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Introduction While bio‐behavioural interventions (BIs) for sexually transmitted infections (STIs) and HIV prevention have shown their effectiveness (e.g. treatment for syphilis, HPV vaccination or pre‐exposure prophylaxis [PrEP]), they have also aroused major concerns regarding behavioural changes that could counteract their benefit. Risk compensation (RC) fears concerning BIs in the HIV/STIs prevention field are intimately linked to representations, judgements and social control on sexual behaviour. With an increasing number of PrEP studies describing a rise in STIs due to RC, this paper argues for a shift away from the focus on RC and proposes a more constructive approach to respond to the needs of people living with HIV and populations most at risk. Discussion The concept of RC, stemming from road safety and derived from economic theory, relies on rational theoretical models of human behaviour. Although widely applied in several contexts its use has been reasonably questioned. Major methodological issues regarding RC have been raised within HIV/AIDS literature. Although behavioural changes (e.g. condomless sex and number of sexual partners) are often erroneously assimilated with RC, there is no evidence that behavioural changes have undermined the effectiveness of previous and current BIs. Still, PrEP has not escaped RC concerns. Increases in condomless sex within the context of growing uptake of PrEP signals a continued need for integrated and innovative HIV and STI prevention strategies and a comprehensive sexual health approach. Routine HIV/STI testing, peer‐led counselling, and identification of sexual health needs within the PrEP model of care could become a gold standard in the sexual health field for all populations. Conclusions RC remains a frequent argument against the availability and provision of prevention methods for vulnerable populations. Individuals should be able to benefit from the full panel of BIs options available, to find and adapt methods according to their needs. Current, past and future PrEP users, with other stakeholders, may provide valuable insight into innovative solutions and programmes to control HIV and other STIs.

Since 2022, Europe has had 4 cases of extensively drug-resistant Neisseria gonorrhoeae, sequence type 16406, that is resistant to ceftriaxone and highly resistant to azithromycin. We report 2 new cases from France in 2023 involving strains genetically related to the 4 cases from Europe as well as isolates from Cambodia.

Introduction In contrast to the global trend showing a decline in new HIV infections, the number reported in the World Health Organization (WHO) region of Europe is increasing. Health systems are disparate, but even countries with free access to screening and treatment observe continuing high rates of new infections in key populations, notably men who have sex with men (MSM). Pre‐exposure prophylaxis (PrEP) is only available in France. This commentary describes the European epidemics and healthcare settings where PrEP could be delivered, how need might be estimated for MSM and the residual barriers to access. Discussion Health systems and government commitment to HIV prevention and care, both financial and political, differ considerably between the countries that make up Europe. A common feature is that funds for prevention are a small fraction of funds for care. Although care is generally good, access is limited in the middle‐income countries of Eastern Europe and central Asia, and only 19% of people living with HIV received antiretroviral therapy in 2014. It is challenging to motivate governments or civil society to implement PrEP in the context of this unmet treatment need, which is driven by limited national health budgets and diminishing assistance from foreign aid. The high‐income countries of Western Europe have hesitated to embrace PrEP for different reasons, initially due to key gaps in the evidence. Now that PrEP has been shown to be highly effective in European MSM in two randomized controlled trials, it is clear that the major barrier is the cost of the drug which is still on patent, although inadequate health systems and diminishing investment in civil society are also key challenges to overcome. Conclusions The momentum to implement PrEP in European countries is increasing and provides a welcome opportunity to expand and improve clinical services and civil society support focused on HIV and related infections including other sexually transmitted and blood‐borne infections.

Efavirenz with tenofovir-disoproxil-fumarate and emtricitabine is a preferred antiretroviral regimen for treatment-naive patients infected with HIV-1. Rilpivirine, a new non-nucleoside reverse transcriptase inhibitor, has shown similar antiviral efficacy to efavirenz in a phase 2b trial with two nucleoside/nucleotide reverse transcriptase inhibitors. We aimed to assess the efficacy, safety, and tolerability of rilpivirine versus efavirenz, each combined with tenofovir-disoproxil-fumarate and emtricitabine. We did a phase 3, randomised, double-blind, double-dummy, active-controlled trial, in patients infected with HIV-1 who were treatment-naive. The patients were aged 18 years or older with a plasma viral load at screening of 5000 copies per mL or greater, and viral sensitivity to all study drugs. Our trial was done at 112 sites across 21 countries. Patients were randomly assigned by a computer-generated interactive web response system to receive either once-daily 25 mg rilpivirine or once-daily 600 mg efavirenz, each with tenofovir-disoproxil-fumarate and emtricitabine. Our primary objective was to show non-inferiority (12% margin) of rilpivirine to efavirenz in terms of the percentage of patients with confirmed response (viral load <50 copies per mL intention-to-treat time-to-loss-of-virological-response [ITT-TLOVR] algorithm) at week 48. Our primary analysis was by intention-to-treat. We also used logistic regression to adjust for baseline viral load. This trial is registered with ClinicalTrials.gov, number NCT00540449. 346 patients were randomly assigned to receive rilpivirine and 344 to receive efavirenz and received at least one dose of study drug, with 287 (83%) and 285 (83%) in the respective groups having a confirmed response at week 48. The point estimate from a logistic regression model for the percentage difference in response was −0·4 (95% CI −5·9 to 5·2), confirming non-inferiority with a 12% margin (primary endpoint). The incidence of virological failures was 13% (rilpivirine) versus 6% (efavirenz; 11% vs 4% by ITT-TLOVR). Grade 2–4 adverse events (55 [16%] on rilpivirine vs 108 [31%] on efavirenz, p<0·0001), discontinuations due to adverse events (eight [2%] on rilpivirine vs 27 [8%] on efavirenz), rash, dizziness, and abnormal dreams or nightmares were more common with efavirenz. Increases in plasma lipids were significantly lower with rilpivirine. Rilpivirine showed non-inferior efficacy compared with efavirenz, with a higher virological-failure rate, but a more favourable safety and tolerability profile. Tibotec.

The HIV integrase strand transfer inhibitor elvitegravir (EVG) has been co-formulated with the CYP3A4 inhibitor cobicistat (COBI), emtricitabine (FTC), and tenofovir disoproxil fumarate (TDF) into a once-daily, single tablet. We compared EVG/COBI/FTC/TDF with a ritonavir-boosted (RTV) protease inhibitor regimen of atazanavir (ATV)/RTV+FTC/TDF as initial therapy for HIV-1 infection. This phase 3, non-inferiority study enrolled treatment-naive patients with an HIV-1 RNA concentration of 5000 copies per mL or more and susceptibility to atazanavir, emtricitabine, and tenofovir. Patients were randomly assigned (1:1) to receive EVG/COBI/FTC/TDF or ATV/RTV+FTC/TDF plus matching placebos, administered once daily. Randomisation was by a computer-generated random sequence, accessed via an interactive telephone and web response system. Patients, and investigators and study staff who gave treatments, assessed outcomes, or analysed data were masked to the assignment. The primary endpoint was HIV RNA concentration of 50 copies per mL or less after 48 weeks (according to the US FDA snapshot algorithm), with a 12% non-inferiority margin. This trial is registered with ClinicalTrials.gov, number NCT01106586. 1017 patients were screened, 715 were enrolled, and 708 were treated (353 with EVG/COBI/FTC/TDF and 355 with ATV/RTV+FTC/TDF). EVG/COBI/FTC/TDF was non-inferior to ATV/RTV+FTC/TDF for the primary outcome (316 patients [89·5%] vs 308 patients [86·8%], adjusted difference 3·0%, 95% CI −1·9% to 7·8%). Both regimens had favourable safety and tolerability; 13 (3·7%) versus 18 (5·1%) patients discontinued treatment because of adverse events. Fewer patients receiving EVG/COBI/FTC/TDF had abnormal results in liver function tests than did those receiving ATV/RTV+FTC/TDF and had smaller median increases in fasting triglyceride concentration (90 μmol/L vs 260 μmol/L, p=0·006). Small median increases in serum creatinine concentration with accompanying decreases in estimated glomerular filtration rate occurred in both study groups by week 2; they generally stabilised by week 8 and did not change up to week 48 (median change 11 μmol/L vs 7 μmol/L). If regulatory approval is given, EVG/COBI/FTC/TDF would be the first integrase-inhibitor-based regimen given once daily and the only one formulated as a single tablet for initial HIV treatment. Gilead Sciences.

Dexamethasone is standard of care for the treatment of patients with COVID-19 requiring oxygen. The objective is to assess the clinical benefit of adding remdesivir to dexamethasone. A retrospective cohort study of hospitalized patients with COVID-19 pneumonia requesting low-flow oxygen who received dexamethasone. Patients admitted to infectious diseases wards also received remdesivir. Primary outcome was duration of hospitalization after oxygen initiation. Secondary outcomes were in-hospital death, and death and/or transfer to the intensive care unit. To handle potential confounding by indication bias, outcome comparison was performed on propensity score-matched populations. Propensity score was estimated by a multivariable logistic model including prognostic covariates; then 1:1 matching was performed without replacement, using the nearest neighbor algorithm with a caliper of 0.10 fold the standard deviation of the propensity score as the maximal distance. Balance after matching was checked on standardized mean differences. From August 15th 2020, to February 28th, 2021, 325 patients were included, 101 of whom received remdesivir. At admission median time from symptoms onset was 7 days, median age: 68 years, male sex; 61%, >1 comorbidity: 58.5%. Overall 180 patients matched on propensity score were analyzed, 90 each received remdesivir plus dexamethasone or dexamethasone alone. Median duration of hospitalization was 9 (IQR: 7-13) and 9 (IQR: 5-18) days with and without remdesivir, respectively (p = 0.37). In-hospital death rates and rates of transfer to the intensive care unit or death were 8.9 and 17.8% (HR: 0.46, 95% CI: 0.21-1.02, p = 0.06) and 20.0 and 35.6% with and without remdesivir, respectively (HR: 0.45, 95% CI: 0.23-0.89, p = 0.015). In hospitalized patients with COVID-19 pneumonia receiving low-flow oxygen and dexamethasone, the addition of remdesivir was not associated with shorter hospitalization or lower in-hospital mortality but may have reduced the combined outcome of death and transfer to the intensive care unit.

Introduction In France, oral pre‐exposure prophylaxis (PrEP) for HIV prevention has been publicly available since 2016, mainly targeting at men who have sex with men (MSM). Reliable and robust estimations of the actual PrEP uptake among MSM on a localized level can provide additional insights to identify and better reach marginalized MSM within current HIV prevention service provision. This study used national pharmaco‐epidemiology surveillance data and regional MSM population estimations to model the spatio‐temporal distribution of PrEP uptake among MSM in France 2016–2021 to identify marginalized MSM at risk for HIV and increase their PrEP uptake. Methods We first applied Bayesian spatial analyses with survey‐surveillance‐based HIV incidence data as a spatial proxy to estimate the size of (1) regional HIV‐negative MSM populations and (2) MSM who could be eligible for PrEP use according to French PrEP guidelines. We then applied Bayesian spatio‐temporal ecological regression modelling to estimate the regional prevalence and relative probability of the overall‐ and new‐PrEP uptake from 2016 to 2021 across France. Results HIV‐negative and PrEP‐eligible MSM populations vary regionally across France. Île‐de‐France was estimated to have the highest MSM density compared to other French regions. According to the final spatio‐temporal model, the relative probability of overall PrEP uptake was heterogeneous across France but remained stable over time. Urban areas have higher‐than‐average probabilities of PrEP uptake. The prevalence of PrEP use increased steadily (ranging from 8.8% [95% credible interval 8.5%;9.0%] in Nouvelle‐Aquitaine to 38.2% [36.5%;39.9%] in Centre‐Val‐de‐Loire in 2021). Conclusions Our results show that using Bayesian spatial analysis as a novel methodology to estimate the localized HIV‐negative MSM population is feasible and applicable. Spatio‐temporal models showed that despite the increasing prevalence of PrEP use in all regions, geographical disparities and inequalities of PrEP uptake continued to exist over time. We identified regions that would benefit from greater tailoring and delivery efforts. Based on our findings, public health policies and HIV prevention strategies could be adjusted to better combat HIV infections and to accelerate ending the HIV epidemic.

The interconnectedness of the global HIV and sexually transmitted infection (STI) epidemics necessitates integrated strategies to address both. This Series paper highlights the biological link between HIV and STIs, and describes the successful progress in HIV response versus STI response over the past decades. The concept of undetectable=untransmissible (U=U) in HIV treatment has revolutionised HIV prevention by reducing stigma and promoting early treatment. In line with this approach, we discuss the role of chronic suppressive therapy for herpes simplex virus type 2 and the importance of the accurate diagnosis and treatment of curable STIs to prevent transmission between sexual partners. This Series paper explores the potential of pre-exposure prophylaxis (PrEP) for HIV in different forms (eg, daily oral PrEP, event-driven PrEP, and long-acting injectable PrEP), and highlights the challenges of adherence to daily regimens and the promise of longer-acting agents, such as cabotegravir and lenacapavir. The potential of doxycycline post-exposure prophylaxis for the prevention of bacterial STIs is also discussed, with concerns about antimicrobial resistance. Although vaccine development for HIV and STIs is a key biomedical advance, we discuss the challenges and possibilities of developing effective vaccines, including lessons learnt from previous HIV vaccine trials, the potential of mRNA-based vaccines for herpes simplex virus, ongoing trials for gonorrhoea and chlamydia vaccines, and the impact of existing human papillomavirus and mpox vaccines. Diagnostic innovations emphasise the importance of point-of-care tests for HIV and STIs. This Series paper discusses the benefits, landscape, and pipeline of rapid diagnostic tests (eg, lateral flow tests and molecular assays) and the challenges of implementing these tests in low-resource settings, particularly the need for rapid results to inform clinical decisions, promote convenience, and reduce cost. This Series paper also addresses innovations in service delivery and advocates for integrated and person-centred approaches (eg, differentiated services) that combine HIV and STI services, and highlights the potential of community-based and home-based models to improve access and reduce stigma.

Background The use of long acting injectable (LAA) antiretroviral drugs may be an alternative option for HIV treatment and prevention. Our study focused on patient perspectives to understand which individuals, among people with HIV (PWH) and pre-exposure prophylaxis (PrEP) users, would constitute the preferential target for such treatments in terms of expectations, tolerability, adherence and quality of life. Methods The study consisted in one self-administrated questionnaire. Data collected included lifestyle issues, medical history, perceived benefits and inconveniences of LAA. Groups were compared using Wilcoxon rank tests or Fisher’s exact test. Results In 2018, 100 PWH and 100 PrEP users were enrolled. Overall, 74% of PWH and 89% of PrEP users expressed interest for LAA with a significantly higher rate for PrEP users (p = 0.001). No characteristics were associated with acceptance of LAA in both groups in term of demographics, lifestyle or comorbidities. Conclusion PWH and PrEP users expressed a high level of interest in LAA, since a large majority seems to be in favor of this new approach. Further studies should be conducted to better characterize targeted individuals.

Although interferon-free regimens are approved for patients co-infected with HIV and genotype-2 or genotype-3 hepatitis C virus (HCV), interferon-based regimens are still an option for those co-infected with HIV and HCV genotypes 1 or 4. These regimens are limited by clinically significant toxic effects and drug interactions with antiretroviral therapy. We aimed to assess the efficacy and safety of an interferon-free, all-oral regimen of sofosbuvir plus ribavirin in patients with HIV and HCV co-infection. We did this open-label, non-randomised, uncontrolled, phase 3 study at 45 sites in seven European countries and Australia. We enrolled patients (aged ≥18 years) co-infected with stable HIV and chronic HCV genotypes 1–4, including those with compensated cirrhosis. Once-daily sofosbuvir (400 mg) plus twice-daily ribavirin (1000 mg in patients with bodyweights <75 kg and 1200 mg in those with weights ≥75 kg) was given for 24 weeks to all patients except treatment-naive patients with genotype-2 HCV, who received a 12-week regimen. The primary efficacy endpoint was sustained virological response 12 weeks after treatment. We did analysis by modified intention to treat. This study is registered with ClinicalTrials.gov, number NCT01783678. Between Feb 7, 2013, and July 29, 2013, we enrolled 275 eligible patients, of whom 262 (95%) completed treatment; 274 patients were included in the final analysis. Overall rates of sustained virological response 12 weeks after treatment were 85% (95% CI 77–91) in patients with genotype-1 HCV, 88% (69–98) in patients with genotype-2 HCV, 89% (81–94) in patients with genotype-3 HCV, and 84% (66–95) in patients with genotype-4 HCV. Response rates in treatment-naive patients with HCV genotypes 2 or 3 (89% [95% CI 67–99] and 91% [81–97], respectively) were similar to those in treatment-experienced patients infected with those genotypes (83% [36–100] and 86% [73–94], respectively). There was no emergence of sofosbuvir-resistance mutations in patients with HCV viral relapse. Six (2%) patients discontinued treatment because of adverse events. The most common adverse events were fatigue, insomnia, asthenia, and headache. Four (1%) patients had serious adverse events regarded as related to study treatment. Additionally, four (1%) patients receiving antiretroviral treatment had a transient HIV viral breakthrough; however, none required changes in antiretroviral regimen. Sofosbuvir and ribavirin provided high rates of sustained virological response after 12 weeks of treatment in treatment-naive and treatment-experienced patients co-infected with HIV and HCV genotypes 1–4. The characteristics of this interferon-free combination regimen make sofosbuvir plus ribavirin a useful treatment option for this patient population. Gilead Sciences.