UK guideline for the use of HIV post-exposure prophylaxis 2021.

We present the updated British Association for Sexual Health and HIV (BASHH) guidelines for post-exposure prophylaxis (PEP) to HIV following sexual exposures, occupational exposures and other nonoccupational exposures in the community. This serves as an update to the 2015 BASHH guideline on PEP following sexual exposures and the 2008 Expert Advisory Group on AIDS guidelines on HIV PEP. We aim to provide evidence-based guidance on best clinical practice in the provision, monitoring and support of PEP for the prevention of HIV acquisition following sexual, occupational and other nonoccupational exposures in the community. The guideline covers when to prescribe PEP, what antiretroviral agents to use and how to manage PEP. This includes (i) evidence of PEP efficacy; (ii) evidence relating to individual-level efficacy of antiretroviral therapy to prevent the sexual transmission of HIV; (iii) data on the detectable (transmissible) prevalence of HIV in specific populations; (iv) risk of HIV transmission following different types of sexual and occupational exposure; (v) baseline risk assessment; (vi) drug regimens and dosing schedules; (vii) monitoring PEP; (viii) baseline and follow-up blood-borne virus testing; (ix) the role of PEP within broader HIV prevention strategies, for example, HIV pre-exposure prophylaxis (PrEP). The guideline also covers special scenarios such as PEP in pregnancy, breastfeeding and chronic hepatitis B virus infection, and when PEP should be considered in people using HIV PrEP. The guidelines are aimed at clinical professionals directly involved in PEP provision and other stakeholders in the field. A proforma to assist PEP consultations is included. A public consultation process was undertaken prior to finalizing the recommendations.

Self-start HIV postexposure prophylaxis (PEPSE), to reduce time to first dose and increase efficacy.

BACKGROUND: Effectiveness of HIV postexposure prophylaxis (PEPSE) correlates with speed of uptake following HIV exposure. Time to first dose has not improved in the UK for over 10 years. On-demand pre-exposure prophylaxis (PrEP) has shown that people can self-start medication for HIV prevention.We hypothesised that advanced provision of PEPSE (HOME PEPSE) for men who have sex with men (MSM) to self- initiate would reduce time to first dose following HIV exposure. METHODS: Phase IV, randomised, prospective, 48-week, open-label study was carried out. MSM at medium risk of acquiring HIV were randomised (1:1) to immediate or deferred standard of care (SOC) HOME PEPSE. Every 12 weeks, participants self-completed mental health/risk behaviour surveys and had HIV/sexually transmitted infection (STI) testing.HOME PEPSE comprised a 5-day pack of emtricitabine/tenofovir disoproxil fumarate/maraviroc 600 mg once daily initiated following potential exposure to HIV. If taken, participants completed a risk survey; PEPSE continuation was physician directed. Primary outcome was time from potential exposure to HIV to first PEPSE dose. FINDINGS: 139 participants randomised 1:1; 69 to immediate HOME PEPSE and 70 to deferred HOME PEPSE. Median age 30 years (IQR 26-39), 75% white, 55% UK born and 72% university educated. 31 in HOME PEPSE and 15 in SOC arm initiated PEPSE. Uptake of HOME PEPSE was appropriate in 27/31 cases (87%, 95% CI: 71% to 95%). Median time from exposure to first dose was 7.3 hours (3.0, 20.9) for HOME PEPSE and 28.5 hours (17.3, 34.0) for SOC (p<0.01). HOME PEPSE was well tolerated with no discontinuations.No significant differences in missed opportunities for PEPSE uptake, sexual behaviour or bacterial STI infections between treatment arms. INTERPRETATION: HOME PEPSE reduced the time from exposure to first-dose PEPSE by 21+ hours, with no impact on safety. This significantly improves the efficacy of PEPSE and provides an option for people declining PrEP.

Symptoms of post-traumatic stress and associations with sexual behaviour and PrEP preferences among young people in South Africa, Uganda and Zimbabwe.

BACKGROUND: It is not known whether post-traumatic stress disorder (PTSD) increases HIV-risk behaviours among young people in sub-Saharan Africa. We assessed associations of PTSD symptoms with sexual behaviour, HIV risk perception, and attitudes towards PrEP among young people taking part in the CHAPS community survey. We hypothesised that PTSD symptoms would increase sexual behaviours associated with HIV risk, hinder PrEP uptake and influence preference for daily versus on-demand PrEP. METHODS: Young people without HIV, aged 13-24 years, were purposively recruited in Johannesburg and Cape Town in South Africa, Wakiso in Uganda, and Chitungwiza in Zimbabwe, and surveyed on socio-demographic characteristics, PrEP knowledge and attitudes, sexual behaviour, HIV perception and salience, and mental health. PTSD symptoms were measured using the Primary Care PTSD Screen for the Diagnostic and Statistical Manual of Mental Disorders 5 (PC-PTSD-5). Logistic and ordinal logistic regression was used to assess associations between PC-PTSD-5 score and socio-demographic characteristics, sexual behaviour, HIV risk perception, PrEP attitudes, and substance use, adjusting for age, sex, setting, depression and anxiety. RESULTS: Of 1330 young people (51% male, median age 19 years), 522 (39%) reported at least one PTSD symptom. There was strong evidence that having a higher PC-PTSD-5 score was associated with reported forced sex (OR 3.18, 95%CI: 2.05-4.93), self-perception as a person who takes risks (OR 1.12, 95%CI: 1.04-1.20), and increased frequency of thinking about risk of HIV acquisition (OR 1.16, 95%CI: 1.08-1.25). PTSD symptoms were not associated with willingness to take PrEP, preference for on-demand versus daily PrEP, or actual HIV risk behaviour such as condomless sex. CONCLUSIONS: Symptoms consistent with probable PTSD were common among young people in South Africa, Uganda and Zimbabwe but did not impact PrEP attitudes or PrEP preferences. Evaluation for PTSD might form part of a general assessment in sexual and reproductive health services in these countries. More work is needed to understand the impact of PTSD on HIV-risk behaviour, forced sex and response to preventive strategies including PrEP.

The potential effect of pre-exposure prophylaxis (PrEP) roll-out on sexual-risk behaviour among adolescents and young people in East and southern Africa.

Pre-exposure prophylaxis (PrEP) is an HIV-prevention strategy recommended for those at high-risk of infection, including adolescents and young people (AYP). We explored how PrEP roll-out could influence sexual risk behaviour among AYP in East and southern Africa. Twenty-four group discussions and 60 in-depth interviews were conducted with AYP between 13 and 24 years old, recruited from community settings in Uganda, Zimbabwe and South Africa, from September 2018 to January 2019. Participants perceived that PrEP availability could change sexual behaviour among AYP, influencing: (1) condom use (increased preference for condomless sex, reduced need and decrease in use of condoms, relief from condom use discomfort, consistent condom use to curb sexually transmitted infections and pregnancies); (2) sexual activities (increase in sexual partners and sexual encounters, early sexual debut, sexual experimentation and peace of mind during risky sex, sexual violence and perversion); (3) HIV risk perception (neglect of other HIV prevention strategies, unknown sexual partner HIV status, adoption of PrEP). PrEP initiation may be associated with increased interest in sexual activities and risky sexual behaviour among AYP. PrEP should be included as part of a combination package of HIV prevention strategies for AYP with methods to prevent other sexually transmitted infections and unwanted pregnancies.

Pharmacokinetic/pharmacodynamic investigation of raltegravir with or without lamivudine in the context of HIV-1 pre-exposure prophylaxis (PrEP).

BACKGROUND: To characterize their potential use in pre-exposure prophylaxis (PrEP) we compared the pharmacokinetics of raltegravir and lamivudine in genital tissue against ex vivo tissue infection with HIV-1. METHODS: Open-label trial of 36 HIV-negative females and males randomized to 7 days raltegravir 400 mg twice daily and 7 days raltegravir 400 mg+lamivudine 150 mg twice daily (after washout), or vice versa. Blood, saliva, rectal fluid, rectal tissue, vaginal fluid and vaginal tissue were sampled at baseline and on and off PrEP during a total of 12 days, for pharmacokinetics and antiviral activity via ex vivo HIV-1BaL challenge. Ex vivo infectivity was compared with baseline. The trial has been registered in https://clinicaltrials.gov/ with the identifier NCT03205566. RESULTS: Steady state for both drugs was reached by day 4. Dosing with raltegravir alone provided modest ex vivo HIV protection with higher drug levels in rectal tissue and vaginal tissue than in plasma on and off PrEP. Off PrEP, plasma and vaginal concentrations declined rapidly, while persisting in the rectum. On PrEP, the highest lamivudine concentrations were in the rectum, followed by vaginal tissue then plasma. Lamivudine washout was rapid in plasma, while persisting in the rectum and vagina. Raltegravir/lamivudine increased ex vivo protection on and off PrEP compared with raltegravir alone, reaching maximum protection at day 2 in rectal tissue and at day 8 in vaginal tissue. CONCLUSIONS: Raltegravir 400 mg+lamivudine 150 mg showed high levels of ex vivo HIV protection, associated with high drug concentrations persisting after discontinuation in vaginal and rectal compartments, supporting further investigation of these agents for PrEP.

Exploring Perceived Barriers and Facilitators of PrEP Uptake among Young People in Uganda, Zimbabwe, and South Africa.

Pre-exposure prophylaxis (PrEP) is an effective HIV prevention strategy. Few studies have explored adolescents and young people's perspectives toward PrEP. We conducted 24 group discussions and 60 in-depth interviews with males and females aged 13-24 years in Uganda, Zimbabwe, and South Africa between September 2018 and February 2019. We used the framework approach to generate themes and key concepts for analysis following the social ecological model. Young people expressed a willingness to use PrEP and identified potential barriers and facilitators of PrEP uptake. Barriers included factors at individual (fear of HIV, fear of side effects, and PrEP characteristics), interpersonal (parental influence, absence of a sexual partner), community (peer influence, social stigma), institutional (long waiting times at clinics, attitudes of health workers), and structural (cost of PrEP and mode of administration, accessibility concerns) levels. Facilitators included factors at individual (high HIV risk perception and preventing HIV/desire to remain HIV negative), interpersonal (peer influence, social support and care for PrEP uptake), community (adequate PrEP information and sensitization, evidence of PrEP efficacy and safety), institutional (convenient and responsive services, provision of appropriate and sufficiently resourced services), and structural (access and availability of PrEP, cost of PrEP) levels. The findings indicated that PrEP is an acceptable HIV prevention method. PrEP uptake is linked to personal and environmental factors that need to be considered for successful PrEP roll-out. Multi-level interventions needed to promote PrEP uptake should consider the social and structural drivers and focus on ways that can inspire PrEP uptake and limit the barriers.

A qualitative study to identify critical attributes and attribute-levels for a discrete choice experiment on oral pre-exposure prophylaxis (PrEP) delivery among young people in Cape Town and Johannesburg, South Africa.

BACKGROUND: The uptake and adherence of daily oral PrEP has been poor in high-risk populations in South Africa including young people. We used qualitative research methods to explore user preferences for daily and on-demand oral PrEP use among young South Africans, and to inform the identification of critical attributes and attribute-levels for quantitative analysis of user preferences, i.e. a discrete choice experiment (DCE). METHODS: Data were collected between September and November 2018 from eight group discussions and 20 in-depth interviews with young people 13 to 24 years in Cape Town and Johannesburg. Using a convenience sampling strategy, participants were stratified by sex and age. Interviewers used a semi-structured interview guide to discuss several attributes (dosing regimen, location, costs, side effects, and protection period) for PrEP access and use. Group discussions and in-depth interviews were audio-recorded, transcribed verbatim and translated to English. We used framework analysis to explore context-specific attributes and attribute-levels for delivering oral PrEP in South Africa. The adolescent community advisory board, expert and study team opinions were consulted for the final DCE attributes and levels. RESULTS: We enrolled 74 participants who were 51% (n = 38/74) male, had a median age of 18.5 [Interquartile range = 16-21.25] years, 91% (n = 67/74) identified as heterosexual and 49% (n = 36/74) had not completed 12th grade education. Using the qualitative data, we identified five candidate attributes including (1) dosing regimen, (2) location to get PrEP, (3) cost, (4) route of administration and (5) frequency. After discussions with experts and the study team, we revised the DCE to include the following five attributes and levels: dosing regime: daily, and on-demand PrEP; location: private pharmacy, public clinic, mobile clinic, ATM); cost: free-of-charge, R50 (~2GBP), R265 (~12GBP); side effects: nausea, headache, rash; and duration of protection: fulltime protection versus when PrEP is used). CONCLUSIONS: There is limited literature on qualitative research methods describing the step-by-step process of developing a DCE for PrEP in adolescents, especially in resource-constrained countries. We provide the process followed for the DCE technique to understand user preferences for daily and on-demand oral PrEP among young people in South Africa.

Immediate Versus Deferred Switching From a Boosted Protease Inhibitor-based Regimen to a Dolutegravir-based Regimen in Virologically Suppressed Patients With High Cardiovascular Risk or Age ≥50 Years: Final 96-Week Results of the NEAT022 Study.

Background: Both immediate and deferred switching from a ritonavir-boosted protease inhibitor (PI/r)-based regimen to a dolutegravir (DTG)-based regimen may improve lipid profile. Methods: European Network for AIDS Treatment 022 Study (NEAT022) is a European, open-label, randomized trial. Human immunodeficiency virus (HIV)-infected adults aged ≥50 years or with a Framingham score ≥10% were eligible if HIV RNA was <50 copies/mL. Patients were randomized to switch from PI/r to DTG immediately (DTG-I) or to deferred switch at week 48 (DTG-D). Week 96 endpoints were proportion of patients with HIV RNA <50 copies/mL, percentage change of lipid fractions, and adverse events (AEs). Results: Four hundred fifteen patients were randomized: 205 to DTG-I and 210 DTG-D. The primary objective of noninferiority at week 48 was met. At week 96, treatment success rate was 92.2% in the DTG-I arm and 87% in the DTG-D arm (difference, 5.2% [95% confidence interval, -.6% to 11%]). There were 5 virological failures in the DTG-I arm and 5 (1 while on PI/r and 4 after switching to DTG) in the DTG-D arm without selection of resistance mutations. There was no significant difference in terms of grade 3 or 4 AEs or treatment-modifying AEs. Total cholesterol and other lipid fractions (except high-density lipoprotein) significantly (P < .001) improved both after immediate and deferred switching to DTG overall and regardless of baseline PI/r strata. Conclusions: Both immediate and deferred switching from a PI/r to a DTG regimen in virologically suppressed HIV-infected patients ≥50 years old or with a Framingham score ≥10% was highly efficacious and well tolerated, and improved the lipid profile. Clinical Trials Registration: NCT02098837 and EudraCT: 2013-003704-39.

The Context of Sexual Risk Behaviour Among Men Who Have Sex with Men Seeking PrEP, and the Impact of PrEP on Sexual Behaviour.

There are still important gaps in our understanding of how people will incorporate PrEP into their existing HIV prevention strategies. In this paper, we explore how PrEP use impacted existing sexual risk behaviours and risk reduction strategies using qualitative data from the PROUD study. From February 2014 to January 2016, we conducted 41 in-depth interviews with gay, bisexual and other men who have sex with men (GBMSM) enrolled in the PROUD PrEP study at sexual health clinics in England. The interviews were conducted in English and were audio-recorded. The recordings were transcribed, coded and analysed using framework analysis. In the interviews, we explored participants' sexual behaviour before joining the study and among those using or who had used PrEP, changes to sexual behaviour after starting PrEP. Participants described the risk behaviour and management strategies before using PrEP, which included irregular condom use, sero-sorting, and strategic positioning. Participants described their sexual risk taking before initiating PrEP in the context of the sexualised use of drugs, geographical spaces linked with higher risk sexual norms, and digitised sexual networking, as well as problematic psychological factors that exacerbated risk taking. The findings highlight that in the main, individuals who were already having frequent condomless sex, added PrEP to the existing range of risk management strategies, influencing the boundaries of the 'rules' for some but not all. While approximately half the participants reduced other risk reduction strategies after starting PrEP, the other half did not alter their behaviours. PrEP provided an additional HIV prevention option to a cohort of GBMSM at high risk of HIV due to inconsistent use of other prevention options. In summary, PrEP provides a critical and necessary additional HIV prevention option that individuals can add to existing strategies in order to enhance protection, at least from HIV. As a daily pill, PrEP offers protection in the context of the sex cultures associated with sexualised drug use, digitised sexual applications and shifting social norms around sexual fulfilment and risk taking. PrEP can offer short or longer-term options for individuals as their sexual desires change over their life course offering protection from HIV during periods of heightened risk. PrEP should not be perceived or positioned in opposition to the existing HIV prevention toolkit, but rather as additive and as a tool that can and is having a substantial impact on HIV.

A qualitative study to explore daily versus on-demand oral pre-exposure prophylaxis (PrEP) in young people from South Africa, Uganda and Zimbabwe.

BACKGROUND: Adolescents in sub-Saharan Africa (SSA) remain vulnerable to HIV infection. While pre-exposure prophylaxis (PrEP) is highly effective in preventing HIV transmission as a daily or on-demand regimen, tailored approaches are necessary. The Combined HIV Adolescent PrEP and Prevention Study (CHAPS) is a mixed-methods research program investigating the acceptability and feasibility of implementing daily and on-demand PrEP among young people in SSA. It also aims to determine an on-demand dosing schedule for insertive sex. For this paper, we explored preferences for daily versus on-demand PrEP amongst adolescents as part of CHAPS. METHODS: Purposive sampling was used to recruit participants from Soweto and Cape Town (South Africa), Wakiso district (Uganda) and Chitungwiza (Zimbabwe). At the time of the study in 2018/2019, Uganda had not rolled out PrEP to the general population; in Zimbabwe, PrEP for young people was only available at selected sites with one located within the study recruitment area. In South Africa, PrEP was made available to selected high-risk groups. We conducted 60 in-depth interviews and 24 group discussions amongst young people aged 13-24 without HIV in South Africa, Uganda, and Zimbabwe. All in-depth interviews and group discussions were audio-recorded, transcribed verbatim and translated to English. Data were analysed using framework analysis. The main themes were centered around preferences for daily and on-demand PrEP. RESULTS: Reasons for on-demand preferences included stigma, pill fatigue, adherence and side effects. Reasons for daily PrEP preferences included factors related to sexual risk behaviour, continuous protection against incidents of unintentional exposure, and the increased efficacy of a daily dose. Participants at all sites preferring daily PrEP identified the same reasons, with more males than females citing inadvertent blood contact or perceived increased efficacy. Similarly, participants at all sites preferring on-demand PrEP gave the same reasons for their preferences for on-demand PrEP; the exception was South Africans who did not mention the hope of having fewer side effects by not taking daily PrEP. Additionally, more males than females cited intermittent sex as a reason for opting for on-demand PrEP. CONCLUSIONS: Our study is the first known to explore and describe youth preferences for daily versus on-demand PrEP. While the choice is clear-cut, the reasons cited in the different options provide invaluable insights into their decisions, and the actual and perceived facilitators and barriers to access to PrEP. Further education is needed amongst young people, not only about PrEP but also in other areas of comprehensive sexuality education. Exploring all options of HIV prevention is crucial to provide a tailored, one-size-does-not-fit-all approach to adolescent care in SSA to reduce and, the continued and increasing risk of this preventable infection.

Assessing the effectiveness of portable HEPA air cleaners for reducing particulate matter exposure in King County, Washington homeless shelters: Implications for community congregate settings.

Over four thousand portable air cleaners (PACs) with high-efficiency particulate air (HEPA) filters were distributed by Public Health - Seattle & King County to homeless shelters during the COVID-19 pandemic. This study aimed to evaluate the real-world effectiveness of these HEPA PACs in reducing indoor particles and understand the factors that affect their use in homeless shelters. Four rooms across three homeless shelters with varying geographic locations and operating conditions were enrolled in this study. At each shelter, multiple PACs were deployed based on the room volume and PAC's clean air delivery rate rating. The energy consumption of these PACs was measured using energy data loggers at 1-min intervals to allow tracking of their use and fan speed for three two-week sampling rounds, separated by single-week gaps, between February and April 2022. Total optical particle number concentration (OPNC) was measured at 2-min intervals at multiple indoor locations and an outdoor ambient location. The empirical indoor and outdoor total OPNC were compared for each site. Additionally, linear mixed-effects regression models (LMERs) were used to assess the relationship between PAC use time and indoor/outdoor total OPNC ratios (I/OOPNC). Based on the LMER models, a 10 % increase in the hourly, daily, and total time PACs were used significantly reduced I/OOPNC by 0.034 [95 % CI: 0.028, 0.040; p < 0.001], 0.051 [95 % CI: 0.020, 0.078; p < 0.001], and 0.252 [95 % CI: 0.150, 0.328; p < 0.001], respectively, indicating that keeping PACs on resulted in significantly lower I/OOPNC. The survey suggested that keeping PACs on and running was the main challenge when operating them in shelters. These findings suggested that HEPA PACs were an effective short-term strategy to reduce indoor particle levels in community congregate living settings during non-wildfire seasons and the need for formulating practical guidance for using them in such an environment.

Mobilization of systemic CCL4 following HIV pre-exposure prophylaxis in young men in Africa.

HIV-1 pre-exposure prophylaxis (PrEP) relies on inhibition of HIV-1 replication steps. To understand how PrEP modulates the immunological environment, we derived the plasma proteomic profile of men receiving emtricitabine-tenofovir (FTC-TDF) or emtricitabine-tenofovir alafenamide (FTC-TAF) during the CHAPS trial in South Africa and Uganda (NCT03986970). The CHAPS trial randomized 144 participants to one control and 8 PrEP arms, differing by drug type, number of PrEP doses and timing from final PrEP dose to sampling. Blood was collected pre- and post-PrEP. The inflammatory profile of plasma samples was analyzed using Olink (N=92 proteins) and Luminex (N=33) and associated with plasma drug concentrations using mass spectrometry. The proteins whose levels changed most significantly from pre- to post-PrEP were CCL4, CCL3 and TNF-α; CCL4 was the key discriminator between pre- and post-PrEP samples. CCL4 and CCL3 levels were significantly increased in post-PrEP samples compared to control specimens. CCL4 was significantly correlated with FTC drug levels in plasma. Production of inflammatory chemokines CCL4 and CCL3 in response to short-term PrEP indicates the mobilization of ligands which potentially block virus attachment to CCR5 HIV-1 co-receptor. The significant correlation between CCL4 and FTC levels suggests that CCL4 increase is modulated as an inflammatory response to PrEP.

Reductions in HIV transmission risk behaviour following diagnosis of primary HIV infection: a cohort of high-risk men who have sex with men.

BACKGROUND: Risk-reduction counselling is a standard preventive intervention, but behaviour change is difficult to sustain over the duration of HIV infection. However, primary HIV infection (PHI) is highly infectious and plays a key role in transmission - especially through dense sexual networks - but is short term, so even transient risk reduction can mitigate its high infectivity. Targeting behaviour-change interventions at recently infected individuals may be highly effective, particularly in higher risk groups. We explored the potential impact on HIV transmission-risk behaviour of PHI diagnosis in men who have sex with men (MSM). METHODS: MSM with PHI were interviewed at diagnosis and after 3 months of follow-up about their sexual behaviour in the 12-week periods before and after diagnosis and standard counselling. RESULTS: A total of 98 of 104 eligible MSM (94%) participated in the study, with 100% follow-up. PHI was associated with high levels of recreational drug use, low levels of condom use, high numbers of sexual partners and a history of sex work. In the 12 weeks post-diagnosis, 76% of participants eliminated risk of onward transmission entirely and, overall, there was a significant reduction in transmission-risk behaviour, with patients reporting greater condom use and fewer sexual partners. Those with continued transmission-risk behaviour were more likely to have another sexually transmitted infection (STI), use ketamine and have more sexual partners at baseline. CONCLUSIONS: Most MSM recently diagnosed with PHI changed their behaviour to substantially reduce the risk of onward HIV transmission. Strategies are needed to (a) increase diagnoses of PHI to target prevention efforts effectively and (b) further reduce risk behaviours by targeting enhanced counselling to those most likely to continue with risk behaviours.

Acceptability of an open-label wait-listed trial design: Experiences from the PROUD PrEP study.

BACKGROUND: PROUD participants were randomly assigned to receive pre-exposure prophylaxis (PrEP) immediately or after a deferred period of one-year. We report on the acceptability of this open-label wait-listed trial design. METHODS: Participants completed an acceptability questionnaire, which included categorical study acceptability data and free-text data on most and least liked aspects of the study. We also conducted in-depth interviews (IDI) with a purposely selected sub-sample of participants. RESULTS: Acceptability questionnaires were completed by 76% (415/544) of participants. After controlling for age, immediate-group participants were almost twice as likely as deferred-group participants to complete the questionnaire (AOR:1.86;95%CI:1.24,2.81). In quantitative data, the majority of participants in both groups found the wait-listed design acceptable when measured by satisfaction of joining the study, intention to remain in the study, and interest in joining a subsequent study. However, three-quarters thought that the chance of being in the deferred-group might put other volunteers off joining the study. In free-text responses, data collection tools were the most frequently reported least liked aspect of the study. A fifth of deferred participants reported 'being deferred' as the thing they least liked about the study. However, more deferred participants disliked the data collection tools than the fact that they had to wait a year to access PrEP. Participants in the IDIs had a good understanding of the rationale for the open-label wait-listed study design. Most accepted the design but acknowledged they were, or would have been, disappointed to be randomised to the deferred group. Five of the 25 participants interviewed reported some objection to the wait-listed design. CONCLUSION: The quantitative and qualitative findings suggest that in an environment where PrEP was not available, the rationale for the wait-listed trial design was well understood and generally acceptable to most participants in this study.

Raltegravir-induced Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome - implications for clinical practice and patient safety.

This case report describes two severe antiretroviral drug adverse reactions that occurred in the same patient. A 55-year-old HIV-positive African woman received a single epidural triamcinolone injection for pain relief of postherpetic neuralgia. Forty-one days later, she developed severe iatrogenic Cushing's syndrome due to the drug-drug interaction between triamcinolone and her boosted protease inhibitor therapy. The patient's antiretroviral regimen was thus changed to replace her protease inhibitor with the integrase inhibitor raltegravir. Shortly after commencing the drug, the patient developed a severe adverse drug reaction manifesting as Drug Reaction (or Rash) with Eosinophilia and Systemic Symptoms (DRESS) syndrome. First described in 1996, this hypersensitivity syndrome presents with severe skin reaction as well as fever, rash, lymphadenopathy and internal organ involvement with marked eosinophilia. Clinicians should be aware of raltegravir-induced DRESS syndrome as well as the potential for drug-drug interactions due to protease inhibitor-based therapy.