To assess in real life whether two-drug regimens (2-DRs) given 4-5 days a week in virally suppressed patients can maintain viral suppression over 48 and 96 weeks. METHODS: This observational single-centre study enrolled all patients who initiated an intermittent 2-DR between 01/01/2016 and 30/06/2019. The primary outcome was the rate of virological failure (VF), defined as confirmed plasma viral load (pVL) ≥50 copies/mL or single pVL ≥50 copies/mL followed by ART change at week 48 (W48) and W96. Secondary outcomes were the 2-DR intermittent strategy success rate (pVL <50 copies/mL with no ART change), change in CD4 count, CD4/CD8 ratio and rate of residual viraemia. RESULTS: Eighty-five patients were included; 67/85 (79%) were men, median age = 57 years (IQR = 50-63), CD4 nadir = 233 cells/mm3 (110-327), ART duration = 21 years (13-24), duration of virological suppression = 6.5 years (3.7-10.8) and CD4 count = 658 cells/mm3 (519-867). Intermittent 2-DRs consisted of integrase strand transfer inhibitor (INSTI)/NNRTI (58%), INSTI/NRTI (13%), two NRTIs (11%), PI/NRTI (7%) and other combinations (11%). The median follow-up was 90 weeks (IQR = 64-111). Overall, four VFs occurred, leading to a virological success rate of 98.8% (95% CI = 93.6-100) at W48 and 95.3% (95% CI = 88.4-98.7) at W96. Resuming the same 2-DR 7 days a week led to viral resuppression in three patients, whereas the M184V mutation emerged in one patient, leading to ART modification. There was no significant change in the CD4 count or residual viraemia rate, but a small increase in the CD4/CD8 ratio (P = 0.009) occurred over the study period. CONCLUSIONS: This observational study shows the potential for intermittent 2-DRs to maintain a high virological success rate, which should be assessed in larger prospective randomized studies.

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.

Pitfalls of HIV genotypic tropism testing after treatment interruption.

OBJECTIVES: The genotypic method is reliable enough for the determination of tropism and largely preferred in Europe. However, careful interpretation is essential when assessing HIV genotypic resistance during treatment interruption (TI) due to the possible disappearance of resistant strains. The results of HIV genotypic tropism testing in such a context remain unknown. METHODS: First, we studied changes in tropism in patients included in a structured TI assay: the Reverse study. Second, we investigated the unexpected tropism switches from X4 to R5 recorded in our routine database. RESULTS: Tropism determination was possible in 21 patients of the Reverse study, 9 of whom had an X4 virus (43%) at baseline. Two patients displayed a change of tropism during TI, both switching from X4 to R5. Regarding the database investigation, 7 of the 222 patients with at least two plasma tropism determinations recorded in the database displayed a switch from X4 to R5. TI due to non-compliance at the time of the tropism change was reported for five of these seven patients. CONCLUSIONS: We have shown that the redistribution of the HIV population caused by TI could potentially result in X4 viruses becoming undetected and inappropriate prescription of a CCR5 receptor antagonist. Therefore, genotypic tropism results should be interpreted with caution in such a context.

Highly multidrug-resistant HIV: clonal analysis and therapeutic strategies.

OBJECTIVES: There are today HIV-infected patients in therapeutic impasses because of highly multidrug-resistant (HMDR) viruses. We studied the distribution of resistance mutations at clonal level, and we analysed the therapeutic strategies used in such cases to achieve undetectable viraemia. METHODS: The HMDR profile was defined as a genotypic sensitivity score (GSS) ≤ 1.5 for etravirine and raltegravir with full resistance to darunavir. About 30 clones per gene and per patient were sequenced. Virtual phenotypes were determined. Efficacy of therapeutic strategies was evaluated by follow-up of viral loads, CD4 cell counts and trough concentrations of drugs. RESULTS: Among 1310 patients on treatment and with genotypic resistance testing, 25 (2%) were resistant to darunavir and 11 (0.8%) had an HMDR profile. Five-hundred clones could be analysed for four of them. HMDR profiles were harboured by the great majority of clones and all resistance mutations were located on the same strains for all genes. Despite this and a regimen with a GSS <2.0 in three patients, they achieved a viraemia <20 copies/mL. These results were obtained using different strategies: high doses of drugs; combination of antiretrovirals with full or intermediate susceptibility, such as tipranavir, etravirine or maraviroc; and use of alternative compounds, such as foscarnet or interferon. CONCLUSION: Patients with HMDR HIV were uncommon, but, in such cases, all resistance mutations were borne on the same majority strains. In this study, tipranavir was the only protease inhibitor with full or intermediate susceptibility. Despite very limited therapeutic options, an undetectable viraemia can be achieved by combining different strategies.

Switching to darunavir/ritonavir 800/100 mg once-daily containing regimen maintains virological control in fully suppressed pre-treated patients infected with HIV-1.

The objective of this study was to evaluate the switch to once-daily darunavir/ritonavir 800/100 mg in treatment-experienced patients with suppressed HIV-1 replication on a twice-daily ritonavir-boosted protease-inhibitor (bid PI/r) containing regimen, that is in a setting where genotypic resistance test cannot be performed. In this open label, non-comparative, multicenter study, patients on a bid PI/r-containing triple combination, with suppressed viral replication, were switched to once-daily darunavir/r 800/100 mg containing triple combination. The primary endpoint was the proportion of patients with plasma HIV-RNA < 50 copies/ml 24 weeks after the switch. Intensive darunavir pharmacokinetic evaluation was performed at Week 4 (W4) in 11 patients. Eighty-five patients were enrolled. All had HIV-RNA < 50 copies/ml at screening with a pre-exposure to a median of 2 PI/r (1-5). By intent-to-treat analysis (missing = failure), 78/85 patients (92%, 95% CI [83;96]) maintained an HIV-RNA < 50 copies/ml at W24. Seven patients experienced protocol-defined treatment failure between baseline and W24: Two had confirmed low-level viral rebound, one discontinued study treatment for adverse event, three withdrew their consent, and one was lost to follow-up. By on-treatment analysis, 78/80 patients (97%, 95% CI [91;99]) maintained an HIV-RNA < 50 copies/ml at W24. Results were similar at Week 48. The median area under the darunavir plasma concentration-time curve measured in 11 patients was 61,380 ng hr/ml; darunavir median trough concentration 1,340 ng/ml and darunavir half-life was 12.2 hr. Tolerability of once-daily darunavir/r 800/100 mg was excellent. Optimally suppressed, treatment-experienced patients can switch safely from a twice-daily PI/r regimen to a once-daily darunavir/r 800/100 mg containing regimen.

HIV disease progression despite suppression of viral replication is associated with exhaustion of lymphopoiesis.

The mechanisms of CD4(+) T-cell count decline, the hallmark of HIV disease progression, and its relationship to elevated levels of immune activation are not fully understood. Massive depletion of CD4(+) T cells occurs during the course of HIV-1 infection, so that maintenance of adequate CD4(+) T-cell levels probably depends primarily on the capacity to renew depleted lymphocytes, that is, the lymphopoiesis. We performed here a comprehensive study of quantitative and qualitative attributes of CD34(+) hematopoietic progenitor cells directly from the blood of a large set of HIV-infected persons compared with uninfected donors, in particular the elderly. Our analyses underline a marked impairment of primary immune resources with the failure to maintain adequate lymphocyte counts. Systemic immune activation emerges as a major correlate of altered lymphopoiesis, which can be partially reversed with prolonged antiretroviral therapy. Importantly, HIV disease progression despite elite control of HIV replication or virologic success on antiretroviral treatment is associated with persistent damage to the lymphopoietic system or exhaustion of lymphopoiesis. These findings highlight the importance of primary hematopoietic resources in HIV pathogenesis and the response to antiretroviral treatments.

Birth Country Influences the Choice of Antiretroviral Therapy in HIV-Infected Individuals: Experience From a French HIV Centre.

OBJECTIVES: To assess whether antiretroviral therapy (ART) prescriptions differ between naive and virally suppressed HIV patients born in France (PBFs) and in Sub-Saharan Africa (PBSSAs). SETTING: Observational single-center study. METHODS: We included all PBFs and PBSSAs who entered into care at Pitié-Salpêtrière Hospital, Paris, France, from 01/01/2000 to 31/12/2018, with plasma HIV-RNA>200 copies/mL. We first compared the initial ART in naive PBFs and PBSSAs. Second, we compared the last-prescribed ART (including drug-reduced ART: daily 2-drug regimens, daily 1-drug regimens and intermittent 3-drug regimens) in virally suppressed PBFs and PBSSAs, by focusing on patients in care in 2018 with HIV-RNA <50 copies for at least 24 months. A univariable and multivariable logistic regression model was used to assess the impact of geographical origin on ART prescriptions. RESULTS: A total of 1944 naive patients were included (915 PBSSAs and 1029 PBFs). PBSSAs were more frequently women, hepatitis B coinfected, with a lower pretherapeutic CD4 T-cell count, and most had tuberculosis at HIV diagnosis. After adjustment for confounders, PBSSAs were more likely to receive a first-line protease inhibitor-based regimen (OR 1.61, 95% CI: 1.31 to 1.98), and less likely to receive an integrase inhibitor-based regimen (OR 0.61, 95% CI: 0.42 to 0.88). Of the 968 virally suppressed patients (431 PBSSAs and 537 PBFs), PBSSAs were less likely to receive drug-reduced ART, including 2-drug regimens and intermittent three-drug regimens (OR 0.48, 95% CI: 0.36 to 0.65). CONCLUSIONS: Differences in ART prescriptions between PBSSAs and PBFs were not only explained by different clinical and virologic situations. Personal motivations of doctors in choosing ART according to country of birth need to be explored.

Intermittent Bictegravir/Emtricitabine/Tenofovir Alafenamide Treatment Maintains High Level of Viral Suppression in Virally Suppressed People Living with HIV.

In this observational study, we aimed to evaluate whether bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) administered 5 or 4 days a week is able to maintain viral suppression in people living with HIV (PLHIV). We enrolled 85 patients who initiated intermittent B/F/TAF between 28 November 2018 and 30 July 2020: median (IQR) age 52 years (46-59), duration of virological suppression 9 years (3-13), CD4 633/mm3 (461-781). Median follow-up was 101 weeks (82-111). The virological success rate (no virological failure [VF]: confirmed plasma viral load [pVL] ≥ 50 copies/mL, or single pVL ≥ 200 copies/mL, or ≥50 copies/mL with ART change) was 100% (95%CI 95.8-100) and the strategy success rate (pVL < 50 copies/mL with no ART regimen change) was 92.9% (95%CI 85.3-97.4) at W48. Two VF occurred at W49 and W70, in 2 patients self-reporting poor compliance. No resistance mutation emerged at time of VF. Eight patients presented strategy discontinuation for adverse events. There was no significant change in the CD4 count, residual viraemia rate, neither body weight during follow-up, but a slight increase in CD4/CD8 ratio (p = 0.02). In conclusion, our findings suggest that B/F/TAF administered 5 or 4 days a week could maintain the control of HIV replication in virologically suppressed PLHIV while reducing cumulative exposition of ART.

Adherence to and effectiveness of highly active antiretroviral treatment for HIV infection: assessing the bidirectional relationship.

BACKGROUND: It is well established that high adherence to HIV-infected patients on highly active antiretroviral treatment (HAART) is a major determinant of virological and immunologic success. Furthermore, psychosocial research has identified a wide range of adherence factors including patients' subjective beliefs about the effectiveness of HAART. Current statistical approaches, mainly based on the separate identification either of factors associated with treatment effectiveness or of those associated with adherence, fail to properly explore the true relationship between adherence and treatment effectiveness. Adherence behavior may be influenced not only by perceived benefits-which are usually the focus of related studies-but also by objective treatment benefits reflected in biological outcomes. METHODS: Our objective was to assess the bidirectional relationship between adherence and response to treatment among patients enrolled in the ANRS CO8 APROCO-COPILOTE study. We compared a conventional statistical approach based on the separate estimations of an adherence and an effectiveness equation to an econometric approach using a 2-equation simultaneous system based on the same 2 equations. RESULTS: Our results highlight a reciprocal relationship between adherence and treatment effectiveness. After controlling for endogeneity, adherence was positively associated with treatment effectiveness. Furthermore, CD4 count gain after baseline was found to have a positive significant effect on adherence at each observation period. This immunologic parameter was not significant when the adherence equation was estimated separately. In the 2-equation model, the covariances between disturbances of both equations were found to be significant, thus confirming the statistical appropriacy of studying adherence and treatment effectiveness jointly. CONCLUSIONS: Our results, which suggest that positive biological results arising as a result of high adherence levels, in turn reinforce continued adherence and strengthen the argument that patients who do not experience rapid improvement in their immunologic and clinical statuses after HAART initiation should be prioritized when developing adherence support interventions. Furthermore, they invalidate the hypothesis that HAART leads to "false reassurance" among HIV-infected patients.

Poppers, by Inducing HHV-8 Virion Production, Can Act as a Promoter for HHV-8 Transmission in Men Who Have Sex With Men.

Environmental factors were reported to increase the risk of human herpesvirus 8 (HHV-8) transmission. In a population of men who have sex with men (MSM), we found evidence that chemsex was associated with human herpesvirus 8 seropositivity in vivo and that poppers induced HHV-8 virion production in vitro. Our finding may explain the higher HHV-8 transmission in MSM.

Raltegravir has no residual antiviral activity in vivo against HIV-1 with resistance-associated mutations to this drug.

OBJECTIVES: Emergence of major resistance mutations has already been associated with raltegravir regimen failure. Because of few remaining therapeutic options, the maintenance of raltegravir in the salvage regimen is often considered despite the risk of worsening resistance to integrase inhibitors. We determined whether raltegravir retains residual antiretroviral activity in vivo against viruses harbouring raltegravir mutations, and thus whether the drug can contribute to the subsequent regimen. METHODS: This retrospective observational study reports the changes in the viral load (VL) after the withdrawal of raltegravir from patients carrying virus with resistance mutations. We selected patients under stable treatment and with stable VL during at least the previous 2 months before the withdrawal. RESULTS: Five patients (A-E) were selected. The median changes in VL and CD4 counts at the end of the raltegravir interruption were -0.04 log copies/mL (range, -0.20 to +0.19) and +58 cells/mm(3) (range, -56 to +252), respectively. CONCLUSIONS: All VL changes were well below the clinically relevant variation of 0.5 log copies/mL at the end of the interruption. Thus, this study indicates that, for viruses harbouring one of the two main resistance pathways described for raltegravir, no relevant antiviral activity seems to persist in vivo. Even if further observations would be useful to reinforce this conclusion, the cost/benefit and risk/benefit of maintaining raltegravir as part of a salvage regimen in the presence of raltegravir mutations seem debatable, especially in the absence of relevant antiretroviral activity in this context.

Bariatric surgery in HIV patients: experience of an Obesity Reference Center in France.

BACKGROUND: Few data on bariatric surgery are available regarding obese human immunodeficiency virus (HIV)-infected patients. SETTINGS: Antoine Beclere hospital, Clamart, Paris-sud University, France METHODS: Prospective observational follow-up study recruited HIV-infected patients who underwent bariatric surgery from 2009 to 2015. Baseline demographic characteristics, surgery characteristics, perioperative outcomes, changes in weight loss, HIV markers, antiretroviral drug plasma levels are described. RESULTS: There were 10 patients followed before and after sleeve gastrectomy: 2 men and 8 women; 50% of African origin; median age, 48.5 years, median time since HIV infection, 7.5 years; median body mass index, 48.5 kg/m2. Of patients, 8 had co-morbidities. All except 2 patients received antiretroviral drugs at the time of surgery with a median CD4 cell count at 709/mm3. There was no death or postoperative infectious complications. The median follow-up was 18 months (range, 15-55). The median postoperative weight loss was 43 kg (range, 17-83). Median percentage of excess weight loss was 82.5% (range, 35-119) at the latest visit after surgery. All co-morbidities were resolutive with weight loss. We observed no significant modification of CD4 cell count before and after surgery. Pharmacokinetics of antiretroviral drugs remains adequate and efficacious. CONCLUSION: Our prospective series is the largest one on sleeve gastrectomy procedures performed on obese-treated HIV-infected patients. The sleeve generates good results in weight loss, with no significant impact on HIV infection, and with improvement of obesity-associated co-morbidities. Optimal management of HIV-infected patients with morbid obesity may include classical surgical procedures.

No benefit of a structured treatment interruption based on genotypic resistance in heavily pretreated HIV-infected patients.

OBJECTIVE: To evaluate the potential benefits of a tailored antiretroviral treatment interruption with duration based on the observed reversion of resistance mutations. METHODS: In this open single-arm pilot study, 23 patients with multiple treatment failure interrupted therapy and underwent longitudinal genotypic resistance testing. Salvage gigatherapy was started when resistance mutations to at least two antiretroviral drug classes reverted. The primary endpoint was a fall in viral load by > 1 log10 copies/ml after 12 weeks of salvage therapy. RESULTS: Baseline median viral load was 5.14 log copies/ml and CD4 cell count 43 x 10 cells/l. Genotypic resistance testing showed a median of six, two and nine resistance mutations to nucleoside analogue reverse transcriptase inhibitors, non-nucleoside analogue reverse transcriptase inhibitors and protease inhibitors, respectively; viral strains were susceptible to no more than one drug in 17/23 patients. The median duration of treatment interruption was 24 weeks (range, 12-37), leading to median changes from baseline of + 0.54 log10 copies/ml and -30 x 10(6) cells/l. At the end of treatment interruption, plasma HIV was susceptible to at least three drugs in 16/23 patients. After 12 weeks of salvage multitherapy, only one patient had a decrease in viral load > 1 log copies/ml. All baseline resistance mutations recurred after treatment resumption. AIDS-defining events occurred in two-thirds of patients during the study period. CONCLUSION: In HIV-infected patients with multiple failures and no therapeutic options at baseline, significant reversion of resistance mutations after prolonged treatment interruption failed to restore antiviral efficacy of a salvage regimen and was clinically deleterious.