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.
Background
The European AIDS Clinical Society (EACS) guidelines were revised in 2023 for the 19th time, and all aspects of HIV care were updated.
Key Points of the Guidelines Update
Version 12.0 of ...the guidelines recommend the same six first‐line treatment options for antiretroviral treatment (ART)‐naïve adults as versions 11.0 and 11.1: tenofovir‐based backbone plus an unboosted integrase inhibitor or doravirine; abacavir/lamivudine plus dolutegravir; or dual therapy with lamivudine or emtricitabine plus dolutegravir. The long‐acting section has been expanded in the ART and drug–drug interaction (DDI) panels. Tables for preferred and alternative ART in children and adolescents have been updated, as has the section on prevention of vertical transmission, particularly with new guidance for breastfeeding. A new DDI table has been included for the ART and anti‐infective drugs used for opportunistic infections, sexually transmitted infections, and other infectious conditions; lenacapavir has been included in all DDI tables. New sections on alcohol use and patient‐reported outcome measures (PROMs) have been included in the comorbidity panel, in addition to updates on many relevant topics, such as new resource guidance for deprescribing in people with HIV. Other sections, including travel, cognitive impairment, cancer screening, sexual health, and diabetes have also been revised extensively. The algorithm for the management of acute hepatitis C virus infection has been removed, as current guidelines recommend immediate treatment of all people with recently acquired hepatitis C virus. Updates on vaccination for hepatitis B virus and recommendations for simplification to tenofovir‐free two‐drug regimens in people with isolated anti‐hepatitis B core antibodies are provided. In the opportunistic infections and COVID‐19 panel, guidance on the management of COVID‐19 in people with HIV has been updated according to the most up‐to‐date evidence, and a new section on monkeypox has been added.
Conclusions
In 2023, the EACS guidelines were updated extensively and now include several new sections. The recommendations are available as a free app, in interactive web format, and as a pdf online.
Several studies have analyzed antiviral immune pathways in late-stage severe COVID-19. However, the initial steps of SARS-CoV-2 antiviral immunity are poorly understood. Here we have isolated primary ...SARS-CoV-2 viral strains and studied their interaction with human plasmacytoid predendritic cells (pDCs), a key player in antiviral immunity. We show that pDCs are not productively infected by SARS-CoV-2. However, they efficiently diversified into activated P1-, P2-, and P3-pDC effector subsets in response to viral stimulation. They expressed CD80, CD86, CCR7, and OX40 ligand at levels similar to influenza virus-induced activation. They rapidly produced high levels of interferon-α, interferon-λ1, IL-6, IP-10, and IL-8. All major aspects of SARS-CoV-2-induced pDC activation were inhibited by hydroxychloroquine. Mechanistically, SARS-CoV-2-induced pDC activation critically depended on IRAK4 and UNC93B1, as established using pDC from genetically deficient patients. Overall, our data indicate that human pDC are efficiently activated by SARS-CoV-2 particles and may thus contribute to type I IFN-dependent immunity against SARS-CoV-2 infection.
Data from randomized trials are lacking on the benefits and risks of initiating antiretroviral therapy in patients with asymptomatic human immunodeficiency virus (HIV) infection who have a CD4+ count ...of more than 350 cells per cubic millimeter.
We randomly assigned HIV-positive adults who had a CD4+ count of more than 500 cells per cubic millimeter to start antiretroviral therapy immediately (immediate-initiation group) or to defer it until the CD4+ count decreased to 350 cells per cubic millimeter or until the development of the acquired immunodeficiency syndrome (AIDS) or another condition that dictated the use of antiretroviral therapy (deferred-initiation group). The primary composite end point was any serious AIDS-related event, serious non-AIDS-related event, or death from any cause.
A total of 4685 patients were followed for a mean of 3.0 years. At study entry, the median HIV viral load was 12,759 copies per milliliter, and the median CD4+ count was 651 cells per cubic millimeter. On May 15, 2015, on the basis of an interim analysis, the data and safety monitoring board determined that the study question had been answered and recommended that patients in the deferred-initiation group be offered antiretroviral therapy. The primary end point occurred in 42 patients in the immediate-initiation group (1.8%; 0.60 events per 100 person-years), as compared with 96 patients in the deferred-initiation group (4.1%; 1.38 events per 100 person-years), for a hazard ratio of 0.43 (95% confidence interval CI, 0.30 to 0.62; P<0.001). Hazard ratios for serious AIDS-related and serious non-AIDS-related events were 0.28 (95% CI, 0.15 to 0.50; P<0.001) and 0.61 (95% CI, 0.38 to 0.97; P=0.04), respectively. More than two thirds of the primary end points (68%) occurred in patients with a CD4+ count of more than 500 cells per cubic millimeter. The risks of a grade 4 event were similar in the two groups, as were the risks of unscheduled hospital admissions.
The initiation of antiretroviral therapy in HIV-positive adults with a CD4+ count of more than 500 cells per cubic millimeter provided net benefits over starting such therapy in patients after the CD4+ count had declined to 350 cells per cubic millimeter. (Funded by the National Institute of Allergy and Infectious Diseases and others; START ClinicalTrials.gov number, NCT00867048.).
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.
A 36-year-old man attended our hospital with an 8-day history of two vesiculopustular lesions on his penis (figure); he reported no fever or inguinal lymphadenopathy. PCR on a sample from a penile ...swab was negative for herpes simplex virus types 1 and 2, and varicella zoster virus, although a concurrent pharyngeal gonorrhoea infection was found. Comparisons between the sequences from the different episodes showed the viruses differed at 14 single nucleotides, one DNA sequence insertion, and one DNA sequence deletion (appendix).
Summary Background 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. Methods 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. Findings 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. Interpretation Rilpivirine showed non-inferior efficacy compared with efavirenz, with a higher virological-failure rate, but a more favourable safety and tolerability profile. Funding Tibotec.
Data on the use of antiretroviral drugs, including new drugs and formulations, for the treatment and prevention of HIV infection continue to guide optimal practices.
To evaluate new data and ...incorporate them into current recommendations for initiating HIV therapy, monitoring individuals starting on therapy, changing regimens, preventing HIV infection for those at risk, and special considerations for older people with HIV.
New evidence was collected since the previous International Antiviral (formerly AIDS) Society-USA recommendations in 2018, including data published or presented at peer-reviewed scientific conferences through August 22, 2020. A volunteer panel of 15 experts in HIV research and patient care considered these data and updated previous recommendations.
From 5316 citations about antiretroviral drugs identified, 549 were included to form the evidence basis for these recommendations. Antiretroviral therapy is recommended as soon as possible for all individuals with HIV who have detectable viremia. Most patients can start with a 3-drug regimen or now a 2-drug regimen, which includes an integrase strand transfer inhibitor. Effective options are available for patients who may be pregnant, those who have specific clinical conditions, such as kidney, liver, or cardiovascular disease, those who have opportunistic diseases, or those who have health care access issues. Recommended for the first time, a long-acting antiretroviral regimen injected once every 4 weeks for treatment or every 8 weeks pending approval by regulatory bodies and availability. For individuals at risk for HIV, preexposure prophylaxis with an oral regimen is recommended or, pending approval by regulatory bodies and availability, with a long-acting injection given every 8 weeks. Monitoring before and during therapy for effectiveness and safety is recommended. Switching therapy for virological failure is relatively rare at this time, and the recommendations for switching therapies for convenience and for other reasons are included. With the survival benefits provided by therapy, recommendations are made for older individuals with HIV. The current coronavirus disease 2019 pandemic poses particular challenges for HIV research, care, and efforts to end the HIV epidemic.
Advances in HIV prevention and management with antiretroviral drugs continue to improve clinical care and outcomes among individuals at risk for and with HIV.
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