Introduction
Despite the advent of HIV cure‐related clinical trials (HCRCT) for people living with HIV (PLWH), the risks and uncertainty involved raise ethical issues. Although research has provided ...insights into the levers and barriers to PLWH and physicians' participation in these trials, no information exists about stakeholders' preferences for HCRCT attributes, about the different ways PLWH and physicians value future HCRCT, or about how personal characteristics affect these preferences. The results from the present study will inform researchers' decisions about the most suitable HCRCT strategies to implement, and help them ensure ethical recruitment and well‐designed informed consent.
Methods
Between October 2016 and March 2017, a discrete choice experiment was conducted among 195 virally controlled PLWH and 160 physicians from 24 French HIV centres. Profiles within each group, based on individual characteristics, were obtained using hierarchical clustering. Trade‐offs between five HCRCT attributes (trial duration, consultation frequency, moderate (digestive disorders, flu‐type syndrome, fatigue) and severe (allergy, infections, risk of cancer) side effects (SE), outcomes) and utilities associated with four HCRCT candidates (latency reactivation, immunotherapy, gene therapy and a combination of latency reactivation and immunotherapy), were estimated using a mixed logit model.
Results
Apart from severe SE – the most decisive attribute in both groups – PLWH and physicians made different trade‐offs between HCRCT attributes, the latter being more concerned about outcomes, the former about the burden of participation (consultation frequency and moderate SE). These different trades‐offs resulted in differences in preferences regarding the four candidate HCRCT. PLWH significantly preferred immunotherapy, whereas physicians preferred immunotherapy and combined therapy. Despite the heterogeneity of characteristics within the PLWH and physician profiles, results show some homogeneity in trade‐offs and utilities regarding HCRCT.
Conclusions
Severe SE, not outcomes, was the most decisive attribute determining future HCRCT participation. Particular attention should be paid to providing clear information, in particular on severe SE, to potential participants. Immunotherapy would appear to be the best HCRCT candidate for both PLWH and physicians. However, if the risk of cancer could be avoided, gene therapy would become the preferred strategy for the latter and the second choice for the former.
Giant viruses such as Mimivirus isolated from amoeba found in aquatic habitats show biological sophistication comparable to that of simple cellular life forms and seem to evolve by similar ...mechanisms, including extensive gene duplication and horizontal gene transfer (HGT), possibly in part through a viral parasite, the virophage. We report here the isolation of "Marseille" virus, a previously uncharacterized giant virus of amoeba. The virions of Marseillevirus encompass a 368-kb genome, a minimum of 49 proteins, and some messenger RNAs. Phylogenetic analysis of core genes indicates that Marseillevirus is the prototype of a family of nucleocytoplasmic large DNA viruses (NCLDV) of eukaryotes. The genome repertoire of the virus is composed of typical NCLDV core genes and genes apparently obtained from eukaryotic hosts and their parasites or symbionts, both bacterial and viral. We propose that amoebae are "melting pots" of microbial evolution where diverse forms emerge, including giant viruses with complex gene repertoires of various origins.
Mimivirus is the largest known virus whose genome and physical size are comparable to some small bacteria, blurring the boundary between a virus and a cell. Structural studies of Mimivirus have been ...difficult because of its size and long surface fibers. Here we report the use of enzymatic digestions to remove the surface fibers of Mimivirus in order to expose the surface of the viral capsid. Cryo-electron microscopy (cryoEM) and atomic force microscopy were able to show that the 20 icosahedral faces of Mimivirus capsids have hexagonal arrays of depressions. Each depression is surrounded by six trimeric capsomers that are similar in structure to those in many other large, icosahedral double-stranded DNA viruses. Whereas in most viruses these capsomers are hexagonally close-packed with the same orientation in each face, in Mimivirus there are vacancies at the systematic depressions with neighboring capsomers differing in orientation by 60 degrees . The previously observed starfish-shaped feature is well-resolved and found to be on each virus particle and is associated with a special pentameric vertex. The arms of the starfish fit into the gaps between the five faces surrounding the unique vertex, acting as a seal. Furthermore, the enveloped nucleocapsid is accurately positioned and oriented within the capsid with a concave surface facing the unique vertex. Thus, the starfish-shaped feature and the organization of the nucleocapsid might regulate the delivery of the genome to the host. The structure of Mimivirus, as well as the various fiber components observed in the virus, suggests that the Mimivirus genome includes genes derived from both eukaryotic and prokaryotic organisms. The three-dimensional cryoEM reconstruction reported here is of a virus with a volume that is one order of magnitude larger than any previously reported molecular assembly studied at a resolution of equal to or better than 65 Angstroms.
Despite huge advances in the fight against HIV concerning diagnosis, clinical efficacy of antiretroviral treatments (ART), patient survival and quality of life, there is still no cure. Recent ...developments in HIV cure research have opened the way for clinical trials which could lead to a temporary or definitive end to ART. However, ethical questions exist about related trial-participation risks. The main goal of the ANRS-APSEC survey was, using Q-methodology, to investigate the viewpoints of people living with HIV (PLWH) and HIV healthcare providers (HHP) regarding motivations for and barriers to participation in HIV Cure-related clinical trials (HCRCT).
Thirty-three statements were defined encompassing seven dimensions: treatment and follow-up; risks; benefits; patient-physician relationship; beliefs and attitudes; information; target population. Forty-one PLWH and 41 HHP from five French HIV services were asked to rank-order the statements.
Five main viewpoints were elicited from "the most motivated" to "the most reluctant" vis-à-vis HCRCT participation. All placed importance on the wish to participate in HIV research. This result is in line with the HIV-specific culture of joint mobilization. For some viewpoints, the motivation to participate in/propose HCRCT was primarily conditioned by side-effects and/or by constraints, which overall were more accepted by PLWH than HHP. Some viewpoints placed particular importance on HCRCT recruitment strategies. Finally, some expressed a high acceptance of risks and constraints but emphasized the need for information.
HIV cure research clinical trials (HCRCT) constitute a risky yet unavoidable step towards the goal of finding a cure. To improve future HCRCT and informed consent designs, based on PLWH and HHP preferences and expectations, we need greater knowledge about how these populations perceive the risks and the benefits of HCRCT. Our results confirmed the importance of careful, studied HCRCT design, management and communication, to ensure PLWH and HHP acceptability and convergence of their expectations.
ANRS-IPERGAY was a community-based randomized trial investigating the efficacy of sexual activity-based HIV pre-exposure prophylaxis (PrEP) in a population of males and transgender females who had ...sex with men and were at high risk of HIV infection. We qualitatively analyzed the support provided to participants by community-based health workers (CBHW) throughout the trial's double-blind and open-label extension phases. In particular, we showed that the relationship between participants and CBHW strongly influenced self-managed pill intake. The delicate construction of this relationship, balanced between trust and dependence, played an important role in PrEP adherence. CBHW had to deal with various issues surrounding participants' feelings of empowerment regarding their role in the trial, as well as related tensions between various logics and rationalities. They were essential to participants' continued involvement.
Acanthamoeba polyphaga Mimivirus is a giant double-stranded DNA virus defining a new genus, the Mimiviridae, among the Nucleo-Cytoplasmic Large DNA Viruses (NCLDV). We used utrastructural studies to ...shed light on the different steps of the Mimivirus replication cycle: entry via phagocytosis, release of viral DNA into the cell cytoplasm through fusion of viral and vacuolar membranes, and finally viral morphogenesis in an extraordinary giant cytoplasmic virus factory (VF). Fluorescent staining of the AT-rich Mimivirus DNA showed that it enters the host nucleus prior to the generation of a cytoplasmic independent replication centre that forms the core of the VF. Assembly and filling of viral capsids were observed within the replication centre, before release into the cell cytoplasm where progeny virions accumulated. 3D reconstruction from fluorescent and differential contrast interference images revealed the VF emerging from the cell surface as a volcano-like structure. Its size dramatically grew during the 24 h infectious lytic cycle. Our results showed that Mimivirus replication is an extremely efficient process that results from a rapid takeover of cellular machinery, and takes place in a unique and autonomous giant assembly centre, leading to the release of a large number of complex virions through amoebal lysis.
The community-based AERLI intervention provided training and education to people who inject drugs (PWID) about HIV and HCV transmission risk reduction, with a focus on drug injecting practices, other ...injection-related complications, and access to HIV and HCV testing and care. We hypothesized that in such a population where HCV prevalence is very high and where few know their HCV serostatus, AERLI would lead to increased HCV testing.
The national multisite intervention study ANRS-AERLI consisted in assessing the impact of an injection-centered face-to-face educational session offered in volunteer harm reduction (HR) centers ("with intervention") compared with standard HR centers ("without intervention"). The study included 271 PWID interviewed on three occasions: enrolment, 6 and 12 months. Participants in the intervention group received at least one face-to-face educational session during the first 6 months.
The primary outcome of this analysis was reporting to have been tested for HCV during the previous 6 months. Statistical analyses used a two-step Heckman approach to account for bias arising from the non-randomized clustering design. This approach identified factors associated with HCV testing during the previous 6 months.
Of the 271 participants, 127 and 144 were enrolled in the control and intervention groups, respectively. Of the latter, 113 received at least one educational session. For the present analysis, we selected 114 and 88 participants eligible for HCV testing in the control and intervention groups, respectively. In the intervention group, 44% of participants reported having being tested for HCV during the previous 6 months at enrolment and 85% at 6 months or 12 months. In the control group, these percentages were 51% at enrolment and 78% at 12 months. Multivariable analyses showed that participants who received at least one educational session during follow-up were more likely to report HCV testing, compared with those who did not receive any intervention (95%CI = 4.131.03;16.60).
The educational intervention AERLI had already shown efficiency in reducing HCV at-risk practices and associated cutaneous complications and also seems to have a positive impact in increasing HCV testing in PWID.
Pleasure-seeking plays a role in prevention (means choices and use), and in the sexual quality of life of men who have sex with men (MSM). Since HIV is a major threat to MSM health, new means of ...prevention, like pre-exposure prophylaxis (PrEP), must meet the needs of MSM to be fully efficient. Using a psychosocial approach, we examined how pleasure-seeking plays a role in participation of MSM in “ANRS-IPERGAY,” a community-based trial on sexual health which included sexual on-demand PrEP. Thirteen semistructured collective interviews were conducted with 45 participants. First, we analyzed participants’ search for new prevention means due to previous failures in condom use. We found that participants perceived condoms as a barrier—both materially and symbolically—to pleasure and desire, causing anxiety and stress considering sexual intercourse. Second, we explored representations and attitudes concerning pleasure within the context of PrEP. We found that PrEP allowed participants to freely choose their desired sexual positions and to better enjoy intimacy. Third, we studied the sexual quality of life for PrEP users in ANRS-IPERGAY and found an improvement. Thanks to the community-based design of the trial, this new prevention tool became a means to develop agency and empowerment for participants, not only in negotiating individual prevention but also in opposing the normative and stigmatizing discourse on sexuality and HIV. In conclusion, pleasure-seeking appears to be an essential element of sexual fulfillment that needs to be integrated as a positive notion in the study of HIV prevention.
•Unsafe injecting practices are associated with infectious and non-infectious diseases.•This educational intervention seems to be effective in reducing unsafe practices.•It affects hygiene practices, ...the use of sterile equipment and injecting technique.•This intervention needs to be evaluated in different contexts.
People who inject drugs face several health issues because of unsafe injecting practices. We aimed to evaluate changes in supervised drug-injecting practices following the implementation of a face-to-face educational intervention.
The national study ANRS-AERLI was conducted in 17 harm reduction (HR) facilities in France between 2011 and 2013. Eight offered the intervention and nine did not. We conducted a pre-post analysis focusing on injecting practices data, collected in the 8 HR facilities providing the intervention. The intervention consisted of providing face-to-face educational sessions including direct observation of injecting practices, counseling about safer injecting, and shared discussion. Injecting practices were collected following a checklist and classified as safe or unsafe. To assess changes in injecting practices, practices were compared before (at baseline) and after at least one educational session.
Mixed logistic models showed that the 78 participants included were more likely to improve in the following drug-use steps: setting up a clean preparation area (Adjusted Odds Ratio (AOR) = 3.4, 95% Confidence Interval (95% CI) = 1.6–7.6), hand washing (AOR = 7.2, 95% CI = 3.1–16.4), skin cleaning (AOR = 5.6, 95% CI = 2.5–12.1), choice of safe injection site (AOR = 6.5, 95% CI = 1.5–28.8) and post-injection bleeding management (AOR = 12.8, 95% CI = 5.5–29.9). Furthermore, participants were less likely to lick their needles before injecting (AOR = 8.1, 95% CI = 1.5–43.4) and to perform booting/flushing (AOR = 2.5, 95% CI = 1.2–5.3).
The AERLI intervention seems to be effective in increasing safe drug-injecting practices.
Little is known about the public health benefits of community-based, non-medicalized rapid HIV testing offers (CBOffer) specifically targeting men who have sex with men (MSM), compared with the ...standard medicalized HIV testing offer (SMOffer) in France. This study aimed to verify whether such a CBOffer, implemented in voluntary counselling and testing centres, could improve access to less recently HIV-tested MSM who present a risk behaviour profile similar to or higher than MSM tested with the SMOffer.
This multisite study enrolled MSM attending voluntary counselling and testing centres' during opening hours in the SMOffer. CBOffer enrolees voluntarily came to the centres outside of opening hours, following a communication campaign in gay venues. A self-administered questionnaire was used to investigate HIV testing history and sexual behaviours including inconsistent condom use and risk reduction behaviours (in particular, a score of "intentional avoidance" for various at-risk situations was calculated). A mixed logistic regression identified factors associated with access to the CBOffer.
Among the 330 participants, 64% attended the CBOffer. Percentages of inconsistent condom use in both offers were similar (51% CBOffer, 50% SMOffer). In multivariate analyses, those attending the CBOffer had only one or no test in the previous two years, had a lower intentional avoidance score, and met more casual partners in saunas and backrooms than SMOffer enrolees.
This specific rapid CBOffer attracted MSM less recently HIV-tested, who presented similar inconsistent condom use rates to SMOffer enrolees but who exposed themselves more to HIV-associated risks. Increasing entry points for HIV testing using community and non-medicalized tests is a priority to reach MSM who are still excluded.
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