Incidence and factors associated with PrEP discontinuation in France.

OBJECTIVES: HIV pre-exposure prophylaxis (PrEP) is effective in preventing HIV, but some seroconversions occur due to poor adherence or PrEP discontinuation. Our objective was to estimate the incidence of PrEP discontinuation and describe the reasons and factors associated with discontinuations. METHODS: A retrospective cohort was conducted in three French hospitals between January 2016 and June 2022. PrEP users who attended at least twice within 6 months during study period were included and followed up until December 2022. The incidence rate of PrEP discontinuation was estimated by censoring lost to follow up individuals. Factors associated with PrEP discontinuations were identified using a multivariate Cox model. RESULTS: A total of 2785 PrEP users were included, with 94% men and 5% transgender people. Median age was 35 years. By December 2022, 653 users had stopped PrEP (24%). The incidence rate was 10.8 PrEP discontinuations for 100 person-years (PY). The main causes of discontinuation were being in a stable relationship (32%), and not judging the treatment useful anymore (12%). Individuals who discontinued PrEP were younger [<29, HR = 1.45 (1.17-1.80)], and more likely to be women [HR = 2.44 (1.50-3.96)] or sex workers [HR = 1.53 (0.96-2.44)]. They were more likely to report PrEP side effects [HR = 2.25 (1.83-2.77)] or ≥2 sexually transmitted infections [HR = 1.87 (1.53-2.27)] during the last year. CONCLUSION: The incidence of PrEP discontinuations was quite low compared to rates observed in other cohorts. Users who stopped PrEP were sometimes still exposed to HIV, emphasizing the need for targeted interventions to prepare and support PrEP discontinuations and limit seroconversion risk.

Proof of concept of a sexual health outreach program led by community health workers in homeless hostels in the greater Paris region.

Context: Homeless individuals face exacerbated risks of infectious diseases, including sexually transmitted infections (STIs). Programs led by Community Health Workers (CHWs) have demonstrated potential to enhance healthcare access for marginalized groups such as homeless families. This study aims to evaluate the feasibility and effectiveness of a novel CHW-based outreach program addressing sexual health issues among individuals residing in homeless hostels. Methods: Twelve social homeless hostels in the greater Paris region were selected as program implementation sites. An outreach program was developed consisting of two interventions: sexual health workshops and STI screening sessions (HIV and hepatitis B and C) accompanied by individual interviews, both conducted by CHWs within each hostel over an 8-week period and scheduled weekly. Feasibility, participation and engagement were evaluated using complementary methods including qualitative field observations, semi-structured interviews and focus groups with CHWs, satisfaction questionnaires for participants, and quantitative outcome data collection of each intervention. Results: A total of 80 program activities (workshops and screening sessions) were conducted. Among the participants, 542 women and 30 men engaged in workshops. During the 30 Rapid Diagnostic Testing sessions, 150 individuals underwent testing for HIV, hepatitis B, and/or hepatitis C. Positivity rates were 6.7% for hepatitis B and 0.9% for hepatitis C. No HIV infections were detected. Participant satisfaction rates were consistently high (>76%) across workshops. Qualitative analysis unveiled two critical axes influencing program feasibility and effectiveness: program organization and CHW involvement. Discussion: This assessment of the program highlights its feasibility among a population that is difficult to reach through conventional healthcare efforts. The intervention's potential effectiveness is suggested by self- and CHW-reported improvements in sexual health literacy and high rates of referral to the healthcare system, as well as holistic well-being considerations. CHW involvement is a vital determinant of program success, as are robust coordination among stakeholders, deep understanding of the target population, and strong partner engagement. Conclusion: This outreach program amplifies the voices of often-overlooked populations while empowering them to navigate health and social challenges. Although these workshops serve as lifelines for those frequently excluded from mainstream services, long-term improvements to the health and wellbeing of homeless populations will necessitate systemic governmental intervention.

Contribution of Clinical Metagenomics to the Diagnosis of Bone and Joint Infections.

Bone and joint infections (BJIs) are complex infections that require precise microbiological documentation to optimize antibiotic therapy. Currently, diagnosis is based on microbiological culture, sometimes complemented by amplification and sequencing of the 16S rDNA gene. Clinical metagenomics (CMg), that is, the sequencing of the entire nucleic acids in a sample, was previously shown to identify bacteria not detected by conventional methods, but its actual contribution to the diagnosis remains to be assessed, especially with regard to 16S rDNA sequencing. In the present study, we tested the performance of CMg in 34 patients (94 samples) with suspected BJIs, as compared to culture and 16S rDNA sequencing. A total of 94 samples from 34 patients with suspicion of BJIs, recruited from two sites, were analyzed by (i) conventional culture, (ii) 16S rDNA sequencing (Sanger method), and (iii) CMg (Illumina Technology). Two negative controls were also sequenced by CMg for contamination assessment. Based on the sequencing results of negative controls, 414 out of 539 (76.7%) bacterial species detected by CMg were considered as contaminants and 125 (23.2%) as truly present. For monomicrobial infections (13 patients), the sensitivity of CMg was 83.3% as compared to culture, and 100% as compared to 16S rDNA. For polymicrobial infections (13 patients), the sensitivity of CMg was 50% compared to culture, and 100% compared to 16S rDNA. For samples negative in culture (8 patients, 21 samples), CMg detected 11 bacteria in 10 samples from 5 different patients. In 5/34 patients, CMg brought a microbiological diagnosis where conventional methods failed, and in 16/34 patients, CMg provided additional information. Finally, 99 antibiotic resistance genes were detected in 24 patients (56 samples). Provided sufficient genome coverage (87.5%), a correct inference of antibiotic susceptibility was achieved in 8/8 bacteria (100%). In conclusion, our study demonstrated that the CMg provides complementary and potentially valuable data to conventional methods of BJIs diagnosis.

Pre-exposure HIV prophylaxis (PrEP) among transgender women: 3 years of follow-up in a university hospital in Paris.

OBJECTIVES: The principal outcome was to describe clinical characteristics of a transgender male-to-female (TGW) cohort followed for pre-exposure HIV prophylaxis (PrEP). INTRODUCTION: Few efforts and preventive interventions have targeted transgender population, despite them being at great risk of HIV infection. METHODS: This was a retrospective transgender male-to-female (TGW) cohort followed for PrEP at Bichat Hospital Sexual Health Clinic between February 2016 and January 2019.The principal outcome was to describe clinical characteristics of this TGW population: modalities of PrEP uptake, treatment adherence and tolerance, sanitary system retention, hormonal therapy and STIs.Data about age, ethnicity, language, sex work and sanitary healthcare insurance coverage were also collected. RESULTS: Forty-nine TGW were included, with a median age of 33 years; 43/49 (87.7%) were from South America and 43/49 (87.7%) were sex workers. Forty-four 44/49 TGW (89.7%) had no regular healthcare insurance coverage. Nineteen out of 49 (38.7%) had a history of STI in the last 12 months. Hormone intake was reported in 16/49 (32.60%). PrEP with oral TDF/FTC was prescribed on a daily basis for 45/49 TG (91.8%). Two TGW discontinued PrEP for gastrointestinal intolerance. No case of renal toxicity or HIV seroconversion has been reported. Retention rate was high (71.4%), but average follow-up was 9 months. CONCLUSIONS: Our data showed a very vulnerable population, with a high proportion of migrants, sex workers and with a low healthcare insurance coverage. Retention rate was high (71.4%). Further multi-component interventions are needed to improve global sex health approach, PreP follow-up and sanitary system retention among TGW population.

SARS-COV2 infection in 30 HIV-infected patients followed-up in a French University Hospital.

INTRODUCTION: An acute respiratory disease caused by a novel coronavirus (SARSCOV2) is spreading from China since January 2020. Surprisingly, few cases of Covid-19 have been reported in people living with HIV (PLWHIV). METHODS: Here we present a series of 30 PLWHIV diagnosed for SARS-COV2 infection. The principal outcome was to describe clinical characteristics of this population. RESULTS: Eighteen (60%) patients were men, 10/30 (33,3%) women and 2/30 (6,7%) transgender women. Median age was 53,7 years (range 30-80 years) and 23/30 patients (76,7%) were born in a foreign country (out of France). The most common comorbidities were cardiovascular disease (11/30, 36,7%), hypertension (11/30, 36,7%), diabetes (9/30,30%) obesity (7/30, 23%) and chronic renal disease (5/30, 16,7%). Twenty (66,7%) patients presented overweight. Five patients (16,7%) had a Charlson comorbidity (Quan et al., 2011) score ≥3. Twenty-seven (90%) patients were virologically suppressed.CD4 count was >500cell/mm 3 in 23/30 (76,6%) patients. An antiviral treatment for SARS-COV2 was administered, in addition to HIV treatment, in 5/30 patients (16,3%). Twenty-four patients (80%) recovered from covid-19, 3/30 (10%) required invasive mechanical ventilation, 2/30 (6,7%) patients died and 4/30 (13,3%) patients were still hospitalized. CONCLUSIONS: Most of the patients were virologically suppressed with CD4>500 mm3. Risk factors were the same as those described in other SARS-COV2 series, suggesting that HIV infection is probably not an independent risk factor for covid-19.

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.

High virological suppression regardless of the genotypic susceptibility score after switching to a dolutegravir-based regimen: week 48 results in an observational cohort.

Objectives: To assess, in a clinical cohort, the efficacy of switching current ART in virologically suppressed patients to a dolutegravir-based regimen, regardless of the genotypic susceptibility score (GSS). Patients and methods: This was an observational single-centre study assessing ART-treated patients with plasma viral load (pVL) <50 copies/mL who were switched to a dolutegravir-based regimen with 1 year of follow-up. PCR negative was defined as an undetected PCR signal. Trough plasma concentration (C24) was determined using UPLC-MS/MS. Results: Two hundred and thirty-nine patients initiated a dolutegravir-based regimen: 12%, 29% and 59% had a total GSS of 1 or 1.5 (group 1), 2 or 2.5 (group 2) and 3 (group 3), respectively. At switch initiation, the median time since first ART and the median duration with pVL <50 copies/mL were 13 years (IQR = 6-19) and 3 years (IQR = 1-6), respectively. Median times since last genotype were 9, 10 and 5 years for groups 1, 2 and 3, respectively. Twenty patients (8.4%) discontinued the dolutegravir-based regimen due to adverse events. During the study, 96.4% (n = 661/686) of all pVL were <50 copies/mL. Four patients (1.7%) experienced virological failure (two pVL >50 copies/mL) without emergence of resistance; these patients' GSSs were 2, 2.5, 3 and 3. The median dolutegravir C24 was 1545 ng/mL (IQR = 1150-2097). Of the patients with pVL <20 copies/mL, 72% were PCR negative during the follow-up, with no difference between the three groups of patients. Conclusions: This observational cohort study showed a high level of virological suppression maintenance in the first year following the switch to a dolutegravir-based regimen, even in patients with GSS ≤2.

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.

Getting pregnant in HIV clinical trials: women's choice and safety needs. The experience from the ANRS12169-2LADY and ANRS12286-MOBIDIP trials.

INTRODUCTION: Pregnancy is an exclusion criteria in most clinical trials involving antiretroviral therapy (ART) and modern contraception methods are systematically proposed to women of childbearing age. Nevertheless pregnancies are often observed. Reproductive choices during clinical trials should be understood to adapt interventions to the level of risk for mother and baby safety. Our goal was to describe the reproductive behavior and pregnancy outcomes among HIV-infected women on second-line antiretroviral treatment enrolled in two clinical trials and to compare them with those of HIV-positive women in non-research settings. METHODS: The number and outcomes of pregnancies were recorded among 281 non menopausal women enrolled in the ANRS 12169-2LADY and ANRS 12286-MOBIDIP clinical trials in Cameroon, Senegal and Burkina Faso. All participants had agreed to use a least one contraceptive method (barrier or non-barrier) which was provided for free during the study. Data were collected through revision of pregnancy notification forms and by data extraction from the study database, regularly updated and checked during the study. RESULTS: Sixty-six women had 84 pregnancies between January 2010 and July 2015 resulting in a pregnancy rate of 8.0 per 100 women-years (WY) (95% CI 6.5-9.9) which is similar to the ones observed in cohort studies in Sub-Saharan Africa (varying from 2.5 to 9.4 pregnancies per 100 WY). Among 60 live births, 10 (16.6%) were born prematurely and 9 (15%) had a low birth weight. Sixteen miscarriages/stillbirths occurred (19.5%). This percentage is comparable to the one expected in the seronegative population which is reassuring for HIV-positive women considering pregnancy on ART. Only one minor birth defect was diagnosed. In univariate and multivariate analysis, miscarriages/stillbirths were not associated either with age, nadir of CD4 count, duration of ART, CD4 count, or viral load at the beginning of pregnancy. CONCLUSION: HIV-positive women participating in clinical trials conducted in Sub-Saharan Africa tend to get pregnant as often as seropositive women who received medical care in non-research settings. It is therefore essential to adopt a pragmatic approach by re-evaluating the relevance of the criteria for exclusion of pregnant women according to the risk associated with exposure and to seek more effective and innovating contraceptive strategies when using potentially teratogenic molecules.

Incidence of infectious morbidity events after second-line antiretroviral therapy initiation in HIV-infected adults in Yaoundé, Cameroon.

BACKGROUND: Since antiretroviral therapy (ART), HIV-infected individuals experience mainly non-AIDS-related conditions, among which infectious events are prominent. We aimed to estimate incidence and describe overall spectrum of infectious events, including all grade events, among HIV-1-infected adults failing first-line ART in Yaoundé, Cameroon. METHODS: All patients from Cameroon enrolled in the second-line ART 2LADY trial (ANRS12169) were included in this secondary analysis. Medical files were reviewed with predefined criteria for diagnosis assessment. Incidence rates (IR) were estimated per 100 person-years (% PY). RESULTS: A total of 302 adult patients contributing 840 PY experienced 596 infectious events (IR 71% PY). Only 29 (5%) events were graded as severe. Most frequent infections were upper respiratory tract infections (15% PY), diarrhoea (9% PY) and malaria (9% PY). A total of 369 (62%) infections occurred during the first year (IR 130% PY) followed by a persistent lower incidence during the following 3 years. Higher IR were observed in patients with CD4+ T-cell count <200 cells/mm3 for all infectious events except for mycobacterial and parasitic infections. IR of viral, bacterial and parasitic infectious events were lower in case of co-trimoxazole use in patients with CD4+ T-cell count <200 cells/mm3. CONCLUSIONS: Infectious events are common and mainly occur during the first year after treatment initiation. Second-line ART initiation had a positive impact on the entire spectrum of infectious morbidity.

Predictive value of liver enzymes and inflammatory biomarkers for the severity of liver fibrosis stage in HIV/HCV co-infected patients.

OBJECTIVE: The aim of our study was to assess a possible association between plasma inflammatory biomarkers (CRP, IL-6, soluble CD14) and the extent of fibrosis or cirrhosis using a FibroScan® in HIV/HCV co-infected patients. METHODS: This cross-sectional study assessed 60 HIV/HCV co-infected patients who had paired plasma samples and FibroScan® values available. All included patients were controlled for HIV infection (HIV-1 RNA <50 copies/mL) and had detectable HCV RNA levels. Levels of three biomarkers were measured in all samples using commercial ELISA kits. Multivariate logistic regression models identified factors associated with the METAVIR stages of fibrosis (F0-F2 vs. F3-F4). RESULTS: In univariate logistic regression analyses, in addition to sCD14 (odds ratio [OR] = 3.23, 95% confidence interval [95%CI] = 1.30-7.97, P = 0.01), aspartate aminotransferase (AST), alanine aminotransferase, platelet counts, and CD4 cell counts were associated with the stage of liver fibrosis and, thus, were introduced into the model. However, only AST (OR = 1.06, 95%CI = 1.02-1.10, P = 0.0009) was independently associated with F3-F4 stage liver fibrosis. CONCLUSIONS: In our study of HIV/HCV co-infected patients, sCD14 plasma level, a biomarker of monocyte activation, was not independently associated with the F3-F4 stage of liver fibrosis. We hypothesize that the higher levels of inflammation markers observed in HIV/HCV co-infected patients, compared to HCV mono-infected patients, prevent this association being observed within this population.