Epidemiological impact of Neisseria gonorrhoeae and Chlamydia trachomatis screening in men having sex with men: a modelling study.

OBJECTIVES: The impact of the systematic screening of Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) in men having sex with men (MSM) on these pathogens' epidemiology remains unclear. We conducted a modelling study to analyse this impact in French MSM. METHODS: We modelled NG and CT transmission using a site-specific deterministic compartmental model. We calibrated NG and CT prevalence at baseline using results from MSM enrolled in the Dat'AIDS cohort. The baseline scenario was based on 1 million MSM, 40 000 of whom were tested every 90 days and 960 000 every 200 days. Incidence rate ratios (IRRs) at steady state were simulated for NG, CT, NG and/or CT infections, for different combinations of tested sites, testing frequency and numbers of frequently tested patients. RESULTS: The observed prevalence rate was 11.0%, 10.5% and 19.1% for NG, CT and NG and/or CT infections. The baseline incidence rate was estimated at 138.2 per year per 100 individuals (/100PY), 86.8/100PY and 225.0/100PY for NG, CT and NG and/or CT infections. Systematically testing anal, pharyngeal and urethral sites at the same time reduced incidence by 14%, 23% and 18% (IRR: 0.86, 0.77 and 0.82) for NG, CT and NG and/or CT infections. Reducing the screening interval to 60 days in frequently tested patients reduced incidence by 20%, 29% and 24% (IRR: 0.80, 0.71 and 0.76) for NG, CT and NG and/or CT infections. Increasing the number of frequently tested patients to 200 000 reduced incidence by 29%, 40% and 33% (IRR: 0.71, 0.60 and 0.67) for NG, CT and NG and/or CT infections. No realistic scenario could decrease pathogens' incidence by more than 50%. CONCLUSIONS: To curb the epidemic of NG and CT in MSM, it would not only be necessary to drastically increase screening, but also to add other combined interventions.

Drastic Reduction in Time to Controlled Viral Load in People With Human Immunodeficiency Virus in France, 2009-2019: A Longitudinal Cohort Study.

BACKGROUND: Aspirational targets to end AIDS by 2030 include having 95% of people with human immunodeficiency virus (HIV; PWH) diagnosed, 95% treated, and 95% with controlled viral load (VL). Our objective was to describe, using a large French prospective cohort, the median transition times through the cascade of care between 2009 and 2019. METHODS: We analyzed patients whose first HIV diagnosis was made between 1 January 2009 and 31 December 2019. Using the Kaplan-Meier method, we estimated the time to linkage to care (from HIV diagnosis to first biological assessment), to treatment (date of first antiretroviral therapy [ART] prescription), and to controlled VL (first value <200 copies/mL). Analyses were disaggregated by time periods and patients' characteristics. Censoring date was 31 December 2021. RESULTS: Among the 16 864 patients linked to care since 2009, the median [Q1; Q3] time from HIV diagnosis to controlled VL decreased from 254 [127-745] to 73 [48-132] days in 2009-2011 and 2018-2019, respectively. Transition times from linkage to care to first ART decreased from 67 [17; 414] in 2009-2011 to 13 [5; 26] days in 2018-2019, and from ART to controlled VL from 83 [35; 130] in 2009-2011 to 38 [28; 90] days in 2018-2019. Differences were observed depending on patients' characteristics. CONCLUSIONS: We describe drastic reductions in transition time through the cascade of care, allowing reduction in the transmission period following each new infection. Delayed diagnosis remains the main obstacle to ending AIDS in the next decade.

No Association Between HLA-B*57:01 and Prevalence and/or Outcome of Progressive Multifocal Leukoencephalopathy in a French Nationwide Human Immunodeficiency Virus Cohort.

Among 34,351 patients living with human immunodeficiency virus with available HLA-B*57:01 included in the Dat'AIDS cohort, 194 patients (0.56%) had a history of progressive multifocal leukoencephalopathy (PML) and 1,746 (5.08%) were carriers of HLA-B*57:01. The frequency of HLA-B*57:01 was similar among patients with history of PML compared with patients without a history of PML (6.19% [95% confidence interval, CI 2.8%-9.6%] vs. 5.08% [95% CI 4.8%-5.3%]; p = .48). Among patients with PML, clinical and biological characteristics at PML diagnosis and the PML outcome were not different according to HLA-B*57:01 status.

Country of birth is associated with discrepancies in the prescription of two-drug regimens in successfully treated people with HIV in France.

OBJECTIVES: We aimed to examine the association of the country of birth and the other patients' characteristics with the prescription of two-drug regimens (2DRs) in virally suppressed people with HIV (PWH) in France. DESIGN: Observational study conducted from the national Dat'AIDS prospectively collected database. METHODS: We included all adults who were actively in care on 31 December 2020 in 26 French centers, with an HIV plasma viral load (pVL) <50 copies/ml for at least 6 months while on antiretroviral therapy (ART). Patients with chronic hepatitis B were excluded because they are not eligible to 2DRs. Univariate and multivariate logistic regressions were built to analyze relationships between patients' characteristics and receiving a 2DR. RESULTS: We analyzed data from 28 395 PWH: 41.7% men who have sex with men, 31.7% women and 26.5% heterosexual men; 35% born abroad. Median age was 53 years [interquartile range (IQR) 44-60]; ART duration 14 years (8-23); duration of virological suppression 87 months (42-142). 2DRs (mainly dolutegravir/rilpivirine, 53.8%, or dolutegravir/lamivudine, 41.7%) were prescribed in 16.3% of the patients and were less common in the 'born abroad' group (18.9% versus 11.5%). The multivariate model showed that individuals born in France were more likely to receive a 2DR [adjusted odds ratio (aOR): 1.62 [1.50-1.74]], independently of other characteristics. Older PLWH and those with higher CD4 + T-cell counts were also more likely to receive a 2DR. CONCLUSION: Despite unrestricted access to ART in France, independently from HIV disease parameters, PWH born abroad were less likely to receive 2DRs as a maintenance regimen than those born in France. Qualitative data are needed to better understand physicians' prescribing practices.

Country of birth is associated with antiretroviral therapy choice in treatment-naive persons with HIV in France.

OBJECTIVES: We aimed to describe factors associated with the choice of first antiretroviral therapy (ART) in persons with HIV (PWH) in France, included the country of birth, as well as the time to undetectable viral load and treatment discontinuation. DESIGN: Observational study conducted from the national Dat'AIDS prospectively collected database. METHODS: We included all adults who started their first ART between 01 January 2014 and 31 December 2020, with a pretherapeutic plasma viral load (pVL) at least 400 copies/ml. Univariable and multivariable logistic regressions were used to analyze PWH characteristics driving to an integrase strand transfer inhibitors (INSTI)-based first prescribed regimen. We also analyzed time to first line discontinuation, and to a first undetectable pVL, using Kaplan-Meier model. RESULTS: We analyzed data from 9094 PWH: 45% MSM, 27% women and 27% heterosexual men; 48% born abroad; 4.7 and 2.8% with concomitant hepatitis B and tuberculosis, respectively. INSTIs were prescribed as first-line therapy in 50% of PWH, which increased over time. Native French PWH were more likely to receive an INSTI-based regimen than PWH born abroad [adjusted prevalence ratio 1.47, 95% confidence interval (CI) 1.33-1.60], as were high pVL at diagnosis, hepatitis B or concomitant tuberculosis. Time before discontinuation of the first ART and reaching a first undetectable pVL was not different according to the place of birth. CONCLUSION: Despite unrestricted access to INSTIs in France, independently from HIV disease parameters, PWH born abroad received INSTIs less frequently as a first regimen than those born in France. Qualitative data are needed to better understand physicians' prescribing practices.

Low-level viral loads and virological failure in the integrase strand transfer era.

OBJECTIVES: To analyse the occurrence of virological failure (VF) in patients starting ART with an integrase strand transfer inhibitor (INSTI)-based regimen in recent years, in relation with previous episodes of low-level viral load (LLVL). PATIENTS AND METHODS: Patients starting a first ART between 1 January 2015 and 31 December 2020 based on two NRTIs and one INSTI were included if after virological control (two measures of VL < 50 copies/mL) they had a minimum of two additional VL measurements. Cox models adjusted for sex, age, acquisition group, hepatitis B or C coinfection, place of birth, year of ART initiation, CD4+ T cells and VL at ART initiation, duration of known HIV infection and of ART regimen were used to assess the association between the time to VF and the occurrence of LLVL. ART regimen was evaluated as time-varying covariate. RESULTS: LLVL was described in 13.7% and VF in 11% of the 3302 patients. LLVL was associated with VF [adjusted HR (aHR) 1.76, 95% CI 1.28-2.41], as well as age (aHR 0.97/year, 95% CI 0.96-0.98), CD4+ T cell count at ART initiation (aHR 0.93, 95% CI 0.87-0.98), heterosexual transmission (aHR 1.76, 95% CI 1.30-2.37) and being born abroad (aHR 1.50, 95% CI 1.17-1.93). CONCLUSIONS: LLVL was related to VF. Even in the absence of subsequent failure, LLV episodes have a cost. Thus any VL value above 50 copies/mL should lead to enhanced adherence counselling.

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.

COVID-19 and Pasteurella multocida Pulmonary Coinfection: A Case Series.

OBJECTIVES: In COVID-19 patients, bacterial and fungal pulmonary coinfections, such as Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, or Aspergillus, have been reported, but to our knowledge, no case has been reported due to Pasteurella multocida. PATIENTS AND METHODS: We describe three cases of Pasteurella multocida coinfections occurring during the 4th wave of COVID-19 in Martinique (French West Indies). RESULTS: All three cases were fatal; thus, Pasteurella multocida has to be considered as a potentially severe coinfection agent. CONCLUSIONS: Alteration of the epithelial-endothelial barrier due to a SARS-CoV-2 infection probably promotes the expression of a Pasteurella infection. In addition, the SARS-CoV-2 infection induced immunosuppression, and an inflammatory cascade could explain the infection's severity. The use of corticosteroids, which are part of the first-line therapeutic arsenal against COVID-19, may also promote the pathogenicity of this agent.

Economic impact of generic antiretrovirals in France for HIV patients' care: a simulation between 2019 and 2023.

BACKGROUND: In a context where the economic burden of HIV is increasing as HIV patients now have a close to normal lifespan, the availability of generic antiretrovirals commonly prescribed in 2017 and the imminence of patent expiration are expected to provide substantial savings in the coming years. This article aims to assess the economic impact of these generic antiretrovirals in France and specifically over a five-year period. METHODS: An agent-based model was developed to simulate patient trajectories and treatment use over a five-year period. By comparing the results of costs for trajectories simulated under different predefined scenarios, a budget impact model can be created and sensitivity analyses performed on several parameters of importance. RESULTS: The potential economic savings from 2019 to 2023 generated by generic antiretrovirals range from €309 million when the penetration rate of generics is set at 10% to €1.5 billion at 70%. These savings range from €984 million to €993 million as the delay between patent and generic marketing authorisation varies from 10 to 15 years, and from €965 million to €993 million as the Negotiated Price per Unit (NPU) of generics at market-entry varies from 40 to 50% of the NPU for patents. DISCUSSION: This economic savings simulation could help decision makers to anticipate resource allocations for further innovation in antiretrovirals therapies as well as prevention, especially by funding the Pre-Exposure Prophylaxis (PrEP) or HIV screening.

No increased risk of Kaposi sarcoma relapse in patients with controlled HIV-1 infection after switching protease inhibitor-based antiretroviral therapy.

OBJECTIVES: Our aim was to assess if switching from a protease inhibitors (PI)-based regimen to a PI-free one is associated with an increased risk of Kaposi Sarcoma (KS) relapse among patients living with HIV (PLHIV) with history of KS and controlled HIV replication. METHODS: In a retrospective analysis of the prospectively collected Dat'AIDS database we selected patients who both had a past KS history and a HIV-1 viral load below 200 copies/mL while being PI-treated. We searched for KS relapses while persistent virological success was maintained for at least 6 months, whether patients kept taking the PI, or switched to PI-free regimen. RESULTS: Among the 216 patients with past KS event and a history of HIV-1 infection efficiently treated by a PI-based regimen, 148 patients (68.5%) later switched to a PI-sparing regimen. Their baseline characteristics were not different from non-switching patients. We described 7 cases of relapse (3.2% of the 216 patients). Five cases of relapse occurred in switching patients (3.4%). The remaining two relapses occurred in PI-treated patients (2.9%). At KS relapse, CD4 cell count was 459 cells/µL (range 225-560) for switching patients, compared with 362 and 136 cells/µL for the other two patients. CONCLUSIONS: In this large cohort of PLHIV with a history of KS and ART-controlled HIV replication, KS relapses were described in 3.2% of the patients, and were not more frequent when a PI-containing ART regimen has been switched to a PI-free regimen. Our results do not support a specific effect of PI on KS.

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.

Dolutegravir-based dual maintenance regimens combined with lamivudine/emtricitabine or rilpivirine: risk of virological failure in a real-life setting.

BACKGROUND: Maintenance ART with dolutegravir-based dual regimens have proved their efficacy among HIV-1-infected subjects in randomized trials. However, real-life data are scarce, with limited populations and follow-up. OBJECTIVES: We assessed virological failure (VF) and resistance-associated mutations (RAMs) on dolutegravir maintenance regimens in combination with rilpivirine or with lamivudine or emtricitabine (xTC) and analysed the factors associated with VF. METHODS: Between 2014 and 2018, all HIV-1-infected adults included in the Dat'AIDS cohort and starting dolutegravir/rilpivirine or dolutegravir/xTC as a maintenance dolutegravir-based dual regimen were selected. VF was defined as two consecutive HIV RNA values >50 copies/mL or a single value >400 copies/mL. We compared cumulative genotypes before initiation of a maintenance dolutegravir-based dual regimen with genotype at VF. RESULTS: We analysed 1374 subjects (799 on dolutegravir/rilpivirine and 575 on dolutegravir/xTC) with a median follow-up of 20 months (IQR = 11-31) and 19 months (IQR = 11-31), respectively. VF occurred in 3.8% (n = 30) of dolutegravir/rilpivirine subjects and 2.6% (n = 15) of dolutegravir/xTC subjects. Among subjects receiving dolutegravir/rilpivirine, two genotypes harboured emerging RAMs at VF: E138K on NNRTI (n = 1); and E138K+K101E on NNRTI and N155H on INSTI (n = 1). Among subjects receiving dolutegravir/xTC, no new RAM was detected. The only predictive factor of VF on dolutegravir/rilpivirine was the history of failure on an NNRTI-based regimen (adjusted HR = 2.97, 95% CI = 1.28-6.93). No factor was associated with VF on dolutegravir/xTC. CONCLUSIONS: In this large real-life cohort, dolutegravir/rilpivirine and dolutegravir/xTC sustained virological suppression and were associated with a low rate of VF and RAM emergence. Careful virological screening is essential before switching to dolutegravir/rilpivirine in virologically suppressed patients with a history of NNRTI therapy.

No barrier to care, yet disparities in the HIV care continuum in France: a nationwide population study.

OBJECTIVES: Even in an 'optimal' health system, patients' characteristics may have an impact on their care. We investigated whether age, gender and place of birth have an impact in the HIV care continuum in France, a country with a universal free healthcare system. METHODS: We estimated differences in the 5 year restricted mean percentage of person-time spent (i) in care, (ii) receiving ART and (iii) on ART and virally suppressed among 2432 (30.2%) women, 3925 MSM (48.7%) and 1709 men who have sex with women (MSW; 21.2%) entering care in the Dat'AIDS French prospective cohort between 1 January 2013 and 31 December 2017. Trial registration: Clinicaltrials.gov reference NCT02898987. RESULTS: Men and women spent 85.6% and 82.8% of person-time on ART and 69.9% and 65% suppressed, respectively. MSM, MSW and women spent 86.9%, 82.6% and 82.8% of person-time on ART and 72.5%, 63.7% and 65% suppressed, respectively. Patients born in France (47%) and patients born abroad spent 87.9% and 81.9% of person-time on ART and 74.6% and 62.9% suppressed, respectively. Young men born abroad were found to spend the smallest person-time with non-detectable viral load (53% for MSW and 58.1% for MSM). CONCLUSIONS: Despite free access to care and universal ART in France, disparities remain in the HIV continuum care across age, country of birth and way of HIV acquisition. Clinical and public health interventions targeting specific patients' conditions are needed.

The effects of chikungunya virus infection on people living with HIV during the 2014 Martinique outbreak.

Our objective was to describe the clinical presentation of chikungunya virus (CHIKV) infection in patients living with HIV (PLHIV) during the 2014 Martinique outbreak. During the outbreak and the 6 following months, all PLHIV coming in our unit for a medical evaluation answered questions about potential CHIKV related symptoms, and had blood tests to assess the diagnosis. For patients coming in at the acute phase of infection, we are able to provide and analyze CD4+, CD8+ T-cells and HIV viral load evolution before, during and after CHIK infection. Among the 1 003 PLHIV in care in the center at the time of the outbreak, 188 (94 men and 94 women) had confirmed (following the WHO definition) CHIKV infection. Clinical presentation was common in 63% of the cases, severe and atypical forms were scarce. During the acute phase, CD4+ and CD8+ T-cells (evaluated in 30 PLHIV, 15 men and 15 women) absolute numbers dropped significantly, but returned to pre-CHIKV values after the acute phase. Reassuringly, CD4 and CD8 T cells proportions did not decrease during the acute phase. CHIKV infection had no significant impact on this anti-retroviral treated population.

Factors associated with psoriasis in a French Nationwide HIV cohort: the independent role of HLA-B*57:01.

OBJECTIVE: Psoriasis is a T-cell-mediated inflammatory disease with genetic factors involved in its etiopathogenesis. In non-HIV populations, HLA-B57:01 has been associated with a higher risk of psoriasis. The aim of this study was to investigate demographic and immunovirological characteristics associated with psoriasis, and to assess whether HLA-B57:01 is associated with psoriasis among people living with HIV (PLHIV) followed in a large French multicenter Dat'AIDS cohort. METHODS: All PLHIV followed up from January 2000 to December 2018 with an available result for HLA-B57:01 were included. Logistic regression models were used to identify associations between psoriasis (outcome variable) and explanatory variables. RESULTS: Among 31 076 PLHIV, the overall prevalence of psoriasis and HLA-B57:01 were 2.25 and 4.73%, respectively and varied according to ethnicity. By multivariate analysis, male gender [OR 1.81 (95% CI 1.46-2.24), P < 10], positive HLA-B57:01 [OR 2.66 (95% CI 2.12-3.33), P < 10], nadir CD4 cell count less than 200 cells/µl [OR 1.41 (95% CI 1.19-1.67), P < 10] and positive HCV serology [OR 1.45 (95% CI 1.20-1.76), P < 10] were significantly associated with a higher risk of psoriasis. Being born in West and Central Africa [OR 0.15 (95% CI 0.10-0.25), P < 10], the Caribbean islands [OR 0.14 (95% CI 0.05-0.45), P = 0.0008] or Latin America [OR 0.31 (95% CI 0.14-0.69), P = 0.004] was associated with a lower risk of psoriasis compared with patients born in mainland France. CONCLUSION: PLHIV carrying HLA-B57:01 have around a three-fold increased risk of psoriasis. This association might provide a possible explanation for the observed differences in psoriasis prevalence between ethnic groups.

Reaching the Second and Third Joint United Nations Programme on HIV/AIDS 90-90-90 Targets Is Accompanied by a Dramatic Reduction in Primary Human Immunodeficiency Virus (HIV) Infection and in Recent HIV Infections in a Large French Nationwide HIV Cohort.

BACKGROUND: In late 2013, France was one of the first countries to recommend initiation of combination antiretroviral therapy (cART) irrespective of CD4 cell count. METHODS: To assess the impact of achieving the second and third Joint United Nations Programme on HIV/AIDS 90-90-90 targets (ie, 90% of diagnosed people on sustained cART, and, of those, 90% virologically controlled) on human immunodeficiency virus (HIV) incidence, we conducted a longitudinal study to describe the epidemiology of primary HIV infection (PHI) and/or recent HIV infection (patients with CD4 cell count ≥500/mm3 at HIV diagnosis; (PRHI) between 2007 and 2017 in a large French multicenter cohort. To identify changes in trends in PHI and PRHI, we used single breakpoint linear segmented regression analysis. RESULTS: During the study period, 61 822 patients were followed in the Dat'AIDS cohort; 2027 (10.0%) had PHI and 7314 (36.1%) had PRHI. The second and third targets were reached in 2014 and 2013, respectively. The median delay between HIV diagnosis and cART initiation decreased from 9.07 (interquartile range [IQR], 1.39-33.47) months in 2007 to 0.77 (IQR, 0.37-1.60) months in 2017. A decrease in PHI (-35.1%) and PRHI (-25.4%) was observed starting in 2013. The breakpoints for PHI and PRHI were 2012.6 (95% confidence interval [CI], 2010.8-2014.4) and 2013.1 (95% CI, 2011.3-2014.8), respectively. CONCLUSIONS: Our findings show that the achievements of 2 public health targets in France and the early initiation of cART were accompanied by a reduction of about one-third in PHI and PRHI between 2013 and 2017. CLINICAL TRIALS REGISTRATION: NCT02898987.