PrEP in Europe - expectations, opportunities and barriers

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

Examining oral pre-exposure prophylaxis (PrEP) literacy among participants in an HIV vaccine trial preparedness cohort study

Background: PrEP literacy is influenced by many factors including the types of information available and how it is interpreted. The level of PrEP literacy may influence acceptability and uptake. Methods: We conducted 25 in-depth interviews in a HIV vaccine trial preparedness cohort study. We explored what participants knew about PrEP, sources of PrEP knowledge and how much they know about PrEP. We used the framework approach to generate themes for analysis guided by the Social Ecological Model and examined levels of PrEP literacy using the individual and interpersonal constructs of the SEM. Results: We found that PrEP awareness is strongly influenced by external factors such as social media and how much participants know about HIV treatment and prevention in the local community. However, while participants highlighted the importance of the internet/social media as a source of information about PrEP they talked of low PrEP literacy in their communities. Participants indicated that their own knowledge came as a result of joining the HIV vaccine trial preparedness study. However, some expressed doubts about the effectiveness of the drug and worried about side effects. Participants commented that at the community level PrEP was associated with being sexually active, because it was used to prevent the sexual transmission of HIV. As a result, some participants commented that one could feel judged by the health workers for asking for PrEP at health facilities in the community. Conclusion: The information collected in this study provided an understanding of the different layers of influence around individuals that are important to address to improve PrEP acceptability and uptake. Our findings can inform strategies to address the barriers to PrEP uptake, particularly at structural and community levels. Trial registration: https://clinicaltrials.gov/ct2/show/NCT0406688

Priming with a Simplified Intradermal HIV-1 DNA Vaccine Regimen followed by Boosting with Recombinant HIV-1 MVA Vaccine Is Safe and Immunogenic: A Phase IIa Randomized Clinical Trial

<div><p>Background</p><p>Intradermal priming with HIV-1 DNA plasmids followed by HIV-1MVA boosting induces strong and broad cellular and humoral immune responses. In our previous HIVIS-03 trial, we used 5 injections with 2 pools of HIV-DNA at separate sites for each priming immunization. The present study explores whether HIV-DNA priming can be simplified by reducing the number of DNA injections and administration of combined versus separated plasmid pools.</p><p>Methods</p><p>In this phase IIa, randomized trial, priming was performed using 5 injections of HIV-DNA, 1000 μg total dose, (3 Env and 2 Gag encoding plasmids) compared to two “simplified” regimens of 2 injections of HIV-DNA, 600 μg total dose, of Env- and Gag-encoding plasmid pools with each pool either administered separately or combined. HIV-DNA immunizations were given intradermally at weeks 0, 4, and 12. Boosting was performed intramuscularly with 10⁸ pfu HIV-MVA at weeks 30 and 46.</p><p>Results</p><p>129 healthy Tanzanian participants were enrolled. There were no differences in adverse events between the groups. The proportion of IFN-γ ELISpot responders to Gag and/or Env peptides after the second HIV-MVA boost did not differ significantly between the groups primed with 2 injections of combined HIV-DNA pools, 2 injections with separated pools, and 5 injections with separated pools (90%, 97% and 97%). There were no significant differences in the magnitude of Gag and/or Env IFN-γ ELISpot responses, in CD4+ and CD8+ T cell responses measured as IFN-γ/IL-2 production by intracellular cytokine staining (ICS) or in response rates and median titers for binding antibodies to Env gp160 between study groups.</p><p>Conclusions</p><p>A simplified intradermal vaccination regimen with 2 injections of a total of 600 μg with combined HIV-DNA plasmids primed cellular responses as efficiently as the standard regimen of 5 injections of a total of 1000 μg with separated plasmid pools after boosting twice with HIV-MVA.</p><p>Trial Registration</p><p>World Health Organization International Clinical Trials Registry Platform <a href="http://apps.who.int/trialsearch/Trial2.aspx?TrialID=PACTR2010050002122368" target="_blank">PACTR2010050002122368</a></p></div

Antibody endpoint titers.

<p>Antibody endpoint titers to native HIV-1_IIIB subtype B gp160 one month after the second HIV-MVA vaccination. Data is shown for each of the HIV-DNA priming groups. The dashed line shows a titer of 100, corresponding to a 1:100 serum dilution, the lowest dilution used in the assay.</p

Number of individuals screened, randomized and allocated to the three vaccination groups and withdrawn from the trial.

<p>Number of individuals screened, randomized and allocated to the three vaccination groups and withdrawn from the trial.</p

The proportion of ICS responders to Gag or Env peptide pools two weeks after the first and second HIV-MVA vaccination in each of the HIV-DNA primed groups.

<p>The proportion of ICS responders to Gag or Env peptide pools two weeks after the first and second HIV-MVA vaccination in each of the HIV-DNA primed groups.</p

Randomized study groups, doses and routes of HIV-DNA and HIV-MVA vaccinations.

<p>Note: ID = intradermal, IM = intramuscular, pfu = plaque forming units.</p><p>Combined refers to a combination of plasmid pools 1 and 2, separated refers to each plasmid pool given separately.</p><p>Randomized study groups, doses and routes of HIV-DNA and HIV-MVA vaccinations.</p

Baseline characteristics.

<p>Note: Values are numbers (%) or medians (interquartile ranges).</p><p>Combined refers to a combination of plasmid pools 1 and 2, separated refers to each plasmid pool given separately.</p><p>Baseline characteristics.</p

Proportion of ELISpot responders to Gag and/or Env peptides two weeks post first and second HIV-MVA vaccination in each of the HIV-DNA primed groups.

<p>Proportion of ELISpot responders to Gag and/or Env peptides two weeks post first and second HIV-MVA vaccination in each of the HIV-DNA primed groups.</p