Questioning the "Ease" in disease: Was living with HIV a burden or boost during the first wave of Covid-19 in France? A qualitative study (COVIDHIV).

INTRODUCTION: Clinical research has focused on risk factors and treatment for severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), particularly in people with a comorbidity including the human immunodeficiency virus (HIV), but little attention has been paid to the care pathway. This article aims to show how living with HIV may have been a biopsychosocial burden or boost in care pathways for Covid-19. METHOD: People living with HIV (PLHIV) from 9 clinical centers were invited to participate in this qualitative study. The sampling was purposive with a maximum variation in their sociodemographic profiles. Semi-structured interviews were conducted until data saturation, then coded for thematic analysis, using an inductive general approach. RESULTS: We interviewed 34 PLHIV of which 20 had SARS-COV-2 once. They were 24 males, 26 born in France; median age: 55. Twenty had a CD4 number above 500, and all were on antiretroviral therapy (ART). HIV appeared as a burden when Covid-19 symptoms reminded HIV seroconversion, fear of contamination, and triggered questions about ART effectiveness. HIV was not considered relevant when diagnosing Covid-19, caused fear of disclosure when participants sought SARS-COV-2 testing, and its care in hospitals was disrupted by the pandemic. ART-pill fatigue caused avoidance for Covid-19 treatment. As a boost, living with HIV led participants to observe symptoms, to get advice from healthcare professionals, and screening access through them. Some participants could accept the result of screening or a clinical diagnosis out of resilience. Some could consider ART or another drug prescribed by their HIV specialist help them to recover from Covid-19. CONCLUSION: Living with HIV could function as a burden and/or a boost in the care pathways for Covid-19, according to patients' relationship to their HIV history, comorbidities and representation of ART. Covid-19 in PLHIV needs further qualitative study to gain a more comprehensive assessment of the pandemic's consequences on their lives and coping strategies.

Mortality and comorbidities in a Nationwide cohort of HIV-infected adults: comparison to a matched non-HIV adults' cohort, France, 2006-18.

BACKGROUND: Human immunodeficiency virus (HIV) remains a significant cause of morbidity and mortality worldwide. The aim of this study was to describe the mortality rate and associated comorbidities in a nationwide population-based cohort of persons living with HIV (PLWHIV) and to compare it with mortality in an age and gender-matched cohort of non-HIV individuals in France. METHODS: Using data from the French national health data system, we identified and included 173 712 PLWHIV (66.5% men) and 173 712 non-HIV participants (66.5% men) matched for age and gender. PLHIV were identified based on ICD-10 HIV diagnoses, HIV-specific laboratory tests, and/or prescriptions for antiretroviral therapy specific to HIV. Hazard ratios (HRs) of mortality were assessed using multiple Cox regression models. RESULTS: During the 13 years of follow-up (2006-18), we observed 20 018 deaths among PLWHIV compared with 6262 deaths among non-HIV participants (11.52% vs. 3.60%, P < 0.001). The over-mortality of PLWHIV was expressed by univariable HR = 2.135 (2.072-2.199), which remained significant after adjustment for region, Complementary Universal Health Insurance and AME, with multivariable HR = 2.182 (2.118-2.248). The results remained significant after adjusting for comorbidities, including infectious diseases [HR = 1.587 (1.538-1.638)]. Notably, PLWHIV were more importantly associated with mortality in women [HR = 2.966 (2.767-3.180)], compared in men [HR = 1.961 (1.898-2.027)]. CONCLUSION: Although the life expectancy of PLWHIV has globally increased, the causes of death should be prioritized in prevention policies and care management. Gender-specific policies should be highlighted, as we observed a higher impact of HIV mortality in women.

Comparison of the Alinity M STI with the GeneXpert CT/NG for the detection of sexually transmitted microorganisms.

We assess the performances of the Alinity M STI assay (Abbott Molecular) in comparison to the Xpert CT/NG assay (Cepheid). We first retrospectively used a collection of 70 frozen samples of which 33, 31, and 6 were positives for Chlamydia trachomatis (CT), Neisseria gonorrhoea (NG), and both micro-organisms respectively. The Alinity M STI and the Xpert CT/NG results were in accordance for all. The mean difference in cycle threshold values between the Xpert CT/NG and the Alinity M STI were -1.6 and 0.0 for CT and NG respectively. Then 214 fresh samples collected from 121 patients were prospectively tested with both instruments. Anal swabs, throat swabs, vaginal swabs, and urines accounted each for about 25%. Seven (3.2%) samples of which 5 anal swabs, provided inconclusive results with the Alinity M STI. In conclusion, the Alinity M STI is an accurate device for the microbiological diagnosis of NG and CT infections.

Monkeypox Virus Infection in 18-Year-Old Woman after Sexual Intercourse, France, September 2022.

A monkeypox virus outbreak has spread worldwide since April 2022. We report a young woman in France positive for monkeypox virus transmitted through oral and vaginal sex. Ulceronecrotic lesions developed intravaginally and around her vulva. Health professionals should become familiar with all aspects of infection from this virus, including possible vertical transmission.

Prevalence of post-acute coronavirus disease 2019 symptoms twelve months after hospitalization in participants retained in follow-up: analyses stratified by gender from a large prospective cohort.

OBJECTIVES: Persistent post-acute coronavirus disease 2019 (COVID-19) symptoms (PACSs) have been reported up to 6 months after hospital discharge. Herein we assessed the symptoms that persisted 12 months (M12) after admission for COVID-19 in the longitudinal prospective national French coronavirus disease cohort. METHODS: Hospitalized patients with a confirmed virological diagnosis of COVID-19 were enrolled. Follow-up was planned until M12 after admission. Associations between persistence of ≥3 PACSs at M12 and clinical characteristics at admission were assessed through logistic regression according to gender. RESULTS: We focused on participants enrolled between 24 January 2020 and 15 July 2020, to allow M12 follow-up. The M12 data were available for 737 participants. Median age was 61 years, 475 (64%) were men and 242/647 (37%) were admitted to intensive care units during the acute phase. At M12, 27% (194/710) of the participants had ≥3 persistent PACS, mostly fatigue, dyspnoea and joint pain. Among those who had a professional occupation before the acute phase, 91 out of 339 (27%) were still on sick leave at M12. Presence of ≥3 persistent PACS was associated with female gender, both anxiety and depression, impaired health-related quality of life and Medical Muscle Research Council Scale <57. Compared with men, women more often reported presence of ≥3 persistent PACSs (98/253, 39% vs. 96/457, 21%), depression and anxiety (18/152, 12% vs. 17/268, 6% and 33/156, 21% vs. 26/264, 10%, respectively), impaired physical health-related quality of life (76/141, 54% vs. 120/261, 46%). Women had less often returned to work than men (77/116, 66% vs. 171/223, 77%). CONCLUSIONS: One fourth of the individuals admitted to hospital for COVID-19 still had ≥3 persistent PACSs at M12 post-discharge. Women reported more often ≥3 persistent PACSs, suffered more from anxiety and depression and had less often returned to work than men.

Risk Prediction Score for Screening Asymptomatic Sexually Transmitted Infections in HIV-positive French Men Who Have Sex with Men (ANRS 9520 DRIVER).

OBJECTIVES: Asymptomatic sexually transmitted infections (STI) are frequent among men who have sex with men (MSM). Identifying asymptomatic STIs is a crucial issue, not only for secondary but also for primary prevention, as early treatment can reduce transmission risk. We aimed to develop a self-reported predictive score for early identification of asymptomatic STIs. METHODS: Participants provided clinical data and completed a self-administered questionnaire including sociodemographic variables and behaviors during the 6 previous months. We used multivariable logistic regression to identify factors associated with asymptomatic STIs. We calculated the accuracy of the model by the non-parametric area (AUC) under the receiver-operating-characteristic (ROC) curve to find the optimal discriminant threshold for screening. RESULTS: A total of 781 HIV-positive MSM were included with a mean age of 46.8 years. Asymptomatic STI prevalence was 13.2%. Detectable plasma HIV RNA (adjusted odds ratio (aOR [95% CI): 2.54 [1.23;5.25]), inconsistent condom use during anal sex (2.20 [1.36;3.56]), group sex (2.00 [1.15;3.45]), during or-genital practices (1.83 [1.12;3.01]), not being in stable relationship (1.70 [1.01;2.66] and an item from a sensation-seeking behavioral scale "I don't like watching porn videos" (1.61 [1.01;2.59] were associated with asymptomatic STI. AUC was 0.7 and with optimal threshold of 0.1082 for this model; sensitivity was 80.4%. Self-reported asymptomatic STI predictive score was built with this threshold according to the 6 factors in the final model. CONCLUSIONS: As this predictive score is not designed to be diagnostic, but to provide indications for diagnostic tests, its ease of administration and sensitivity remain the most important features. Its use in clinical practice for early detection of asymptomatic STIs potentially can reinforce STI primary and secondary prevention.

Monkeypox Vaccine Hesitancy in French Men Having Sex with Men with PrEP or Living with HIV in France.

People with pre-exposure prophylaxis (PrEP) or living with HIV are a high-risk population for monkeypox virus (MPXV) infection. It is important to achieve high MPXV vaccination coverage rates in this group. This project used self-reporting to assess vaccine hesitancy for the smallpox vaccine and acceptance among men having sex with men with PrEP or living with HIV. In total, 52 (33.6%) participants among the 155 declared their hesitancy to be vaccinated against MPXV. Moreover, 20.7% patients with PrEP declared a hesitant attitude towards the smallpox vaccine compared to 40.2% of the HIV patients, p = 0.013. This difference remained not significant after adjustment for age (p = 0.119) and after adjustment for both age and number of different sexual partners (p = 0.406). Among PrEP people, those who expressed concerns about people getting more vaccines than needed (p = 0.012) were less likely to accept vaccination, whereas an increased number of different sexual partners during the previous month was significantly associated with acceptance of vaccination (p = 0.034). Among HIV people, those who expressed concerns about being infected by MPXV (p < 0.001), those who expressed that the smallpox vaccine should be compulsory for people at risk (p < 0.001) and those with an increased the number of different sexual partners the previous month (p = 0.018) were significantly associated with higher acceptance of MPXV vaccination. Our results suggest that vaccine strategy would be efficient in France with a communication strategy emphasizing the benefits of vaccination and the potential MPXV risk infection for health in PrEP and HIV people. Other preventive actions should be implemented, including reduction in sexual partners.

The COVID-19 Pandemic and the Migrant Population for HIV Diagnosis and Care Follow-Up: They Are Left Behind.

The coronavirus 2019 (COVID-19) pandemic has posed numerous worldwide challenges. The level of social vulnerability of the migrant population is disproportionately higher than other populations. Recent reports have shown that the access to care for the migrant population (i.e., non-French nationality patients) were greatly impacted during this pandemic. Thus, we would like to highlight the significant impact of the COVID-19 pandemic on care follow-up in those migrant people infected with HIV who receive HIV care in France. Two groups of patients were defined: that is, patients with continuous care and patients with a loss of follow-up of at least one year during the COVID-19 pandemic. Among 672 HIV patients, 19 (2.7%) patients were lost to follow-up for at least one year during the COVID-19 pandemic. We found no significant difference for gender (p = 0.332) or age (p = 0.115) between the two groups. However, patients with a loss of follow-up were mainly migrants rather than from the other group (p < 0.001), and the same results were observed for the nation of birth (89.5% vs. 44%, p < 0.001). In our hospital, most of the patients who were living abroad but had HIV care in France before the COVID epidemic (mainly retired migrants) were lost to follow-up during the COVID-19 pandemic. To date, most of them have not resumed HIV care in France and we do not know their present situation. We can only observe that the COVID-19 pandemic has predominately disrupted the HIV care of migrant populations. Do not let them be left behind!

Electronic medical record alert increases HIV screening rates: the Foch hospital pilot POP-up project.

BACKGROUND: Despite significant national human immunodeficiency virus (HIV) screening activity, there are persistent delays in screening, and many missed diagnostic opportunities. To facilitate targeted screening, an electronic medical record (EMR) alert reminder was applied in the Foch hospital. Screening rates after implementation were reported. METHODS: A prospective cohort analysis was performed in Foch Hospital between 24 April 2018 and 4 October 2019 among hospitalized patients born in high HIV prevalence countries and/or having social vulnerability criteria (universal health coverage). From the admissions software, when specific low health coverage was provided and/or high-prevalence country of birth was registered, an electronic alert (EMR alert) appeared on the ward where the patient was hospitalized. The EMR alert database was examined for HIV screening and activity responses from each service of the Hospital. RESULTS: Eight thousand one hundred eighty-one alerts were recovered during the period for 1448 patients. 27 services used the EMR alert. Most of the alerts were directly closed (74.4%), 14.5% of the alerts were closed due to doctors declaring that they did not have time to respond. 297 (3.6%) of the 8181 alerts resulted in a prescription of HIV serology corresponding for 20.5% of the patients. CONCLUSION: EMR alert can help to increase the rate of HIV screening in hospital care practice. Through this EMR alert system, HIV screening can be implemented as a common practice like any other medical alternative. Future research should examine the factors influencing physicians' attitudes to this alert system to improve the HIV screening rate.

To what extent do people living with HIV, people on pre-exposure prophylaxis, doctors and pharmacists endorse 90-day dispensing of antiretroviral therapy in France?

JUSTIFICATION: The WHO 95-95-95 targets for 2030 do not imply that people living with HIV (PLHIV) achieve a good quality of life. The current 30-day dispensing interval for antiretroviral (ART) burdens the healthcare system. Lengthening dispensing intervals could alleviate this burden as well as enhance patient well-being. OBJECTIVES: To capture perceptions on 90-day dispensing interval (90D) for ART from the perspective of PLHIV, people on pre-exposure prophylaxis (PrEP), doctors, and pharmacists. METHODS: Multi-centre observational survey led in France from 16 to 20 October 2020, among doctors agreeing to participate via regional coordinated care organisations for HIV, all PLHIV or people on PrEP consulting these outpatient-clinic doctors, and pharmacists doing ART dispensing. RESULTS: The survey was completed by 220 doctors who saw 1087 people (999 PLHIV; 88 on PrEP) and 176 pharmacists from 55 centres. Among the PLHIV, 855 (85.6%, 95% CI: 83.2%-87.7%) and among the patients on PrEP, 70 (79.5%, 95% CI: 69.6%-87.4%) stated they would be interested in 90D. All in all, patients who were more likely to endorse 90D are those who opt exclusively for hospital dispensing (OR 3.22 [1.57-6.58]) and who rotate between hospital and community pharmacy dispensing (OR 3.29 [1.15-9.32]). Patients who were less likely to endorse 90-D were those who consult in a city located outside the 3 French high HIV prevalence regions (OR 0.66 [0.44-0.99]), receive 2 vs 1 pill QD regimens (OR 0.53 [0.31-0.91]), and anticipate at least one vs no limitation to 90D (OR 0.27 [0.17-0.42]). 90D was perceived as possible by 152 pharmacists (86.4%), including 8 (5%) without restriction, and 219 doctors (99.6%), including 42 (19.2%) regardless of PLHIV's immunovirologic status or social conditions (health insurance coverage, access to housing or accommodation, access to rights, resources). Comparison of the benefits and limitations of a 90-day ART dispensing interval as perceived by PLHIV and people on PrEP, doctors and pharmacists shows that doctors anticipate a higher number of benefits than people on ART and/or pharmacists, chiefly that 90D would be more convenient and create less risk of drug shortages and that patients would gain autonomy and a better quality of life. Pharmacists were found to clearly perceive the economic benefits (90D would be less expensive) but anticipate more drawbacks than doctors and the people on ART themselves: more administrative burdens, more non-dispensing if doses get lost, harder to track adherence and more drug-drug interaction issues, and more work as they shall have to warn the patient of potential risks of shortages due to the cost of the stock. CONCLUSION: A clear majority of PLHIV, people on PrEP, doctors, and pharmacists endorsed 90D of ART. Most patients thought that 90D would be a good option, whereas most pharmacists and doctors thought that eligibility for 90D dispensing should depend on immunovirologic factors and social condition criteria. Moreover, pharmacists thought it would be necessary to commit regulatory resources and a better follow-up on adherence and drug-drug interactions.

HCV cure: an appropriate moment to reduce cannabis use in people living with HIV? (ANRS CO13 HEPAVIH data).

BACKGROUND: Thanks to direct-acting antivirals, hepatitis C virus (HCV) infection can be cured, with similar rates in HCV-infected and HIV-HCV co-infected patients. HCV cure is likely to foster behavioral changes in psychoactive substance use, which is highly prevalent in people living with HIV (PLWH). Cannabis is one substance that is very commonly used by PLWH, sometimes for therapeutic purposes. We aimed to identify correlates of cannabis use reduction following HCV cure in HIV-HCV co-infected cannabis users and to characterize persons who reduced their use. METHODS: We used data collected on HCV-cured cannabis users in a cross-sectional survey nested in the ANRS CO13 HEPAVIH cohort of HIV-HCV co-infected patients, to perform logistic regression, with post-HCV cure cannabis reduction as the outcome, and socio-behavioral characteristics as potential correlates. We also characterized the study sample by comparing post-cure substance use behaviors between those who reduced their cannabis use and those who did not. RESULTS: Among 140 HIV-infected cannabis users, 50 and 5 had reduced and increased their use, respectively, while 85 had not changed their use since HCV cure. Cannabis use reduction was significantly associated with tobacco use reduction, a decrease in fatigue level, paying more attention to one's dietary habits since HCV cure, and pre-HCV cure alcohol abstinence (p = 0.063 for alcohol use reduction). CONCLUSIONS: Among PLWH using cannabis, post-HCV cure cannabis reduction was associated with tobacco use reduction, improved well-being, and adoption of healthy behaviors. The management of addictive behaviors should therefore be encouraged during HCV treatment.

Low CCR5 expression protects HIV-specific CD4+ T cells of elite controllers from viral entry.

HIV elite controllers maintain a population of CD4 + T cells endowed with high avidity for Gag antigens and potent effector functions. How these HIV-specific cells avoid infection and depletion upon encounter with the virus remains incompletely understood. Ex vivo characterization of single Gag-specific CD4 + T cells reveals an advanced Th1 differentiation pattern in controllers, except for the CCR5 marker, which is downregulated compared to specific cells of treated patients. Accordingly, controller specific CD4 + T cells show decreased susceptibility to CCR5-dependent HIV entry. Two controllers carried biallelic mutations impairing CCR5 surface expression, indicating that in rare cases CCR5 downregulation can have a direct genetic cause. Increased expression of ß-chemokine ligands upon high-avidity antigen/TCR interactions contributes to autocrine CCR5 downregulation in controllers without CCR5 mutations. These findings suggest that genetic and functional regulation of the primary HIV coreceptor CCR5 play a key role in promoting natural HIV control.

An Immunogenicity Report for the Comparison between Heterologous and Homologous Prime-Boost Schedules with ChAdOx1-S and BNT162b2 Vaccines.

BACKGROUND: There is a small amount of immunological data on COVID-19 heterologous vaccination schedules in humans. We assessed the immunogenicity of BNT162b2 (Pfizer/BioNTech) administered as a second dose in healthcare workers primed with ChAdOx1-S (Vaxzevria, AstraZeneca). METHODS: 197 healthcare workers were included in a monocentric observational study in Foch hospital, France, between June and July 2021. The main outcome was the immunogenicity measured by serum SARS-CoV-2 IgG antibodies. RESULTS: 130 participants received the ChAdOx1-S/BNT vaccine and 67 received the BNT/BNT vaccine. The geometric mean of IgG antibodies was significantly higher in the BNT/BNT vaccine group compared to the ChAdOx1-S/BNT vaccine group, namely 10,734.9, 95% CI (9141.1-12,589.3) vs. 7268.6, 95% CI (6501.3-8128.3), respectively (p < 0.001). However, after adjustment for time duration between the prime and second vaccinations, no significant difference was observed (p = 0.181). A negative correlation between antibody levels and time duration between second dose and serology test was observed for the BNT/BNT vaccine (p < 0.001), which remained significant after adjustment for all covariates (p < 0.001), but not for the ChAdOx1-S/BNT vaccine (p = 0.467). CONCLUSIONS: Heterologous and homologous schedules of ChAdOx1-S and BNT vaccines present robust immune responses after the second vaccination. The results observed were equivalent after adjustment for covariates and emphasize the importance of flexibility in deploying mRNA and viral vectored vaccines. Nevertheless, applying the ChAdOx1-S schedule vaccination for the heterologous second dose of BNT was associated with decreased IgG antibody levels compared to the homologous BNT/BNT vaccination.

Direct, indirect and total effect of HIV coinfection on the risk of non-liver-related cancer in hepatitis C virus-infected patients treated by direct-acting antivirals: a mediation analysis.

OBJECTIVES: HIV-coinfected patients experience higher incidences of non-liver-related cancers than HCV-monoinfected patients. Chronic inflammation, immunosuppression, but also higher tobacco or alcohol consumption and metabolic dysregulation could explain this higher risk. We aimed to estimate the direct, indirect and total effects of HIV coinfection on the risk of non-liver-related cancers in HCV participants treated with direct-acting antivirals (DAAs). METHODS: Up to four HCV-monoinfected participants from the ANRS CO22 HEPATHER cohort were matched by age and sex to HIV/HCV-coinfected participants from the ANRS CO13 HEPAVIH cohort. Participants were followed from DAA initiation until the occurrence of a non-liver-related cancer. Counterfactual mediation analysis was carried out to estimate the direct (chronic inflammation and immunosuppression), indirect (tobacco and alcohol consumption and metabolic syndrome) and total effect of HIV coinfection on the risk of non-liver-related cancers. RESULTS: 548 HIV/HCV-coinfected and 2016 monoinfected participants were included. Overall, HIV coinfection was associated with a 3.7-fold [95% confidence interval (CI): 1.7-7.0] higher risk of non-liver-related cancers in HCV participants. This increased risk was explained by significant direct effect [hazard ratio (HR) = 3.4, 95% CI: 1.7-6.6] but not indirect effect (HR = 1.1, 95% CI: 0.8-1.5) of HIV coinfection. CONCLUSIONS: In HCV participants treated with DAAs, the direct effect of HIV coinfection, reflecting chronic inflammation and immunosuppression, was associated with a 3.7-fold higher risk of non-liver-related cancer. By contrast, the indirect effect of HIV coinfection, reflecting higher tobacco and alcohol consumption and metabolic dysregulation, was not significantly associated with the risk of non-liver-related cancers.